renal cell carcinoma ( rcc ) , which accounts for 2% to 3% of all malignant neoplasms in adults , is one of the most lethal of the common urologic cancers . the total number of patients suffering from malignancies of the kidney in 2011 was approximately 25,000 ( 19,000 males and 6,000 females ) . this is an increase from 1996 , when the number of individuals with renal malignancies was 15,000 ( 10,000 males and 5,000 females ) . the total number of fatalities from rcc was 4,439 ( 3,032 males and 1,407 females ) ; approximately 90% of these patients were over 60 years of age . although early - stage rcc shows no signs , various symptoms arise as the cancer progresses , such as macroscopic hematuria , pain or palpable masses . with advances in diagnostic imaging , many asymptomatic rccs have been discovered incidentally in their early stages with ultrasonography or computed tomography . reported survival is near 90% in stage i , 70% in stage ii , 50% in stage iii , and 20% in stage iv . in recent years however , treatment response to these therapies has been limited for advanced or metastatic rcc . traditionally the standard surgical treatment for clinical stage t1 rcc has been radical nephrectomy , in the absence of concerns about renal function on the contralateral side . partial nephrectomy was performed only in cases with complicating factors , such as solitary kidney , renal insufficiency , or bilateral rcc . partial nephrectomy , however , has become more commonly performed for kidney tumors 4 cm or less in diameter , even in patients with normal contralateral kidney function . the long - term oncological outcomes of partial nephrectomy through laparoscopic or open surgery are excellent and hardly differ from those of radical nephrectomy . the cancer - specific 5-year survival rate after partial nephrectomy in patients with rcc is 89% to 96% . there are other reasons for this change in treatment approach : approximately 10% of small tumors are benign , and with radical nephrectomy there is a risk of deterioration in renal function resulting from hyperfiltration in the single kidney postoperatively . in 2011 the guideline recommends partial nephrectomy for t1a tumors ( 4 cm ) as standard of care , because the procedure achieves equivalent cancer control and has good results in preserving renal function , compared with radical nephrectomy . however , there have been few reports on cancer control and postoperative renal function after partial nephrectomy for tumors greater than 4 cm in diameter . therefore , it is too early to judge whether partial nephrectomy works well in the long term . in contrast , the 2014 national comprehensive cancer network guideline recommends partial nephrectomy or nephrectomy as standard surgical treatment for tumors between 4 and 7 cm in diameter , because they achieve equivalent cancer control . the european association of urology guidelines for kidney cancer also recommend partial nephrectomy for t1 renal tumors ( < 7 cm ) . as these guidelines show , partial nephrectomy through laparoscopic surgery or open surgery controls ct1 kidney cancers as well as radical nephrectomy and is associated with a good long - term prognosis for renal function . robot - assisted partial nephrectomy ( rapn ) for ct1 kidney cancer patients may also be useful . choi et al .   reported that rapn is preferable to laparoscopic partial nephrectomy ( lpn ) , with a lower conversion rate to radical nephrectomy , favorable renal function as indicated by 1estimated glomerular filtration rate ( egfr ) , shorter length of hospital stay , and shorter warm ischemia time . every person in japan is covered by some form of public insurance and thus can receive necessary medical services at low cost by paying insurance premiums and copayments ( 10% to 30% of charges ) . free access ,  which means that everyone can receive medical services at any medical institution nationwide . people are protected by the universal health insurance system , in which everyone can receive high - quality medical services at a predetermined cost , regardless of their income or type of work . however , because of increases in national medical expenditure , the financial management of universal health care has been increasingly challenging in recent years and thus measures to curtail this trend have become an urgent issue . a system of mixed medical services , with both publically and privately funded services , is not accepted in japan . therefore , having a treatment recognized by insurance is an important step for that treatment to spread to the public . to be covered by insurance , the safety and validity of a treatment need to be demonstrated in a prospective clinical trial in japan . the only robot - assisted surgery covered by medical services in japan until april 2016 was robot - assisted radical prostatectomy . advanced medical treatment in japan means accepting the combination of advanced medicine and covered medical services . treatments need to be evaluated to determine whether they should be covered by public insurance in the future . the goals of this approach are securing public safety , preventing increased costs for the patient , extending patients ' choices , and improving convenience for the public . to evaluate whether rapn should be