[Port Site Recurrence After Laparoscopic Nephrectomy for Renal Cell Carcinoma --Report of Two Cases and Literature review-].

CASE 1: A male in his 60s underwent a right transperitoneal laparoscopic partial nephrectomy procedure for a right renal tumor. Rupture of a renal cyst located close to the tumor occurred intraoperatively. The histopathological diagnosis was clear cell renal cell carcinoma (CCRCC), pT1aN0M0, G2, v0, with negative resection margins. At 84 months after surgery, computed tomography (CT) revealed a 10 mm mass in the rectus abdominis muscle at the camera port site used for the partial nephrectomy. An open lumpectomy was then performed and the histopathological diagnosis was CCRCC. One year later, a 40 mm sized mass was detected in the mesentery of the small intestine by CT, which was removed laparoscopically with part of the mesentery and diagnosed as CCRCC. Since that surgery, the patient has been free from recurrence for 8 years. CASE 2: A male in his 60s underwent a left retroperitoneal laparoscopic nephrectomy procedure for a left renal tumor. The histopathological diagnosis was CCRCC, pT1aN0M0, G1, v0, with negative resection margins. At 31 months after surgery, CT revealed a 32 mm mass in the retroperitoneal cavity at the right hand port site used for the laparoscopic nephrectomy. The mass was removed with part of the twelfth rib and erector spinae muscles in a lump, and the histopathological diagnosis was CCRCC. Since that surgery, the patient has been free from recurrence for 19 months. For the treatment of solitary port site recurrence of renal cell carcinoma after a laparoscopic radical/partial nephrectomy, we recommend surgical resection for a good prognosis.

Risk prediction for metastasis of clear cell renal cell carcinoma using digital multiplex ligation-dependent probe amplification.

Precise quantification of copy-number alterations (CNAs) in a tumor genome is difficult. We have applied a comprehensive copy-number analysis method, digital multiplex ligation-dependent probe amplification (digitalMLPA), for targeted gene copy-number analysis in clear cell renal cell carcinoma (ccRCC). Copy-number status of all chromosomal arms and 11 genes was determined in 60 ccRCC samples. Chromosome 3p loss and 5q gain, known as early changes in ccRCC development, as well as losses at 9p and 14q were detected in 56/60 (93.3%), 31/60 (51.7%), 11/60 (18.3%), and 33/60 (55%), respectively. Through gene expression analysis, a significant positive correlation was detected in terms of 14q loss determined using digitalMLPA and downregulation of mRNA expression ratios with HIF1A and L2HGDH (P = .0253 and .0117, respectively). Patients with early metastasis (<1 y) (n = 18) showed CNAs in 6 arms (in median), whereas metastasis-free patients (n = 34) showed those in significantly less arms (3 arms in median) (P = .0289). In particular, biallelic deletion of CDKN2A/2B was associated with multiple CNAs (≥7 arms) in 3 tumors. Together with sequence-level mutations in genes VHL, PBRM1, SETD2, and BAP1, we performed multiple correspondence analysis, which identified the association of 9p loss and 4q loss with early metastasis (both P < .05). This analysis indicated the association of 4p loss and 1p loss with poor survival (both, P < .05). These findings suggest that CNAs have essential roles in aggressiveness of ccRCC. We showed that our approach of measuring CNA through digitalMLPA will facilitate the selection of patients who may develop metastasis.

[A Case of Giant Multilocular Prostatic Cystadenoma Resected by Laparoscopic Pelvic Cystectomy : A Case Report].

A 60-year-old man visited our hospital to treat a large cystic mass in the pelvis which had been found by abdominal ultrasonography in December 201X. Computed tomography (CT) and magnetic resonance imaging (MRI) showed a multilocular cyst with a maximum diameter of about 10 cm. CT-guided drainage and sclerotherapy with minocycline reduced the size of tumor by 40%, but symptoms such as difficulty of defecation and urinary frequency appeared a year and a half later due to re-enlargement of the cysts. Laparoscopic resection of the multilocular cysts was performed, and all cysts were removed almost completely using transrectal ultrasonography. The multilocular cyst was positive for NKX3.1 by immunohistochemical staining, and was diagnosed as a giant multilocular prostatic cystadenoma. After surgery, the symptoms such as difficulty of defecation and urinary frequency were relieved promptly. One year after the surgery, the patient was free from recurrence of the disease.

