Orthotopic intestinal transplantation using the cuff method in rats: a histopathological evaluation of the anastomosis.

Segmental small intestine transplantation (SIT) in rats, using a cuff technique, has achieved a high success rate. However, there have been few reports on the influence of the foreign body reaction to polyethylene cuff on vessel anastomoses and graft after SIT. This study involves the histopathological examination of the site of cuff anastomosis and grafts in the short- and long-term survival of segmental SIT. The data obtained from the suture anastomosis model also served as a control. One week after heterotopic segmental SIT using the cuff technique, orthotopic continuations were carried out in syngeneic combination. Twenty-five of 30 rats surviving >200 days (83.3%) were examined for vessel anastomosis. All arterial anastomoses were patent, but the portovenous anastomoses in 10 grafts (33%) were totally occluded and were associated with the formation of collateral vessels. Histopathological examination demonstrated good patency of the artery and vein anastomotic site in the short term, but granulation, fibrosis, and neovascularization at the anastomosis site surrounding the cuffs in the long-surviving group. However, the grafts appeared to be intact, with normal features of the villi. On the contrary, the site of the sutured anastomosis in the long-survival rats showed no inflammatory reaction. Although a polyethylene cuff caused foreign body reaction, the graft blood supplies were maintained by collateral vessels. Considering the low mortality and high success rate, polyethylene cuff is good for short-term study and an alternative method for long-term SIT experiments.     

Merits and Demerits of Operative Procedure to the Trachea in Patients with Differentiated Thyroid Cancer

Local radical thyroidectomy, including cervical lymph node dissection and combined circumferential resection of the trachea, has been performed over the past 20 years in 31 patients with differentiated cancer invading the trachea. The 5- and 10-year survival rates for these patients were 77.4% and 66.7%, respectively. In 19 of the 31 (61%) cases the recurrent nerve was resected because of direct cancer invasion. Bilateral recurrent nerve palsy occurred in 12 patients, 3 of whom were managed postoperatively using a T-shaped tube for preservation of the larynx. Hoarseness remained in 21 patients. In two patients with recurrent cancer invasion of the larynx, partial laryngectomy and hemilaryngectomy were performed, and reconstruction was done using ear cartilage without postoperative dyspnea or dysphagia. Parathyroid function is an important factor in regard to the quality of life of patients. In 22 patients at least one of the parathyroids was preserved. Postoperative calcium administration was necessary in 14 patients. Our long-term observations indicate that local radical thyroidectomy with combined resection of the trachea can serve as a useful treatment for advanced differentiated cancer invading the airway.     

Long-term follow-up of 5 patients with intracranial germinoma initially treated by chemotherapy alone

Summary Background. High rates of overall- and event-free survival have been reported in patients with intracranial germinoma treated by radiotherapy. We report the long-term results after treatment initially with chemotherapy, but without radiation. Patients and method. Five patients with an intracranial germinoma were treated with 2 cycles of etoposide and cisplatin, without radiotherapy. All achieved complete remission; 3 suffered recurrence within 2 years and were again treated with 2 cycles of etoposide and cisplatin followed by radiotherapy. Results. At long-term follow-up, each of the 5 patients was in complete remission without further recurrence. Each patient with a neurohypophyseal germinoma who presented with endocrinopathy had initially recovered endocrinological function. Conclusion. In a patient with a germinoma chemotherapy, and restriction of radiation to those with recurrence may allow restoration of hypophyseal function damaged by the intracranial germinoma without compromising long term survivial.     

Radiographic characteristics of fibrous dysplasia of the clivus: a case report and review of the literature

Whereas fibrous dysplasia is a well-known, developmental skeletal disorder with a benign clinical course, fibrous dysplasia of the clivus is extremely rare and has seldom been reported. Differentiating this benign entity from more aggressive diseases involving the clivus is important for the proper management of lesions in this area. We here report a case of fibrous dysplasia of the clivus and discuss its radiographic features. The patient was 55-year-old male who had suffered from headache for months. Physical and neurological examinations found no abnormalities. The computed tomographic (CT) scan and magnetic resonance imaging (MRI) showed an abnormal mass lesion in the lower of the third clivus. On CT scan, the mass lesion exhibited a ground-glass appearance. The lesion was detected as hypointense and a mixture of hyperintense and isointense areas on T1-weighted and T2-weighted MRI, respectively. Heterogenous enhancement was noted after infusion of GD-DTPA. The patient underwent a transsphenoidal resection of the mass and the histopathologic diagnosis was fibrous dysplasia.     