covered by public insurance in japan , we conducted a multi - institutional , prospective , nonrandomized clinical trial to assess its efficacy and safety . rapn is an innovative technology aimed at cancer control , postoperative renal function preservation , and minimized invasiveness . the forceps used on the robotic arm in rapn are highly flexible compared with those used in conventional laparoscopic surgery . with the removal of the tremor of the surgeon , minute surgery is accurately reproduced . this enables not only precise tumor excision in a limited space but also dissection and suturing of fine vessels and urinary tracts . thus robot - assisted laparoscopic surgery is expected to be advantageous for cancer control and renal function preservation . in highly challenging cases such as hilar tumors or endophytic tumors , which are considered very difficult to resect with a laparoscopic approach , rapn enables tumor resection equivalent to open surgery , with minimal invasion . considering these facts , radical tumor resection and preservation of renal function we defined radical tumor resection and preservation of renal function as : ( 1 ) no conversion to laparoscopic or open surgery , ( 2 ) negative surgical margins , and ( 3 ) warm ischemic time under 25 minutes . before this trial started , about 75 rapns had been performed in japan ( as of the end of december 2012 , according to a survey by the japanese society of endourology ) . from 2011 to january 2013 kobe university hospital performed rapn in 26 patients whose kidney tumors were surgically removable and who wanted to receive this surgery at their own expense . our study revealed that rapn resulted in less blood loss , no extension of ischemic time , and good postoperative renal function compared with conventional lpn and open partial nephrectomy ( opn ) . although it takes time to master the techniques of rapn , we believe that the learning curve is shorter than that for laparoscopic surgery . the spread of rapn , with its low invasiveness , high cancer cure rates , and simultaneous preservation of renal function , will contribute to the radical curability of cancer in patients with localized renal cancer , will help avoid postoperative chronic kidney disease ( ckd ) and will provide good long - term prognosis , thus improving public health . the endpoint of effectiveness ( both renal function preservation and curative resection ) was compared with the  historical control ,  which was lpn performed at multiple institutions in japan ( 541 institutions , 1,375 cases ) . the achievement rate of both renal function preservation and radical resection , which were the primary endpoints of the present trial , was 91.3% ( 95% confidence interval , 84.195.9 ) . this value significantly exceeded the threshold level ( 23.3% ) determined beforehand ( p<0.001 ) . according to the existing research , patients with less than 25 minutes of renal ischemic time have significantly less impaired renal function 6 months postoperatively and significantly lower incidence of ckd ( ckd stage iv ; < 30% egfr ) , compared with those having ischemic time over 25 minutes . a multi - institutional observational study used as a historical control suggested that with lpn the renal ischemia time was 25 minutes or less in 25% of patients at most . when planning this project , we hypothesized that increasing the percentage of patients with renal ischemic time of 25 minutes or less by 5% to 10% ( corresponding to the number needed to treat=1020 ) with the rapn protocol would be clinically significant . to achieve a significant change in medical economics it was determined that an increase of 15% would be required , taking into account the incremental costs related to the introduction of this novel treatment . accordingly , the expected percentage of rapn patients with renal ischemic time within 25 minutes was set at 40% . additionally we anticipated that approximately 37.2% of patients would achieve the primary endpoint of both renal function preservation and curative resection , taking into account that in some cases rapn would need to be converted into conventional laparoscopic or open surgery , or would have positive surgical margins . in the present prospective trial , 91.3% of patients achieved both renal function preservation and curative resection , far exceeding our expectations . thus , the results of this trial revealed good efficacy with rapn , compared with the historical control . the historical control used to set the basis of threshold was reported in 2012 based on data from a multi - institutional observational study on lpn ( 54 institutions , 1,375 cases ) conducted in japan from 1998 to 2008 . therefore , when comparing the results of the two studies , it may be necessary to consider differences in the technical maturity between the present and the time when the multi - institutional joint observational study on lpn was performed . however , even if this difference in technical maturity is taken into consideration , the results of the present study show an obvious advantage of rapn . when ischemic time alone was examined , we found a clear shortening compared with historical controls ( meanstandard deviation : 19.06.4 minutes for rapn , 4119 minutes for lpn ) . the reported rates of