Pre-operative Serum Albumin Predicts Native Liver Survival in Biliary Atresia.

BACKGROUND: To predict native liver survival (NLS) after Kasai portoenterostomy (KP) for biliary atresia (BA) using pre-operative clinical data. METHODS: Pre-operative data were collected from 29 patients with BA who underwent KP at our department between 1989 and 2017 and were analysed including serum albumin, bilirubin, prothrombin time-international normalised ratio, body height, body weight, age at KP, paediatric end-stage liver disease score calculated using the pre-operative data and the period of NLS. RESULTS: The 10-year NLS rate of all patients was 51%. A multivariate analysis revealed that among all factors, the pre-KP serum albumin level was the only independent predictor of NLS (P = 0.04, hazard ratio = 0.269, 95% confidence interval = 0.077-0.934). The area under the receiver operating characteristic curve for NLS, determined using pre-KP serum albumin was 0.760 and 3.75 mg/dl was selected as the cut-off value. There was a significant difference in NLS between patients with high (≥3.8 mg/dl) and low (≤3.7 mg/dl) pre-KP serum albumin (90.0% vs. 31.5%, P < 0.01). CONCLUSIONS: Decreased pre-KP serum albumin may reflect not only functional impairment of the liver, but also the inflammatory process, which is hypothesized to occur during its advancement. The pre-KP serum albumin level may be a good prognostic factor for NLS in post-KP BA patients.

Single-incision laparoscopic full-thickness anterior abdominal wall repair of a Morgagni hernia using a suture-assisting needle in a child: A case report.

Single-incision laparoscopic repair of a congenital Morgagni diaphragmatic hernia using a suture-assisting needle was performed in a 1-year-old boy. Three ports were inserted through a single umbilical incision to repair the 2.5 × 2.3-cm defect. The full-thickness muscle layer of the anterior abdominal wall and the posterior rim of the defect were penetrated with the suture-assisting needle holding a thread, which was then released. The needle tip was pulled back over the muscle layer, shifted laterally, and again passed through the muscle layer and the posterior rim. The thread was then captured by the needle and pulled out through the anterior abdominal wall. Five mattress sutures were placed in this way and tied subcutaneously. The postoperative course was uneventful, and the cosmetic outcome was favorable. A suture-assisting needle is useful for completing full-thickness anterior abdominal wall repair, which is important for preventing the recurrence of a congenital Morgagni diaphragmatic hernia.

Congenital perianal lipoma: a case report and review of the literature.

BACKGROUND: The surgical strategy for congenital perineal lipoma varies depending on the size, location, and accompanying congenital anomalies, with the optimum approach remaining to be determined. We herein report a case of congenital perianal lipoma that was first detected by prenatal ultrasound and review the literature. CASE PRESENTATION: A female neonate was referred to us for the evaluation of a perianal mass. She had been considered to be male prenatally because fetal ultrasound showed a perineal mass similar to a scrotum and penis. A postnatal examination revealed an appropriate-for-age neonate with a soft round mass 1.5 cm in diameter just to the left of the anal verge. She passed urine and stool smoothly, and contrast enema confirmed no anorectal malformation. Magnetic resonance imaging showed that the lesion had a signal intensity consistent with fat located close to the anal sphincter, and no spinal anomaly (e.g., spina bifida) was identified. We excised the lesion (pathologically confirmed to be lipoma) simply at 2 months old, taking care to avoid damaging the anal sphincter by using a muscle stimulator. She has been doing well with good bowel movement and satisfactory cosmetic results for a follow-up period of one and a half years. Our literature search revealed 49 cases of perineal lipoma reported in English in the last 25 years, and 74% of them-including ours-had other congenital anomalies, the breakdown of which was anorectal malformation in 40% of cases, labioscrotal fold or accessory scrotum in 28%, and urogenital malformation, congenital pulmonary airway malformation, and disorder of sex differentiation. The prenatal detection of the lesion, as in our case, was quite rare. CONCLUSION: A thorough physical examination after birth, magnetic resonance imaging and contrast enema to identify the nature of the perineal lipoma and accompanying anomalies are crucial for planning the surgical strategy. The lesion may be deeply interspersed between the sphincter muscle, especially when it accompanies anorectal anomaly. A muscle stimulator is useful for preserving and repairing the sphincter muscles during resection in order to ensure satisfactory bowel movement.

