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295 Pancreatic phenotype in CF infants identified by two neonatal mutational screening programs
Journal of Cystic Fibrosis 4 (2005) $ 7 4 ~ 7 9
$77
293 Liver kansplantation in CF: lO-year experience at a supra-regional liver cenke
295* Pancreatic phenotype in CF infants idenEfied by two neonatal mutational screening programs
F.M. B art lett 1, S. Hegde 1, R.G.G. R u i z 1, H.A. Wyatt 1, N.D. Heat on 2, M. Rela 2, J.F. Price 1
M. Cipolli 1, C. Cartellani 1, B. Wilcken4, J. M a r r i e 3, K. M c K a y ~, M. Gruca ~ , B .M. A r r a e l 1, K. Garkin 2~
~RegionaI Cystic Fibrosis Service, King's College Hospital, Lo~ulo~ UK, 2Institute of Liver Studies, King's College Hospital, Lo~ulo~ UK
~Cystic Fibrosis Centre, Azietula Ospedaliera di l/?rona, l/?rona, Italy, 2Department of Gastroenterology, 3Department of Respiratory Medicine, 4New South Wales Newborn Screening Program, sJames Fairfax Institute, Royal AIexandra Hospital for Children, Sydney, Australia
I n r m d u e t l o n : Current knowledge of orthotopic liver tranrplantation (OLT) in CF comes from a f e w small series. We present our experience. M e t h o d s : Retrorpective review of cases conridered for OLT in the last 10 yearr. M i d upper arm circumference ( M A C ) w a r the primary nutritional outcome parameter ar pre t r a n r p l a n t f l u i d retention and o r g a n o m e g a l y complicated interpretation of weight. Respiratory rtatur w a r arrerred by F E V 1. Results: 21 patients w e r e arrerred for OLT. 9 w e r e conridered unsuitable d u e to: severe l u n g disease (4), psychological d i r t u r b a n c e (3), n o n t u b e r c u l o u r mycobacterial infection (1), active aspergillorir (1). 5 of t h e r e non~ranrplanted patients h a v e rince died from respiratory failure. A further patient died of variceal haemordaage w h e n lifted. 11 patients (6 males) received 13 graftr. The median (range) age at tranrplant ation w a r 14.5 (7.8 30.5) yearr. A l l s~arvived at least 1 year. 3 patients died; 2 from complications of immtmorupprerrion angioinvarive arpergillorir (after 38 months) and lymphoproliferative disease (35 monthr). T h e third died from complications of long term n o n adherence (after 52 months). T h e r e m a i n i n g 8 h a v e fur vived a median (range) of 4 6 (12 109) monthr. A l l but 2 h a v e shown an improvement in M A C . FEV~ % predicted range immediately pre OLT w a r 45 79%. Rerpiratot3, rtatur h a t generally rtabilired or improved post OLT. Conclusion: Liver tranrplant ation for selected CF patients in our centre h a t a 100% 1 year rurvival and currently 88% of recipientr are alive. Nutritional outcome ir also good. Our careful confider ation of pre~exirt i n g lung disease and psychological state before tranrplant ation may h a v e influenced thir outcome.