[A case of Endocrine Active Retroperitoneal Ganglioneuroma, Difficult to Differentiate From Adrenal Pheochromocytoma].

A 66-year-old woman who had been receiving medication for hypertension and hyperlipidemia was referred to our hospital for evaluation of a left adrenal tumor (12×8 mm) that was incidentally detected on computed tomography. Her 24-hour urinary catecholamine level was elevated, and metaiodobenzylguanidine (MIBG) scintigraphy revealed increased uptake in the area around the left adrenal gland, necessitating laparoscopic adrenalectomy for preoperative diagnosis of left adrenal pheochromocytoma. Intraoperatively, we detected a para-aortic tumor behind the adrenal gland, and this lesion was excised together with the adrenal gland. However, manipulation of the para-aortic tumor led to elevation in the blood pressure to 170 mmHg. Histopathological examination of the resected specimens revealed an adrenocortical adenoma and a para-aortic ganglioneuroma, consisting of ganglion cells, nerve fibers, and Schwann cells. The patient's blood pressure normalized immediately postoperatively, and MIBG scintigraphy revealed a negative result. Endocrine active ganglioneuromas are rare, and to our knowledge, currently only 8 cases (including ours) have been reported in the Japanese and English literature.

Analysis of the association between paternity and reoperation for urethral obstruction in adult hypospadias patients who underwent two-stage repair in childhood.

BACKGROUND: The association between surgical outcome of hypospadias repair and long-term male reproductive function has not been documented. The purpose of this study was to clarify association between paternity in adult hypospadias patients and reoperation for urethral obstruction after two-stage repair during childhood. METHODS: Ninety hypospadias patients who underwent the same kind of two-stage repair in our institute by a single surgeon, were initially treated at < 18 years old, and who were ≥ 18 years old during the survey were included in the study. Present physical, social, and life status were evaluated by a mailed self-entry questionnaire, and clinical background and surgical outcome data were evaluated by medical records. National survey data of the general population were used as external control. The paternity rate of the patient groups was evaluated by Kaplan-Meier curve analysis and log-rank tests. RESULTS: Twenty-six patients (28.9%) underwent 43 reoperations after completion of the initial repair. Twelve patients were reoperated for obstructive complication (Study group) and were compared with 14 patients who were reoperated only for non-obstructive causes and 64 patients who were not reoperated as Study control group (N = 78). The Study group patients showed sexual intercourse rate and marriage rate not statistically different in comparison with the Study control, although marriage rate at 32.5 years old were lower than the general population (p = 0.048, z-test). None of the Study group achieved paternity, which showed a significant difference to the Study control (p = 0.032, log-rank test). The difference was also statistically significant in the analysis among the 31 married patients (p = 0.012, log-rank test). Patients reoperated for obstructive complication documented worsened Quality of Life score in the International Prostate Symptom Score (2.3 ± 2.0 vs. 1.4 ± 1.2, p = 0.031, t-test) and ejaculation problems (66.7% vs. 17.4%, p = 0.003, chi-square test). CONCLUSIONS: History of reoperation for obstructive complication was associated with lower paternity rate in patients with hypospadias, presumably for multifactorial causes associated with marriage age and ejaculation problems. The present results may implicate importance of uncomplicated urethroplasty during childhood for achieving paternity, although it should be further tested in the future for larger groups of hypospadias patients.

Inhibition of the Mammalian Target of Rapamycin May Augment the Increase in Soluble Klotho Levels in Renal Transplantation Recipients.

BACKGROUND/AIMS: α-Klotho is mainly expressed in the kidneys, and its soluble form can prevent vascular calcifications. Inhibition of the mammalian target of rapamycin (mTOR) upregulates Klotho. We assessed serial changes in the levels of soluble Klotho (sKlotho) in recipients before and after renal transplantation and investigated the effects of an mTOR inhibitor. METHODS: Serum sKlotho levels were measured in 36 recipients before and 1 year after transplantation and compared between those taking everolimus and those not taking everolimus. RESULTS: sKlotho levels were higher after transplantation than before transplantation (369.3 vs. 211.8 pg/mL). After transplantation, sKlotho levels were significantly higher in recipients taking everolimus than in those not taking everolimus (536.7 vs. 332.4 pg/mL). CONCLUSION: Our results suggest that mTOR inhibition may augment the increase in sKlotho levels in transplant recipients. Further studies are needed to examine whether mTOR inhibitors suppress the development of vascular complications via upregulation of Klotho expression in renal transplant recipients.