Combined Fundal and Segmental Adenomyomatosis of the Gallbladder in a Child: A Rare Case Report.

Adenomyomatosis of the gallbladder (AMG) is characterized by mucosal hyperplasia leading to invagination through the thickened muscle layer, which is relatively common in adults, but is rare in childhood. We report a 12-year-old boy with adenomyomatosis of the gallbladder combined segmental and fundal type. This combined type is rare in adults and is first reported here in childhood. Although initial imaging with computed tomography (CT) suggested the presence of a circular solid mass-like lesion because of its rare morphology, repeated ultrasonography (US) was useful for leading to a correct diagnosis.

A single institution experience of Eppikajutsuto for the treatment of lymphatic malformations in children.

BACKGROUND: Eppikajutsuto (TJ-28) is an herbal medicine recently reported to be effective in treating lymphatic malformations (LMs). We report our experience concerning the clinical efficacy of TJ-28 for LMs. METHODS: Medical records of 10 LM cases treated with TJ-28 between 2016 and 2018 were reviewed. TJ-28 was given at 0.3 g/kg/day and then increased to 0.5 if no improvement was noted after the first three months of treatment. Their clinical data were collected, and LM volume indices (depth×width×height) were measured with the first (LMVI-F) and latest (LMVI-L) imaging studies. The response rates were calculated as 1-LMVI-L / LMVI-F (%). RESULTS: The median age at the diagnosis and treatment period was 1.5 years and 17.5 months, respectively. LMs were located in the neck (six), mesenterium or retroperitoneum (three), and inguinal region (one). The median response rate was 83%, including 100% in three cases and the apparent improvement of obstructive airway symptoms in one case. One case underwent surgery for insufficient improvement, and another that showed no effect is being considered for surgery. Most of the satisfactory outcomes were demonstrated in the first six months of treatment. CONCLUSION: TJ-28 seems to be effective in treating LMs in children, especially early in treatment. LEVEL OF EVIDENCE: IV.

Prognostic significance of inflammation-based prognostic scoring in patients with upper urinary tract urothelial carcinoma

ABSTRACT Objectives: To investigate whether Glasgow Prognostic Score has prognostic significance in patients with upper urinary urothelial carcinoma. Patients and methods: We retrospectively reviewed the clinical records of 74 patients with upper urinary urothelial carcinoma. We set the cut-off value for C-reactive protein as 1.0mg/dL, and 3.5mg/dL for albumin as Glasgow Prognostic Score. Their blood data including albumin and C-reactive protein for Glasgow Prognostic Score and cytokeratin 19 fragment 21-1 as a tumor marker were measured before starting treatment. The patients were stratified into three groups with Glasgow Prognostic Score: The Group-1, albumin ≥3.5g/dL and C-reactive protein < 1.0mg/dL; Group-2, albumin < 3.5g/dL or C-reactive protein ≥1.0mg/dL; Group-3, albumin < 3.5g/dL and C-reactive protein ≥1.0mg/dL. Results: The median follow-up for all patients was 26.9 months (range: 10.9-91.1 months), during which 37 (50%) patients died. There was a significant difference in the estimated survival rate among the 3 groups stratified by Glasgow Prognostic Score. The estimated survival rate in the Group-1 was significantly higher than those in Groups 2 and 3. In the univariate analysis C-reactive protein, serum cytokeratin 19 fragment 21-1 and Glasgow Prognostic Score were significant predictors of overall survival. On the multivariate analysis, serum cytokeratin 19 fragment 21-1 and Glasgow Prognostic Score were independently associated with shorter overall survival. Conclusion: Our review suggests Glasgow Prognostic Score may play as a prognostic predictor for upper urinary urothelial carcinoma.

Prognostic significance of inflammation-based prognostic scoring in patients with upper urinary tract urothelial carcinoma.