T h e current rtudy w a r derigned to evaluate the pancreatic phenotype of a large group of CF infantr diagnored by two mutational neonatal rcreening (NS) programr. A l l CF infantr diagnored by NS during a 9 "fear rpan at the Verona CF Centre (VCFC) Italy, and thore referred to the Children'r Horpital at Wertmead (CHW) ha Sydney from the NS program of N e w South W a l e r (NSW) Aurtralia, w e r e included. In the C H W only F508del w a r terted (72% detection rate), in the VCFC more mutationr w e r e included (79% detection rate of revere mutationr). C I ~ V had a greater number of F508del homozygoter than V C F C (89 vr 37, p < 0.C~)1), VCFC had a greater number of F508del compound heter ozygoter (67 vr 57, p < 0.025) and non F508del ptr (45 vr 19, p < 0.001). Pancreatic function assessment by 3 5 day fat balance rtudier and/or pancreatic stimulation tests demonrtrated that 82/315 (26%) w e r e PS, w i t h rimilar proportionr of PS ha N S W and Veneto (29% vr 23%, p 0.43). Twelve ptr ha N S W and 6 ha Veneto w h o w e r e initially PS became PI at varying times from 2 monthr to 5 yearr of age. T h e r e 18 (22%) w e r e F508del/F508del, or F508del/revere mutation. In conclusion, a large proportion of CF infantr diagnored by mutational rcreening h a v e normal fat absorption. Thir finding, w h i c h appearr independent of geographical location mad genetic background, empharizer the necerrity of determing pancreatic phenotype and thur e n r u r i n g appropriate therapy for PI patients w h i l e avoiding unnecerrary treatments in PS patients.
294 VEFlpost-liver transplantation in cystic fibrosis
Discrepancies between exocrine pancreatic status and enzyme
E.F. Andrade 1, S. Vieira~, C.T. Fetreira ~, T.R. da Silveira~, M.L. Zanotellil, G. Cantir anil, F.A. A b r e u e Silva 1
L. N a e h r lich
~Pediatric Pulmonology Unit ?Pediatric Gastroenterology Unit. 3Department of Surgery - Hospital de Cllnicas de Porto AIegre - Brazil L i v e r t r a n r p l a n t a t i o n (Tx) ir conridered a n effective t r e a t m e n t for portal hyper tenrion mad revere hepatic dysfunction in CF without advanced lung direare. A i m : to verify the change in F E V 1 ha CF after Tx. Methodr: FEV1 before and after Tx w e r e compared (mort recent F E V 1 before Tx compared w i t h firrt F E V 1 after T x w i t h a stable clinical condition). Rerultr: 5 Tx rince A p r i l / 0 2 : 4 boyr and 1 girl. M e a n age: 13.98 yearr (17, 10, 10, 14 and 17 yearr). A l l patientr colonized w i t h / ~ aeruginosa, 1 B.cepacia and 2 MRSA. One had diabeter before Tx; 3 developed diabeter after Tx. A l l fur rived. One developed revere deprer rion and could perform an adequate rpirometry only 15 monthr after Tx. F E V 1 before Tx w a r 84.81%, 71.51%, 74.14%, 71.33% and 104.58%, rerpectively. FEV1 changer w e r e variable: 2 got w o r r e e 3 got better: (A ~ i 3 . 4 0 % , +5.76%, 28.52%, +4.18% and +7.25%, after 15, 8, 4, 4 and 5 monthr o f T x , rerpectively). M e a n change w a r 8.72 %. T h e worrt changer w e r e found in one patient colonized w i t h B.cepacia and M R S A for 10 yearr, good FEV1, radiological rcore and compliance before Tx, but w h o developed a deprer r i v e dir order mad no compliance after T x and in one patient who developed a hepatic hydrothorax w i t h chert drainage mad pulmonary infection. Conclurionr: T x can improve pulmonary function and be w e l l tolerated in relected patientr w i t h CF. B e r i d e r clinical and laboratory analyrir, intenrive prychological evaluation ir errential, mainly during the adolercence. Pulmonary direare ir rtill prerent, ro the patient h a t to cooperate w i t h the treatment ar much ar partible. I f pulmonary involvement ir revere, combined lung and liver tranrplantation rhould be conridered.