Endogenous endotoxin participates in causing a panenteric inflammatory ileus after colonic surgery

OBJECTIVE: To investigate muscularis inflammation and endogenous endotoxin as causes of postoperative ileus. BACKGROUND: Postoperative inflammatory ileus of the colon is associated with a significant delay in gastrointestinal transit. We investigated whether these changes are caused by the downstream obstructive barrier of the surgically altered colon or by small intestinal muscularis inflammation itself. Furthermore, we evaluated the mechanistic role of gut derived endotoxin in the development of postoperative intestinal dysfunction. METHODS: Rats underwent surgical manipulation of the colon. Isolated gastrointestinal transit was analyzed in animals with ileostomy. The perioperative emigration of intracolonic particles was investigated by colonic luminal injection of fluorescently labeled LPS and microspheres. Mediator mRNA induction was quantified by real-time RT-PCR. Muscularis leukocytic infiltrates were characterized. In vitro circular muscle contractility was assessed in a standard organ bath. RESULTS: Ileostomy rats presented with a significant delay in small intestinal transit after colonic manipulation. This was associated with leukocyte recruitment and inflammatory mediator mRNA induction within the small intestinal muscularis. Colonic manipulation caused the transference of intracolonic LPS and microspheres into the intestinal muscularis. Postoperative in vitro small intestinal circular muscle contractility was impaired by 42% compared with controls. Gut decontamination and TLR-4 deletion significantly alleviated the small intestinal muscularis inflammation and prevented intestinal muscle dysfunction. CONCLUSIONS: Selective colonic manipulation initiates a distant inflammatory response in the small intestinal muscularis that contributes to postoperative ileus. The data provide evidence that gut-derived bacterial products are mechanistically involved in the initiation of this remote inflammatory cascade.     

Risk factors of the progression of abdominal aortic calcification in patients on chronic haemodialysis

Background. Vascular calcification is an independent determinantof cardiovascular events in maintenance haemodialysis (HD) patients.It is not known whether acute changes of the serum calcium concentrationbefore and after HD (Ca) are associated with the developmentof aortic calcification. Methods. We enrolled 71 patients dialysed with a dialysate with3.0 mEq/l calcium and determined their aortic calcificationindex (ACI) by abdominal computed tomography twice at an intervalof 3 years. To identify the factors contributing to the rateof progression of aortic calcification, we analysed the averagevalues for clinical and laboratory data obtained between thefirst and second evaluations of ACI. Results. The second ACI (mean ± SD: 80.2 ± 63.9)was significantly greater than the first ACI (61.0 ±61.0) after an interval of 35.8 ± 4.2 months. The annualizedchange of ACI (ACI/year) was significantly and directly associatedwith the Ca and C-reactive protein (CRP) (both P < 0.001,P for trend). Stepwise multivariate regression analysis revealedthat ACI/year was positively and independently associated withCRP, presence of diabetes mellitus and Ca, but negatively associatedwith a premenopausal status in women. Similarly, Ca was positivelyand independently associated with ACI/year and the ultrafiltrationrate, but was negatively associated with pre-HD Ca. Conclusion. The increase of serum calcium after HD was relatedto the rate of progression of aortic calcification. Excess calciumis transferred into patients on HD when using a dialysate of3.0 mEq/l calcium. This may be a risk factor for the developmentof vascular calcification.     