OBJECTIVES: To investigate whether Glasgow Prognostic Score has prognostic significance in patients with upper urinary urothelial carcinoma. PATIENTS AND METHODS: We retrospectively reviewed the clinical records of 74 patients with upper urinary urothelial carcinoma. We set the cut-off value for C-reactive protein as 1.0mg/dL, and 3.5mg/dL for albumin as Glasgow Prognostic Score. Their blood data including albumin and C-reactive protein for Glasgow Prognostic Score and cytokeratin 19 fragment 21-1 as a tumor marker were measured before starting treatment. The patients were stratified into three groups with Glasgow Prognostic Score: The Group-1, albumin ≥3.5g/dL and C-reactive protein < 1.0mg/dL; Group-2, albumin < 3.5g/dL or C-reactive protein ≥1.0mg/dL; Group-3, albumin < 3.5g/dL and C-reactive protein ≥1.0mg/dL. RESULTS: The median follow-up for all patients was 26.9 months (range: 10.9-91.1 months), during which 37 (50%) patients died. There was a signifi cant difference in the estimated survival rate among the 3 groups stratified by Glasgow Prognostic Score. The estimated survival rate in the Group-1 was significantly higher than those in Groups 2 and 3. In the univariate analysis C-reactive protein, serum cytokeratin 19 fragment 21-1 and Glasgow Prognostic Score were significant predictors of overall survival. On the multivariate analysis, serum cytokeratin 19 fragment 21-1 and Glasgow Prognostic Score were independently associated with shorter overall survival. CONCLUSION: Our review suggests Glasgow Prognostic Score may play as a prognostic predictor for upper urinary urothelial carcinoma.

Surgical closure of the larynx for intractable aspiration pneumonia: cannula-free care and minimizing the risk of developing trachea-innominate artery fistula.

There is a risk of developing a fatal trachea-innominate artery fistula following laryngotracheal separation for the prevention of intractable aspiration pneumonia. We developed a novel technique of surgical closure of the larynx to avoid this complication and provide long-term cannula-free care.

Efficient Gene Transduction of Dispersed Islet Cells in Culture Using Fiber-Modified Adenoviral Vectors.

To establish novel islet-based therapies, our group has recently developed technologies for creating functional neo-islet tissues in the subcutaneous space by transplanting monolithic sheets of dispersed islet cells (islet cell sheets). Improving cellular function and viability are the next important challenges for enhancing the therapeutic effects. This article describes the adenoviral vector-mediated gene transduction of dispersed islet cells under culture conditions. Purified pancreatic islets were obtained from Lewis rats and dissociated into single islet cells. Cells were plated onto laminin-5-coated temperature-responsive polymer poly(N-isopropylacrylamide)-immobilized plastic dishes. At 0 h, islet cells were infected for 1 h with either conventional type 5 adenoviral vector (Ad-CA-GFP) or fiber-modified adenoviral vector (AdK7-CA-GFP) harboring a polylysine (K7) peptide in the C terminus of the fiber knob. We investigated gene transduction efficiency at 48 h after infection and found that AdK7-CA-GFP yielded higher transduction efficiencies than Ad-CA-GFP at a multiplicity of infection (MOI) of 5 and 10. For AdK7-CA-GFP at MOI = 10, 84.4 ± 1.5% of islet cells were found to be genetically transduced without marked vector infection-related cellular damage as determined by viable cell number and lactate dehydrogenase (LDH) release assay. After AdK7-CA-GFP infection at MOI = 10, cells remained attached and expanded to nearly full confluency, showing that this adenoviral infection protocol is a feasible approach for creating islet cell sheets. We have shown that dispersed and cultured islet cells can be genetically modified efficiently using fiber-modified adenoviral vectors. Therefore, this gene therapy technique could be used for cellular modification or biological assessment of dispersed islet cells.

Transanal endoscopic microsurgery for surgical repair of rectovesical fistula following radical prostatectomy.

BACKGROUND: Rectovesical fistula is a rare complication following prostatectomy, associated with significant symptoms such as urinary drainage from anus or faecaluria. While several surgical procedures have been described to treat this condition, none of them has been accepted as the universal standard. Transanal endoscopic microsurgery (TEM) is a well-established endoluminal procedure for local excision of rectal tumors. But its application to the repair of rectovesical fistula has been almost unknown. METHODS: We performed TEM as a surgical repair for refractory rectovesical fistula developing after radical prostatectomy in 10 patients. Under the magnified three-dimensional view, through the stereoscope, the fistula and the surrounding rectal mucosa were precisely resected. The defect and the muscle layer of the rectum were closed by hand-sew technique in four layers. RESULTS: Fistula was completely closed in 7 patients, who eventually underwent enterostomy closure, while in the other 3 patients the fistula recurred. In the three recurrent cases, the fistula was associated with wide, tough scar tissue due to previous irradiation, HIFU, or repeated surgical repair attempts. CONCLUSIONS: Rectovesical fistulas associated with wide, tough scar tissue due to multi-time attempt of surgical repair or any type of energy ablation should not be indicated for repair by TEM. However, for simple fistulas without tough, fibrotic surroundings, TEM can be indicated as a minimally invasive surgical option with very low morbidity, without any incision in healthy tissue for approach.

