[Show abstract][Hide abstract] ABSTRACT: Long-term histopathologic changes after bladder augmentation (BA) in rats using living-related partial bladder transplantation (LPBTx) or conventional ileocystoplasty (ICP) were compared. In this study, BA (n = 37), LPBTx (n = 18), and ICP (n = 19) were performed in 16-wk-old Lewis rats. Five donors and seven nontransplanted normal Lewis rats (controls) were also studied. Rats that survived >10 mo after BA were killed after blood biochemistry and neobladder imaging. Harvested bladders were examined with hematoxylin and eosin and proliferating cell nuclear antigen (PCNA). When the rats were killed, there were 16 rats in the LPBTx group and 12 rats in the ICP group; ICP rats were significantly smaller than LPBTx rats (p < 0.05). Mean duration of follow-up for the LPBTX group was 17.3 mo, for the ICP group was 13.7 mo, for the donor group was 16.1 mo, and for the control group was 19.7 mo. Mean serum pH in the LPBTx group was 7.41 +/- 0.78 and in the ICP group was 7.25 +/- 0.38. Mean base excess in the ICP group was significantly lower than in the LPBTx group (p < 0.05). Incidence of bladder calculi in the LPBTx group (6.3%) was significantly lower than in the ICP group (33.3%; p < 0.05). There was no dysplasia/malignancy/increase in PCNA in the LPBTx group. PCNA increased in the ICP group, compared with controls (p < 0.05); two (16.7%) of 12 of ICP rats had dysplasia with mitosis. Bladder capacity increased in LPBTx and ICP compared with controls (both p < 0.05). We hope to show that BA using LPBTx may result in a neobladder with fewer complications than BA using ICP; LPBTx may also decrease the risk for malignancy.
[Show abstract][Hide abstract] ABSTRACT: The aim of this study was to assess the feasibility of allogenic penile transplantation (PTx) for creating a source of viable penile tissue for use in penile reconstruction.
The entire penis from an adult Brown-Norway rat was transplanted into a pouch created in the omentum of an adult Lewis rat (fully allogenic PTx, n = 23). Recipients were divided into 2 groups according to immunosuppressant (FK506) usage: in the FK+ group, FK506 (0.6 mg/kg/d) was administered intraperitoneally until a predetermined day (day 3, 5, 7, 10, 14, or 21) after PTx, and then the grafts were harvested. No FK506 was used in the FK- group. Syngeneic PTx (n = 8) patients were used as controls. All grafts were stained with H&E for histologic examination.
At laparotomy, each successfully transplanted penis appeared as a cylindrical mass in the omentum. Grafts could be mobilized to the genital area because of a long omental pedicle. Graft survival in the control and FK+ groups was 100%. Rejection was minimal to moderate in FK+ grafts harvested on days 3 and 5 after PTx and minimal or absent in FK+ grafts harvested on days 7, 10, 14, and 21. Penile structure on H&E staining was normal in FK+ and control specimens. Rejection with massive cellular infiltration was observed in all FK- grafts.
FK506 successfully prevented rejection in allogenic PTx, and the authors' technique has potential for creating viable penile tissue that could be used as an option for penile reconstruction.
Journal of Pediatric Surgery 01/2004; 38(12):1802-5. DOI:10.1016/j.jpedsurg.2003.08.015 · 1.39 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To assess the feasibility of transplanting adult bladder tissue to its offspring as a source of neobladder tissue for bladder augmentation.
The dome of the bladder of an adult Lewis rat was excised and transplanted into the omentum of a 6-week-old offspring (living-related partial bladder transplant: n = 15). The bladder remnant of the donor rat was closed. Two weeks after transplantation, a laparotomy was performed to mobilize the bladder graft with its omental pedicle into the pelvis. Bladder augmentation (BA) was performed by anastomosing the graft to the recipient's bladder. Thirty days after BA, the entire neobladder was excised and histopathologically examined.
At laparotomy, each bladder graft appeared macroscopically as a thin-walled cyst in the recipient's omentum. Each graft could be mobilized into the pelvis and anastomosed to the recipient's bladder. BA was successful in all 15 recipients, and histopathologic studies showed that the mucosa was normal throughout each neobladder. Postoperatively, donors and recipients were clinically well without any sign of urinary incontinence or obstruction.