positive surgical margins with lpn were 0% to 4% ; the rate of the historical control was 1.7% . these excellent results were due to the features of a robot - assisted approach , such as precise 3-dimensional visualization , highly flexible forceps with 7 degrees of freedom , and the correction of tremor . although it is difficult to perform lpn in some cases , depending on conditions such as tumor diameter or location even in the case of t1 tumors , rapn had good results , with no big difference in achievement rate regardless of the diameter or location of the tumor . when an analysis object group ( full analysis set ) was evaluated with the r.e.n.a.l . nephrometry score , which is an index of the difficulty of partial nephrectomy mainly based on tumor location and diameter , we found 38 low - complexity cases ( 36.9% ) , 62 intermediate - complexity cases ( 60.2% ) and 3 high - complexity cases ( 2.9% ) . these percentages are comparable to the patient composition in past reports ( 48 low - score cases [ 44% ] , 57 intermediate - score cases [ 53% ] , and 3 high - score cases [ 3% ] ) , which reveals that arbitrary patient selection was not performed . in addition , although we have only short - term results at present , there was no report of death , and the probability of survival for 90 days after surgery was 100.0% . a comparison of outcomes in past studies and in the present trial is shown in table 1 . longer average length of hospital stay observed in the present study was due to japanese public health insurance system ; burden of hospitalization cost is light in japan . the positive surgical margins rate in this study was 0% . compared with the results of the historical control ( 1.7% ) , the protocol treatment was performed evenly in all locations and the achievement rate of the primary endpoint was as high as 87.5%93.7% , irrespective of tumor location . as mentioned above , in cancer control ( negative margin rate ) and renal function preservation ( ischemic time within 25 minutes ) , rapn achieved better results than conventional laparoscopic surgery . the operative time ( meanstandard deviation ) in this trial was 3.891.10 hours ; blood loss was 60.7894.50 ml . compared with clinical studies on rapn performed in other countries and those on lpn in japan , surgery time was almost the same ( historical control , 4.321.52 hours ) . blood loss , however , was less with rapn than with the conventional surgical procedure ( 210426 ml for historical control ) . among safety analysis object groups , the rate of adverse events during the operation was 53.3% ( 56 of 105 ) , which was high compared with the rate of postoperative complications ( 10.6% [ 11 of 104 ] ) . the serious adverse event in this study was postoperative renal arterial aneurysm ( 9 cases ) . renal artery aneurysm is a known complication after opn or lpn . when the renal artery is damaged during suturing after tumor resection , or if insufficient hemostasis in the thin vulnerable renal artery results in rebleeding when blood flow increases after surgery , hematoma around an artery in resected defects can form a pseudoaneurysm . we examined the relationships between pseudoaneurysm and sex , age , body mass index , anamnesis , tumor location , and renal nephrometry score . the reported probability of symptomatic aneurysm with signs such as macrohematuria is 0.4%4.2% in opn , 1.0%12.0% in lpn , and 0.2%10.2% in rapn . these numbers , however , vary depending on the report . in one study in japan , asymptomatic renal pseudoaneurysm was detected with enhanced computed tomography in 17 out of 117 early postoperative patients ( 15% ) after rapn . according to that report , arterial embolization was performed in 1 case that had bleeding and in 11 cases to prevent future bleeding ( size4 mm ) , though they were asymptomatic . therefore , even though pseudoaneurysm can occur , small pseudoaneurysms generally follow a course of natural regression . therefore the estimated incidence of symptomatic aneurysm is 10.2% ( 12 of 117 ) . in the present study pseudoaneurysm occurred in 8 cases ( 7.6% ) , indicating that renal pseudoaneurysm did not occur frequently . the preferred treatment of pseudoaneurysm is coil embolization via arterial catheter because of its low invasiveness and high success rate . all cases of pseudoaneurysm in the present study were mild and recovered with minimally invasive catheter coil embolization . this is because the artery that caused rebleeding was quite small and hemostasis of the main arteries was ensured with the precise manipulation of the robot - assisted approach . pseudoaneurysm is an adverse event that can occur after rapn ; this possible complication must be kept in mind during postoperative patient care , and must be treated quickly and appropriately when it does occur . when open tumor resection of the renal pelvis or calyx is performed , urine can leak into the abdominal cavity from the suture line , and can cause clinically significant effects . in the historical control , urine leakage was found in 2.5% of all patients and in 1.7% of those who were grade 3 or higher . this is a point that should be noted , because it shows the advantages of robotic assistance . robotic assistance allows easy and accurate suturing compared with a