Evaluation of Treatment Response in Prostate Cancer and Renal Cell Carcinoma Patients Using 11C-choline PET/CT Findings.

We investigated the effectiveness of 11C-choline-positron emission tomography/computed tomography (PET/CT) for evaluating treatment response in patients with prostate cancer or renal cell carcinoma. We performed 34 11C-choline PET/CT scans before/after a combined total of 17 courses of treatment in 6 patients with prostate cancer and 2 with renal cell carcinoma. The 17 treatments including hormonal therapy, radiotherapy, chemotherapy, radium-223, molecular target therapy, radiofrequency ablation, transcatheter arterial embolization, and cancer immunotherapy yielded 1 (5.9%) complete metabolic response (CMR), 3 (17.6%) partial metabolic responses (PMRs), 2 (11.8%) stable metabolic diseases (SMDs), and 11 (64.7%) progressive metabolic diseases (PMDs). Target lesions were observed in bone (n=14), lymph nodes (n=5), lung (n=2), prostate (n=2), and pleura (n=1), with CMR in 4, PMR in 10, SMD in 8 and PMD in 2 lesions. SUVmax values of the target lesions before and after treatment were 7.87±2.67 and 5.29±3.98, respectively, for a mean reduction of -35.4±43.6%. The response for the 8 prostate cancer-treatment courses was PMD, which correlated well with changes in serum prostatic specific antigen (PSA) (7 of 8 cases showed increased PSA). 11C-choline-PET/CT may be an effective tool for detecting viable residual tumors and evaluating treatment response in prostate cancer and renal cell carcinoma patients.

Diagnostic Performance of 11C-choline PET/CT and FDG PET/CT in Prostate Cancer.

We compared 11C-choline and FDG PET/CT scan findings for the staging and restaging of prostate cancer. Twenty Japanese prostate cancer patients underwent 11C-choline and FDG PET/CT before (n=5) or after (n=15) treatment. Using a five-point scale, we compared these scanning modalities regarding patient- and lesion-based diagnostic performance for local recurrence, untreated primary tumor, and lymph node and bony metastases. Of the 20 patients, documented local lesions, and node and bony metastases were present in 11 (55.0%), 9 (45.0%), and 13 (65.0%), respectively. The patient-based sensitivity/specificity/accuracy/area under the receiver-operating-characteristic curve (AUC) values for 11C-choline-PET/CT for diagnosing local lesions were 90.9% /100%/ 95.0% / 1.0, whereas those for FDG-PET/CT were 45.5% /100%/ 75.0% / 0.773. Those for 11C-choline-PET/CT for node metastasis were 88.9% /100%/ 95.0% / 0.944, and those for FDG-PET/CT were 44.4%/100%/75.0%/0.722. Those for 11C-choline-PET/CT for bone metastasis were 84.6%/100%/90.0%/0.951, and those for FDG-PET/CT were 76.9% /100%/ 85.0% / 0.962. The AUCs for local lesion and node metastasis differed significantly (p=0.0039, p=0.011, respectively). The lesion-based detection rates of 11C-choline compared to FDG PET/CT for local lesion, and node and bone metastases were 91.7% vs. 41.7%, 92.0% vs. 32.0%, and 94.8% vs. 83.0% (p=0.041, p=0.0030, p<0.0001), respectively. 11C-choline-PET/CT is more useful for the staging and restaging of prostate cancer than FDG-PET/CT in Japanese men.

[The Usefulness of 11C-Choline PET/CT for Detecting Metastasis and Treatment Monitoring of Renal Cell Carcinoma : Report of Two Cases].

Although fluorodeoxyglucose (FDG) positron emission tomography (PET)/computed tomography (CT) has been widely used as a powerful tool in clinical oncologic imaging, its application in urological malignancies is limited. Recently, choline PET/CT has been successfully used for prostate cancer restaging. Here, we report the utility of choline PET/CT for the detection and monitoring of metastatic disease in two cases of renal cell carcinoma (RCC). A 53-year-old woman and a 45-year-old woman underwent FDG and choline PET/CT for evaluation of metastatic lesions in lymph nodes and bone following left and right RCC, respectively, and choline PET/CT demonstrated significantly higher uptake when compared with FDGPET/CT in both cases. Choline PET/CT accurately reflected the remission and progression of diseases in their clinical course, indicating that choline PET/CT could be a useful imaging modality in metastatic RCC.