This is the first report of adult tissue being transplanted successfully into a recipient without vascular reconstruction in a rat. Living-related partial bladder transplantation for the purpose of BA is feasible using our technique and could have application as an alternative technique for BA in a rat.
Journal of Pediatric Surgery 07/2003; 38(6):913-5. DOI:10.1016/S0022-3468(03)00122-2 · 1.39 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The opening of the papilla of Vater represents the orifice of the embryonic hepatic diverticulum from which the ventral pancreas, common bile duct, and liver are derived. Recently, we found a strong association between congenital biliary dilatation (CBD), certain types of pancreatic ductal anatomy (PDA), and ectopic distal location of the papilla of Vater which prompted us to study the relationship between the location of the papilla of Vater and abnormal PDA.
A total of 118 patients with CBD were studied. Cholangiograms documented the presence of pancreaticobiliary malunion (PBMU), the location of the papilla of Vater, and the PDA. Eleven age-matched patients with intermittent jaundice were used as controls.
In the control group, the papilla of Vater was located normally in the descending portion of the duodenum in all cases. In the 118 CBD patients, the papilla of Vater was located normally in 38 (32.2%), but in 80 (67.8%), the papilla was located distal to the descending portion of the duodenum. When the papilla was located distally, the incidences of the specific types of PDA studied were significantly higher than when the papilla was located normally (p<0.01). Pancreatic duct dilatation was also more frequent if the papilla was located distally (28.7%) compared with CBD patients with a normal papilla (7.9%) or normal controls (0%) (both p<0.01). PBMU was present in all CBD patients and absent in all controls.
Our study strongly suggests that abnormalities occurring during early embryological development of the hepatic diverticulum are responsible for the association between abnormal PDA and ectopic distal location of the papilla of Vater in CBD.
Pediatric Surgery International 05/2003; 19(3):180-5. DOI:10.1007/s00383-002-0914-0 · 1.00 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The aim of this study was to see if allogeneic transplantation (Tx) of newborn esophagus can create viable esophageal tissue that may be used for treating long gap esophageal atresia.
Specimens of thoracic esophagus from newborn Brown-Norway rats, each were transplanted into a pouch created in the distal omentum of 5-week-old Lewis rats. In group I no immunosuppressant was used. FK-506 was used in group II (0.2 mg/kg), group III (0.6 mg/kg), and group IV (1.2 mg/kg) until a predetermined day of graft harvesting (1, 2, 3, 4, 5, 6, and 8 weeks after Tx). FK-506 was used for only 2 weeks in group V (0.6 mg/kg), and group VI (1.2mg/kg), and transplanted esophageal grafts were harvested 1, 2, 3, and 4 weeks after cessation of 2 weeks course FK-506. Syngeneic esophagus transplants were used as controls. All grafts were examined by H&E staining to assess graft viability and degree of rejection.
Each successfully transplanted esophagus appeared macroscopically as a tube like mass. Each graft could be mobilized to the thoracic cavity, because of the long omental pedicle. Graft survival in the control group was 100%. Rejection was observed in all grafts from groups I, II, V, and VI. In contrast, grafts from groups III and IV showed only minimal or no rejection. There was no evidence of side effects of FK-506 in rats in groups III and IV, except significantly slower weight gain compared with controls (P <.05).
FK-506 successfully prevented rejection, although immunologic tolerance was not achieved. These observations suggest that the authors' procedure has the potential to produce viable esophageal tissue that could be a new option for treating long gap esophageal atresia.
Journal of Pediatric Surgery 09/2001; 36(8):1255-7. DOI:10.1053/jpsu.2001.25789 · 1.39 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Ncx/Hox11L.1-deficient (Ncx-/-) mice specifically created by the authors had mega-ileo-ceco-colon (mega-ICC) with a caliber change in the proximal colon. The authors studied the nerve distribution in the bowel of these Ncx-/- mice to determine the cause of their bowel dysmotility.