conventional laparoscopic approach , enables surgery to be performed with an enlarged field of view , and provides secure suturing in the case of open resection of the renal pelvis or calyx . other defined adverse events in this trial were bleeding , venous thrombosis , pulmonary embolism , wound infection , multiorgan damage , renal hypertension , wound infection , and acute renal dysfunction . the events reported during the observation period were 29 cases of bleeding ( 27.6% ) and 3 of acute renal dysfunction ( 2.9% ) . in the patients with acute renal dysfunction , the frequency and outcome of bleeding and acute renal dysfunction were not different from those of other treatments in this domain . no factors correlating with adverse events were identified , although the number of examples of each background factor varied . the adverse events that occurred most frequently in the perioperative period were wound complications ( 31 cases ) , macrohematuria ( 22 cases ) , and fever ( 13 cases ) , all of which occur frequently with any surgical procedure . egfr , which is an indicator of renal function , never fell below 60 ml / min/1.73 m in any patient after protocol treatment and showed recovery with passage of time , indicating preservation of renal function . moreover , in 91.3% of cases resection and suturing were performed within 25 minutes , which is considered the cutoff for ideal ischemic time . minimizing renal ischemia time leads to long - term preservation of renal function and to the control of progression to ckd , contributing significantly to the improvement in patients ' quality of life . among safety analysis object groups , 146 postoperative adverse events were reported in 56 patients , yielding a complication rate of 53.3% ( 56 out of 105 cases ) . the adverse event that occurred most frequently in the perioperative period was wound complications ( 31 cases , 29.5% ) , followed by macroscopic hematuria ( 22 cases , 21.0% ) and fever ( 13 cases , 12.4% ) . the perioperative critical adverse event that occurred most frequently in this trial was symptomatic pseudoaneurysm in 8 cases ( 7.6% ) . furthermore , they were required to meet the following conditions : experience of more than 10 cases of laparoscopic or open partial nephrectomy , more than 30 cases of laparoscopic or open radical nephrectomy , more than 20 cases of robot - assisted radical prostatectomy , and approved as laparoscopic surgeon by the japanese society of endourology . although the experience of 10 cases of rapn can not be considered vast experience , 91.3% of patients attained the primary endpoint . although mastering this technology takes some training and technical experience , as with open surgery or conventional laparoscopy , it is possible to gain the skills in a short period of time . accordingly rapn is considered to be a useful surgical technique to minimize invasiveness , provide radical cancer curability and preserve renal function . surgery for renal hilar tumors and full endophytic - type tumors has been considered difficult with a conventional laparoscopic approach . in the future , however , a robotic approach will make it possible to remove such tumors with minimal invasiveness , which has previously been attained only through open surgery . this study found that rapn achieves minimal invasiveness , good cancer control , and renal function preservation , indicating that this technology will improve the surgical treatment of patients with nonmetastatic rcc , will decrease the occurrence of postoperative ckd , and will improve long - term prognosis . rapn will contribute considerably to the public health , which will lead to reduced medical expenses . the endpoint of effectiveness ( both renal function preservation and curative resection ) was compared with the  historical control ,  which was lpn performed at multiple institutions in japan ( 541 institutions , 1,375 cases ) . the achievement rate of both renal function preservation and radical resection , which were the primary endpoints of the present trial , was 91.3% ( 95% confidence interval , 84.195.9 ) . this value significantly exceeded the threshold level ( 23.3% ) determined beforehand ( p<0.001 ) . according to the existing research , patients with less than 25 minutes of renal ischemic time have significantly less impaired renal function 6 months postoperatively and significantly lower incidence of ckd ( ckd stage iv ; < 30% egfr ) , compared with those having ischemic time over 25 minutes . a multi - institutional observational study used as a historical control suggested that with lpn the renal ischemia time was 25 minutes or less in 25% of patients at most . when planning this project , we hypothesized that increasing the percentage of patients with renal ischemic time of 25 minutes or less by 5% to 10% ( corresponding to the number needed to treat=1020 ) with the rapn protocol would be clinically significant . to achieve a significant change in medical economics it was determined that an increase of 15% would be required , taking into account the incremental costs related to the introduction of this novel treatment . accordingly , the expected percentage of rapn patients with renal ischemic time within 25 minutes was set at 40% . additionally we anticipated that