296 therapy in CF-patients
University hospital for children a~uladolescents, Erlangen/Germany A i m s : T h e g e r m a n CF regirtry reportr that 93% of all patientr w e r e treated w i t h pancreatic enzymer, but only 7 7 % w e r e judged ar pancreatic inrufficient. To determine dircrepancier between e n z y m e therapy and exc~rine pancreatic function w e mearured faecal pancreatic elartare (FE 1), a highly renritive and rpecific rcreening tert to classify exc~rine pancreatic rtatur. M e t h o d s : ha a cohort rtudy rtool rampler w e r e analyzed for F E 1 w i t h the u r e of h u m a n monc~lonale (Schebo, G i e r r e n / G e r m a n y ) or polyclonale (Biorerv, R o t tc¢ldGer many ) E L I S A tertr. Pancreatic rufficiency w a r defined ar having F E 1 > 2C~) ~tg/g rtool. T h e initial treatment decirion for pancreatic e n z y m e r w a r bared on clinical r i g h t of rteatorrhoea. Results: W e mearured F E 1 ha 117 patientr (age between 6 weeks and 4 2 yearr (median 11,6 yearr)). 54% of our patient r w e r e homozygour, 39% heter ozygote for F508 and 7% had two Non F508 mut ationr. A hirtory of meconiumileur ir poritive in 18% of our population. Fe 1 w a r meas~ared < 1C~)~tg/g rtool in 53%, between 100 and 2C~) ~tg/g rtool ha 29% and > 2C~) ~tg/g stool ha 18% our rampler. Only tbree patientr h a v e a F E 1 > 5C~)~tg/g rtool. In 4 5 % the FE 1 value w a r between 100 and 300 pg/g rtool. 6 out of 9 6 pancreatic ins~afficient patientr (definition: Fe 1 < 2 0 0 ~tg/g rtool) do not take e n z y m e r ha contrart to the medical advice. 14 out 21 patient r w i t h an F E 1 > 2C~)~tg/g rtool w e r e treated w i t h enzymer. Concluslous: According to the FE 1 m e a r u r e m e n t r 8 2 % of our patientr are pancreatic rufficient, ha contrart to other r tudier 4 5 % of all FE 1 valuer are between 100 mad 3C~)~tg/g rtool. In 18% of our patientr dircrepancier between the exc~rine pancreatic rtatur bared on FE 1 and the pancreatic e n z y m e r therapy could be detected.
$77
293 Liver kansplantation in CF: lO-year experience at a supra-regional liver cenke
295* Pancreatic phenotype in CF infants idenEfied by two neonatal mutational screening programs
F.M. B art lett 1, S. Hegde 1, R.G.G. R u i z 1, H.A. Wyatt 1, N.D. Heat on 2, M. Rela 2, J.F. Price 1
M. Cipolli 1, C. Cartellani 1, B. Wilcken4, J. M a r r i e 3, K. M c K a y ~, M. Gruca ~ , B .M. A r r a e l 1, K. Garkin 2~
~RegionaI Cystic Fibrosis Service, King's College Hospital, Lo~ulo~ UK, 2Institute of Liver Studies, King's College Hospital, Lo~ulo~ UK
~Cystic Fibrosis Centre, Azietula Ospedaliera di l/?rona, l/?rona, Italy, 2Department of Gastroenterology, 3Department of Respiratory Medicine, 4New South Wales Newborn Screening Program, sJames Fairfax Institute, Royal AIexandra Hospital for Children, Sydney, Australia
I n r m d u e t l o n : Current knowledge of orthotopic liver tranrplantation (OLT) in CF comes from a f e w small series. We present our experience. M e t h o d s : Retrorpective review of cases conridered for OLT in the last 10 yearr. M i d upper arm circumference ( M A C ) w a r the primary nutritional outcome parameter ar pre t r a n r p l a n t f l u i d retention and o r g a n o m e g a l y complicated interpretation of weight. Respiratory rtatur w a r arrerred by F E V 1. Results: 21 patients w e r e arrerred for OLT. 9 w e r e conridered unsuitable d u e to: severe l u n g disease (4), psychological d i r t u r b a n c e (3), n o n t u b e r c u l o u r mycobacterial infection (1), active aspergillorir (1). 5 of t h e r e non~ranrplanted patients h a v e rince died from respiratory failure. A further patient died of variceal haemordaage w h e n lifted. 11 patients (6 males) received 13 graftr. The median (range) age at tranrplant ation w a r 14.5 (7.8 30.5) yearr. A l l s~arvived at least 1 year. 3 patients died; 2 from complications of immtmorupprerrion angioinvarive arpergillorir (after 38 months) and lymphoproliferative disease (35 monthr). T h e third died from complications of long term n o n adherence (after 52 months). T h e r e m a i n i n g 8 h a v e fur vived a median (range) of 4 6 (12 109) monthr. A l l but 2 h a v e shown an improvement in M A C . FEV~ % predicted range immediately pre OLT w a r 45 79%. Rerpiratot3, rtatur h a t generally rtabilired or improved post OLT. Conclusion: Liver tranrplant ation for selected CF patients in our centre h a t a 100% 1 year rurvival and currently 88% of recipientr are alive. Nutritional outcome ir also good. Our careful confider ation of pre~exirt i n g lung disease and psychological state before tranrplant ation may h a v e influenced thir outcome.