Enhancement of death receptor 4-mediated apoptosis and cytotoxicity in renal cell carcinoma cells by anisomycin.

Renal cell carcinoma (RCC) is one of the most drug-resistant malignancies, and an effective therapy is lacking for metastatic RCC. Anisomycin is known to inhibit protein synthesis and induce ribotoxic stress. The aim of this study was to explore whether anisomycin enhances the cytotoxic effects of mapatumumab, a human agonistic monoclonal antibody specific for death receptor 4 (DR4), in human RCC cells. We examined the cytotoxicity of anisomycin alone and in combination with mapatumumab in human RCC cell lines and primary RCC cell cultures. RCC cells treated with anisomycin showed cytotoxicity in a dose-dependent manner. Anisomyin in combination with mapatumumab showed a synergistic effect not only in two human RCC cell lines but also in five primary RCC cell cultures. The synergy between anisomycin and mapatumumab for cytotoxicity was also observed for apoptosis. Interestingly, anisomycin significantly increased DR4 expression at both the mRNA and the protein level. Furthermore, the combination-induced cytotoxicity was significantly suppressed by a human recombinant DR4:Fc chimeric protein. The combination of anisomycin and mapatumumab also enhanced the activity of caspases 8 and 3, the downstream molecules of death receptors. These findings indicate that anisomycin sensitizes RCC cells to DR4-mediated apoptosis through the induction of DR4, suggesting that combinational treatment with anisomycin and mapatumumab might represent a novel therapeutic strategy for the treatment of RCC.

Diagnostic performance of 11C-choline PET/CT and bone scintigraphy in the detection of bone metastases in patients with prostate cancer.

The aim of this study was to compare 11C-choline PET/CT and bone scintigraphy (BS) for detection of bone metastases in patients with prostate cancer. Twenty-one patients with histologically proven prostate cancer underwent 11C-choline PET/CT and BS before (n = 4) or after (n = 17) treatment. Patient-, region-, and lesion-based diagnostic performances of bone metastasis of both 11C-choline PET/CT and BS were evaluated using a five-point scale by two experienced readers. Bone metastases were present in 11 (52.4%) of 21 patients and 48 (32.7%) of 147 regions; 111 lesions were found to have bone metastases. Region-based analysis showed that the sensitivity, specificity, accuracy, and area under the receiver-operating-characteristic curves (AUC) of 11C-choline PET/CT were 97.9%, 99.0%, 98.6%, and 0.9989, respectively; those of BS were 72.9%, 99.0%, 90.5%, and 0.8386, respectively. Sensitivity, accuracy, and AUC significantly differed between the two methods (McNemar test, p = 0.0015, p = 0.0015, and p < 0.0001, respectively). 11C-choline PET/CT detected 110/111 metastatic lesions (99.1%); BS detected 85 (76.6%) (p < 0.0001). According to the CT morphological type, the visualization rates of 11C-choline-PET/BS were 100%/90.3% for the blastic type, 91.7%/8.3% for the lytic type, 100%/100% for the mixed type, and 100%/53.3% for the invisible type, respectively. Significant differences in blastic, lytic, and invisible types were observed between the two methods (p = 0.013, p = 0.0044, and p = 0.023, respectively). In conclusion, 11C-choline PET/CT had greater sensitivity and accuracy than BS for detection of bone involvement in patients with prostate cancer.

11C-Choline positive but 18F-FDG negative pancreatic metastasis from renal cell carcinoma on PET.

Choline is a new PET tracer, which uptake may occur via a choline-specific transporter protein and be accelerated during the proliferation of tumor cells. We report a 61-year-old woman with a metastatic pancreatic tumor from renal cell carcinoma, measuring 35×40 mm. PET scans demonstrated accumulation of 11C-choline in the metastatic pancreatic tumor, but no accumulation of 18F-FDG. Choline PET/CT may play a useful and complementary imaging modality, especially when FDG-PET/CT does not show expected findings or when the evaluation of tumor viability is needed, in patients with renal cell carcinoma.

[Clinical Study of Testicular Fasciotomy for Testicular Torsion].