Mizoribine as sole immunosuppressive agent in islet xenotransplantation models: a candidate immunosuppressant causing no adverse effects on islets.

Mizoribine (MZ) inhibits the differentiation and proliferation of helper T and B cells after antigen recognition by suppressing the purine biosynthesis pathway and nucleic acid synthesis. MZ has been used in kidney transplantation, but distinct data are unavailable for islet transplantation. The present study investigated the efficacy of MZ for islet xenotransplantation. Immunosuppressive effects of MZ were determined by mixed lymphocyte reaction (MLR) assay in vitro. Toxicities for Wistar rat islets were determined by adenosine triphosphate (ATP) contents of islets during 3-day culture and stimulation index in response to glucose after culture. Immunosuppressive effects in vivo were tested in a Wistar-to-B6 islet xenotransplantation model. MZ was administered continuously for 28 days subcutaneously or intramuscularly. MZ inhibited MLR response by approximately 50% at 0.1 µg/ml. ATP contents decreased with MZ >100 µg/ml, while stimulation index was maintained. Continuous infusion of MZ at 10 mg/kg maintained blood concentrations at 0.13-0.19 µg/ml, while intramuscular injection of MZ at 100 mg/kg/day (peak 520 µg/ml at 1 h postinjection) resulted in below measurable levels (<0.03 µg/ml) within 24 h. Graft survival was significantly prolonged following continuous infusion of 10 mg/kg/day compared to controls (31.0 ± 9.5 vs. 13.2 ± 5.2 days; p = 0.002). Furthermore, animals with intramuscular injection at doses of 3.2, 10, or 100 mg/kg/day showed significantly longer graft survival (20.0 ± 7.5, 22.0 ± 7.31, and 24.5 ± 8.1 days, respectively; p < 0.05 each). Histological examination showed significant suppression of lymphocyte infiltration by MZ administration. MZ showed immunosuppressive effects in an experimental islet xenotransplantation model without adverse effects on endocrine function of islet grafts.

A cytotoxic peptide from a marine sponge exhibits ion channel activity through vectorial-insertion into the membrane.

A cytotoxic peptide, polytheonamide B (pTB), from marine sponge was examined for cytotoxic spectrum and specific activity to mammalian cells was demonstrated. pTB is composed of alternative D- and L-amino acid residues throughout the 48-mer peptide. This suggests the formation of a ß-helix similar to gramicidin channels. Planar bilayer experiments revealed that pTB forms monovalent cation-selective channels, being compatible with the inner pore diameter of ∼4Å for a ß-helical structure. pTB penetrated vectorially into the membrane, formed a channel by means of a single molecule, and remained in the membrane. These functional properties may account for specific cytotoxic activity.

Congenital esophageal stenosis because of tracheobronchial remnant and treated by circular myectomy: a case report.

Congenital esophageal stenosis (CES) is a rare anomaly, and appropriate management is not well established. We performed myectomy of the esophageal wall in a child with critical esophageal stenosis caused by tracheobronchial remnant (TBR). An 18-month-old boy was admitted to our hospital having frequent vomiting and failure to thrive. Esophagography and esophagoscopy showed abrupt stenosis at the lower esophageal wall. Balloon dilatation was performed but was ineffective. Surgery was performed under a diagnosis of CES because of TBR. Cartilage was palpable in the stenotic esophageal wall, and extirpation of the muscular layer of the stenotic portion was performed, leaving the mucosal layer intact. The muscular layer was closed loosely using interrupted 5-0 absorbable sutures to match the oral and anal sides together. Postoperatively, the esophageal passage was improved to the point that the patient was able to take solid foods without vomiting. This successful outcome suggests that circular myectomy of the TBR is worth recommending as a surgical procedure for short segment and stenosis of patients with CES because of TBR.

Topological mapping of the asymmetric drug binding to the human ether-à-go-go-related gene product (HERG) potassium channel by use of tandem dimers.

