[Current Status and Issues in Drug Development for Rare Cancers].

Since 1993, the"R & D Promotion System for Orphan Drugs and Orphan Medical Devices"has been in operation to support the development of orphan drugs in Japan. Various supportive measures are in place for indications that target less than 50,000 patients, have high medical needs and high probability of successful development(which means regulatory approval). However, recently a trend was observed that the designation for orphan drugs occurred most often in late phase of development, because clinical data for late stage clinical studies were required to show the high probability of successful regulatory approval. The Ministry of Health, Labour and Welfare are trying to make efforts to expand the orphan drug designation, and have made the decision to include the related expenses will be included in the FY 2023 budget request. It is expected that the expansion of orphan drug designation will lead to promote drug development in rare disease area. On the other hand, fundamental reform is considered necessary for this system. Among the approved anti-cancer drugs that obtained orphan designation in the U. S. and EU as of 2020, there are 24 drugs that have not been approved in Japan. Of these, there are at least 16 drugs approved in either China, Taiwan, and South Korea. From viewpoint of development pathway of an orphan drug, participation in a multi-regional clinical trial(MRCT)is useful, but there are cases that Japan cannot join MRCT in time due to the requirement of Japanese safety data prior to the participation. In that case, it is impossible to conduct a separate clinical trial to obtain Japan regulatory approval due to very limited patients(eg several to several tens of Ultra-Orphan). A review system that allows earlier patient access is desired.

Phylogenetic Placement and Morphological Characterization of Sclerotium rolfsii (Teleomorph: Athelia rolfsii) Associated with Blight Disease of Ipomoea batatas in Korea.

In this study, we aimed to characterize fungal samples from necrotic lesions on collar regions observed in different sweetpotato growing regions during 2015 and 2016 in Korea. Sclerotia appeared on the root zone soil surface, and white dense mycelia were observed. At the later stages of infection, mother roots quickly rotted, and large areas of the plants were destroyed. The disease occurrence was monitored at 45 and 84 farms, and 11.8% and 6.8% of the land areas were found to be infected in 2015 and 2016, respectively. Fungi were isolated from disease samples, and 36 strains were preserved. Based on the cultural and morphological characteristics of colonies, the isolates resembled the reference strain of Sclerotium rolfsii. Representative strains were identified as S. rolfsii (teleomorph: Athelia rolfsii) based on phylogenetic analysis of the internal transcribed spacer and large subunit genes along with morphological observations. To test the pathogenicity, sweetpotato storage roots were inoculated with different S. rolfsii strains. 'Yulmi' variety displayed the highest disease incidence, whereas 'Pungwonmi' resulted in the least. These findings suggested that morphological characteristics and molecular phylogenetic analysis were useful for identification of S. rolfsii.

Comparison of Non-contrast-Enhanced Computed Tomography and Intravenous Pyelogram for Detection of Patients With Urinary Calculi.

PURPOSE: The aim of this study was to investigate the changing pattern in the use of intravenous pyelogram (IVP), conventional computed tomography (CT), and non-contrast-enhanced computed tomography (NECT) for evaluation of patients with acute flank pain. MATERIALS AND METHODS: We retrospectively reviewed the medical records of 2,180 patients with acute flank pain who had visited Bundang Jesaeng General Hospital between January 2008 and December 2012 and analyzed the use of IVP, conventional CT, and NECT for these patients. RESULTS: During the study period there was a significant increase in NECT use (p<0.001) and a significant decrease in IVP use (p<0.001). Conventional CT use was also increased significantly (p=0.001). During this time the proportion of patients with acute flank pain who were diagnosed with urinary calculi did not change significantly (p=0.971). CONCLUSIONS: There was a great shift in the use of imaging study from IVP to NECT between 2008 and 2012 for patients with acute flank pain.

Comparison of Non-contrast-Enhanced Computed Tomography and Intravenous Pyelogram for Detection of Patients With Urinary Calculi

PURPOSE: The aim of this study was to investigate the changing pattern in the use of intravenous pyelogram (IVP), conventional computed tomography (CT), and non-contrast-enhanced computed tomography (NECT) for evaluation of patients with acute flank pain. MATERIALS AND METHODS: We retrospectively reviewed the medical records of 2,180 patients with acute flank pain who had visited Bundang Jesaeng General Hospital between January 2008 and December 2012 and analyzed the use of IVP, conventional CT, and NECT for these patients. RESULTS: During the study period there was a significant increase in NECT use (p<0.001) and a significant decrease in IVP use (p<0.001). Conventional CT use was also increased significantly (p=0.001). During this time the proportion of patients with acute flank pain who were diagnosed with urinary calculi did not change significantly (p=0.971). CONCLUSIONS: There was a great shift in the use of imaging study from IVP to NECT between 2008 and 2012 for patients with acute flank pain.

