Incidence and visual outcome of endophthalmitis associated with intraocular foreign bodies Purpose To determine the risk factors and visual outcome of endophthalmitis associated with traumatic intraocular foreign body -LRB- IOFB -RRB- removal and its allied management . Introduction Intraocular foreign body -LRB- IOFB -RRB- caused ocular trauma is a significant and unique type of trauma that requires skillful investigation and an early intervention . Endophthalmitis is an uncommon but potentially catastrophic complication of penetrating ocular injury with retained intraocular foreign bodies -LRB- IOFB -RRB- -LSB- 1 -RSB- . Studies have reported incidence of endophthalmitis ranging from none to as high as 13.5 % -LSB- 1 -- 5 -RSB- . Management of endophthalmitis associated with retained IOFB is a challenging subject . With advancement in vitreous surgery , a large number of eyes with ocular trauma and IOFB are being saved . Visual prognosis , however , is affected by the complexity of the confluent factors surrounding the IOFB , which include the size , site , material , trajectory , reactivity of foreign body , inflammatory response , degree and type of tissue damage , length of time since injury and any associated endophthalmitis -LSB- 2 -RSB- . Limited information is available regarding ocular trauma and IOFB-associated endophthalmitis outside of the United States and other developed countries -LSB- 6 -- 10 -RSB- . In particular , very limited information on this entity is available from the Middle East . The current study was undertaken to analyze and report our experience at a large tertiary eye care referral center in the Middle East regarding the management of eyes with IOFBs and associated endophthalmitis . We identify the risk factors for the development of clinical endophthalmitis and visual outcome of such eyes at a major referral center in the Middle East . Methods A detailed retrospective review was conducted of all patients who presented to King Khaled Eye Specialist Hospital , a JCIA -LRB- Joint Commission International Accreditation , USA -RRB- accredited tertiary eye care referral center in Riyadh , Saudi Arabia , from January 1983 to August 2004 with penetrating ocular trauma and retained intraocular foreign bodies -LRB- IOFB -RRB- . Methods of IOFB extraction has varied during these years . For simplicity , the study period was divided into the first decade from 1983 to 1993 and the second decade from 1994 to 2004 . For the past decade pars plana vitrectomy has been used more often for the posteriorly located IOFBs . Prior to removal of the foreign body -LRB- FB -RRB- all adhesions around the FB were released and it was freed from encapsulation where indicated . All IOFBs were removed by using IOFB forceps . Where necessary the sclerotomy was enlarged to facilitate easy removal of the FB . Endophotocoagulation was applied to the retina adjacent to the site of the IOFB . After removal of the FB , vitrectomy was utilized to remove any remains of FB capsule or fibrous tissue with the vitrectomy cutter . Only those eyes which showed any clinical evidence of endophthalmitis after trauma and retained IOFB were included in the study . Patients demographic studied included , age at presentation , sex , place of trauma , occupation , mode of injury and time between injury and repair . Other parameters included initial and final best corrected Snellen visual acuity , entry and location of IOFB and associated cataract , vitreous hemorrhage , retinal detachment , development of endophthalmitis , diagnostic studies performed , treatment rendered , type and size of IOFB . Complications such as cataract , retinal detachment and secondary procedures performed were also noted . Causes of visual loss such as corneal scarring , cataract , retinal detachment , retinal scars and loss of an eye were also investigated . In particular , all eyes with a retained IOFB and associated endophthalmitis were investigated and analyzed in detail . Statistical analysis was carried out using SPSS version 10 -LRB- SPSS Inc. , Chicago , IL , USA -RRB- . We studied the association between the variables using the chi-square test because the data was categorical . Further multiple logistic regression analysis was conducted to predict the factors that were associated with favorable or poor visual outcome . A P < 0.05 was taken as a level of statistical significance . Results Among the 589 eyes of 565 patients -LRB- 90.3 % males ; 9.7 % females ; 24 bilateral -RRB- with retained intraocular foreign bodies -LRB- IOFB -RRB- after trauma , 44 eyes -LRB- 7.5 % -RRB- had evidence of clinical endophthalmitis at the time of initial evaluation or subsequent to removal of the IOFB -LRB- Table 1 -RRB- . The setting of the injury resulting in IOFB varied , with the majority occurring at the place of employment in younger patients . The size of the IOFBs recovered ranged from 0.5 mm to 18 mm -LRB- average 4.2 mm -RRB- . At presentation visual acuity -LRB- VA -RRB- of 20/200 or better was found in 8 eyes -LRB- 18.1 % -RRB- , 20/400 to counting fingers in 6 -LRB- 13.6 % -RRB- and hand motion -LRB- HM -RRB- to light perception -LRB- LP -RRB- in 30 eyes -LRB- 68.2 % -RRB- -LRB- Table 2 -RRB- . Delay in treatment was mostly due to late patient referral after the trauma or lack of understanding on the part of the patient about the urgency in presentation to the primary care center . Endophthalmitis was recognized preoperatively in 32 eyes -LRB- 72.7 % -RRB- and post-operatively in 12 eyes -LRB- 27.3 % -RRB- . In general , the size of the IOFB posed no significant risk of causing endophthalmitis except in cases where larger IOFB was associated with a significant trauma to the eye . The most important predictive factor of developing endophthalmitis was delayed repair of the globe and removal of IOFB . A delay in intervention of more than 24-hours was associated with a risk of clinical endophthalmitis -LRB- Fig. 1 -RRB- . In fact , only 11 eyes -LRB- 25 % -RRB- which developed endophthalmitis were repaired and IOFB removed within 24 hours after their trauma compared with 33 eyes -LRB- 75 % -RRB- that were repaired and IOFB removed more than 24 hours after trauma -LRB- range 2 -- 42 days -RRB- . In other words , a delay of more than 2 days in the repair of the traumatic globe and removal of IOFB was associated with a significant risk of endophthalmitis development -LRB- P < 0.05 -RRB- . The composition of IOFB had no significant effect on the development of clinical endophthalmitis . In particular , eyes with wood IOFB did not appear to be associated with increased risk of endophthalmitis compared to eyes with metallic IOFBs . The age of the patient had no bearing on the development of clinical endophthalmitis . However , when age and delayed repair of the trauma and removal of IOFB was correlated , an association with increased evidence of endophthalmitis was observed . The risk of endophthalmitis development and poor visual outcome was less common in eyes where the location of IOFB was in the anterior chamber or lens compared to the eyes having IOFB in the vitreous or retina . Among the 10 eyes where the final vision of no light perception -LRB- NLP -RRB- was recorded after the treatment of IOFB trauma and associated endophthalmitis , only 2 eyes had anterior location of foreign bodies compared with 8 eyes where IOFB were found in the posterior chamber , the difference being significant -LRB- P < 0.05 -RRB- . There were 24 cases of endophthalmitis during the first decade -LRB- 1983 -- 1993 -RRB- and 20 cases of endophthalmitis during the second decade -LRB- 1994 -- 2004 -RRB- of the study ; the difference however was not statistically different . Table 1Reported incidence of endophthalmitis with IOFBStudiesEyes with endophthalmitis -LRB- total eyes -RRB- PercentBrinton et al. -LSB- 11 -RSB- 11 -LRB- 103 -RRB- 10.7 Khan et al. -LSB- 12 -RSB- 10 -LRB- 198 -RRB- 5.1 Williams et al. -LSB- 3 -RSB- 14 -LRB- 105 -RRB- 13.3Behrens-Baumann and Praetorius -LSB- 5 -RSB- 14 -LRB- 297 -RRB- 4.7 Thompson et al. -LSB- 1 -RSB- 34 -LRB- 492 -RRB- 6.9El-Asrar et al. -LSB- 4 -RSB- 13 -LRB- 96 -RRB- 13.5 Present study -LRB- Chaudhry et al. -RRB- 44 -LRB- 589 -RRB- 7.5 Table 2Presenting and final visual acuity of patients with IOFB and endophthalmitisVisual acuity -LRB- VA -RRB- PresentingFinal20/20 -- 20/6031120/80 -- 20/2005920/400 -- CF64HM -- LP3010NLP010VA visual acuity , CF count finger , HM hand motion , LP light perception , NLP no light perceptionFig . 