The human ether-à-go-go related gene product (HERG) channel is essential for electrical activity of heart cells, and block of this channel by many drugs leads to lethal arrhythmias. Tyr(652) and Phe(656) of the sixth transmembrane helix are candidates for the drug binding site. In the tetrameric HERG channel, a drug with asymmetric structure should interact unevenly with multiple residues from different subunits. To elucidate the topology of the drug-binding site, we constructed tandem dimers of HERG channels and the aromatic Tyr(652) and Phe(656) residues were replaced by alanine singly or doubly. Eight types of HERG channels, including homotetrameric mutants, having different numbers and arrangements of aromatic residues at the blocking site, were studied. Effects of cisapride on channels expressed in Xenopus laevis oocytes were examined electrophysiologically. The inhibition constants (K(i)) were increased significantly as the diagonal Tyr(652) were deleted, whereas those for the diagonal Phe(656)-deleted mutant were not changed. These results suggest that Tyr(652) residues from adjacent subunits contributed to the binding. Two types of double mutants of tandem dimers showed significantly distinct affinities, suggesting that the coexistence of Tyr(652) and Phe(656) on a subunit in diagonal position is crucial to having a high affinity. Thermodynamic double-mutant cycle analyses revealed interactions between Tyr(652) and Phe(656) upon binding. The kinetics and voltage-dependence of blocking suggested transitions of the binding site from low to high affinity. These approaches using a set of mutant HERG channels gave a dynamic picture of the spatial arrangements of residues that contribute to the drug-channel interaction.

Surface structure and its dynamic rearrangements of the KcsA potassium channel upon gating and tetrabutylammonium blocking.

KcsA is the first potassium channel for which the molecular structure was revealed. However, the high resolution structural information is limited to the transmembrane domain, and the dynamic picture of the full KcsA channel remains unsolved. We have developed a new approach to investigate the surface structure of proteins, and we applied this method to investigate the full length of the KcsA channel. Single-cysteine substitution was introduced into 25 sites, and specific reaction of these mutated channels to a bare surface of a flat gold plate was evaluated by surface plasmon resonance measurements. The surface plasmon resonance signals revealed the highest exposure for the mutant of the C-terminal end. When the gate of the KcsA channel is kept closed at pH 7.5, the extent of exposure showed periodic patterns for the consecutive sites located in the cytoplasmic (CP) and N-terminal domain. This suggests that these stretches take the alpha-helical structure. When the channel was actively gated at pH 4.0, many sites in the CP domain became exposed. Compared with the rigid structure in pH 7.5, these results indicate that the CP domain became loosely packed upon active gating. The C-terminal end of the M2 helix is a moving part of the gate, and it is exposed to the outer surface slightly at pH 4.0. By adding a channel blocker, tetrabutylammonium, the gate is further exposed. This suggests that in the active gating tetrabutylammonium keeps the gate open rather than being trapped in the central cavity.

Coupled K+-water flux through the HERG potassium channel measured by an osmotic pulse method.

The streaming potential (V(stream)) is a signature feature of ion channels in which permeating ions and water molecules move in a single file. V(stream) provides a quantitative measure of the ion and water flux (the water-ion coupling ratio), the knowledge of which is a prerequisite for elucidating the mechanisms of ion permeation. We have developed a method to measure V(stream) with the whole-cell patch-clamp configuration. A HEK293 cell stably expressing the HERG potassium channel was voltage clamped and exposed to hyperosmotic solutions for short periods of time (<1 s) by an ultrafast solution switching system (the osmotic pulse [quick jump-and-away] method). The reversal potentials were monitored by a series of voltage ramps before, during, and after the osmotic pulse. The shifts of the reversal potentials immediately after the osmotic jump gave V(stream). In symmetrical K+ solutions (10 mM), the V(stream)s measured at different osmolalities showed a linear relationship with a slope of -0.7 mV/DeltaOsm, from which the water-ion coupling ratio (n, the ratio of the flux of water to the flux of cations; Levitt, D.G., S.R. Elias, and J.M. Hautman. 1978. Biochim. Biophys. Acta. 512:436-451) was calculated to be 1.4. In symmetrical 100 mM K+ solutions, the coupling ratio was decreased significantly (n = 0.9), indicating that the permeation process through states with increased ion occupancy became significant. We presented a diagrammatic representation linking the water-ion coupling ratio to the mode of ion permeation and suggested that the coupling ratio of one may represent the least hydrated ion flux in the single-file pore.