Between November 2011 and November 2014, we performed a tunica albuginea incision with tunica vaginalis flap coverage (TAI＋TVFC) on 5 out of 15 patients who underwent surgery for testicular torsion. Of those 15 patients, 7 underwent orchidopexy alone (Group A), 5 underwent TAI＋TVFC (Group B), and 3 underwent an orchidectomy procedure (Group C). All were followed for 1 year and preservation of testicular volume ＞50% on the contralateral side in ultrasound measurements was considered as salvaged. During the follow-up examinations, no testicular atrophy was noted in Group A. In Group B, tension and testis color were immediately improved in all 5 patients after TAI＋TVFC, while blood perfusion was also improved after the operation. Also 3 patients in Group B were considered to be salvaged, while testicular atrophy occurred in 2 after 8 or more hours from onset until surgery. Our results indicated that TAI＋ TVFC is useful for restoring blood flow after surgery for testicular torsion, although the so-called'Golden time'for torsion surgery has a significant impact in such cases.

Multivariate Analysis of the Factors Associated With Sexual Intercourse, Marriage, and Paternity of Hypospadias Patients.

INTRODUCTION: Patients with hypospadias are treated surgically during childhood, which has the intention of enabling a satisfactory sexual life in adulthood. However, it is unclear whether patients with corrected hypospadias can lead a satisfactory sexual life and sustain a marital relationship and produce offspring. AIM: To evaluate factors associated with achievement of sexual intercourse, marriage, and paternity in patients with hypospadias who have reached adulthood. METHODS: Self-completion questionnaires were mailed in April 2012 to patients with hypospadias at least 18 years old who had been treated at our institution during childhood from 1973 through 1998 by a single surgeon and the same surgical policy. Assessments included the International Prostate Symptom Score, the International Index for Erectile Function-5, and non-validated questions related to current social and physical status and sexual, marital, and paternity experiences. Candidate factors were extracted from patients' neonatal data, surgical findings and results, and current physical and social status obtained by the questionnaires. MAIN OUTCOME MEASURES: Candidate factors associated with heterosexual intercourse, marriage, and paternity experiences were analyzed using univariate and multivariate proportional hazard models and log-rank test of Kaplan-Meier curves. RESULTS: Of the 518 patients contacted, 108 (age = 18-50 years, median = 28 years) met the inclusion criteria. Two- and one-stage repairs were performed as the initial treatment in 79 and 12, respectively, and 17 of the analyzed cases were reoperations for patients initially treated elsewhere. Fifty-seven patients had the milder type (31 glandular, 26 penile), 36 had the proximal type (13 penoscrotal, 23 scrotal-perineal), and 15 had an unknown type. Multivariate analyses by Cox proportional hazard model and log-rank tests confirmed that experience of sexual intercourse was associated with the milder type of hypospadias (P = .025 and .0076 respectively), marriage was associated with stable employment (P = .020 and .026, respectively), and paternity was associated with the absence of additional surgery after completion of the initial repair (P = .013 by multivariate analysis). CONCLUSION: There was scant overlap of factors associated with the three events. The present findings provide reference information for surgeons and parents regarding future sexual and marriage experiences of children treated for hypospadias.

Cotyledonoid dissecting leiomyoma of the uterus: report of two cases.

BACKGROUND: Cotyledonoid dissecting leiomyoma (Sternberg tumor) is a rare variant of the uterine smooth muscle tumor. Although this tumor is a benign tumor clinically and pathologically, the appearance and growth pattern is unusual, so it may be misdiagnosed as malignancy. CASE REPORTS: We report two cases of cotyledonoid dissecting leiomyoma of the uterus that occurred in two 44- and 31-year-old women, respectively. Total hysterectomy and bilateral salpingo-oophorectomy were performed in one of the patients, and myomectomy was done in the other one. Macroscopically, both tumors were grape-like exophytic masses resembling placental tissue. The patients were well after surgery, and one patient gave birth. To our knowledge, this is the first case report of a successful delivery after myomectomy of this tumor. CONCLUSION: To prevent aggressive surgery it is important to recognize that this tumor is a benign and unusual appearing variant of leiomyoma. A fertility-sparing surgical procedure should be considered if the patient wishes to preserve her fertility.

[An Adult Case of Transperineal Repair of Congenital Rectourethral Fistula Using Gracilis Muscle Flap Interposition].

A man in his 50s was referred to our hospital after recurrent severe urinary tract infection. He had undergone anoplasty for anorectal malformation during early infancy. He noticed urinary leakage from the anus for a long time. Under diagnosis of congenital rectourethral fistula, we performed fistula closure. The fistula was transsected via transperineal incision and each stump was closed. A gracilis muscle flap approximately 30 cm long was harvested from the left thigh, brought into the deepest part between the separated rectum and urethra through a subcutaneous tunnel and fixed there. The urinary leakage from the anus disappeared, and the infection resolved. Application of gracilis muscle flap for congenital diseases is rare, but was useful in the present case.

