Japanese linguistic validation of the ureteral stent symptom questionnaire.

OBJECTIVE: We validated the Japanese version of the ureteral stent symptom questionnaire in patients with an indwelling ureteric stent. METHODS: The English version of the ureteral stent symptom questionnaire was translated into Japanese using a multistep process by three urologists and two independent translators. A total of 70 patients with indwelling ureteral stents completed the Japanese ureteral stent symptom questionnaire, as well as validated instruments, namely, the International Prostate Symptom Score or Overactive Bladder Symptom Score and the EuroQoL 5-dimension questionnaires. Patients completed questionnaires at 2 weeks after stent insertion and 4 weeks after stent removal. The second group included 87 healthy individuals who agreed to complete the questionnaires. The reliability of the Japanese version was evaluated for internal consistency using Cronbach's α test. Psychometric properties of the questionnaire were analyzed, and included convergent validity, sensitivity to change and discriminant validity. RESULTS: A total of 70 cases and 87 controls were suitable for the analysis. A comparison of patients with ureteric stents and healthy individuals was carried out, and the convergent validity determined by the correlation between other instruments and the corresponding ureteral stent symptoms questionnaire domains was satisfactory (P < 0.05). Internal consistencies (Cronbach's α coefficients 0.73-0.80) were satisfactory, except for the sexual matters domain. Test-retest reliability was good, except for the sexual matters domain (Spearman's coefficient 0.71-0.93). CONCLUSIONS: The Japanese version of the ureteral stent symptom questionnaire proved to be a reliable and robust instrument for the evaluation of ureteral stent-associated morbidity for both men and women.

Randomized Controlled Study of the Efficacy, Safety and Quality of Life with Low Dose bacillus Calmette-Guérin Instillation Therapy for Nonmuscle Invasive Bladder Cancer.

PURPOSE: The optimal dose of intravesical bacillus Calmette-Guérin for the treatment of nonmuscle invasive bladder cancer is controversial. We investigated if induction therapy with low dose bacillus Calmette-Guérin could achieve a complete response rate similar to that of standard dose bacillus Calmette-Guérin, with less toxicity and higher quality of life. MATERIALS AND METHODS: After transurethral resection, patients with unresectable multiple nonmuscle invasive bladder cancer and/or carcinoma in situ were randomized to receive standard (80 mg) or low dose (40 mg) bacillus Calmette-Guérin instillation induction therapy (weekly, 8 times). The primary end point was noninferiority of low dose bacillus Calmette-Guérin with a null hypothesis of a 15% decrease in complete response rate. Secondary end points were recurrence-free survival, progression-free survival, overall survival, patient compliance, adverse events and quality of life using the EORTC QLQ-C30. RESULTS: In an intent to treat analysis of 166 patients the complete response rates for low dose and standard dose bacillus Calmette-Guérin were 79% (95% CI 0.70-0.88) and 85% (95% CI 0.77-0.92), respectively. Dunnett-Gent analysis revealed that the null hypothesis of inferiority of low dose bacillus Calmette-Guérin in terms of complete response could not be rejected (p = 0.119). However, there were no significant differences between the groups in terms of recurrence, progression and overall survival. Low dose bacillus Calmette-Guérin was associated with significantly less fever (p = 0.001) and micturition pain (p = 0.047), and significantly higher quality of life scores for global quality of life, role functioning and functional impairment. CONCLUSIONS: The noninferiority of low dose bacillus Calmette-Guérin was not proven. However, low dose bacillus Calmette-Guérin was associated with lower toxicity and higher quality of life compared to standard dose bacillus Calmette-Guérin in patients with nonmuscle invasive bladder cancer.

Laparoscopic simultaneous bilateral adrenalectomy for testosterone-secreting bilateral adrenal tumors.

Laparoscopic adrenalectomy is widely accepted as a safe and minimally-invasive procedure. Although it is a standard procedure for the surgical treatment of adrenal tumors, its simultaneous use with bilateral adrenalectomy is relatively rare. A 21-year-old woman was referred to Hamamatsu University School of Medicine University Hospital complaining of a deepening voice, hirsutism and secondary amenorrhea. Abdominal computed tomography showed bilateral adrenal tumors, and hormonal examinations showed that the tumors secreted excessive testosterone, resulting in virilizing symptoms. Laparoscopic simultaneous bilateral adrenalectomy was carried out. Postoperatively, serum testosterone levels immediately recovered to within the normal range. Menstruation began the month after the operation, and the hirsutism gradually regressed. This is the third reported case of bilateral virilizing adrenal tumors, and the first to be successfully treated with laparoscopic simultaneous bilateral adrenalectomy.