Surgical outcomes of partial nephrectomy for renal cell carcinoma: A joint study by the Japanese Society of Renal Cancer

OBJECTIVE: A joint study was undertaken by the Japanese Society of Renal Cancer to investigate the present status of partial nephrectomy in Japan and to speculate about what may be the indications for partial nephrectomy in patients with renal cell carcinoma. METHODS: Data were tabulated for 469 patients from participating medical institutions and various clinical factors were investigated with regard to disease progression (local recurrence and distant metastasis). RESULTS: Disease progression was observed in 21 patients (4.5%). No significant relation to disease progression was observed for sex, laterality, tumor histology, grade and tumor size. Although patients with solitary tumors displayed excellent prognosis irrespective of tumor diameter, patients with multiple tumors displayed a high likelihood of disease progression. Patients older than 77 years old and patients with imperative indication were found to have a poorer prognosis. CONCLUSION: In patients with solitary tumors, partial nephrectomy can be actively performed, even if the patient displays elective indications and the tumor is >4 cm in diameter. In patients displaying multiple tumors with imperative indications, the decision whether to perform partial nephrectomy should be made by the patients and their physicians after considering the impact on curability and the quality of life.     

Regeneration of defects in articular cartilage in rat knee joints by CCN2 (connective tissue growth factor).

CTGF/CCN2, a hypertrophic chondrocyte-specific gene product, possessed the ability to repair damaged articular cartilage in two animal models, which were experimental osteoarthritis and full-thickness defects of articular cartilage. These findings suggest that CTGF/CCN2 may be useful in regeneration of articular cartilage. INTRODUCTION: Connective tissue growth factor (CTGF)/CCN2 is a unique growth factor that stimulates the proliferation and differentiation, but not hypertrophy, of articular chondrocytes in vitro. The objective of this study was to investigate the therapeutic use of CTGF/CCN2. MATERIALS AND METHODS: The effects of recombinant CTGF/CCN2 (rCTGF/CCN2) on repair of damaged cartilage were evaluated by using both the monoiodoacetic acid (MIA)-induced experimental rat osteoarthritis (OA) model and full-thickness defects of rat articular cartilage in vivo. RESULTS: In the MIA-induced OA model, quantitative real-time RT-PCR assays showed a significant increase in the level of CTGF/CCN2 mRNA, and immunohistochemical analysis and in situ hybridization revealed that the clustered chondrocytes, in which clustering indicates an attempt to repair the damaged cartilage, produced CTGF/CCN2. Therefore, CTGF/CCN2 was suspected to play critical roles in cartilage repair. In fact, a single injection of rCTGF/CCN2 incorporated in gelatin hydrogel (rCTGF/CCN2-hydrogel) into the joint cavity of MIA-induced OA model rats repaired their articular cartilage to the extent that it became histologically similar to normal articular cartilage. Next, to examine the effect of rCTGF/CCN2 on the repair of articular cartilage, we created defects (2 mm in diameter) on the surface of articular cartilage in situ and implanted rCTGF/CCN2-hydrogel or PBS-hydrogel therein with collagen sponge. In the group implanted with rCTGF/CCN2-hydrogel collagen, new cartilage filled the defect 4 weeks postoperatively. In contrast, only soft tissue repair occurred when the PBS-hydrogel collagen was implanted. Consistent with these in vivo effects, rCTGF/CCN2 enhanced type II collagen and aggrecan mRNA expression in mouse bone marrow-derived stromal cells and induced chondrogenesis in vitro. CONCLUSION: These findings suggest the utility of CTGF/CCN2 in the regeneration of articular cartilage.     

Protective effect of carbon monoxide for organ injury

Heme oxygenase (HO) catabolizes heme into three products: carbon monoxide (CO), biliverdin and free iron. HO-1, inducible form of HO, has been shown to be protective against various stress. CO at a low concentration has been shown to be protective in several disease models mimicking the action of HO-1. We suggest that CO, the byproduct of heme degradation, could be valuable therapeutic agents. We review the functional role of HO-1 and CO and its potential application to clinical settings.     

Release of gastric inhibitory polypeptide in totally pancreatectomized patients

The role of insulin in controlling gastric inhibitory polypeptide (GIP) release was assessed in seven totally pancreatectomized patients, in whom inhibitory effects of endogenous pancreatic hormones on GIP secretion were excluded. In these patients, glucose was ingested on two occasions, once alone and once during insulin infusion using an artificial endocrine pancreas to maintain blood glucose at levels similar to those in normal subjects. Plasma levels of GIP, the maximum response of plasma GIP, and the integrated incremental GIP for 180 min were similar. We conclude that insulin does not alter the secretion of GIP in response to oral glucose when the influence of endogenous pancreatic hormones is excluded.