Selection of pancreaticojejunostomy techniques according to pancreatic texture and duct size

HYPOTHESIS: Selection of proper pancreaticojejunostomy techniques according to pancreatic texture and the main duct size reduces the pancreatic fistula rate. DESIGN AND PATIENTS: Data from 50 consecutive patients undergoing pancreatoduodenectomy with 3 different anastomotic techniques prospectively used according to pancreatic texture and the main duct size were analyzed. Duct-invagination anastomosis was selected for pancreata with a small duct (n = 34 [29 with a soft texture and 5 with a hard texture]). Stitches between the stump parenchyma and the jejunal seromuscular layer were added to this anastomosis procedure only for the hard pancreata. Pancreata with a large duct were reconstructed with a conventional duct-to-mucosa anastomosis (n = 16). SETTING: A university hospital department of digestive surgery. RESULTS: The morbidity was 40% (20 of 50 patients) in this series. Four patients (8%) with a soft pancreas and a small duct developed a pancreatic stump leak after duct-invagination anastomosis, but all of them were removed without sequelae. No pancreatic anastomotic leak was seen in this series, which resulted in no mortality, no remnant pancreatectomy, and only 1 relaparotomy in the consecutive 50 patients. CONCLUSION: The proper selection of pancreatic reconstruction techniques according to our criteria may reduce the pancreatic fistula rate, eliminate risky pancreatic anastomotic leaks, and result in excellent outcomes for those undergoing pancreatoduodenectomy.     

Antitumor effect of TAT-oxygen-dependent degradation-caspase-3 fusion protein specifically stabilized and activated in hypoxic tumor cells

Human solid tumors contain hypoxic regions that have considerably lower oxygen tension than normal tissues. These impart resistance to radiotherapy and anticancer chemotherapy, as well as predisposing to increased tumor metastases. To develop a potentially therapeutic protein drug highly specific for solid tumors, we constructed fusion proteins selectively stabilized in hypoxic tumor cells. A model fusion protein, oxygen-dependent degradation (ODD)-beta-galactosidase (beta-Gal), composed of a part of the ODD domain of hypoxia-inducible factor-1alpha fused to beta-Gal, showed increased stability in cultured cells under a hypoxia-mimic condition. When ODD-beta-Gal was further fused to the HIV-TAT protein transduction domain (TAT(47-57)) and i.p. injected to a tumor-bearing mouse, the biologically active fusion protein was specifically stabilized in solid tumors but was hardly detected in the normal tissue. Furthermore, when wild-type (WT) caspase-3 (Casp3(WT)) or its catalytically inactive mutant was fused to TAT-ODD and i.p. injected to a tumor-bearing mouse, the size of tumors was reduced by the administration of TAT-ODD-Casp3(WT) but not by TAT-ODD-mutant Casp3. TAT-ODD-Casp3(WT) did not cause any obvious side effects on tumor-bearing mice, suggesting specific stabilization and activation of the fusion protein in the hypoxic tumor cells. These results suggest that the combination of protein therapy using a cytotoxic TAT-ODD fusion protein with radiotherapy and chemotherapy may provide a new strategy for annihilating solid tumors.     

Electrical connection between left superior and inferior pulmonary veins in a patient with paroxysmal atrial fibrillation

We report the case of a patient with paroxysmal atrial fibrillation, who underwent pulmonary vein (PV) electrical isolation from the left atrium (LA). Prior to achieving isolation of the left superior PV (LSPV) from the LA, earlier PV potentials were recorded inside the left inferior PV (LIPV) than LA activity during pacing at the distal LSPV. The LSPV finally was isolated by radiofrequency applications at the ostium of the LIPV. The patient had electrical connection between the LSPV and LIPV, and required radiofrequency ablation of the breakthroughs from the LA to LIPV for complete isolation of the LSPV.     