Expression and functional role of ß3 -adrenoceptors in the human ureter.

OBJECTIVES: To investigate the presence of ß-adrenoceptor subtypes in the human ureter, and to examine whether ß(3) -adrenoceptors modulate relaxation of the human ureter. METHODS: Expression of messenger ribonucleic acid of ß-adrenoceptors in the human ureter was determined by reverse transcription polymerase chain reaction, and distribution of ß-adrenoceptors was examined by immunohistochemistry. In functional studies, the relaxant effects of isoproterenol, procaterol, TRK-380, salbutamol and BRL 37344 on KCl-induced contraction of the human ureter were evaluated, and the inhibitory effects of isoproterenol, procaterol and TRK-380 on electrical field stimulation-induced contractions were determined. RESULTS: Expression of ß(1) -, ß(2) - and ß(3) -adrenoceptor messenger ribonucleic acid in the human ureter was confirmed by reverse transcription polymerase chain reaction. Positive staining for ß(1) -, ß(2) - and ß(3) -adrenoceptor was identified not only in smooth muscle, but also in the urothelium of the human ureter. All ß-adrenoceptor agonists decreased the tone of KCl-induced contractions of the human ureter with a rank order of relaxant effects of isoproterenol > procaterol > TRK-380 > salbutamol > BRL 37344. Furthermore, isoproterenol, procaterol and TRK-380 significantly decreased the amplitude of electrical field stimulation-induced contractions with a rank order of inhibitory effects of isoproterenol > procaterol > TRK-380. CONCLUSIONS: Human ureteral relaxation is mediated by both ß(2) - and ß(3) -adrenoceptor stimulation. ß(3) -Adrenoceptor agonists have the potential to relax the human ureter, and their clinical application in the treatment of ureteral stones is expected.

[Long-term survival of metastatic clear cell adenocarcinoma of the female urethra by multidisciplinary treatment: a case report].

We report a case of clear cell adenocarcinoma of the female urethra. A 57-year-old woman presented with complaint of gross hematuria. Abdominal ultrasonography, cystourethroscopy, computed tomography (CT) and magnetic resonance imaging (MRI) revealed the urethral tumor was invasive to bladder neck. Clinical stage was determined as cT3N1M0, then anterior pelvic exenteration and ileal conduit formation were performed. The pathological diagnosis was clear cell adenocarcinoma of urethra and the stage was pT3N1. The patient received TS-1 and cisplatin for postoperative recurrence, but she died from multiple lung metastasis 54 months after the operation. Clear cell adenocarcinoma of the female urethra is rare case in the Japanese literatures. Pathogenesis and management of this rare condition are discussed.

[Bilateral adrenal hemorrhage due to adrenal metastasis of lung cancer].

A 58-year-old man presented with nausea and left flank pain. The patient was referred to our hospital based on clear detection of anemia and computed tomography findings of bilateral adrenal tumors with hemorrhage and a mass in the apex of the left lung. Right adrenal artery embolization had no effect on enlargement of the right adrenal hematoma or advanced anemia. Right adrenalectomy was then performed in an attempt to control hemorrhaging and make a definitive diagnosis, and the patient's anemia improved following the operation. Histopathological diagnosis suggested adrenal metastasis of lung adenocarcinoma, which was subsequently diagnosed given similarities in transbronchial biopsy findings to those in the right adrenal gland. Adrenal hemorrhage due to metastasis of lung cancer is an extremely rare condition; indeed, to our knowledge, the present case is only the 26th reported worldwide. However, prognosis for this mortal condition may be improved should patients receive adrenalectomy followed by an appropriate treatment regimen.

[Guidelines on urolithiasis: update of diagnosis and treatment].

The Japanese urolithiasis clinical guideline was established in 2002. Since that time, the American Urological Associstion (AUA) and European Association of Urology (EAU) nephrolithiasis guideline panel has developed several guidelines on the management of urolithiasis. Recently, the joint AUA/EAU panel published a 2007 update of the original 1997 report on the management of ureteral calculi. The EAU panel yields the publication of guidelines on urolithiasis, with updates almost annually. These guidelines provide useful recommendations on the management of urolithiasis. Based on their findings, the most significant update of guideline concluded that both extracorporeal shockwave lithotripsy and ureteroscopy (URS) are acceptable first-line treatments for patients requiring ureteral stone removal. With the development of smaller caliber ureteroscopes and the introduction of improved instrumentation, including the holmium : yttrium aluminum garnet laser, URS has evolved into a safer and more efficacious modality for treatment of stones in all locations in the ureter during the last decade. The other change is the establishment of effective medical expulsive therapy to facilitate spontaneous stone passage.