Optimal shock wave rate for shock wave lithotripsy in urolithiasis treatment: a prospective randomized study.

PURPOSE: We aimed to compare the effects of a fast shock wave rate (120 shocks per minute) and a slow shock wave rate (60 shocks per minute) on the shock wave lithotripsy (SWL) success rate, patient's pain tolerance, and complications. MATERIALS AND METHODS: A total of 165 patients with radiopaque renal pelvis or upper ureter stones were included in the study. Patients were classified by use of a random numbers table. Group I (81 patients) received 60 shock waves per minute and group II (84 patients) received 120 shock waves per minute. For each session, the success rate, pain measurement, and complication rate were recorded. RESULTS: No statistically significant differences were observed in the patients according to age, sex, body mass index, stone size, side, location, total energy level, or number of shocks. The success rate of the first session was greater in group I than in group II (p=0.002). The visual analogue pain scale was lower in group I than in group II (p=0.001). The total number of sessions to success and the complication rate were significantly lower in group I than in group II (p=0.001). CONCLUSIONS: The success rate of SWL is dependent on the interval between the shock waves. If the time between the shock waves is short, the rate of lithotripsy success decreases, and the pain measurement score and complications increase. We conclude slow SWL is the optimal shock wave rate.

Optimal Shock Wave Rate for Shock Wave Lithotripsy in Urolithiasis Treatment: A Prospective Randomized Study

PURPOSE: We aimed to compare the effects of a fast shock wave rate (120 shocks per minute) and a slow shock wave rate (60 shocks per minute) on the shock wave lithotripsy (SWL) success rate, patient's pain tolerance, and complications. MATERIALS AND METHODS: A total of 165 patients with radiopaque renal pelvis or upper ureter stones were included in the study. Patients were classified by use of a random numbers table. Group I (81 patients) received 60 shock waves per minute and group II (84 patients) received 120 shock waves per minute. For each session, the success rate, pain measurement, and complication rate were recorded. RESULTS: No statistically significant differences were observed in the patients according to age, sex, body mass index, stone size, side, location, total energy level, or number of shocks. The success rate of the first session was greater in group I than in group II (p=0.002). The visual analogue pain scale was lower in group I than in group II (p=0.001). The total number of sessions to success and the complication rate were significantly lower in group I than in group II (p=0.001). CONCLUSIONS: The success rate of SWL is dependent on the interval between the shock waves. If the time between the shock waves is short, the rate of lithotripsy success decreases, and the pain measurement score and complications increase. We conclude slow SWL is the optimal shock wave rate.

Optimal Shock Wave Rate for Shock Wave Lithotripsy in Urolithiasis Treatment: A Prospective Randomized Study

PURPOSE: We aimed to compare the effects of a fast shock wave rate (120 shocks per minute) and a slow shock wave rate (60 shocks per minute) on the shock wave lithotripsy (SWL) success rate, patient's pain tolerance, and complications. MATERIALS AND METHODS: A total of 165 patients with radiopaque renal pelvis or upper ureter stones were included in the study. Patients were classified by use of a random numbers table. Group I (81 patients) received 60 shock waves per minute and group II (84 patients) received 120 shock waves per minute. For each session, the success rate, pain measurement, and complication rate were recorded. RESULTS: No statistically significant differences were observed in the patients according to age, sex, body mass index, stone size, side, location, total energy level, or number of shocks. The success rate of the first session was greater in group I than in group II (p=0.002). The visual analogue pain scale was lower in group I than in group II (p=0.001). The total number of sessions to success and the complication rate were significantly lower in group I than in group II (p=0.001). CONCLUSIONS: The success rate of SWL is dependent on the interval between the shock waves. If the time between the shock waves is short, the rate of lithotripsy success decreases, and the pain measurement score and complications increase. We conclude slow SWL is the optimal shock wave rate.