Kazunori Tahara

Pancreatic Complications in Choledochal Cyst and Their Surgical Outcomes

AbstractFollow-up results were analyzed to evaluate the surgical managements of pancreatic complications such as pancreatitis and protein plug formation in patients with choledochal cysts. Sixty-two patients with choledochal cysts treated between 1976 and 1999 were reviewed. Twenty-four were children and 38 were adults. Fifty-four patients showed primary cases. Cyst excision and hepaticoenterostomy were finally performed in 56 patients. Surgical sphincteroplasty or endoscopic sphincterotomy was performed to prevent recurrent protein plugs in six patients. The follow-up period was 8.1 ± 6.1 years. Acute pancreatitis and protein plug formation was observed in 18 (33.3%) and 11 (20.4%) of 54 patients showing primary cases, respectively. Both acute pancreatitis and protein plug formation were observed more frequently in children from 1 to 15 years of age (70.6% and 41.2%, respectively) than in adults (18.6% and 12.5%, respectively). Acute pancreatitis and/or protein plug formation developed in four (57.1%) of seven patients who underwent cystenterostomy. Protein plug formation in the residual cyst after cyst excision was observed in two patients, one of whom had undergone sphincteroplasty. Diabetes mellitus due to chronic pancreatitis developed in one patient who was diagnosed late. No other pancreatitis or protein plug recurred postoperatively in this series. Our results suggested that cystenterostomy did not resolve pancreatic complications of choledochal cysts, and that surgical sphincteroplasty was ineffective in preventing the recurrent protein plug formation in the residual duct. In conclusion, complete cyst excision and an early diagnosis are necessary to prevent the development of chronic or recurrent pancreatitis after surgery.

Experimental orthotopic lung transplantation model in rats with cold storage

This report describes a new experimental procedure, a rat unilateral, orthotopic lung transplantation with cold storage, and evaluates its relevancy and reliability to study the early events during cold ischemia/reperfusion (I/R) injury. This model, using the cuff technique, does not require extensive training and is relatively easy to be established. The model can induce reproducible degrees of pulmonary graft injury including impaired gas exchange, proinflammatory cytokine upregulation, or inflammatory infiltrates, depending on the preservation time. The results are consistent with the previous clinical evidence, thus suggesting that this model is a valid and reliable animal model of cold I/R injury.

Acute rejection and the muscularis propria after intestinal transplantation: the alloresponse, inflammation, and smooth muscle function.

Background. It has been shown that in transplantation the intestinal muscularis may act as an immunologically active layer via the activation of resident macrophages and the recruitment of leukocytes. Thus we hypothesized that inflammation within the intestinal muscularis is involved in the promotion of acute rejection in intestinal allografts and that this causes smooth muscle dysfunction. Methods. Orthotopic allogenic and small bowel transplantation (Brown-Norway rats–Lewis rats) was performed without immunosuppression. Animals were sacrificed 1, 4, and 7 days after small bowel transplantation. Isogenic transplanted grafts (Brown-Norway rats–Brown-Norway rats) as well as nontransplanted bowel served as controls. Mediator mRNA expression was determined by real-time reverse-transcriptase polymerase chain reaction. Leukocyte infiltration was evaluated in muscularis whole mounts by immunohistochemistry. Apoptosis was evaluated by TdT-mediated dUTP-X nick end labeling assay. Contractility was assessed in a standard organ bath under bethanechol stimulation. Statistical analysis was performed using a Student’s t test and one-way analysis of variance. Results. Transplanted animals showed a significant early inflammatory response within the graft muscularis because of reperfusion injury. Only allogenic transplanted animals exhibited a significant second molecular inflammatory peak in the muscularis during rejection (mRNA induction for interleukin (IL)-6, intercellular adhesion molecule-1, monocyte chemoattractant protein (MCP)-1, interferon-&ggr;, IL-2, tumor necrosis factor-&agr;, IL-10, inducible nitric oxide synthase). These findings were associated with significant leukocyte infiltration within the muscularis, increasing apoptotic cells and massive impairment of smooth muscle contractile activity by 78%. Conclusions. The data shows that transplantation results in an early and temporary inflammatory response within the intestinal graft muscularis, that is reactivated and intensified during acute allograft rejection. The immunoreaction within the intestinal muscularis leads to intestinal allograft smooth muscle dysfunction.