Four-week-old Ncx-/- mice (n = 10; 5 with mega-ICC, 5 without mega-ICC) were killed and the bowel harvested. Half of each specimen was snap frozen for AchE and NADPH-diaphorase histochemistry, and the other half were fixed with 10% formalin for H&E staining and immunohistochemistry using PGP9.5 antibody (a marker for neurons), C-kit antibody (a marker for intestinal pacemaker cells), and stem cell factor antibody (a marker for C-kit ligand). Age-matched wild-type normal mice (n = 5) served as controls.
In the ileum, cecum, and proximal colon from all Ncx-/- mice (irrespective of the association of mega-ICC), typical findings of human intestinal neuronal dysplasia (IND) ie, obvious hyperganglionosis in neuronal plexuses on PGP9.5 immunohistochemistry, ectopic ganglia in the mucosal and muscular layers on AchE histochemistry, and ghostlike ganglia on NADPH-diaphorase histochemistry were found. Likewise, in normal caliber distal colon from these mice, the distribution of ganglion cells, C-kit, and stem cell factor was normal. In control specimens, there was no ectopic ganglia or hyperganglionosis.
These findings suggest that the Ncx/Hox11L.1 gene is required for the proper innervation of the enteric nervous system in mice, and our deficient strain may be useful as a model for studying IND in humans.
Journal of Pediatric Surgery 09/2001; 36(8):1293-6. DOI:10.1053/jpsu.2001.25797 · 1.39 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: We created viable bladder tissue by transplantation with immunosuppression.
For bladder transplantation the bladder of newborn Brown-Norway rats was excised and each was transplanted into a pouch created in the distal omentum of a 5-week-old Lewis rat. In 15 group 1 rats no immunosuppressive agent was used. In 20 group 2 rats 0.6 mg./kg. FK-506 daily were given intramuscularly until a predetermined day of harvest. Recipient rats were sacrificed on day 3, 5, 7 or 14 after bladder transplantation, and the bladder grafts were harvested and formalin fixed. Hematoxylin and eosin staining was done to examine bladder graft survival and the degree of rejection, and immunohistochemical testing was performed for assessing the vesical nervous system. In 5 rats in the control group bladder augmentation was performed by anastomosing the bladder graft to the native bladder. Each augmented bladder was harvested 21 days later for histopathological assessment.
Overall bladder graft survival was 96.4%. Each successfully transplanted bladder graft appeared macroscopically as a thin walled cyst. In group 1 all bladder grafts showed rejection with cellular infiltration. In group 2 there was mild rejection in 5 rats and no evidence of rejection in the remaining 15. All group 2 bladder grafts had intact nerve distribution. Bladder augmentation was successful in all 5 cases and the mucosa was normal throughout each augmented bladder.
Because FK-506 successfully prevents rejection, our technique would appear to have the potential for creating viable bladder tissue that may be used for bladder augmentation in cases of vesical exstrophy or neurogenic bladder.
The Journal of Urology 08/2001; 166(1):259-62. DOI:10.1016/S0022-5347(05)66141-1 · 4.47 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Our purpose was to evaluate whether bladder transplantation (BTx) can be used for bladder augmentation (BA).
Bladders from infantile Brown-Norway rats (less than 21 days old) were excised and each transplanted into a pouch created in the distal omentum of a 6-week-old Lewis rat (fully allogeneic BTx). No immunosuppressant was used in group I (n=12). Intramuscular FK506 was used daily from the day of BTx in group II (n=16; 0.2 mg/kg), group III (n=22; 0.6 mg/kg), and group IV (n=16; 1.2 mg/kg) until harvesting 3, 4, 5, or 6 weeks after BTx. FK506 was used for only 2 weeks in group V (n=12; 0.6 mg/kg/day) and group VI (n=12; 1.2 mg/kg/day). Syngeneic bladder transplants acted as controls (n=16). Hematoxylin and eosin staining was used to examine all grafts. In six rats from group III, BA was performed by anastomosing the graft to the recipient bladder 10 days after BTx.
Each successfully transplanted graft appeared macroscopically as a thin-walled cyst. Rejection was seen in all grafts from groups I, II, V, and VI, and was minimal or absent in groups III and IV. On medium to long-term follow-up the only side effect of FK506 observed was reduced weight gain. Graft survival in the control group was 100%. BA was successful in all six cases, and the mucosa was normal throughout each augmented bladder.