1Patient with endophthalmitis associated with retained intraocular foreign body Positive cultures were obtained from 17 eyes -LRB- 38.6 % -RRB- with clinical signs of endophthalmitis -LRB- Fig. 1 -RRB- . In addition , 10 eyes showed evidence of microorganisms on the Gram stain but no growth was observed in cultures . Staphylococcus and Streptococcus species were most often recovered -LRB- 9 eyes -RRB- ; the other species included Hemophilus , Bacillus , Pseudomonas , Eikenella , Corynebacterium , Propionebacterium acnea and Escherichea coli . None of the eyes with Bacillus , Pseudomonas or Corynebacterium attained any useful vision . All eyes suspected of endophthalmitis were administered intravitreal antibiotics and in some cases the treatment was repeated to obtain resolution of the signs . Most common intraocular antibiotics administered included vancomycin , ceftazidime and amikacin . Systemic preoperative antibiotics were administered in eyes with signs of endophthalmitis at approximately the same frequency as eyes without any signs of clinical endophthalmitis . However , systemic antibiotics were continued postoperatively for longer duration in eyes with signs of infectious endophthalmitis . Thirty-one eyes -LRB- 70 % -RRB- underwent primary pars plana vitrectomy and 20 eyes -LRB- 45 % -RRB- had pars plana lensectomy at the time of IOFB removal and primary repair . Secondary procedures included scleral buckle around 8 globes , endolaser or external cryotherapy in 10 eyes and gas tamponade using SF6/C3F8 in 10 eyes for retinal breaks or retinal detachments . In addition , 11 eyes required cataract surgery , 12 eyes developed retinal detachment requiring additional treatment after the removal of IOFB and treatment of endophthalmitis . Vitreous hemorrhage was noted in 24 eyes that were associated with posteriorly located IOFBs but none among the eyes with IOFBs located in the anterior part of the eye . The final VA was 20/200 or better -LRB- defined as a good visual outcome -RRB- in 20 eyes -LRB- 45 % -RRB- . Twenty-four eyes -LRB- 55 % -RRB- had final VA of less then 20/200 -LRB- defined as poor visual outcome -RRB- . Twenty eyes -LRB- 45 % -RRB- had a final VA of hand motion or worse -LRB- Fig. 2 -RRB- . The causes of final vision of HM or worse in 20 eyes were phthisis -LRB- Fig. 3 -RRB- or enucleation in 10 eyes , retinal detachment with proliferative vitroretinopathy in 5 eyes and corneal or macular scar in 5 eyes . Overall , 22 eyes -LRB- 50 % -RRB- that developed endophthalmitis due to trauma and retained IOFB had improvement in their VA. . Ten eyes -LRB- 22.7 % -RRB- with endophthalmitis became NLP compared to 58 eyes -LRB- 10.6 % -RRB- from the larger group which became NLP but had no evidence of endophthalmitis , the difference being significant -LRB- P < 0.05 -RRB- . Among the 10 eyes with endophthalmitis where the final vision of NLP was recorded after the treatment of IOFBs and associated endophthalmitis , only 2 eyes had anterior location of FBs compared to 8 eyes where FBs were found in the posterior chamber . Among the patients with endophthalmitis , 4 eyes -LRB- 12.9 % -RRB- from the vitrectomy group -LRB- 31 eyes -RRB- had final vision of NLP , while from the eyes without vitrectomy -LRB- 11 eyes -RRB- , 5 eyes -LRB- 45.4 % -RRB- had final vision of NLP , the difference between these two groups being significant -LRB- P < 0.05 -RRB- . Fig. 2Patient with light perception vision after treatment of endophthalmitis and removal of intraocular foreign bodyFig . 3Patient with phthisical left eye and no light perception after treatment of endophthalmitis and removal of intraocular foreign body Discussion Ocular trauma associated with retained intraocular foreign bodies -LRB- IOFB -RRB- constitutes a significant proportion -LRB- 18 -- 40 % -RRB- of all ocular injuries requiring surgical management -LSB- 1 , 2 -RSB- . Despite advances in vitreoretinal and microsurgical techniques , the management of these injuries remains a challenge . The risk of endophthalmitis developing after penetrating ocular injury with retained IOFB is relatively low with the current techniques of surgical repair -LSB- 1 -RSB- . The incidence of infectious endophthalmitis after retaining an IOFB has been reported to be as low as 0 % to as high as 13.5 % -LSB- 3 -- 5 , 13 -RSB- , the mean incidence being 6.8 % -LRB- Table 1 -RRB- . The results from the present study are in agreement with the above studies of endophthalmitis associated with retained IOFB . A delay in management of more than 24 hours was found to increase the risk of infectious endophthalmitis in the present study . From a large study of the National Eye Trauma System Registry , 91 % of the eyes in which infectious endophthalmitis developed had such evidence at the time of initial evaluation -LSB- 1 -RSB- . Delay in primary repair at our tertiary care eye hospital in the Middle East was either due to the patient presenting late or being referred to our facility later in the course of trauma and retained IOFB . Despite methods of improved transportation , early diagnosis and referral to properly trained eye care professionals , morbidity due to IOFB associated trauma has not decreased over the last decade . The risk of an infectious endophthalmitis developing with IOFB has been reported to increase with age -LSB- 1 -RSB- ; although , no such trend was observed in the present study . However , when age and delayed repair of the trauma and removal of IOFB was correlated , an association with increased evidence of endophthalmitis in our group of patients was observed . These results are in agreement with previous observations that older patients with delayed primary repair do appear to have an increased susceptibility to developing infectious endophthalmitis compared with younger patients -LSB- 1 -RSB- . Visual acuity -LRB- VA -RRB- appears to be significantly affected in the eyes with IOFB that subsequently developed endophthalmitis . From a previous large study of retained IOFB , Roper-Hall -LSB- 14 -RSB- reported 555 cases over a 19 year period , where there were no bilateral cases : in 60 eyes IOFB was not removed , size of IOFB was recorded in only 89 eyes and the enucleation rate was 20 % . From a more recent report of 96 cases of posterior segment IOFBs studied over a 14 year period with 8.6 months of average follow-up , endophthalmitis was recorded in 13.5 % of cases -LSB- 4 -RSB- . The overall rate of 7.5 % cases with endophthalmitis in the current study are within the reported range of larger series -LSB- 1 , 3 -- 5 , 14 , 12 -RSB- . Several preoperative and operative factors have been found to have prognostic value in the final visual outcome of the traumatized eye with retained IOFB and endophthalmitis . Initial VA is an indicator of final VA and is a well recognized predictor of visual outcome in most of the previously published studies on IOFBs -LSB- 4 , 15 -RSB- . In our study , poor initial VA of HM or light perception was significant in predicting a poor visual outcome -LRB- Table 2 -RRB- . The risk of endophthalmitis development and poor visual outcome appeared to be significantly increased when the IOFBs were recovered from the posterior chamber -LRB- vitreous or retina -RRB- , compared to the IOFBs recovered from the anterior chamber . Among the 10 eyes with endophthalmitis