Oral L-arginine prevents murine coxsackievirus B3 myocarditis

We have previously demonstrated that administration of nitric oxide (NO) synthase inhibitor, N(G)-nitro-L-arginine methyl ester (L-NAME), aggravated murine coxsackievirus B3 myocarditis. In the present study, we evaluated the effects of L-arginine, a precursor of NO, upon acute and chronic myocarditis. Dietary L-arginine and L-arginine plus L-NAME (L-arginine+L-NAME group) were administered to coxsackievirus B3 (CB3)-infected C(3)H/He mice for 2 weeks (experiment I), and to CB3-infected mice from the second week until the fourth week after virus inoculation (experiment II). Infected control was prepared in each experiment. In experiment I, survival was higher in the L-arginine group compared with the other two groups, and cardiac damage was less. In addition, plasma concentrations of L-arginine and NO were elevated in the L-arginine group. In experiment II, cardiomyopathic lesion in the L-arginine group was less prominent associated with lower plasma catecholamine and lower myocardial collagen concentrations compared with the other two groups. Thus, L-arginine treatment may be effective not only in preventing the development of acute CB3 myocarditis but in ameliorating cardiac dysfunction in chronic myocarditis.     

Report on the 13th European Congress of Radiology (ECR): Comparison of primary proton beams and secondary charged-particles

PURPOSE: In the proton radiotherapy, primary proton beams contribute to the absorbed dose and the share of secondary charged-particles is small. The purpose is to discuss about the ratio of average dose of primary proton beams and secondary charged-particles. METHODS: We performed the dosimetry of 70 MeV proton beams in water using ionization chamber. The ratio of average dose for secondary charged-particles in some range shifter was calculated by the dose ratio of primary and scatter. To exclude the influence of lateral secondary charged-particles, the ratio of average dose for secondary charged-particles was extrapolated to zero field size of each. RESULTS: The ratio of average dose for secondary charged-particles was extrapolated to zero field size by the bi-exponential fit. The ratio of average dose for longitudinal secondary charged-particles for zero fields at each depth is almost the same; the different at the shallow depth is decreased. CONCLUSIONS: The secondary charged-particles from collimator is affected by the dose of shallow depth. The influence of lateral secondary charged-particles in water phantom was excluded with the extrapolation method for zero field size in each depth.     

Prevalence of FOXP3+ regulatory T cells increases during the progression of pancreatic ductal adenocarcinoma and its premalignant lesions.

PURPOSE: Antitumor immune response changes drastically during the progression of cancers. Established cancers often escape from the host immune system, although specific immune surveillance operates in the early stages of tumorigenesis in murine models. CD4+CD25+ regulatory T cells (TR) play a central role in self-tolerance and suppress effective antitumor immune responses. The aim of this study was to investigate the clinical significance and roles of TR in the progression and multistep carcinogenesis of pancreatic ductal adenocarcinoma. EXPERIMENTAL DESIGN: We raised anti-FOXP3 antibodies and used them in immunohistochemical studies of the prevalence of FOXP3+CD4+CD25+ TR in the CD4+ T cells, which infiltrated in tissue and draining lymph nodes of 198 pancreatic ductal adenocarcinomas, their premalignant lesions (84 lesions of pancreatic intraepithelial neoplasias and 51 intraductal papillary-mucinous neoplasms), and 15 nonneoplastic pancreatic lesions. RESULTS: The prevalence of TR was significantly increased in the ductal adenocarcinomas compared with that in the stroma of nonneoplastic inflammation (P<0.0001). The increased prevalence of T(R) was significantly correlated with certain clinicopathologic factors. A better prognosis was observed in patients with a low prevalence of T(R), and this was independent of other survival factors (P<0.0001). Infiltration of intraepithelial CD8+TIA-1+ cytotoxic T cells in pancreatic ducts was marked in low-grade premalignant lesions but diminished during the progression of both pancreatic intraepithelial neoplasias and intraductal papillary-mucinous neoplasms. Conversely, the prevalence of TR increased significantly during the progression of premalignant lesions. CONCLUSIONS: T(R) play a role in controlling the immune response against pancreatic ductal carcinoma from the premalignant stage to established cancer. In pancreatic ductal carcinoma, a high prevalence of TR seems to be a marker of poor prognosis.     