[Clinico-statistical analysis of renal cell carcinomas in patients on hemodialysis].

Eleven patients on hemodialysis that were surgically treated for renal cell carcinomas during the recent 10 years at our institutes were clinically analyzed. Patients' ages at presentation ranged from 35 to 70 years with an average of 54.8 years. Nine of the 11 patients were males and 2 were females. Periods between the introduction of hemodialysis and the presentation ranged from 1 to 21 years with an average of 11.7 years. The most frequent cause of hemodialysis was chronic glomerulonephritis. Five patients presented with macroscopic hematuria, which was the most frequent clinical manifestation. Transperitoneal nephrectomy through a lumbar oblique incision was performed in 9 of 12 surgical procedures. Transperitoneal resection and retroperitoneal endoscopic resection were performed on 2 patients and 1 patient, respectively. Blood transfusion was performed on 2 patients with retroperitoneal hemorrhage before or after operation and 2 patients with pre-existing renal anemia. Pathologically, 9 patients had pT1a disease. Patients were followed up for up to 7 years and 11 months. One patient died of the disease and 2 patients died of unknown causes. In conclusion, surgical removal of renal cell carcinomas was well tolerated, safe and effective treatment in patients under hemodialysis.

Interaction between tetraethylammonium and permeant cations at the inactivation gate of the HERG potassium channel.

The fast inactivation of the human ether-à-go-go related gene product (HERG) channel is a form of C-type inactivation and is decelerated by external tetraethylammonium (TEA) and potassium. From the time constant of inactivation, the dissociation constants of TEA (K(TEA)) and potassium (K(K)) to the inactivation-impeding site were evaluated. K(TEA) was found to exhibit unexpected voltage dependence: K(TEA) decreased with depolarization. This was opposite the voltage dependence of K(K) on inactivation, in which permeating potassium impeded closure of the inactivation gate upon binding to a site in the pore (a "foot-in-the-door" mechanism). Further experiments on inactivation revealed anomalous mole fraction effects between permeating alkali cations and TEA, while no anomalous effects were seen between permeating ion species (K+, Rb+, Cs+). The results indicate that TEA and permeating ions impede inactivation through binding to different but closely interacting sites. K(TEA) was influenced by permeating ions through their bindings in the pore. As the size of the occupied ion was increased the dissociation constant of TEA to the ion-occupied pore decreased. Thus, we conclude that an ion bound to the inactivation-impeding site in the selectivity filter is located in close proximity to TEA bound at the entrance of the filter. The order of affinity of alkali cations for the inactivation-impeding site, Rb+ > Cs+ > K+, indicated that the selectivity of the site differed significantly from permeation selectivity, K+ > Rb+ > Cs+.

[A case of leiomyosarcoma of the spermatic cord].

A 44-year-old male was referred to our hospital for further treatment of lung and adrenal metastases from leiomyosarcoma occurring in the left spermatic cord. He had undergone high orchiectomy 5 months before, but no adjuvant therapy was done. Although systemic CYVADIC therapy (cyclophosphamide, vincristine, doxorubicin hydrochloride, dacarbazine) was performed in our hospital, he died of metastatic disease 10 months after the initial therapy. Leiomyosarcoma arising in the spermatic cord is a rare entity. We present a case of leiomyosarcoma of the spermatic cord, and to our knowledge, this is the 23rd case reported in Japan.

Thymidine phosphorylase and dihydropyrimidine dehydrogenase in bladder cancer.

Thymidine phosphorylase (TP) and dihydropyrimidine dehydrogenase (DPD) levels in transitional cell carcinoma of the bladder resected from 38 patients were examined by ELISA. TP levels in high-grade and invasive cancer were significantly higher than those in low-grade and superficial cancer, respectively. No significant differences in the DPD levels were observed among grades and stages, but the DPD/TP ratio was significantly lower in grade 3 tumor than in grade 1. These results demonstrated that 5'-deoxy-5-fluorouridine seemed to be useful for managing patients with grade 3 cancer. The present study also suggested that we might be able to exclude cases of bladder cancer in which 5-fluorouracil group medicines would be inappropriate candidates in treatment options by measuring both TP and DPD levels in the tumor.