where the final vision of NLP was recorded after the treatment of IOFBs and associated endophthalmitis , only 2 eyes had anterior location of foreign bodies compared to 8 eyes where foreign bodies were found in the posterior chamber . In our study , positive cultures were obtained in slightly more then one-third of the eyes with clinical signs of endophthalmitis . In general , the culture is often positive in clinically diagnosed endophthalmitis secondary to trauma than due to intraocular surgery . However , considering that our hospital is a tertiary eye care referral center , most of these patients were on topical as well as systemic antibiotics prior to their referral and obtaining cultures at the time of IOFB removal . This view is corroborated by the observations that 10 additional patients who had evidence of microorganisms on Gram stain showed no growth in culture . The microorganisms isolated from the eyes in the present study were similar to those reported in previous studies on the development of infectious endophthalmitis after IOFB trauma -LSB- 1 , 4 -RSB- . Although , from many eyes suspected of infectious endophthalmitis , no definite organism was recovered . The fact that these eyes showed clinical improvement after intravitreal injection of antibiotics supports the notion that an infectious process was involved . In a recent study , reasonable visual outcomes with immediate intravitreal injection of antibiotics and delayed vitrectomy in patients with clinical features of endophthalmitis and retained IOFB have been achieved -LSB- 16 -RSB- . The role of vitrectomy in the treatment of penetrating ocular trauma has been considered a major advance in the last two decades -LSB- 17 -RSB- . Early vitrectomy has helped in attaining useful functional vision in 25 -- 51 % of the eyes with posterior segment trauma -LSB- 17 , 13 -RSB- , and in some series it has helped in significant survival of eyes without improvement of final visual outcome -LSB- 17 -RSB- . In our hospital , during the last decade , pars plana vitrectomy had been used more frequently for the posteriorly located IOFBs . Although there were fewer cases of IOFB-associated endophthalmitis during the second decade of the study period , statistically we did not find a difference between the two decades . In our study of endophthalmitis , only 12.9 % of the eyes in which vitrectomy had been performed initially did the vision later become NLP compared to 38.5 % in which the vision became NLP in the eyes which had not undergone vitrectomy as an initial procedure at the time of IOFB removal and repair of ocular trauma . Vitrectomy removes the vitreous and blood clot scaffold that provides a framework to the visual localization of IOFB ; it helps to find retinal breaks and detachments which may not be visible in the setting of vitreous hemorrhage . Our results corroborate previous reports of beneficial effects of early vitrectomy in the setting of ocular trauma associated with IOFBs -LSB- 13 -RSB- . Removal of lens was not necessary in all cases with corneal entry wound because the lens injury was localized without interfering with view for vitrectomy . Removal of posterior segment IOFB by pars plana vitrectomy has been advocated because it provides direct viewing and controlled removal of the IOFB -LSB- 3 , 18 -RSB- . With the advent of advanced instrumentation and viewing systems used in vitrectomy , most vitrectomies in our hospital were performed in the second decade compared to the first . The size of IOFB has been found to be a significant predictive factor of poor visual outcome in the previous studies of IOFB removal -LSB- 18 -RSB- . A large IOFB is more likely to inflict severe damage at the time of entry because of its higher kinetic energy , leading to a poor visual prognosis -LSB- 18 -RSB- . However , when considering similar sized IOFBs , no particular association between the visual outcome and the size of IOFB in eyes which developed endophthalmitis was found in our study . A preoperative retinal detachment may be present in 5 -- 21 % of the eyes with IOFB and has been reported to be an important risk factor for poor visual outcome -LSB- 3 , 19 -RSB- . The timing of surgery in these eyes for the removal of IOFBs has been found to be an important prognostic factor for better visual outcome . Without delay , removal of IOFB has been found to reduce the chances of endophthalmitis -LSB- 15 , 19 , 20 -RSB- . In the absence of endophthalmitis , many studies have found no significant difference on the visual outcome when IOFB removal was delayed for several weeks -LSB- 3 , 18 , 21 -RSB- . Ahmadieh et al. reported a delay in IOFB removal of more then 4 weeks in 85 % of their patients because a majority of their patients had war related IOFBs -LSB- 22 -RSB- . Lack of suspicion of IOFBs by primary care physicians has led to the delay in the treatment of up to 44 % of patients resulting in a delay of up to 3 years in the diagnosis , treatment , or both , of IOFB -LSB- 18 , 21 -RSB- . In conclusion , the data from this retrospective study reiterate the importance of prompt recognition of retained IOFBs and early repair of related injuries to prevent endophthalmitis and associated complications of visual loss . Final vision appears to be considerably determined by the presenting VA and severity of injury . Eyes with IOFBs in the anterior segment appear to have better prognosis compared to eyes having IOFBs in the posterior segment . Early vitrectomy at the time of IOFB removal may be beneficial for overall visual outcome of the operated eyes . Owing to the retrospective nature of our study and most of the reported studies and the various types of injuries in different settings , results from these studies are difficult to compare . It is hoped that with the advent of modern instruments such as wide-angle viewing systems and high-speed cutters , the chances of complications such as retinal detachment may be greatly reduced . A multi-center prospective study may be required to address some of the confounding factors in the management of IOFB and associated endophthalmitis .

O O O O O B O O O B I O O O O B I O O O O B O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O B O O O O O O O O O B O O O O O O O O O O O O O O B I O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O B O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O B I O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O B I O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O 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O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O B O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O 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O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O B O O O O O O O O B I O O O O O B I O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O B O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O B O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O 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Diagnosis of acute myeloid leukemia according to the WHO classification in the Japan Adult Leukemia Study Group AML-97 protocol We reviewed and categorized 638 of 809 patients who were registered in the Japan Adult Leukemia Study Group acute myeloid leukemia -LRB- AML -RRB- -97 protocol using morphological means . Patients with the M3 subtype were excluded from the study group . According to the WHO classification , 171 patients -LRB- 26.8 % -RRB- had AML with recurrent genetic abnormalities , 133 -LRB- 20.8 % -RRB- had AML with multilineage dysplasia -LRB- MLD -RRB- , 331 -LRB- 51.9 % -RRB- had AML not otherwise categorized , and 3 -LRB- 0.5 % -RRB- had acute leukemia of ambiguous lineage . The platelet count was higher and the rate of myeloperoxidase -LRB- MPO -RRB- - positive blasts was lower in AML with MLD than in the other WHO categories . The outcome was significantly