[Rupture of renal artery aneurysm into the renal pelvis].

We report a case of ruptured renal artery aneurysm into the renal pelvis. A 48-year-old woman presented with complaints of gross hematuria and right back pain. Abdominal ultrasonography, computed tomography (CT) and magnetic resonance imaging (MRI) revealed the aneurysm, which was 5 x 5 cm in diameter. Enhansed CT revealed blood flow from the renal artery aneurysm into the renal pelvis. Radical nephrectomy was performed. Rupture of renal artery aneurysm into the renal pelvis is the 3rd case in the Japanese literatures. Pathogenesis and management of this rare condition are discussed.

[A clinical study of laparoscopic adrenalectomy for pheochromocytoma--analysis of clinical parameters influencing operative time and intraoperative systolic blood pressure].

PURPOSE: We retrospectively analyzed the preoperative clinical parameters which influence operative time and intraoperative maximum systolic blood pressure in patients undergoing laparoscopic adrenalectomy for pheochromocytoma. MATERIALS AND METHODS: Between January 1992 and September 2010, we performed 28 laparoscopic adrenalectomies for pheochromocytoma at Hamamatsu University School of Medicine. These 28 cases were characterized based on the following parameters: body mass index (BMI), tumor size, history of hypertension, preoperative blood pressure, serum concentration of catecholamine, and 24-h urinary excretion of catecholamine metabolite. We retrospectively analyzed whether or not these parameters influenced operative time or intraoperative maximum systolic blood pressure. RESULTS: All 28 cases of laparoscopic adrenalectomy were performed safely and without intraoperative complications and needed neither blood transfusion nor conversion to laparotomy. The median operative time was 203 minutes, and intraoperative hypertension (systolic blood pressure > 200 mmHg) occurred in 46% (13/28) of cases. Median day of discharge in all patients was post-operative day 5. Significant positive correlation was shown between tumor size and operative time and between intraoperative maximum systolic blood pressure and serum concentration of catecholamine or 24-h urinary excretion of catecholamine metabolite (p < 0.05). CONCLUSION: The lengthened operative time for large tumors and elevated intraoperative blood pressure for tumors with high preoperative catecholamine activity necessitate careful perioperative management in patients receiving laparoscopic adrenalectomy for pheochromocytoma.

Analysis of the regulation of fatty acid binding protein 7 expression in human renal carcinoma cell lines.

BACKGROUND: Improving the treatment of renal cell carcinoma (RCC) will depend on the development of better biomarkers for predicting disease progression and aiding the design of appropriate therapies. One such marker may be fatty acid binding protein 7 (FABP7), also known as B-FABP and BLBP, which is expressed normally in radial glial cells of the developing central nervous system and cells of the mammary gland. Melanomas, glioblastomas, and several types of carcinomas, including RCC, overexpress FABP7. The abundant expression of FABP7 in primary RCCs compared to certain RCC-derived cell lines may allow the definition of the molecular components of FABP7's regulatory system. RESULTS: We determined FABP7 mRNA levels in six RCC cell lines. Two were highly expressed, whereas the other and the embryonic kidney cell line (HEK293) were weakly expressed FABP7 transcripts. Western blot analysis of the cell lines detected strong FABP7 expression only in one RCC cell line. Promoter activity in the RCC cell lines was 3- to 21-fold higher than that of HEK293. Deletion analysis demonstrated that three FABP7 promoter regions contributed to upregulated expression in RCC cell lines, but not in the HEK293 cell. Competition analysis of gel shifts indicated that OCT1, OCT6, and nuclear factor I (NFI) bound to the FABP7 promoter region. Supershift experiments indicated that BRN2 (POU3F2) and NFI bound to the FABP7 promoter region as well. There was an inverse correlation between FABP7 promoter activity and BRN2 mRNA expression. The FABP7-positive cell line's NFI-DNA complex migrated faster than in other cell lines. Levels of NFIA mRNA were higher in the HEK293 cell line than in any of the six RCC cell lines. In contrast, NFIC mRNA expression was lower in the HEK293 cell line than in the six RCC cell lines. CONCLUSIONS: Three putative FABP7 promoter regions drive reporter gene expression in RCC cell lines, but not in the HEK293 cell line. BRN2 and NFI may be key factors regulating the expression of FABP7 in certain RCC-derived cell lines.