Dysregulation of IL-13 production by cord blood CD4+ T cells is associated with the subsequent development of atopic disease in infants.

Early intervention strategies in allergic diseases will be dependent on identification of newborns at high risk for later development of atopic disease. In this cohort study of 106 neonates, we investigated whether cytokine production property and responsiveness to IL-12 of neonatal CD4(+) T cells were associated with the subsequent development of atopic disease and whether a skewed cytokine production property was intrinsic to helper T cells. To exclude the effects of contaminating cells, highly purified cord blood CD4(+) T cells were stimulated with anti-CD3 MAb and recombinant B7-2 molecule in the presence or absence of IL-12. Production of IL-13 and interferon-gamma was determined by ELISA. The infants were assessed at 12 mo for the development of atopic diseases. CD4(+) T cells of neonates who manifested allergic symptoms (atopic group) produced higher levels of IL-13 compared with those of the nonatopic group in both the presence and absence of IL-12. No significant difference was noted between the two groups with respect to interferon-gamma production. Moreover, higher IL-13 production was also observed in neonates with chronic eczema than those with short-term eczema. Our data suggest that increased production of IL-13 by neonatal CD4(+) T cells is a useful marker of newborns at high risk for subsequent development of atopic diseases and that an intrinsic abnormality of CD4(+) T cell is associated with the pathogeneses of atopic disease, especially atopic dermatitis in infants.     

The prognostic significance of RCAS1 expression in squamous cell carcinoma of the oesophagus.

Overexpression of RCAS1 (receptor-binding cancer antigen expressed on SiSo cells) protects cancer cells from immune attack and might be related to poor prognosis in several cancers. We investigated the immunoreactivity of RCAS1 and its correlation with clinicopathological features in 95 patients who underwent surgical resection for oesophageal squamous cell carcinoma. Thirty-two of the 95 (33.7%) cases were strongly positive for RCAS1. RCAS1 showed significant correlations with age and stage grouping. Expression of RCAS1 was associated with shorter postoperative survival. Multivariate analysis indicated that RCAS1 positivity was an independent negative prognostic factor. Our study establishes RCAS1 as a novel prognostic marker for surgically resected oesophageal squamous cell carcinoma.     

Vascular encasement by pancreatic cancer: correlation of CT findings with surgical and pathologic results

PURPOSE: The purpose of this study was to correlate thin-slice high-resolution helical CT findings of arterial and venous involvement in pancreatic cancers with surgical and histopathologic results. METHOD: Forty-eight patients with pancreatic cancer underwent preoperative thin-slice high-resolution helical CT, followed by surgical dissection of the pancreatic vessels during curative or palliative surgery. Major vessels running within 1 cm from the tumor margin were evaluated. CT appearance was graded on a 0-4 scale (0: none, 1: <24%, 2: 25-49%, 3: 50-74%, 4: 75-100%) by circumferential contiguity of tumor to vessels. Resected specimens were available from 26 patients. RESULTS: Surgical correlation of CT findings was available in 89 veins and 83 arteries, and both surgical and histologic correlation was available for 42 veins and 29 arteries. At surgical observation, 29 of 35 veins (82.9%) evaluated as CT grade 3 or 4 were found to be involved, whereas only 18 of 30 arteries (60%) evaluated as CT grade 3 or 4 were proved to be involved. On microscopic observation, tumor invasion to the portal venous systems was confirmed in 15 of 42 (35.7%) vessels, and this invasion was depicted as from CT grades 1 to 4. In arteries, tumor invasion was seen in 3 of 29 vessels (10.3%), all of which were graded as 3 or 4 by CT. CONCLUSION: The grading system of vascular invasion should differ between arteries and veins. Involvement of the venous system exceeding one-half circumference of the vessels (grade 3 or 4) was suggestive of vascular invasion; however, this criterion was not always satisfactory for the evaluation of tumor invasion in the arterial system.