better in patients with high -LRB- ≥ 50 % -RRB- than with low -LRB- < 50 % -RRB- ratios of MPO-positive blasts -LRB- P < 0.01 -RRB- . The 5-year survival rates for patients with favorable , intermediate , and adverse karyotypes were 63.4 , 39.1 , and 0.0 % , respectively , and 35.5 % for those with 11q23 abnormalities -LRB- P < 0.0001 -RRB- . Overall survival -LRB- OS -RRB- did not significantly differ between nine patients with t -LRB- 9 ; 11 -RRB- and 23 with other 11q23 abnormalities -LRB- P = 0.22 -RRB- . Our results confirmed that the cytogenetic profile , MLD phenotype , and MPO-positivity of blasts are associated with survival in patients with AML , and showed that each category had the characteristics of the WHO classification such as incidence , clinical features , and OS . Introduction The French-American-British -LRB- FAB -RRB- classification of acute myeloid leukemia -LRB- AML -RRB- , based on morphological and cytochemical findings , was established in 1976 and has since become the standard classification -LSB- 1 , 2 -RSB- . However , specific chromosomal and genetic abnormalities that have been extracted from analyses of prognostic factors for AML are recognized as important in selecting treatment strategies and are reflected in the AML classification as factors that are required to establish the disease entity -LSB- 3 -RSB- . The 1999 World Health Organization -LRB- WHO -RRB- classification includes morphological , immunological , cytogenetic , genetic , and clinical features -LSB- 4 -- 6 -RSB- . The WHO and FAB classifications differ in several aspects . The blast threshold required for a diagnosis of AML was reduced from 30 to 20 % , and new AML categories have been added for cytogenetic abnormalities , the presence of multilineage dysplasia -LRB- MLD -RRB- , as well as a history of chemotherapy and subtypes for acute basophilic leukemia , acute panmyelosis with myelofibrosis , and myeloid sarcoma . The WHO classification comprises more subtypes and is more comprehensive than the FAB classification . Cytogenetic features are important prognostic factors in AML -LSB- 3 , 7 -- 12 -RSB- . However , 11q23 abnormalities have not yet been established as a cytogenetic risk classification . Over 30 partner genes with 11q23 abnormalities have been described , and some reports indicate that patients with t -LRB- 9 ; 11 -RRB- have a relatively more favorable prognosis than those with other partner chromosomes/partner genes -LSB- 13 -- 16 -RSB- . In the present study , we reviewed stained smears of blood and bone marrow from patients who were registered in the Japan Adult Leukemia Study Group -LRB- JALSG -RRB- AML-97 trial , and classified them into FAB subtypes and WHO categories . We also evaluated their survival on the basis of the WHO classification , the myeloperoxidase -LRB- MPO -RRB- - positivity of blasts , and cytogenetic findings including 11q23 abnormalities . Patients and methods Patients Between December 1997 and July 2001 , 809 patients aged from 15 to 66 years with untreated AML -LRB- excluding M3 -RRB- were registered from 103 institutions in the AML-97 trial of the JALSG . The patients were diagnosed with AML according to the FAB criteria at each institution . Patients with a history of MDS , hematological abnormalities before the diagnosis of AML , or a history of chemotherapy were not eligible for the AML-97 trial . Treatment strategies Details of the JALSG AML-97 treatment protocol are described elsewhere -LSB- 17 -RSB- . In brief , all patients underwent induction therapy consisting of idarubicin -LRB- 3 days -RRB- and Ara-C -LRB- 7 days -RRB- . Patients who achieved complete remission were randomized into one of two arms of consolidation chemotherapy alone or in combination with maintenance chemotherapy . Patients who were placed into intermediate/poor risk groups according to the JALSG scoring system -LSB- 17 -RSB- and who had an HLA-identical sibling -LRB- ≤ 50 years old -RRB- were simultaneously assigned to receive allogeneic hematopoietic stem cell transplantation during their first remission . Morphologic and cytochemical analyses Peripheral blood and bone marrow smears from registered patients were sent to Nagasaki University for staining with May-Giemsa , MPO , and esterase , and the diagnosis was then reevaluated by the Central Review Committee for Morphological Diagnosis . Patients were subsequently categorized according to the FAB and WHO classifications . Dyserythropoietic features were defined as > 50 % dysplastic features in at least 25 erythroblasts and dysgranulopoietic features including ≥ 3 neutrophils with hyposegmented nuclei -LRB- pseudo-Pelger -- Heut anomaly -RRB- , and hypogranular or agranular neutrophils -LRB- > 50 % of ≥ 10 neutrophils -RRB- . Dysmegakaryopoietic features were defined as ≥ 3 megakaryocytes that were micronuclear , multiseparate nuclear , or large mononuclear -LSB- 18 -RSB- . We assessed the ratios -LRB- % -RRB- of MPO-positive blasts on MPO-stained bone marrow smears using the diaminobenzidine method -LSB- 19 -RSB- . Cytogenetic analysis Cytogenetic analysis was performed at either laboratories in participating hospitals or authorized commercial laboratories . The karyotypes of leukemic cells were collected through the JALSG AML-97 case report forms and reviewed by the Central Review Committee for Karyotyping . The patients were classified into favorable , intermediate , or adverse risk groups based on karyotypes according to results of the Medical Research Council -LRB- MRC -RRB- AML 10 trial -LSB- 3 -RSB- . The favorable risk group included patients with t -LRB- 8 ; 21 -RRB- and inv -LRB- 16 -RRB- , whether alone or in combination with other abnormalities . The intermediate risk group included those with a normal karyotype and other abnormalities that were not classified as either favorable or adverse . The adverse risk group included patients with a complex karyotype with four or more numerical or structural aberrations , − 5 , deletion -LRB- 5q -RRB- , and − 7 , whether alone or in combination with intermediate risk or other adverse risk abnormalities . Statistical analysis The overall survival -LRB- OS -RRB- for all patients was defined as the interval from the date of diagnosis to that of death . We applied the Kaplan -- Meier method to estimate OS and 5-year survival . We compared survival rates between groups using the log-rank test -LRB- Stat View J 5.0 -RRB- . Differences were examined by the Chi-square test using Excel software . All P-values are two-sided , and values < 0.05 were considered significant . Results Patient characteristics Of the 809 registered patients , 638 were consistent with the WHO classification . Data were incomplete for 10 of the 638 patients . Table 1 lists the characteristics of the patients . The median age of all 638 patients -LRB- 390 males and 248 females -RRB- was 45 years -LRB- range 15 -- 66 years -RRB- . The median values of WBC , hemoglobin -LRB- Hb -RRB- , platelets , and the ratio of blasts in the bone marrow were 13.7 × 109/l , 8.3 g/dl , 52.0 × 109/l , and 56.0 % , respectively . Table 1Patient characteristicsAge -LRB- year -RRB- 45 -LRB- 15 -- 66 -RRB- Male/female390/248WBC count -LRB- × 109/l -RRB- 13.7 -LRB- 0.4 -- 709 -RRB- Hemoglobin -LRB- g/dl -RRB- 8.3 -LRB- 3.8 -- 17.2 -RRB- Platelet count -LRB- × 109/l -RRB- 52 -LRB- 0 -- 890 -RRB- Bone marrow blasts -LRB- % -RRB- 56 -LRB- 6 -- 99 -RRB- Values are presented as the median -LRB- range -RRB- WBC white blood cell FAB classification Table 2 shows the FAB classification of the 638 patients . Most were classified as M2 -LRB- n = 261 ; 40.9 % -RRB- , followed by M4 -LRB- n = 148 ; 23.2 % -RRB- , and M1 -LRB- n = 109 ; 17.1 % -RRB- with M0 , M4Eo , M5a , M5b , M6 , M7 , and acute leukemia of ambiguous lineage comprising the remainder in that order . Table 2Number of patients according to the FAB classificationSubtypeDescriptionNo . of patients % M0Minimally