approximately 37.2% of patients would achieve the primary endpoint of both renal function preservation and curative resection , taking into account that in some cases rapn would need to be converted into conventional laparoscopic or open surgery , or would have positive surgical margins . in the present prospective trial , 91.3% of patients achieved both renal function preservation and curative resection , far exceeding our expectations . thus , the results of this trial revealed good efficacy with rapn , compared with the historical control . the historical control used to set the basis of threshold was reported in 2012 based on data from a multi - institutional observational study on lpn ( 54 institutions , 1,375 cases ) conducted in japan from 1998 to 2008 . therefore , when comparing the results of the two studies , it may be necessary to consider differences in the technical maturity between the present and the time when the multi - institutional joint observational study on lpn was performed . however , even if this difference in technical maturity is taken into consideration , the results of the present study show an obvious advantage of rapn . when ischemic time alone was examined , we found a clear shortening compared with historical controls ( meanstandard deviation : 19.06.4 minutes for rapn , 4119 minutes for lpn ) . the reported rates of positive surgical margins with lpn were 0% to 4% ; the rate of the historical control was 1.7% . these excellent results were due to the features of a robot - assisted approach , such as precise 3-dimensional visualization , highly flexible forceps with 7 degrees of freedom , and the correction of tremor . although it is difficult to perform lpn in some cases , depending on conditions such as tumor diameter or location even in the case of t1 tumors , rapn had good results , with no big difference in achievement rate regardless of the diameter or location of the tumor . when an analysis object group ( full analysis set ) was evaluated with the r.e.n.a.l nephrometry score , which is an index of the difficulty of partial nephrectomy mainly based on tumor location and diameter , we found 38 low - complexity cases ( 36.9% ) , 62 intermediate - complexity cases ( 60.2% ) and 3 high - complexity cases ( 2.9% ) . these percentages are comparable to the patient composition in past reports ( 48 low - score cases [ 44% ] , 57 intermediate - score cases [ 53% ] , and 3 high - score cases [ 3% ] ) , which reveals that arbitrary patient selection was not performed . in addition , although we have only short - term results at present , there was no report of death , and the probability of survival for 90 days after surgery was 100.0% . a comparison of outcomes in past studies and in the present trial is shown in table 1 . longer average length of hospital stay observed in the present study was due to japanese public health insurance system ; burden of hospitalization cost is light in japan . the positive surgical margins rate in this study was 0% . compared with the results of the historical control ( 1.7% ) , the protocol treatment was performed evenly in all locations and the achievement rate of the primary endpoint was as high as 87.5%93.7% , irrespective of tumor location . as mentioned above , in cancer control ( negative margin rate ) and renal function preservation ( ischemic time within 25 minutes ) , rapn achieved better results than conventional laparoscopic surgery . the operative time ( meanstandard deviation ) in this trial was 3.891.10 hours ; blood loss was 60.7894.50 ml . compared with clinical studies on rapn performed in other countries and those on lpn in japan , surgery time was almost the same ( historical control , 4.321.52 hours ) . blood loss , however , was less with rapn than with the conventional surgical procedure ( 210426 ml for historical control ) . among safety analysis object groups , the rate of adverse events during the operation was 53.3% ( 56 of 105 ) , which was high compared with the rate of postoperative complications ( 10.6% [ 11 of 104 ] ) . the serious adverse event in this study was postoperative renal arterial aneurysm ( 9 cases ) . renal artery aneurysm is a known complication after opn or lpn . when the renal artery is damaged during suturing after tumor resection , or if insufficient hemostasis in the thin vulnerable renal artery results in rebleeding when blood flow increases after surgery , hematoma around an artery in resected defects can form a pseudoaneurysm . we examined the relationships between pseudoaneurysm and sex , age , body mass index , anamnesis , tumor location , and renal nephrometry score . the reported probability of symptomatic aneurysm with signs such as macrohematuria is 0.4%4.2% in opn , 1.0%12.0% in lpn , and 0.2%10.2% in rapn . these numbers , however , vary depending on the report . in one study in japan , asymptomatic renal pseudoaneurysm was detected with enhanced computed tomography in 17 out of 117 early postoperative patients ( 15% ) after rapn . according to that report , arterial embolization was performed in 1 case that had bleeding and in 11 cases to prevent future bleeding ( size4 mm ) , though they were asymptomatic . therefore , even though pseudoaneurysm can occur , small pseudoaneurysms generally follow a course of