[A Case of Retroperitoneal Serous Cyst Treated by Open Fenestration : A Case Report].

A 47-year-old woman came to our hospital with left lower abdominal pain in April 2013. An abdominal computed tomographic (CT) examination revealed left hydronephrosis secondary to a 7 cm retroperitoneal cyst near the left common iliac artery and ureter. Serum tumor markers including CEA, CA19-9, and CA125 were negative. Although CT guided needle aspiration of the cyst successfully relieved severe left flank pain, the cyst again increased in size, causing left hydronephrosis, though examinations for fluid tumor markers and cytology were negative. Two months later, the patient underwent open fenestration. The final pathological results demonstrated a mesothelial cyst without malignant findings. Six months after the operation, the patient was doing well without recurrence of symptoms.

[Leiomyosarcoma of the inferior vena cava: a case report and review].

A 37-year-old woman with an incidentally found abdominal mass was referred to our hospital. A fixed, non-tender mass was palpated in the right upper quadrum of her abdomen. There was no elevation of tumor markers. Computed tomography revealed a mass extending from the hepatic vein level to renal hilar level. The tumor completely obstructed the inferior vena cava (IVC). T1-weighted magnetic resonance imaging (MRI) showed that the mass was isointense with muscles. T2-weighted MRI image with contrast medium demonstrated collateral circulation. Upon diagnosis of the IVC tumor, we removed the right kidney and the tumor en bloc without reconstructing IVC. The tumor diameter was 11.6 × 5.5 × 4.7 cm. Pathological examination established a diagnosis of IVC leiomyosarcoma. She is alive without sign of recurrence after operation for seven months. There were 143 reports of IVC leiomyosarcoma in Japan. In 31% of them, IVC was not reconstructed.

[The safety and efficacy of sunitinib using a modified regimen (2 weeks on/1 week off) for treatment of metastatic renal cell carcinoma].

We prospectively investigated the safety and efficacy of sunitinib using a modified regimen (2 weeks on/1 week off) in 24 patients (22 males, 2 females ; age range 39-86 years, median 64 years) with metastatic renal cell carcinoma (RCC). During the observation period (3-62 weeks, median 21 weeks), thrombocytopenia was seen in 13 (54.2%), leukopenia in 11 (45.8%), hand-foot syndrome in 5 (20.8%), hypertension in 4 (16.7%), and hypothyroidism in 3 (12.5%) patients, while grade 3 or higher adverse events were found in 4 (16.7%), 1 (4.2%), 1 (4.2%), 2 (8.3%), and 0 patients, respectively. Of the 21 patients evaluable for response, 5 (23. 8%) showed partial response, 8 (38.1%) stable disease, and 8 (38.1%) progressive disease. This new modified regimen may lead to a reduction in adverse events for treatment of patients with metastatic RCC as a substitute for the standard dosing regimen of sunitinib.

[Verification of reduction in preparation time and cost of cyclophosphamide when using the closed-system drug transfer device].

The closed-system transfer device (CSTD), which is used to prevent the exposure of medical staff to anticancer drugs, has been reported to allow safe preparation and administration of these drugs to patients. At many medical institutions, however, the use of such devices is limited to select anticancer drugs. This could be attributable to the longer preparation time compared to the conventional injection technique with a syringe and needle, as well as the fact that the anticancer drugs are too expensive to be covered by the remuneration available for medical services. Against this background, we measured the time required to prepare cyclophosphamide(CPA)and estimated the cost incurred. Our results indicated that the preparation time for either a single dose of 100 mg CPA or a combination of 100 mg CPA and 500 mg of another drug(100mg+500 mg group)was significantly longer than that for 500 mg of a single drug. On the other hand, use of a CSTD reduced the total cost (drug cost+CSTD cost)on switching to a single dose of 500 mg, resulting in a 5-year savings as follows: 3,755,217 yen for ChemoCLAVE®, 6,302,622 yen for PhaSeal®, and 2,698,451 yen for Chemosafe®. These findings suggest that the appropriate selection of drugs, including a large standard dose of CPA, allows shortened preparation time and reduced total drug cost as well as CSTD cost.