This is the first report of the successful transplantation of infantile tissue without vascular anastomosis. Because of the efficient, safe immunosuppression possible with FK506, our BTx technique could find clinical application for creating viable vesical tissue that could be used for BA.
[Show abstract][Hide abstract] ABSTRACT: The aim of this study was to show that a tubed latissimus dorsi musculocutaneous flap (tubed LDMCF) may be useful for treating circumferential esophageal defects.
A segment of esophagus 3 vertebrae long was excised through a right thoracotomy in each of 6 puppies, and a tubed LDMCF was interposed between the cut ends of esophagus. The puppies were sacrificed after a mean follow-up period of 6.6 years. The tubed LDMCF was examined histologically. Functional integrity was assessed using barium meal and endoscopy before sacrifice.
All puppies survived and grew normally on a normal diet, although 4 vomited occasionally. There was smooth passage of barium through the tubed LDMCF without stenosis, although endoscopy showed regrowth of hair. Histologically, no metaplasia, dysplasia, or malignancy was observed in any tubed LDMCF.
The tubed LDMCF is technically safe, obviates the necessity for laparotomy, and long-term follow-up would suggest that it is histologically stable. Thus, it could become an alternative procedure for bridging esophageal defects.
Journal of Pediatric Surgery 12/2000; 35(11):1623-5. DOI:10.1053/jpsu.2000.18333 · 1.39 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The aim of this study is to determine if fetal esophageal transplantation can create viable esophageal tissue that may be used for treating long gap esophageal atresia.
Fetuses of gestational age 19 to 20 days were obtained by hysterotomy of pregnant 15-week-old Lewis rats. A 10-mm long segment of esophagus was obtained from each fetus by thoracolaparotomy and transplanted by wrapping it in a pouch created in the distal omentum of a 5-week-old Lewis rat (syngeneic transplantation: n = 15). Transplanted fetal esophageal grafts were harvested 10 days post-transplantation and fixed in 10% formalin and embedded in paraffin. H&E was used for histological examination, and PGP 9.5 (a neuronal antibody) was used for immunohistochemistry. Esophageal segments obtained from 10-day-old Lewis rats were used as controls.
Thirteen of 15 (87%) grafts were transplanted successfully. The successfully transplanted graft could be mobilized to the thoracic cavity without tension or compromising of vascularity, because of the long omental pedicle. H&E staining and PGP 9.5 immunohistochemistry showed normal esophageal structure with intact esophageal nervous system, comparable with control specimens.
Fetal esophageal transplantation produces viable esophageal tissue that may find application for treating long gap esophageal atresia providing rejection can be controlled adequately.
Journal of Pediatric Surgery 12/1999; 34(11):1638-40. DOI:10.1016/S0022-3468(99)90633-4 · 1.39 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The aim of this study was to review complications after sigmoidocolocystoplasty (SCP) performed at a single institution from 1984 to 1997.
The medical records of 100 patients who underwent SCP were reviewed retrospectively.
Mean age at SCP was 10.8 years. Urinary control was improved in 75 cases and unchanged in 25. Post-SCP complications included death, abdominal wound infection or dehiscence, adhesive bowel obstruction, vesical calculi, vesicocolonic anastomosis stenosis, metabolic acidosis, and transient renal hypertension. Fifty-one patients underwent ureteric re-implantation (URI) at the time of, or before, SCP, and 7 had recurrence of VUR post-URI (spontaneous regression in 6); 3 patients had new onset of contralateral VUR post-URI (spontaneous regression in 2). Transient pleural effusion was seen after reinsertion of ventriculo-pleural shunts to ventriculo-thoracic in 12 cases, but there was no incidence of infection. Squamous metaplasia of the bladder mucosa was identified in 5 patients on routine mucosal biopsy results but resolved in all cases after regular bladder irrigation was commenced. Preoperative constipation or fecal incontinence was better managed after sigmoidectomy in approximately one third of cases (38%).
SCP with or without URI can improve the quality of life of patients with neurogenic or small-capacity bladder, but it can be associated with long-term complications. Regular bladder irrigation is recommended to maintain bladder mucosa integrity.
Journal of Pediatric Surgery 12/1999; 34(11):1672-7. DOI:10.1016/S0022-3468(99)90642-5 · 1.39 Impact Factor