Fas and its ligand in a general mechanism of T-cell-mediated cytotoxicity.

To investigate the mechanisms of T-cell-mediated cytotoxicity, we estimated the involvement of apoptosis-inducing Fas molecule on the target cells and its ligand on the effector cells. When redirected by ConA or anti-CD3 monoclonal antibody, a CD4+ T-cell clone, BK1, could lyse the target cells expressing wild-type Fas molecule but not those expressing death signaling-deficient mutants. This indicates the involvement of Fas-mediated signal transduction in the target cell lysis by BK1. Anti-CD3-activated but not resting BK1 expressed Fas ligand as detected by binding of a soluble Fas-Ig fusion protein, and the BK1-mediated cytotoxicity was blocked by the addition of Fas-Ig, implicating the inducible Fas ligand in the BK1 cytotoxicity. Ability to exert the Fas-mediated cytotoxicity was not confined to BK1, but splenic CD4+ T cells and, to a lesser extent, CD8+ T cells could also exert the Fas-dependent target cell lysis. This indicates that the Fas-mediated target cell lytic pathway can be generally involved in the T-cell-mediated cytotoxicity. Interestingly, CD4+ T cells prepared from gld/gld mice did not mediate the Fas-mediated cytotoxicity, indicating defective expression of functional Fas ligand in gld mice.     

Assessment of left ventricular function before and after Fontan's operation for the correction of tricuspid atresia

Functional change in the left ventricle was studied in the light of changes in the left ventricular (LV) volume preload before and after Fontan's operation. Six cases with tricuspid atresia (TA) were studied, and they had either types Ib or IIb. The preoperative LV end-diastolic volume index (LVEDVI) was 123 +/- 44 ml/m2, which corresponds to 166% +/- 45% of normal values. This suggests that in TA the preload of the LV volume is increased because of its peculiar hemodynamic situation. After Fontan's operation, the LVEDV decreased by 24.6% to 119.6 +/- 87.7 ml (P = 0.01), which corresponds to 120% +/- 50.9% of normal values. Presenting a striking contrast to the decrease in LVEDV, the postoperative reduction in LV end-systolic volume (LVESV) was approximately 8%. Preoperative and postoperative values for LVESV were 67.1 +/- 50.8 ml and 62 +/- 45.6 ml, thus, the systolic volume was decreased. Because of the small change in LVESV, the ejection fraction (EF) of the left ventricle significantly decreased from 0.61 +/- 0.1 preoperatively to 0.48 +/- 0.1 postoperatively. The cardiac index (CI) remained in the range of 1.9-2.5 l/min/m2 with a mean of 2.2 +/- 0.2 l/min/m2 at 1 month after operation. But, later, improvement in EF was observed in one case, in which the CI increased from 2.5 to 3.2 l/min/m2.(ABSTRACT TRUNCATED AT 250 WORDS)     

Case series of endoscopic balloon dilation to treat a stricture caused by circumferential resection of the gastric antrum by endoscopic submucosal dissection

BACKGROUND: Endoscopic submucosal dissection (ESD) plays an important role in the management of gastric neoplasms. There are few reports regarding stricture development caused by ESD of gastric neoplasms. OBJECTIVE: The present study aimed to determine the incidence of gastric stricture formation after ESD of gastric neoplasms and to report on the outcome and management of this complication: endoscopic intervention (ie, balloon dilation) versus surgery; the outcome of balloon dilation (success or failure/perforation). DESIGN: A case series from a retrospective review of gastric ESDs performed at Saga Medical School over a defined period of time. SETTING: Double-center territory, referral hospital. PATIENTS: An evaluation was performed in 532 patients with gastric mucosal tumors treated by ESD. A stricture was reported in 5 patients. All the 5 cases were located in the antrum. ESD that was performed in the cardia or the proximal stomach did not induce a stricture. RESULTS: Of the 5 cases of symptomatic gastric outlet obstruction, 1 patient required surgical intervention because of a near total gastric outlet obstruction not amenable to endoscopic intervention. The 4 patients underwent step-serial through-the-scope balloon dilations; in 2 patients, the procedure was successful, but in the other 2 patients, the procedure was complicated by a gastric perforation (50% incidence of perforation). LIMITATION: A retrospective study. CONCLUSIONS: Circumferential or subcircumferential resection by ESD in the antrum caused a stricture. Balloon dilation of the ESD gastric outlet obstruction might be a choice, but it is a risky treatment.     