T h e current rtudy w a r derigned to evaluate the pancreatic phenotype of a large group of CF infantr diagnored by two mutational neonatal rcreening (NS) programr. A l l CF infantr diagnored by NS during a 9 "fear rpan at the Verona CF Centre (VCFC) Italy, and thore referred to the Children'r Horpital at Wertmead (CHW) ha Sydney from the NS program of N e w South W a l e r (NSW) Aurtralia, w e r e included. In the C H W only F508del w a r terted (72% detection rate), in the VCFC more mutationr w e r e included (79% detection rate of revere mutationr). C I ~ V had a greater number of F508del homozygoter than V C F C (89 vr 37, p < 0.C~)1), VCFC had a greater number of F508del compound heter ozygoter (67 vr 57, p < 0.025) and non F508del ptr (45 vr 19, p < 0.001). Pancreatic function assessment by 3 5 day fat balance rtudier and/or pancreatic stimulation tests demonrtrated that 82/315 (26%) w e r e PS, w i t h rimilar proportionr of PS ha N S W and Veneto (29% vr 23%, p 0.43). Twelve ptr ha N S W and 6 ha Veneto w h o w e r e initially PS became PI at varying times from 2 monthr to 5 yearr of age. T h e r e 18 (22%) w e r e F508del/F508del, or F508del/revere mutation. In conclusion, a large proportion of CF infantr diagnored by mutational rcreening h a v e normal fat absorption. Thir finding, w h i c h appearr independent of geographical location mad genetic background, empharizer the necerrity of determing pancreatic phenotype and thur e n r u r i n g appropriate therapy for PI patients w h i l e avoiding unnecerrary treatments in PS patients.