Perioperative Glycine Treatment Attenuates Ischemia/reperfusion Injury and Ameliorates Smooth Muscle Dysfunction in Intestinal Transplantation

Background. Ischemia/reperfusion evokes a functionally relevant inflammatory response within the muscularis propria of small bowel grafts by activation of resident macrophages and leukocyte recruitment. We hypothesized that immunomodulatory perioperative treatment with glycine attenuates the proinflammatory cascade and improves smooth muscle dysfunction of small bowel grafts. Methods. Orthotopic SBTx was performed in Lewis rats. Glycine (1 mg/g body weight) was infused (0.1 mL/g/hr) for 2 hr before harvest as preconditioning in the donor, and for 2 hr from the onset of reperfusion in the recipient. Transplanted vehicle (isotonic saline)-treated animals and naive animals served as controls. Rats were sacrificed after 3 hr and 24 hr. Leukocyte infiltration was investigated in muscularis whole mounts by immunohistochemistry. Mediator mRNA expression was determined by real-time-PCR. Jejunal circular smooth muscle contractility was assessed in a standard organ bath. Results. Compared with vehicle controls, glycine-treated graft muscularis expressed a significant alleviation in mRNA peak expression for IL-6, IL-1&bgr;, ICAM-1, MCP-1, TNF&agr;, COX-2, and iNOS. Also glycine-treated grafts exhibited significantly less infiltration with ED-1-positive macrophages and MPO-positive neutrophils as well as reduced apoptosis. Concurrent to these results, vehicle controls showed an 80% decrease in smooth muscle contractility, whereas glycine-treated animals exhibited only a 40% decrease in contractile activity compared with controls. Conclusions. The data indicate that perioperative glycine treatment reduces the molecular and cellular inflammatory response within the grafts and improves smooth muscle dysfunction after transplantation. Therefore, the glycine-activated chloride channel on resident and infiltrating leukocytes could be a promising pharmacologic target to attenuate ischemia/reperfusion injury after ITx.

Splenic Autotransplantation for a Congested and Enlarged Wandering Spleen with Torsion: Report of a Case

In children with diseases of the spleen, every effort should be made to preserve the organ, to prevent severe infections postsplenectomy. We report the case of a 7-year-old girl with torsion of a wandering spleen who we treated by autotransplantation of splenic tissues following splenectomy, when fixation of the enlarged spleen seemed impossible. Spleen scintigraphy showed uptake in the regenerating splenic tissues 9 months after surgery, and evidence of an increase in the size of the tissues 23 months after surgery. Howell–Jolly bodies had disappeared by 16 months after surgery. These findings suggested that the transplanted splenic tissues were resuming splenic functions. Based on our experience with this case, we conclude that autotransplantation after splenectomy is a treatment option for wandering spleen with torsion when fixation seems difficult because of splenic congestion and enlargement.

Efficacy of granulocyte apheresis in pediatric patients with ulcerative colitis: a pilot study.

Objectives: Granulocyte apheresis (GCAP), involving the removal of granulocytes from the blood, may improve clinical symptoms and facilitate a reduction in the dose of steroids in adult patients with ulcerative colitis. As a preliminary trial, GCAP was used to taper the dose of steroids in 4 pediatric patients with ulcerative colitis. Methods: Three males and 1 female ranging from 11 to 17 years old were treated with GCAP once per week for 5 consecutive weeks/course. The ages of patients at clinical onset ranged from 8 to 12 years and the length of time from the clinical onset to GCAP treatment ranged from 28 to 58 months (median, 38.5 months). Results: In 2 patients, symptoms and signs indicating disease activity improved after 2 courses of GCAP. Laboratory data and endoscopic findings also improved after treatment and the clinical efficacy was judged to be excellent in these patients. In 1 patient, GCAP improved laboratory and endoscopic hallmarks, but bloody stools persisted. Finally, the treatment was ineffective in the fourth patient who eventually underwent surgery. Conclusions: GCAP is effective in improving clinical symptoms and may play an important role in converting steroid therapy to other treatments in children with steroid-refractory or steroid-dependent ulcerative colitis.