Should ipsilateral solitary adrenal involvement in renal cell carcinoma be staged as M1?

OBJECTIVE: In 2009, the TNM classification of malignant tumors was revised, and the renewal of the T2-4 stage in renal cell carcinoma was adopted. To date, however, the staging of ipsilateral solitary adrenal involvement in renal cell carcinoma has not been sufficiently evaluated. METHODS: We retrospectively reviewed the adrenal involvement in renal cell carcinoma among 1033 patients admitted to the Department of Urology at Hamamatsu University Hospital, Japan, and affiliated hospitals between 1978 and 2007. RESULTS: We identified 23 of the 1033 patients (2.2%) with adrenal involvement in renal cell carcinoma. In renal cell carcinoma patients with adrenal involvement, a tendency for a high histological grade of tumor and lower overall survival (P< 0.0001) was observed. Ipsilateral solitary adrenal involvement was detected in 4 of the 23 patients (15%), whereas 2 of the 23 (9%) had direct invasion of the adrenal gland. All tumors in the 14 patients without ipsilateral solitary adrenal involvement and recurrent adrenal tumors were classified as Stage IV. The TNM classification of the four renal cell carcinoma patients with ipsilateral solitary adrenal involvement was determined to be either pT3N0M0 or pT1-3N0M1. Among the four patients with ipsilateral solitary adrenal involvement, three patients had recurrent tumors, despite complete surgical resection. Two of these patients died of metastatic renal cell carcinoma after 2 and 10 years of radical nephrectomy, respectively, whereas one was still alive with cancer 3 years after the initial radical nephrectomy. The fourth had no recurrence of renal cell carcinoma, but did develop synchronous gall bladder cancer (pT2N0M0) and bile duct cancer (pT2N0M0). CONCLUSIONS: Adrenal involvement in primary renal cell carcinoma was observed more frequently in patients with advanced tumor stages. In the TNM classification system, we propose that ipsilateral solitary adrenal involvement in renal cell carcinoma should be staged as M1.

Combination therapy with sorafenib and S-1 for renal cell carcinoma producing granulocyte colony-stimulating factor.

We present the first case report of the use of sorafenib and S-1 for the treatment of renal cell carcinoma (RCC) producing granulocyte colony-stimulating factor (G-CSF). This entity is clinically rare and has a poor outcome. A 78-year-old Japanese man presented with macrohematuria, left flank pain, and a palpable mass. Laboratory data showed marked leukocytosis with increased serum and urinary G-CSF. The histopathological diagnosis was unclassified RCC. New combination therapy with sorafenib and S-1 exerted a therapeutic effect and apparently decreased serum and urinary G-CSF levels, although the patient died of gastrointestinal perforation. The use of combined sorafenib and S-1 may be worthy of consideration in the treatment of RCC producing G-CSF.

[Future perspective in the treatment of urolithiasis based on oxalate metabolism].

Urinary excretion of oxalate is one of risk factors in urinary stone formation. Prevention of undesirable overflow into the production of oxalate definitely leads to a decrease of urolithiasis. The activity of serine : pyruvate/alanine : glyoxylate aminotransferase (SPT/AGT) or glyoxylate reductase/hydroxypyruvate reductase (GRHPR), the key enzyme of primary hyperoxlauria type 1 and 2, respectively, and their subcellular distribution highly affects the oxalate production. On the other hand, urolithiasis is tightly related to lifestyle disease, such as diabetes mellitus and insulin resistance. The hypothesis that insulin resistance induces mitochondria dysfunction, resulting in the decrease of mitochondria-related enzyme activity is a very attractive new treatment strategy of urolithiasis. Namely, the improvement of insulin resistance might prevent stone formation.

[A case of ductal adenocarcinoma of the prostate treated with endocrine therapy and radiation therapy].