Association between Ala54Thr substitution of the fatty acid-binding protein 2 gene with insulin resistance and intra-abdominal fat thickness in Japanese men

Summary Alanine to threonine substitution at codon 54 of the fatty acid-binding protein 2 (FABP2) gene was recently shown to be associated with insulin resistance in Pima Indians. It has been hypothesized that the mutation may result in enhanced intestinal uptake of fatty acids, and thereby an impairment of insulin action. We analysed the association of the Ala54Thr substitution with insulin sensitivity and abdominal fat thickness in 395 Japanese men aged 50.5 ± 8.8 years (mean ± SD) with a body mass index of 24.4 ± 3.0 kg/m². The frequency of the Thr54 allele was 0.34. Although the polymorphism was not significantly associated with diabetes or impaired glucose tolerance, subjects homozygous for the Thr54 allele had higher basal insulin levels. Analysis by homeostasis model assessment showed an association between the amino acid substitution and greater insulin resistance, and slightly higher beta-cell function. Oral glucose tolerance tests performed in 392 subjects without fasting hyperglycaemia showed higher 2-h insulin concentrations in individuals homozygous for the Thr54 allele when compared with heterozygotes or homozygotes for the Ala54 allele. No significant association was obtained between the polymorphism of the FABP2 gene and body mass index. However, ultrasound measurements of abdominal fat thickness revealed a greater accumulation of intra-abdominal fat in subjects homozygous for the Thr54 allele, whereas subcutaneous fat thickness was not associated with the polymorphism. These observations suggest that the Ala54Thr substitution in the FABP2 gene is associated with insulin resistance in Japanese men, and that visceral fat accumulation might be involved in the impaired insulin action associated with the substitution. [Diabetologia (1997) 40: 706–710] Received: 30 December 1996 and in revised form: 10 March 1997     

STR and mitochondrial DNA SNP typing of a bone marrow transplant recipient after death in a fire

Personal identification of a house fire victim is described. About 5 years prior to death, the victim had been underwent bone marrow transplantation (BMT) with a graft from an unrelated donor as treatment for acute myelogenous leukemia. Clinically, the victim had been in remission at the time of death. Typing of STRs and sequencing of mitochondrial DNA (mtDNA) were performed using blood from the heart as well as several soft (psoas major muscle, uterine muscle and mucous membrane of the urinary bladder) and hard (costal cartilage and nail) tissues. STR genotypes and amelogenin from each of the tissue samples were successfully typed, and the parentage was identified. The blood STR types demonstrated no relationship with those from other tissues. None of the blood STR loci showed extra peaks arising from those of the recipient. Therefore, the blood stem cells were assumed to have been altered to those of the donor. The genotypes of mtDNA control regions were also examined. The electropherogram of hypervariable region II (nucleotide positions 29-408) obtained from the blood revealed a similar length heteroplasmy, suggesting microchimerism of the blood. Sequence analysis of mtDNA might be applicable as a more sensitive method for determination of chimerisms after BMT.     

Selective bladder-sparing protocol consisting of induction low-dose chemoradiotherapy plus partial cystectomy with pelvic lymph node dissection against muscle-invasive bladder cancer: oncological outcomes of the initial 46 patients

Study Type – Therapy (case series) Level of Evidence 4 What's known on the subject? and What does the study add? TURBT plus full‐dose chemoradiotherapy (CRT) against MIBC allow more than 40% of patients to spare the bladder while maintaining survival outcomes comparable to those of radical cystectomy (RC) series, contributing to improvement of the patients’ quality of life. Limitations of these protocols, however, include 1) MIBC recurrence in the preserved bladder mainly due to subclinical residual disease in the original MIBC site, 2) potential lack of curative intervention to regional lymph nodes and 3) increased mortality of salvage RC due to previous high‐dose pelvic irradiation. We propose a novel selective bladder‐sparing protocol consisting of induction low‐dose CRT plus consolidative partial cystectomy with pelvic lymph node dissection, which potentially contributes to overcoming the limitations of the conventional bladder‐sparing protocols.