differentiated acute myeloid leukemia -LRB- AML -RRB- 304.7 M1AML without maturation10917 .1 M2AML with maturation26140 .9 M4Acute myelomonocytic leukemia -LRB- AMMoL -RRB- 14823.2 M4EoAMMoL with eosinophils233 .6 M5aAcute monoblastic leukemia193 .0 M5bAcute monocytic leukemia243 .8 M6Acute erythroleukemia162 .5 M7Acute megakaryoblastic leukemia50 .8 Acute leukemia of ambiguous lineage30 .5 Total638100 WHO classification and clinical characteristics Table 3 shows the patients categorized according to the WHO classification . The first category of AML with recurrent genetic abnormalities accounted for 171 patients -LRB- 26.8 % -RRB- , 133 -LRB- 20.8 % -RRB- were in the second category of AML with MLD , 331 -LRB- 51.9 % -RRB- were in the fourth category of AML not otherwise categorized , and 3 -LRB- 0.5 % -RRB- were categorized as having acute leukemia of ambiguous lineage . Most patients in the second category were identical to those with a de novo MLD phenotype . We found that 144 patients diagnosed with the MLD phenotype comprised 133 -LRB- 92.4 % -RRB- in the second category , 10 -LRB- 7.0 % -RRB- with 11q23 abnormalities , and 1 -LRB- 0.7 % -RRB- with acute leukemia of ambiguous lineage . Figure 1 shows the OS of each category . The 5-year survival rates of the first , second , and fourth categories were 58.2 , 22.5 , and 40.9 % -LRB- P < 0.0001 -RRB- , respectively . Table 3Number of patients according to the WHO classificationCategory and subtypeNo . of patients % I. AML with recurrent genetic abnormalities17126 .8 t -LRB- 8 ; 21 -RRB- -LRB- q22 ; q22 -RRB- ; -LRB- AML1/ETO -RRB- 11317.7 inv -LRB- 16 -RRB- -LRB- p13 ; q22 -RRB- or t -LRB- 16 ; 16 -RRB- -LRB- p13 ; q22 -RRB- ; -LRB- CBFβ/MYH11 -RRB- 264.1 t -LRB- 15 ; 17 -RRB- -LRB- q22 ; q12 -RRB- -LRB- PML/RARα -RRB- -- -- 11q23 -LRB- MLL -RRB- abnormalities325 .0 II . AML with multilineage dysplasia13320 .8 Following MDS -- -- Without antecedent MDS13320 .8 III . AML and MDS , therapy-related -- -- Alkylating agent-related -- -- Topoisomerase type II inhibitor-related -- -- Other types -- -- IV . AML not otherwise categorized33151 .9 AML , minimally differentiated253 .9 AML without maturation9915 .5 AML with maturation10816 .9 Acute myelomonocytic leukemia -LRB- AMMoL -RRB- 639.9 AMMoL with eosinophilia50 .8 Acute monoblastic leukemia81 .3 Acute monocytic leukemia162 .5 Acute erythroid leukemia60 .9 Acute megakaryoblastic leukemia10 .2 Acute leukemia of ambiguous lineage30 .5 Total638100 Fig. 1Overall survival of patients categorized according to the WHO classification Table 4 compares the clinical features among the WHO categories . The mean values of platelets , WBC , Hb , and the ratio -LRB- % -RRB- of blasts in bone marrow and of MPO-positive blasts significantly differed , whereas age did not significantly differ . Patients in the second category had a higher platelet count -LRB- 111.0 × 109/l -RRB- , whereas those with 11q23 abnormalities had a lower count -LRB- 38.3 × 109/l -RRB- compared with those of other subtypes . Table 4Comparison of clinical findings of patients diagnosed according to the WHO classificationCategoryPlatelets -LRB- × 109/l ± SE -RRB- WBC -LRB- × 109/l ± SE -RRB- Hb -LRB- g/dl ± SE -RRB- Age -LRB- year ± SE -RRB- Blasts in bone marrow -LRB- % ± SE -RRB- MPO positivity of blasts -LRB- % ± SE -RRB- I t -LRB- 8 ; 21 -RRB- 76.7 ± 56.43 -LRB- 113 -RRB- a 1.4 ± 0.6 -LRB- 113 -RRB- 7.8 ± 0.2 -LRB- 113 -RRB- 41.6 ± 1.3 -LRB- 113 -RRB- 49.9 ± 2.0 -LRB- 113 -RRB- 93.3 ± 3.3 -LRB- 108 -RRB- inv -LRB- 16 -RRB- 57.8 ± 52.03 -LRB- 26 -RRB- 6.6 ± 1.2 -LRB- 26 -RRB- 9.2 ± 0.5 -LRB- 26 -RRB- 44.5 ± 2.6 -LRB- 26 -RRB- 50.5 ± 4.1 -LRB- 26 -RRB- 66.9 ± 6.7 -LRB- 26 -RRB- 11q2338 .3 ± 30.8 -LRB- 32 -RRB- 4.3 ± 1.1 -LRB- 32 -RRB- 8.9 ± 0.4 -LRB- 32 -RRB- 41.6 ± 2.4 -LRB- 32 -RRB- 56.3 ± 3.7 -LRB- 32 -RRB- 43.6 ± 6.1 -LRB- 32 -RRB- II111 .0 ± 121.5 -LRB- 133 -RRB- 3.0 ± 0.5 -LRB- 133 -RRB- 8.3 ± 0.2 -LRB- 133 -RRB- 44.2 ± 1.2 -LRB- 133 -RRB- 48.0 ± 1.8 -LRB- 133 -RRB- 34.0 ± 3.1 -LRB- 126 -RRB- IV72 .8 ± 91.7 -LRB- 330 -RRB- 5.1 ± 0.3 -LRB- 331 -RRB- 8.8 ± 0.1 -LRB- 330 -RRB- 43.8 ± 0.7 -LRB- 331 -RRB- 65.7 ± 1.2 -LRB- 328 -RRB- 53.7 ± 1.9 -LRB- 312 -RRB- P < 0.0001 P < 0.0001 P = 0.0004 P = 0.4077 P < 0.0001 P < 0.0001 SE standard error , WBC white blood cell , MPO myeloperoxidase , Hb hemoglobin aNumber of patients The WBC count of patients with t -LRB- 8 ; 21 -RRB- was 1.4 × 109/l and lower than in other subtypes . The MPO-positive rate of blasts among patients with t -LRB- 8 ; 21 -RRB- was higher -LRB- 93.3 % -RRB- and that of patients in the second category was lower -LRB- 34.0 % -RRB- , than in other subtypes . All patients were grouped as high - or low-MPO according to ≥ 50 % or < 50 % of MPO-positive blasts , respectively . A total of 339 patients -LRB- 53.1 % -RRB- were classified as high-MPO , 268 -LRB- 42.0 % -RRB- as low-MPO , and the MPO status of blasts could not be assessed in 31 -LRB- 4.9 % -RRB- . Figure 2 shows the OS of patients with high - or low-MPO . The 5-year survival rate for patients with high or low-MPO was 50.7 and 29.6 % , respectively -LRB- P < 0.0001 -RRB- . Fig. 2Overall survival of patients with high or low MPO-positive blasts Cytogenetics All 638 patients were classified into favorable -LRB- n = 139 ; 21.8 % -RRB- , intermediate -LRB- n = 413 ; 64.7 % -RRB- , and adverse -LRB- n = 54 ; 8.5 % -RRB- cytogenetic risk groups -LRB- Table 5 -RRB- . Figure 3 shows the OS according to this stratification . The 5-year survival rates were 63.4 , 39.3 , and 0.0 % in the favorable , intermediate -LRB- except for those with 11q23 abnormalities -RRB- , and adverse risk groups , respectively , and 35.5 % in the group with 11q23 abnormalities -LRB- P < 0.0001 -RRB- . Table 5Distribution of patients classified by cytogenetic riskCytogenetic risk groupNo . of patients % Favorable13921 .8 t -LRB- 8 ; 21 -RRB- 11317.7 inv -LRB- 16 -RRB- 264.1 Intermediate41364 .7 Normal karyotype26741 .8 11q23325 .0 Ph -LRB- + -RRB- 71.1 t -LRB- 7 ; 11 -RRB- -LRB- p15 ; p15 -RRB- 40.6 t -LRB- 6 ; 9 -RRB- 40.6 Other13120 .5 Adverse548 .5 Complex416 .4 − 720.3 abn350 .8 del5q20 .3 − 510.2 Other30 .5 Total638100 .0 Fig. 3Overall survival of patients stratified according to cytogenetic risk groups . Significant differences were observed between patients with a favorable , intermediate -LRB- except 11q23 -RRB- , and adverse karyotype -LRB- P < 0.0001 -RRB- The numbers of patients with or without MLD and high - or low-MPO in each cytogenetic risk group are listed in Table 6 . None of those with the MLD phenotype were classified into the favorable risk group , while 129 -LRB- 89.6 % -RRB- and 15 -LRB- 10.4 % -RRB- of 144 patients with MLD were classified into intermediate or adverse risk groups , respectively . Only 15 patients -LRB- 4.4 % -RRB- in the high-MPO group were classified as having an adverse risk , while 11 -LRB- 4.1 % -RRB- in the low-MPO group were included in the favorable risk group . Table 6Relationship between cytogenetic risk groups and MLD phenotype or MPO-positive rates of blastsFavorable n = 139Intermediate n = 445Adverse n = 54TotalMLD +0129 -LRB- 89.5 % -RRB- 15 -LRB- 10.4 % -RRB- 144 − 138 -LRB- 28.2 % -RRB- 292 -LRB- 59.6 % -RRB- 38 -LRB- 7.8 % -RRB- 490 Unknown1214MPO High123 -LRB- 36.3 % -RRB- 201 -LRB- 59.3 % -RRB- 15 -LRB- 4.4 % -RRB- 339 Low11 -LRB- 4.1 % -RRB- 221 -LRB- 82.5 % -RRB- 36 -LRB- 13.4 % -RRB- 268 Unknown523331High - and low-MPO indicates a percentage of myeloperoxidase positive blasts ≥ 50 or < 50 % , respectively MLD multilineage dysplasia The 32 patients with 11q23 abnormalities comprised 11 -LRB- 34.4 % -RRB- with t -LRB- 11 ; 19 -RRB- , 9 -LRB- 28.1 % -RRB- with t -LRB- 9 ; 11 -RRB- , 5 -LRB- 15.6 % -RRB- with del -LRB- 11 -RRB- -LRB- q23 -RRB- , 4 -LRB- 12.5 % -RRB- with t -LRB- 6 ; 11 -RRB- , and 3 -LRB- 9.4 % -RRB- with t -LRB- 11 ; 17 -RRB- . Figure 4 shows the OS of the intermediate risk group . The 5-year