natural regression . therefore the estimated incidence of symptomatic aneurysm is 10.2% ( 12 of 117 ) . in the present study pseudoaneurysm occurred in 8 cases ( 7.6% ) , indicating that renal pseudoaneurysm did not occur frequently . the preferred treatment of pseudoaneurysm is coil embolization via arterial catheter because of its low invasiveness and high success rate . all cases of pseudoaneurysm in the present study were mild and recovered with minimally invasive catheter coil embolization . this is because the artery that caused rebleeding was quite small and hemostasis of the main arteries was ensured with the precise manipulation of the robot - assisted approach . pseudoaneurysm is an adverse event that can occur after rapn ; this possible complication must be kept in mind during postoperative patient care , and must be treated quickly and appropriately when it does occur . when open tumor resection of the renal pelvis or calyx is performed , urine can leak into the abdominal cavity from the suture line , and can cause clinically significant effects . in the historical control , urine leakage was found in 2.5% of all patients and in 1.7% of those who were grade 3 or higher . this is a point that should be noted , because it shows the advantages of robotic assistance . robotic assistance allows easy and accurate suturing compared with a conventional laparoscopic approach , enables surgery to be performed with an enlarged field of view , and provides secure suturing in the case of open resection of the renal pelvis or calyx . other defined adverse events in this trial were bleeding , venous thrombosis , pulmonary embolism , wound infection , multiorgan damage , renal hypertension , wound infection , and acute renal dysfunction . the events reported during the observation period were 29 cases of bleeding ( 27.6% ) and 3 of acute renal dysfunction ( 2.9% ) . in the patients with acute renal dysfunction , the serum creatinine level rose transiently , with a decrease in egfr . the frequency and outcome of bleeding and acute renal dysfunction were not different from those of other treatments in this domain . no factors correlating with adverse events were identified , although the number of examples of each background factor varied . the adverse events that occurred most frequently in the perioperative period were wound complications ( 31 cases ) , macrohematuria ( 22 cases ) , and fever ( 13 cases ) , all of which occur frequently with any surgical procedure . egfr , which is an indicator of renal function , never fell below 60 ml / min/1.73 m in any patient after protocol treatment and showed recovery with passage of time , indicating preservation of renal function . moreover , in 91.3% of cases resection and suturing were performed within 25 minutes , which is considered the cutoff for ideal ischemic time . minimizing renal ischemia time leads to long - term preservation of renal function and to the control of progression to ckd , contributing significantly to the improvement in patients ' quality of life . among safety analysis object groups , 146 postoperative adverse events were reported in 56 patients , yielding a complication rate of 53.3% ( 56 out of 105 cases ) . the adverse event that occurred most frequently in the perioperative period was wound complications ( 31 cases , 29.5% ) , followed by macroscopic hematuria ( 22 cases , 21.0% ) and fever ( 13 cases , 12.4% ) . the perioperative critical adverse event that occurred most frequently in this trial was symptomatic pseudoaneurysm in 8 cases ( 7.6% ) . furthermore , they were required to meet the following conditions : experience of more than 10 cases of laparoscopic or open partial nephrectomy , more than 30 cases of laparoscopic or open radical nephrectomy , more than 20 cases of robot - assisted radical prostatectomy , and approved as laparoscopic surgeon by the japanese society of endourology . although the experience of 10 cases of rapn can not be considered vast experience , 91.3% of patients attained the primary endpoint . although mastering this technology takes some training and technical experience , as with open surgery or conventional laparoscopy , it is possible to gain the skills in a short period of time . accordingly rapn is considered to be a useful surgical technique to minimize invasiveness , provide radical cancer curability and preserve renal function . surgery for renal hilar tumors and full endophytic - type tumors has been considered difficult with a conventional laparoscopic approach . in the future , however , a robotic approach will make it possible to remove such tumors with minimal invasiveness , which has previously been attained only through open surgery . this study found that rapn achieves minimal invasiveness , good cancer control , and renal function preservation , indicating that this technology will improve the surgical treatment of patients with nonmetastatic rcc , will decrease the occurrence of postoperative ckd , and will improve long - term prognosis . rapn will contribute considerably to the public health , which will lead to reduced medical expenses . based on the above trial results , rapn was approved by the japanese ministry of health , labour and welfare in april 2016 to be covered by public health insurance in japan .