OBJECTIVE

• ? To evaluate oncological outcomes of muscle‐invasive bladder cancer (MIBC) patients who were treated with a selective bladder‐sparing protocol consisting of induction low‐dose chemoradiotherapy (LCRT) plus partial cystectomy (PC) with pelvic lymph node dissection.

PATIENTS AND METHODS

• ? From 1997–2010, 183 consecutive patients with cT2–4aN0M0 bladder cancer (median age 70 years, women/men = 46/137, T2/3/4a = 100/69/14) underwent debulking transurethral resection followed by LCRT (radiation at 40 Gy to the small pelvis concurrently with two cycles of i.v. cisplatin at 20 mg/day for 5 days).
• ? Criteria for PC include: (i) essentially solitary MIBC or intravesically circumscribed tumours (≈25% or less of the bladder in area, excluding the bladder neck and trigone); (ii) no involvement of bladder neck or trigone; and (iii) clinically, no residual disease or minimal amounts of non‐invasive disease in the original MIBC site after LCRT; otherwise, radical cystectomy (RC) is recommended.
• ? Primary and secondary endpoints were cancer‐specific survival (CSS) and intravesical MIBC recurrence‐free survival (MRFS) for bladder‐preserved patients, respectively.

RESULTS

• ? Of the 183 patients, 87 (48%) achieved a clinical complete response after LCRT and 65 (36%) met the PC criteria; 46 (25%) patients actually underwent PC, 86 (47%) had RC, and the remaining 51 (28%) had neither PC, nor RC.
• ? Histological examination of the 46 PC specimens showed residual muscle‐invasive disease in three (7%).
• ? Overall, 5‐year overall survival and CSS rates were 64% and 71%, respectively (median follow‐up for survivors of 45 months).
• ? In the 46 PC patients, neither MIBC, nor pelvic recurrence was observed; 5‐year CSS and MRFS rates were both 100%.
• ? In 13 non‐PC patients who achieved a complete response after LCRT and who met PC criteria but declined PC, 5‐year CSS and MRFS rates were 74% and 81%, respectively; CSS and MRFS were significantly better in the PC group than in the non‐PC group (P= 0.025 and 0.002, respectively).

CONCLUSIONS

• ? In the current selective bladder‐sparing protocol, one‐third of MIBC patients met the PC criteria; when patients from this group underwent PC with pelvic lymph node dissection, their oncological outcomes were excellent.
• ? Consolidative PC potentially reduces MIBC recurrence in the preserved bladder, eventually improving survival in properly selected MIBC patients.

     

Indications for and surgical complications of rotationplasty

BackgroundRotationplasty is one treatment option for femoral bone sarcomas in skeletally immature patients. This procedure can also be used to save failed limb salvage procedures such as infected prostheses and failed bone grafts in adults. Rotationplasty is only rarely indicated, and the surgical complications and risk factors for failure of the procedure that might influence the treatment or patient choices have not been well described.MethodsWe retrospectively reviewed 19 patients who underwent rotationplasty focusing on surgical indications, surgical procedures such as the type of rotationplasty, and whether vessels were sacrificed and reconstructed with vascular anastomosis or preserved. Risk factors for failure of rotationplasty were categorized into either early or late postoperative complications.ResultsThirteen of 19 rotationplasties were done for patients diagnosed with primary sarcoma, 3 patients for unplanned excisions of sarcomas, and 3 patients for infection. Two of 19 patients did not have sufficient circulation resulting in amputation. Six of 19 patients underwent vascular anastomoses, and all of these anastomoses were successful. Three patients had multiple operations for infection before rotationplasty, and one patient’s treatment failed so an amputation was required. As late complications, one patient had delayed bone union and one had postoperative infection that healed after removal of plate fixation. Two patients had malrotation of the tibia that resolved with revision surgery. One patient had a skin ulcer that healed with conservative treatment. One patient who had an unplanned excision had a hemipelvectomy for non-union 11 months after rotationplasty.ConclusionsRotationplasty was successfully accomplished in 16 of the 19 patients (84 %) with sarcomas, unplanned excision of sarcomas or infection. Vascular anastomosis did not increase the risk of rotationplasty failure in our series. Patients appeared to have a higher risk of failure of rotationplasty after multiple operations, possibly because of inflammation around the vessels. The surgeon should be aware of the higher potential risk and consider vascular anastomosis for these patients.