survival rate was 44.0 % in patients with a normal karyotype , 35.5 % in those with 11q23 abnormalities , and 30.6 % in other patients including those with t -LRB- 7 ; 11 -RRB- , t -LRB- 6 ; 9 -RRB- , and Ph -LRB- + -RRB- abnormalities , respectively -LRB- P = 0.033 -RRB- . Fig. 4Overall survival of patients with subtypes of intermediate cytogenetic risk . Significant differences were observed between patients with a normal karyotype and those with 11q23 abnormalities -LRB- P = 0.033 -RRB- Table 7 shows the relationship between t -LRB- 9 ; 11 -RRB- -LRB- n = 9 -RRB- and other 11q23 abnormalities -LRB- n = 23 -RRB- . More patients with low-MPO , without MLD , or with the FAB M5 subtype were found in the group with t -LRB- 9 ; 11 -RRB- than with other 11q23 abnormalities . The survival rates between the two groups did not significantly differ -LRB- P = 0.22 , data not shown -RRB- . Table 7Comparison of t -LRB- 9 ; 11 -RRB- and other 11q23 abnormalitiesNo . of patientsAuerMPO * MLD * FABMedian age -LRB- year -RRB- Median survival -LRB- day -RRB- + − HighLow + − M1M2M4M4EoM5a ** M5b t -LRB- 9 ; 11 -RRB- 9091809003060391031.00 Other 11q232351813101013131312348520 .00 Total3252714181022131618344 .5531.5 High - and low-MPO indicates a percentage of myeloperoxidase-positive blasts ≥ 50 or < 50 % , respectively MLD multilineage dysplasia * P < 0.05 , ** P < 0.01 Discussion We attempted to classify selected patients who were reviewed morphologically and had available chromosomal data according to the WHO system . However , our series had some limitations in terms of analysis and patient selection . Although we obtained chromosomal data , genetic data were not available . Patients who were diagnosed with AML M3 or who had t -LRB- 15 ; 17 -RRB- , a history of MDS , or preceding hematological abnormalities , or who had previously undergone chemotherapy , were not eligible for the present study . However , multicenter trials might have some advantages in diagnosing AML according to the WHO classification , because morphological diagnoses and karyotypes are reviewed by the corresponding institutional committees . The incidence of each category of the WHO classification was similar to those in several reports when patients with t -LRB- 15 ; 17 -RRB- and therapy-related AML were excluded -LSB- 20 -- 22 -RSB- . We and several others have shown that approximately 30 % of patients have recurrent genetic abnormalities . Multiplex reverse transcriptase-polymerase chain reaction -LRB- RT-PCR -RRB- assays have recently been applied to analyze cytogenetic abnormalities -LSB- 21 , 23 , 24 -RSB- . This method might cause the frequency of the first WHO category to increase . Thus , the multiplex RT-PCR assay might have to be incorporated into the WHO system . The JALSG has started a cohort study in which all AML patients in participating hospitals are registered and analyzed according to the WHO classification . That study should clarify the real ratios of the AML subtypes in the WHO classification . Few reports have included clinical data with the WHO classification . We found that the platelet count was higher among patients in the second category than in other categories . This supports our previous finding that the platelet count is higher in patients with AML accompanied by the MLD phenotype -LSB- 25 -RSB- . Among patients with MLD , none were in the favorable risk group , whereas the intermediate or adverse risk ratios among these patients were 89.6 and 10.4 % , respectively . These differences might influence the finding that OS was better among patients without than with MLD -LRB- P = 0.0002 , data not shown -RRB- . Previous studies have also associated the MLD phenotype with a poorer outcome , although MLD is not significantly prognostic on multivariate analysis -LSB- 18 , 26 -RSB- , and a German group showed that dysplastic features correlate with adverse karyotypes -LSB- 26 -RSB- . Furthermore , patients in the second category had a lower MPO-positive rate of blasts , whereas those with t -LRB- 8 ; 21 -RRB- had a higher rate . Patients with high - and low-MPO were more frequently observed in the favorable and adverse risk groups , respectively . Multivariate analysis has shown that MPO is a significant factor affecting OS -LSB- 19 -RSB- . We did not assess prognostic factors by multivariate analysis here because the main theme of this study was to categorize patients according to the WHO classification , and we have already examined these in a previous series -LSB- 18 , 19 -RSB- . Several studies have demonstrated the impact of specific cytogenetic abnormalities on survival in AML -LSB- 3 , 7 -- 12 , 20 -- 22 -RSB- . The cytogenetic risk groups stratified the AML patients in the present study according to the MRC system , as in these reports -LSB- 3 -RSB- . Therefore , we confirmed the clinical usefulness of cytogenetics as the first category of the WHO classification . We found that 32 patients had 11q23 abnormalities . The MRC system revealed that de novo and secondary AML patients with 11q23 abnormalities had an intermediate outcome with an OS rate of 45 % at 5 years -LRB- n = 60 ; median age , 17 years -RRB- in a younger cohort -LSB- 3 -RSB- and an OS rate of 0 % at 5 years -LRB- n = 11 ; median age 64 years -RRB- in an elderly cohort -LSB- 7 -RSB- . In contrast , SWOG/ECOG trials including adult de novo AML patients -LRB- age , 16 -- 55 years -RRB- assigned those with 11q abnormalities to the unfavorable cytogenetic subgroup -LSB- 8 -RSB- . Our data showed that patients with 11q23 abnormalities have an intermediate rather than adverse outcome . The prognostic effect of 11q23 abnormalities might depend on the partner gene . Several studies have shown that 11q23 abnormalities with t -LRB- 6 ; 11 -RRB- and t -LRB- 10 ; 11 -RRB- are associated with a poor prognosis , whereas t -LRB- 9 ; 11 -RRB- is associated with a superior OS and such patients might respond well to intensive treatment , especially when the chemotherapy regimen includes high-dose cytarabine -LSB- 15 , 27 -- 30 -RSB- . The CALGB study has shown that the median OS of 13.2 months among 23 patients with t -LRB- 9 ; 11 -RRB- was significantly longer than the 7.7 months among 24 patients with other 11q23 rearrangements -LRB- P = 0.009 -RRB- -LSB- 30 -RSB- . In a recent CALGB series of 54 patients with 11q23 abnormalities , 27 patients with t -LRB- 9 ; 11 -RRB- had an intermediate outcome and a median OS of 13.2 months , whereas those with t -LRB- 6 ; 11 -RRB- or t -LRB- 11 ; 19 -RRB- had a poor outcome of 7.2 or 8.4 months -LSB- 15 -RSB- . Conversely , Schoch et al. showed that 14 patients with t -LRB- 9 ; 11 -RRB- had a median OS of 10.0 months compared with the 12.8 months of 26 patients with other MLL rearrangements , and that the two cytogenetic groups did not significantly differ -LSB- 13 -RSB- . Our data showed that nine patients with t -LRB- 9 ; 11 -RRB- were more frequently involved in M5 . The MPO and MLD features significantly differed between patients with t -LRB- 9 ; 11 -RRB- and those with other 11q23 abnormalities . However , the CALGB study found no significant differences in myelodysplastic features between the two cytogenetic groups -LSB- 30 -RSB- . In terms of OS , our results showed no significant differences between patients with t -LRB- 9 ; 11 -RRB- and those with other 11q23 abnormalities -LRB- P = 0.22 -RRB- . Some problems are associated with the analyses of 11q23 abnormalities . We had few patients with these abnormalities , particularly individual translocations , and genetic analysis was not performed . Thus , the prognostic risk of 11q23 abnormalities can not be concluded from the present study . Nonetheless , these abnormalities were never associated with a favorable risk . To classify 11q23 abnormalities into each prognostic risk group , further investigations and genetic analyses of a large number of patients with 11q23 abnormalities are required . The fourth WHO category , which is not otherwise categorized , accounted for 52 % of patients in the present study . Most of them were classified into the intermediate risk group , and no prognostic subdivisions were valuable . Using cytogenetic features as a prognostic factor in groups with a normal karyotype has limitations , and such patients accounted for 64.6 % of the intermediate risk group -LRB- data not shown -RRB- . Additional factors are required to stratify these patients . We and several others suggested that differences could be based on molecular genetic analysis -LSB- 22 , 31 -- 35 -RSB- . For example , FLT3 mutations are important biomarkers of a normal karyotype and might be valuable for stratifying the intermediate risk group . Further follow-up studies might also shed light on the roles of FLT3 ITD mutations in the development of AML and aid their use as novel molecular targeting agents against AML -LSB- 22 , 32 -RSB- . Bienz et al. identified CEBPA mutations , FLT3-ITD , and differing levels of BAALC expression as having independent prognostic significance in patients with a normal karyotype -LSB- 33 -RSB- . If these genetic markers can be confirmed as being of clinical significance , genetic analyses will probably be incorporated into the WHO classification . In summary , our results confirmed those of previous studies showing the prognostic significance of cytogenetics , MLD , and MPO-positivity of blasts in AML . Furthermore , we categorized patients with de novo AML according to the WHO classification and showed the clinical characteristics and OS of each category .

O O O O O O O O B I O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O B I O O O O O O O O B O O O O O O O O O O O B O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B I O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B I O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O B I O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B I O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O B I O O O O O O O O O O O O O O O O B I O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B I O O B O O O O O O O O O O O O B I O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B I O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B I O O O O O O O O O O O O B I O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B I O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O B O O O O B O O O O B O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B I O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B I O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B I O O O O O O O O O O O O O O O O B I O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O B I O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B I O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B I O O O O O O O O O O O O O O O O O O O O O O O O B I O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B I O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O B I O O O O O O O O O O O O O O O O O O O O O B I O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O B I O O O O O O O O O O B O O O B I O O O O O O O O O B I O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B I O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B I O O O O O O O B I O O O O O O O O O O B O O B I O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B I O O O O O O O O O O O O B I O O O O O O O O O O O O B I O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B I O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B I O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B I O O O O O O O O O O O O O O B I O O O O O O O O O O O O O O O O O O O O O O O O O O B I O O O O O O O O O O O O O O O O O O O O O O O B I O O O O O O O O O O O O O O O O O O B I O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B I O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O B O O O B I O O O O O O O O O O O

aml
who classification
myeloperoxidase
11q23 abnormalities


Value of assessment of tricuspid annulus : real-time three-dimensional echocardiography and magnetic resonance imaging Aim To detect the accuracy of real-time three-dimensional echocardiography -LRB- RT3DE -RRB- and two-dimensional echocardiography -LRB- 2DE -RRB- for tricuspid annulus -LRB- TA -RRB- assessment compared with magnetic resonance imaging -LRB- MRI -RRB- . Introduction Evaluation of tricuspid annulus -LRB- TA -RRB- continues to be a major problem in the surgical decision-making process due to its complex three-dimensional shape -LSB- 1 -- 3 -RSB- . Accurate assessment of TA has many values in clinical application . For example , the decision of tricuspid valve repair may change due to discrepancy between pre-operative measurement of TA diameter -LRB- TAD -RRB- by two-dimensional transthoracic -LRB- or transesophageal -RRB- echocardiography -LRB- 2DE -RRB- and direct surgical visualization -LSB- 4 -RSB- . Several studies described a strong correlation between TA motion and right ventricular -LRB- RV -RRB- function -LSB- 5 -- 8 -RSB- . Analysis of TA velocity by tissue Doppler imaging has been found useful for RV functional assessment -LSB- 9 , 10 -RSB- . In these studies , the assessment of TA motion relied on 2DE , M-mode and tissue Doppler recording . Since Real-time three-dimensional echocardiography -LRB- RT3DE -RRB- has become available for clinical practice , it is now possible to examine the TV more completely -LSB- 11 -RSB- . This study aimed to use RT3DE in evaluation of TA morphology , size and cyclic changes during the cardiac cycle . It also aimed to correlate TA function with RV function that was assessed by magnetic resonance imaging -LRB- MRI -RRB- . Subjects and methods The study included 30 patients -LRB- mean age 34 ± 13 years , 60 % were males -RRB- who were scheduled for routine MRI examination for evaluation of right ventricular function -LRB- 10 patients with congenital heart disease , five with chronic pulmonary disease , five with multivalvular affection , and 10 normals -RRB- . 2DE and RT3DE were performed at the same day of MRI examination after their informed consent for assessment of TA . The inclusion criteria for selection were good 2D image quality , sinus rhythm and mild to moderate tricuspid regurgitation . MRI studies were performed with a 1.5 T MRI -LRB- General Electric , Milwaukee WI ; Signa 1.5 T MRI -RRB- equipped with a four-element torso coil . A cardiac-triggered , steady-state , free-precession sequence -LRB- FIESTA ; temporal resolution and repetition time of echo of 3.5 and 1.3 ms , respectively , flip angle of 45 degrees -RRB- was used for quantitative analysis . 10 cine short axis slices were acquired -LRB- slice thickness 10 mm , gap 0 mm -RRB- during a breath-hold period . Additional imaging parameters were a field of view of 320 -- 380 mm and a matrix of 160 × 128 . These series of high quality images encompassing the right ventricle -LRB- RV -RRB- produced a three-dimensional data set with sharp edge between the blood pool and myocardium . Quantitative analysis was performed using standardized software -LRB- MassPlus , Medis Inc. , Leiden , NL -RRB- . By this software , manual tracing was done for TA and RV endocardial border on all images -LRB- end-diastolic and end-systolic -RRB- . The following measures were obtained at end-diastolic and end-systolic frame : -LRB- 1 -RRB- TA area -LRB- TAAMRI -RRB- , -LRB- 2 -RRB- TADMRI , -LRB- 3 -RRB- RV volume , -LRB- 4 -RRB- RV ejection fraction -LRB- RV-EF -RRB- was calculated as -LRB- RV end-diastolic volume - RV end-systolic volume/RV end-diastolic volume -RRB- × 100 % , -LRB- 5 -RRB- TA fractional shortening -LRB- TAFSMRI -RRB- defined as -LRB- end-diastolic TADMRI -- end-systolic TADMRI -RRB- / end-diastolic TADMRI × 100 % and -LRB- 6 -RRB- TA fractional area changes -LRB- TAFACMRI -RRB- defined as -LRB- end-diastolic TAAMRI -- end-systolic TAAMRI -RRB- / end-diastolic TAAMRI × 100 % . 