294 VEFlpost-liver transplantation in cystic fibrosis
Discrepancies between exocrine pancreatic status and enzyme
E.F. Andrade 1, S. Vieira~, C.T. Fetreira ~, T.R. da Silveira~, M.L. Zanotellil, G. Cantir anil, F.A. A b r e u e Silva 1
L. N a e h r lich
~Pediatric Pulmonology Unit ?Pediatric Gastroenterology Unit. 3Department of Surgery - Hospital de Cllnicas de Porto AIegre - Brazil L i v e r t r a n r p l a n t a t i o n (Tx) ir conridered a n effective t r e a t m e n t for portal hyper tenrion mad revere hepatic dysfunction in CF without advanced lung direare. A i m : to verify the change in F E V 1 ha CF after Tx. Methodr: FEV1 before and after Tx w e r e compared (mort recent F E V 1 before Tx compared w i t h firrt F E V 1 after T x w i t h a stable clinical condition). Rerultr: 5 Tx rince A p r i l / 0 2 : 4 boyr and 1 girl. M e a n age: 13.98 yearr (17, 10, 10, 14 and 17 yearr). A l l patientr colonized w i t h / ~ aeruginosa, 1 B.cepacia and 2 MRSA. One had diabeter before Tx; 3 developed diabeter after Tx. A l l fur rived. One developed revere deprer rion and could perform an adequate rpirometry only 15 monthr after Tx. F E V 1 before Tx w a r 84.81%, 71.51%, 74.14%, 71.33% and 104.58%, rerpectively. FEV1 changer w e r e variable: 2 got w o r r e e 3 got better: (A ~ i 3 . 4 0 % , +5.76%, 28.52%, +4.18% and +7.25%, after 15, 8, 4, 4 and 5 monthr o f T x , rerpectively). M e a n change w a r 8.72 %. T h e worrt changer w e r e found in one patient colonized w i t h B.cepacia and M R S A for 10 yearr, good FEV1, radiological rcore and compliance before Tx, but w h o developed a deprer r i v e dir order mad no compliance after T x and in one patient who developed a hepatic hydrothorax w i t h chert drainage mad pulmonary infection. Conclurionr: T x can improve pulmonary function and be w e l l tolerated in relected patientr w i t h CF. B e r i d e r clinical and laboratory analyrir, intenrive prychological evaluation ir errential, mainly during the adolercence. Pulmonary direare ir rtill prerent, ro the patient h a t to cooperate w i t h the treatment ar much ar partible. I f pulmonary involvement ir revere, combined lung and liver tranrplantation rhould be conridered.
296 therapy in CF-patients
University hospital for children a~uladolescents, Erlangen/Germany A i m s : T h e g e r m a n CF regirtry reportr that 93% of all patientr w e r e treated w i t h pancreatic enzymer, but only 7 7 % w e r e judged ar pancreatic inrufficient. To determine dircrepancier between e n z y m e therapy and exc~rine pancreatic function w e mearured faecal pancreatic elartare (FE 1), a highly renritive and rpecific rcreening tert to classify exc~rine pancreatic rtatur. M e t h o d s : ha a cohort rtudy rtool rampler w e r e analyzed for F E 1 w i t h the u r e of h u m a n monc~lonale (Schebo, G i e r r e n / G e r m a n y ) or polyclonale (Biorerv, R o t tc¢ldGer many ) E L I S A tertr. Pancreatic rufficiency w a r defined ar having F E 1 > 2C~) ~tg/g rtool. T h e initial treatment decirion for pancreatic e n z y m e r w a r bared on clinical r i g h t of rteatorrhoea. Results: W e mearured F E 1 ha 117 patientr (age between 6 weeks and 4 2 yearr (median 11,6 yearr)). 54% of our patient r w e r e homozygour, 39% heter ozygote for F508 and 7% had two Non F508 mut ationr. A hirtory of meconiumileur ir poritive in 18% of our population. Fe 1 w a r meas~ared < 1C~)~tg/g rtool in 53%, between 100 and 2C~) ~tg/g rtool ha 29% and > 2C~) ~tg/g stool ha 18% our rampler. Only tbree patientr h a v e a F E 1 > 5C~)~tg/g rtool. In 4 5 % the FE 1 value w a r between 100 and 300 pg/g rtool. 6 out of 9 6 pancreatic ins~afficient patientr (definition: Fe 1 < 2 0 0 ~tg/g rtool) do not take e n z y m e r ha contrart to the medical advice. 14 out 21 patient r w i t h an F E 1 > 2C~)~tg/g rtool w e r e treated w i t h enzymer. Concluslous: According to the FE 1 m e a r u r e m e n t r 8 2 % of our patientr are pancreatic rufficient, ha contrart to other r tudier 4 5 % of all FE 1 valuer are between 100 mad 3C~)~tg/g rtool. In 18% of our patientr dircrepancier between the exc~rine pancreatic rtatur bared on FE 1 and the pancreatic e n z y m e r therapy could be detected.