Regeneration of the rat neonatal intestine in transplantation.

Objective:Based on development of stem cell technology, newborn tissue, even undergoing cryopreservation, possesses promising potential as a donor source in the field of organ transplantation. However, the precise regeneration processes remains unclear. This study was designed to investigate the regenerative potential of newborn intestine with or without cryopreservation in the transplantation. Methods:Newborn rat intestines with or without cryopreservation were transplanted subcutaneously into the syngeneic host, and specimens were evaluated by histology, multiple immunostaining, and comprehensive gene expression analysis. Results:We determined that newborn rat intestine possessed regenerative potential in the syngeneic host even after cryopreservation, where angiogenesis was induced early in the submucosa with subsequent maturation in the crypts. Furthermore, newborn intestinal graft could facilitate the survival of maturation-incompetent 10-day-old graft that lacked regenerating activity (P < 0.01, n = 13). Tissue aggregates from the maturation-incompetent graft underwentreconstitution of their histologic configuration in the presence of newborn intestinal aggregates. Comprehensive gene expression analysis showed that 37 genes were preferentially up-regulated, while 19 genes were down-regulated in the regenerating 10-day-old graft (supported by the newborn graft). Conclusions:Regeneration of newborn intestine is implicated in neo-angiogenesis in the host, and the newborn intestinal graft is capable of mediating the survival of the maturation-incompetent 10-day-old graft. Notwithstanding ethical and legal limitations in the clinic, these results may provide new insights into the regenerative role of newborn grafts.

Impact of graft length on surgical damage after intestinal transplantation in rats

BACKGROUND Intestinal grafts greatly affect nutrition and immunology in the host. The growth of the recipient and incidence of graft-versus-host disease depend on graft length. A larger graft may affect the host immune system, but little is known about how the length of the intestinal graft severely affects surgical intervention. We developed a cervical small bowel transplantation (SBT) rat model that minimized technical variations using a cuff method and studied the effects of graft length on surgical damage in SBT. MATERIALS AND METHODS We transplanted a whole (70 cm) or partial (15 cm) intestine into a syngeneic rat combination of LEW (MHC haplotype: RT1(l)) to LEW and evaluated changes in perioperative hemodynamics and the endogenous endotoxin level. Natural killer (NK) cell activity in the peripheral blood and the immunologic response of the recipient spleen were also studied. RESULTS In the whole SBT model, body weight loss was more severe than in the segmental SBT model; the rats in the former model often died, while all in the latter survived indefinitely. The systemic blood pressure markedly decreased in the whole SBT group immediately after reperfusion. The proliferative activity of splenic lymphocytes stimulated by concanavalin A was also more severely inhibited in the former model than in the latter postoperatively. NK cell activity in the whole SBT rats declined more severely than the segmental SBT rats 3 days postoperatively. CONCLUSION The longer graft severely induced surgical intervention; and influenced host immunosuppression, resulting in the higher mortality in rats undergoing whole SBT.

Association of extrahepatic bile duct duplication with pancreaticobiliary maljunction and congenital biliary dilatation in children: a case report and literature review

We herein report a case of cystic-type congenital biliary dilatation (CBD) in whom an extremely rare anomalous duplication of the common bile duct and pancreaticobiliary maljunction were diagnosed intraoperatively by meticulous surgical manipulations via conventional open surgery. By performing a dissection at the outer epicholedochal layer of the cyst, a thin cord-like structure shown to be the distal part of the common bile duct was identified. A further exploration revealed that the most distal (extra- and intrapancreatic) part of the common bile duct was duplicated, and each branch of the duct was connected to the main and accessory pancreatic ducts. The experience with our case and a literature review showed that extrahepatic bile duct duplication is generally associated with pancreaticobiliary maljunction and CBD. We conclude that an extremely careful exploration with delicate and meticulous surgical manipulation is essential to identify these morphological anomalies and prevent intraoperative and postoperative complications of CBD, such as pancreatic duct injury or pancreatitis.

Rapid immunosurveillance by recirculating lymphocytes in the rat intestine: critical role of unsulfated sialyl-Lewis X on high endothelial venules of the Peyer’s patches

Lymphocytes can transfer from blood to lymph or respond to antigen in Peyer’s patches