We report a case of ductal adenocarcinoma of the prostate. A 81-year-old man presented with a complaint of microhematuria. Serum prostate specific antigen (PSA) was 18. 44 ng/ml. A cystourethroscopic examination revealed a papillary tumor near the verumontanum. Transurethral resection of the tumor and transrectal prostatic needle biopsy was carried out. The pathological diagnosis was ductal adenocarcinoma and acinar adenocarcinoma of the prostate. The tumor responded to endocrine therapy and radiation therapy. At the follow up at 18 months, the PSA level was in the undetectable range (＜0.01 ng/ml), and no reccurence of the tumor was seen. Pathogenesis and management of this rare condition is discussed.

[A case of proliferative cystitis forming ureterovesical junction obstruction].

We report a case of proliferative cystitis forming ureterovesical junction obstruction. A 28-year-old man presented with a complaint of gross hematuria. Abdominal ultrasonography revealed left hydronephrosis and bladder tumor. Drip infusion pyelography (DIP) demonstrated left ureterovesical junction obstruction and cystoscopic findings appeared papillary sessile tumor around the bladder neck, trigone, and bilateral ureteral orifice. Transurethral resection of the bladder tumor (TURBT) was performed. The pathological diagnosis of the tumor was proliferative cystitis and confirmed that left ureterovesical junction obstruction was derived from proliferative cystitis. The tumor was not responsive to medical treatment. After the 4th TURBT, the tumor was completely resected, and left hydronephrosis and ureterovesical junction obstruction were improved. One year after the last operation, there is no evidence of recurrence of the tumor. Tumor formation arising from proliferative cystitis is relatively rare. Pathogenesis and management of this rare condition are discussed.

Reduction of transforming growth factor-beta type II receptor is caused by the enhanced ubiquitin-dependent degradation in human renal cell carcinoma.

Although dysregulation of transforming growth factor-beta (TGF-beta) signaling is implicated in renal carcinogenesis, its precise mechanism is unknown in renal cell carcinoma (RCC). In our study, we investigated Smad-mediated TGF-beta signaling pathway and its regulatory mechanisms in surgical samples from patients with RCC. We found that immunoreactivity for nuclear phosphorylated Smad2 was significantly decreased in RCC compared to normal renal tissues, thereby TGF-beta signaling was suggested to be attenuated in RCC tissues. In accordance with the result, transcriptional downregulation of Smad4 and post-transcriptional downregulation of TGF-beta type II receptor (TbetaR-II) were frequently found in RCC tissues compared to normal renal tissues. Next, to clarify the reason why the protein level of TbetaR-II was decreased in RCC, we investigated the activities of degradation and ubiquitination of TbetaR-II. We found that both proteasome-mediated degradation and ubiquitination of TbetaR-II were markedly enhanced in RCC tissues. Moreover, we found that the level of Smad-ubiquitination regulatory factor 2 (Smurf2), the E3 ligase for TbetaR-II, was increased in RCC tissues of the patients with higher clinical stages compared to the normal tissues and was inversely correlated with the level of TbetaR-II. Our results suggest that the low TbetaR-II protein level is due to augmented ubiquitin-dependent degradation via Smurf2 and might be involved in the attenuation of TGF-beta signaling pathway in RCC.

A phase II study of sunitinib in Japanese patients with metastatic renal cell carcinoma: insights into the treatment, efficacy and safety.

OBJECTIVE: This study aims to assess the efficacy and safety of sunitinib in Japanese patients with metastatic renal cell carcinoma (RCC). METHODS: Fifty-one Japanese patients with prior nephrectomy, 25 treatment-naive patients (first-line group) and 26 cytokine-refractory patients (pretreated group) were enrolled in this phase II trial. Patients received sunitinib 50 mg orally, once daily, in repeated 6-week cycles (4 weeks on treatment, 2 weeks off). The primary endpoint was RECIST-defined objective response rate (ORR) with tumour assessments every 6 weeks via computed tomography or magnetic resonance imaging. Toxicity was assessed regularly. In the primary efficacy analysis of the intent-to-treat (ITT) population, ORR and 95% confidence interval were calculated based on independent review. Secondary time-to-event endpoints, such as progression-free survival (PFS), were estimated using the Kaplan-Meier method. RESULTS: In the ITT population, ORR was 48.0% in the first-line group (after a median 4 cycles), 46.2% in the pretreated group (5 cycles) and 47.1% overall, with median times to tumour response of 7.1, 10.7 and 10.0 weeks, respectively. Median PFS was 46.0, 33.6 and 46.0 weeks, respectively. The most common treatment-related grade 3/4 adverse events and laboratory abnormalities were fatigue (20%), hand-foot syndrome (14%) and hypertension (12%), decreased platelet count (55%), decreased neutrophil count (51%), increased lipase (39%) and decreased lymphocyte count (33%). CONCLUSIONS: In Japanese patients with RCC, sunitinib is consistently effective and tolerable with similar risk/benefit as that in Western patients, though there was a trend toward greater antitumour efficacy and higher incidence of haematological adverse events in Japanese patients.