2DE was done with a Sonos 7500 ultrasound system attached to a S3 transducer -LRB- Philips , Best , The Netherlands -RRB- . The TV was imaged from apical 4-chamber view with the patient in the left lateral decubitus position . The following measures were obtained : -LRB- 1 -RRB- TAD2D was defined as the distance between the insertion sites of septal and anterior TV leaflets and obtained at an end-diastolic and end-systolic still frame and -LRB- 2 -RRB- TA fraction shortening -LRB- TAFS2D -RRB- defined as -LRB- end-diastolic TAD2D -- end-systolic TAD2D -RRB- / end-diastolic TAD2D × 100 % RT3DE was done with the same ultrasound system attached to X4 matrix array transducer capable of providing real-time B-mode images . A full volume 3D data set was collected within approximately 5 -- 10 s of breath holding in full volume mode from an apical window . The 3D data set was transferred for off-line analysis with TomTec software -LRB- Unterschleissheim , Munich , Germany -RRB- . Data were stored digitally and subsequently evaluated by two blinded observers -LRB- AMA , OIIS -RRB- . Data analysis of 3D images was based on a 2D approach relying on images obtained initially from the apical view . The TA was sliced between two narrow lines to exclude other tissues on the 2D image leading to clarification of annulus by a 3D image . TA was viewed and traced manually from the atrial aspect and once this is completed the surface area was automatically calculated and could be visualized from different points of views . Manual modification was made to correct any inconsistence . The following RT3DE variables were obtained from both an end-diastolic and end-systolic still frame : -LRB- 1 -RRB- TA area -LRB- TAA3D -RRB- , and -LRB- 2 -RRB- TAD3D defined as the widest TAD -LRB- see Fig. 1 -RRB- , Subsequently , TAFS3D and TA fractional area changes -LRB- TAFAC3D -RRB- -LRB- % -RRB- were calculated by the same formula used in 2DE . Fig. 1Tricuspid annulus oval shape as seen by graphic representation -LRB- A -RRB- , real-time three-dimensional echocardiography -LRB- B -RRB- , magnetic resonance imaging -LRB- C -RRB- , and tricuspid annulus with 2 lines inside , the larger is the TAD by real-time three-dimensional echocardiography and the smaller is the TAD by two-dimensional echocardiography with large difference in measurements Statistical analysis All data obtained by MRI , 2DE and RT3DE are presented as mean ± SD . A paired t-test and was performed for comparing means of variables . The level of significance was set to P < 0.05 . A SPSS statistical package was used -LRB- SPSS , version 12.1 , SPSS Inc , Chicago -RRB- . Pearson 's coefficient was used for correlation between RT3DE and MRI data . Interobserver agreement for RT3DE measurements was assessed according to the Bland and Altman principle -LSB- 12 -RSB- . Results Acquisition of RT3DE data was performed in all patients in a reasonable time -LRB- approximately 1 min for acquisition and 5 min for data analysis -RRB- . The TA was clearly delineated in all patients . An oval-shaped TA -LRB- not circular -RRB- was visualized by RT3DE and MRI -LRB- Fig. 1 -RRB- . TAD3D was obtained with very good interobserver agreement -LRB- mean difference − 0.4 ± 1.5 mm , agreement − 3.4 -- 2.6 -RRB- . There was a good correlation between TADMRI and TAD3D -LRB- R = 0.75 , P = 0.001 -RRB- , while TAD2D was fairly correlated with TAD3D and TADMRI -LRB- R = 0.5 , P = 0.01 for both -RRB- . There were no significant differences between RT3DE and MRI in TAD , TAA , TAFS , and TAFAC measurements , while TAD2D and TAFS2D were significantly underestimated -LRB- P < 0.001 -RRB- -LRB- Table 1 -RRB- . TAFS2D was not correlated with RV-EF , while TAFS3D and TAFAC3D were fairly correlated with RV-EF -LRB- r = 0.49 , P = 0.01 , and r = 0.47 , P = 0.02 respectively -RRB- . Table 1Comparison between measurements of TA size and function by 2DE , RT3DE and MRI2DERT3DEMRIEnd-diastolic TAD -LRB- mm -RRB- 33.0 ± 8.5 43.2 ± 10.044.1 ± 9.2End-diastolic TAA -LRB- mm2 -RRB- -- -1835 ± 4251869 ± 392End-systolic TAD -LRB- mm -RRB- 27.0 ± 7.832.0 ± 8.732.5 ± 8.2End-systolic TAA -LRB- mm2 -RRB- -- 1120 ± 3071137 ± 288TAFS -LRB- % -RRB- 18.7 ± 4.026.3 ± 5.926.7 ± 5.7 TAFAC -LRB- % -RRB- -- 39.3 ± 4.939.5 ± 4.7 TAD : Tricuspid annular diameter , TAA : Tricuspid annular area , TAFS : Tricuspid annulus fractional shortening and TAFAC : tricuspid annular fractional area change Discussion In the present study , the morphological and functional aspects of TA were assessed by MRI and RT3DE . The main findings of our study are -LRB- 1 -RRB- TA shape was not circular but oval , -LRB- 2 -RRB- TAD measurement by RT3DE is more accurate than by 2DE , and -LRB- 3 -RRB- TA function was fairly correlated with RV function . TAD measurements have an important role in the TV surgical decision-making process not only for the selection of patients undergoing surgery , but also the type of surgical technique -LRB- valve plication or ring placement -RRB- -LSB- 13 -- 15 -RSB- . Although 2DE is helpful to assess TV function and to detect TR severity it has important limitations in describing TV morphological details , such as TAD -LSB- 14 , 15 -RSB- . RT3DE may yield more detailed anatomical description of TA morphology and function -LSB- 16 , 17 -RSB- . In the present study , the TA was visualized well in all subjects allowing even measurements of its area . This is in accordance with Schnabel et al. -LSB- 11 -RSB- who reported well or at least sufficient TA visualization in over 90 % of patients . The measurements of TAD by RT3DE and MRI showed good correlation without significant difference between both techniques . When TAD2D measurements were compared with the TAD3D and TADMRI measurements , 2D measurements were significantly underestimated . Analysis of TA motion by M-mode , 2DE and tissue Doppler imaging has been studied as a feasible marker for RV function reflecting the longitudinal RV shortening and lengthening . All these analyses described the physiological behaviour of TA plane systolic motion towards the apex along the RV long axis -LSB- 5 -- 10 -RSB- . The TA plane systolic displacement is not influenced by its complex structure and asymmetrical shape -LSB- 18 -RSB- In the present study TA circumferential and horizontal motion along the RV short axis was assessed by RT3DE . TA motion along the RV short axis , which was fairly correlated with RV function that was assessed by MRI as a standard method for assessing RV ejection fraction . Fair and not good correlation may be explained by the meridional motion of the muscles and other structures of the RV inflow region . Furthermore , the myocytes are disposed longitudinally in the inflow region and more sensitive to meridional stress -LSB- 19 -RSB- . Despite this fair correlation , the summation of TA motion along both RV long and short axes increases the accuracy and correlation values for estimation of RV function -LSB- 20 -RSB- . Study limitation The main limitation of this study is that RT3DE images more critically depend on image quality than 2DE images and the value of RT3DE should be assessed in a more non-selected -LRB- image quality -RRB- . Due to the high cost of MRI , a small number of patients were included . Conclusions RT3DE helps in accurate assessment of TA comparable to MRI , while 2DE could not be relied on due to underestimation . This may have important implications in the TV surgical decision-making processes . RT3DE analysis of TA function could be used as a marker of RV function .

O O O O B I O O O O O B I I O O O O O O O O O O O O O O O O O O O B I O O O O O O B I I O O O O O O O B I O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B I I O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B I I O O O O O B I O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B I O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O

tricuspid annulus
magnetic resonance imaging