Overall survival and updated results from a phase II study of sunitinib in Japanese patients with metastatic renal cell carcinoma.

BACKGROUND: In a phase II, open-label, multicentre Japanese study, sunitinib demonstrated antitumour activity and acceptable tolerability in metastatic renal cell carcinoma patients. Final survival analyses and updated results are reported. METHODS: Fifty-one Japanese patients with a clear-cell component of metastatic renal cell carcinoma (25 treatment-naïve; 26 cytokine-refractory) received sunitinib 50 mg orally, once daily (Schedule 4/2). Overall and progression-free survivals were estimated by the Kaplan-Meier method. Objective response rate (per Response Evaluation Criteria in Solid Tumours) and safety were assessed with an updated follow-up. RESULTS: First-line and pretreated patients received a median 6.0 and 9.5 treatment cycles, respectively. Investigator-assessed, end-of-study objective response rate was 52.0, 53.8 and 52.9% in first-line, pretreated and overall intent-to-treat populations, respectively. The median progression-free survival was 12.2 and 10.6 months in first-line and pretreated patients, respectively. Fourteen patients per group died (56 and 54%), and the median overall survival was 33.1 and 32.5 months, respectively. The most common treatment-related Grade 3 or 4 adverse events and laboratory abnormalities were fatigue (24%), hand-foot syndrome (18%), decreased platelet count (55%), decreased neutrophil count (53%) and increased lipase (49%). No Grade 5 treatment-related adverse events occurred. Forty patients (78%) required dose reduction, and 13 (25%) discontinued, due to treatment-related adverse events. CONCLUSIONS: With the median overall survival benefit exceeding 2.5 years, and acceptable tolerability, in first-line and pretreated Japanese metastatic renal cell carcinoma patients with Eastern Cooperative Oncology Group performance status 0/1, sunitinib showed a favourable risk/benefit profile, similar to Western studies. However, there was a trend towards greater efficacy and more haematological adverse events in Japanese patients.

[Clinical course of patient with malignant pheochromocytoma who was treated with CVD chemotherapy and alpha-methyl-p-tyrosine].

A 31-years-old woman was diagnosed as pheocromocytoma by the various endocrine testings and 131I-MIBG scintigraphy. The CT scan and bone scintigraphy showed right adrenal tumor, along with liver metastasis, lymph nodes swelling around aorta and multiple bone metastases. She underwent chemotherapy consisting with Cyclophosphamide, Vincristine, Dacarbazine (CVD) and alpha-methyl-p-tyrosine (alphaMT), resulting in stable disease for 27 months. However, catecholamine levels increased gradually four weeks later. We would have planned 131I-MIBG therapy, but bone marrow suppression did not allow us to do it. She died of DIC.

Significance of 5-fluorouracil-related enzyme activities in predicting sensitivity to 5-fluorouracil in bladder carcinoma.

BACKGROUND: The association between 5-fluorouracil (5-FU)-related enzyme activity and the sensitivity of bladder urothelial carcinoma (BUC) to 5-FU were investigated, and methods to improve 5-FU sensitivity were analyzed. MATERIALS AND METHODS: Tumor specimens were obtained from 127 patients. Orotate phosphoribosyl transferase (OPRT) activity was analyzed by the paper disc method and thymidine phosphorylase and dihydropyrimidine dehydrogenase (DPD) activities were measured by ELISA. 5-FU sensitivity was assessed in 99 cases by an in vitro chemosensitivity test. RESULTS: A significant positive correlation between OPRT activity level and the sensitivity of BUC to 5-FU was identified. Moreover, the combination of 5-FU and 5-chloro-2,4-dihydroxypyrimidine significantly enhanced 5-FU sensitivity in BUC, particularly in cases showing higher DPD activity. CONCLUSION: OPRT was the most important enzyme in predicting sensitivity to 5-FU in BUC. These results may have implications for tailor-made medication using 5-FU-related compounds as postoperative adjuvant chemotherapy in BUC patients.