Venous superdrained gastric tube pull-up procedure for hypopharyngeal and cervical esophageal reconstruction reduces postoperative anastomotic leakage and stricture.

Gastric pull-up is a common procedure to reconstruct the continuity of the upper digestive tract after esophageal resection. However, this technique sometimes causes postoperative anastomotic leakage or stricture, resulting from insufficient blood flow at the distal end. To overcome this problem, additional microvascular venous anastomoses were performed. The purpose of this study was to compare the outcomes of post-surgical anastomotic leakage and stricture in patients with and without additional microvascular venous superdrainage after cervical esophageal and hypopharyngeal resection and gastric tube reconstruction. A total of 29 consecutive patients with esophageal or hypopharyngeal cancer who underwent total esophagectomy and hypopharyngectomy with gastric tube reconstruction in the National Organization Nagasaki Medical Center between April 2014 and May 2016 were analyzed in this study. Of these patients, 20 underwent additional venous anastomoses (superdrainage group), and 9 did not undergo additional procedures (standard group). We compared the frequency of post-surgical stricture and leakage in the two groups retrospectively. Three of nine patients (33.3%) developed postoperative leakage in the standard group, and 1 of 20 (5.0%) did so in the superdrainage group. Six of nine patients (66.7%) showed postoperative anastomotic stricture in the standard group, but none did so in the superdrainage group. Patients who did not undergo additional venous superdrainage were significantly more likely to develop postsurgical leakage (P < 0.05, Chi-square test) and anastomotic stricture (P < 0.001, Chi-square test). Our study revealed that only additional venous anastomoses could reduce the incidence of postoperative anastomotic leakage and stricture. This procedure is of merit to perform after total esophagectomy and hypopharyngectomy with gastric tube reconstruction.

Neural correlates of ticklishness in the rat somatosensory cortex.

Rats emit ultrasonic vocalizations in response to tickling by humans. Tickling is rewarding through dopaminergic mechanisms, but the function and neural correlates of ticklishness are unknown. We confirmed that tickling of rats evoked vocalizations, approach, and unsolicited jumps (Freudensprünge). Recordings in the trunk region of the rat somatosensory cortex showed intense tickling-evoked activity in most neurons, whereas a minority of cells were suppressed by tickling. Tickling responses predicted nontactile neural responses to play behaviors, which suggests a neuronal link between tickling and play. Anxiogenic conditions suppressed tickling-evoked vocalizations and trunk cortex activity. Deep-layer trunk cortex neurons discharged during vocalizations, and deep-layer microstimulation evoked vocalizations. Our findings provide evidence for deep-layer trunk cortex activity as a neural correlate of ticklishness.

Comparative study between propofol in a long-chain triglyceride and propofol in a medium/long-chain triglyceride during sedation with target-controlled infusion.

This study was performed to compare the pharmacological characteristics of propofol in an emulsion of both medium- and long-chain triglycerides (MCT/LCT) with those of propofol in an LCT emulsion, by measuring the sedative level and the plasma concentration of propofol during sedation using a target-controlled infusion (TCI) technique. Forty ASA 1 or 2 adult patients who required spinal anaesthesia for surgery were enrolled in this study. The patients were divided into two groups: a propofol LCT group (n = 20) and a propofol MCT/LCT group (n = 20). Propofol was injected intravenously at target blood concentrations of 2.0, 3.0 and 4.0 microg x ml(-1). The bispectral (BIS) index was recorded, and arterial blood was drawn to measure the actual plasma concentrations of propofol at each predicted concentration. Propofol was assayed by high-performance liquid chromatography. Propofol MCT/LCT was associated with significantly less pain than propofol LCT (P < 0.05). There were no significant differences between the two groups in BIS index or in plasma concentration of propofol at each predicted concentration. Computer-generated TCI of propofol MCT/LCT during sedation is comparable with that of propofol LCT with respect to pharmacokinetics and pharmacodynamics. The formulation of MCT/LCT has a beneficial effect with respect to less pain on injection.

Lymph node metastasis as a significant prognostic factor in gastric cancer: a multiple logistic regression analysis.

BACKGROUND: In Japan, the standard treatment policy for all potentially curable patients with gastric cancer is radical resection including extensive lymphadenectomy. This treatment strategy has been used for both early and advanced gastric cancers, and substantial increases in survival time have been reported. In advanced gastric cancer, lymphatic spread is reported to be one of the most relevant prognostic factors for gastric cancer resected for cure. The purpose of this study was to determine the factors affecting lymph node involvement and to establish guidelines for the extent of lymph node dissection most appropriate for the treatment of gastric cancer. METHODS: The clinicopathological features of 926 patients with gastric cancer were reviewed. Information on the clinicopathological features was obtained from the database of gastric cancer at the Department of Gastroenterological Surgery, Sendai National Hospital. Univariate and multivariate analyses of data for patients with gastric cancer tumors were performed to evaluate the prognostic significance of clinicopathological features. The independent risk factors influencing lymph node metastasis were determined by multiple logistic regression analysis. RESULTS: The following clinicopathologic factors were found to be correlated with prognosis of gastric cancer: (1) macroscopic type, (2) depth of invasion, (3) cancer-stromal relationship, (4) histological growth pattern, (5) lymph node involvement, (6) lymphatic invasion, (7) vascular invasion and (8) tumor site. However, a multivariate analysis revealed that macroscopic type, depth of invasion, lymph node involvement and tumor site are independent risk factors for the prognosis of gastric cancer patients. Among these factors, the prognosis of patients with gastric cancer was most strongly influenced by lymph node involvement (odds ratio, 4.632). According to a multiple logistic regression model, depth of cancer invasion and lymphatic invasion was significantly correlated with lymph node metastases. CONCLUSIONS: Lymph node involvement has the strongest influence on the prognosis of gastric cancer. Among the clinicopathological factors, depth of invasion and microscopically lymphatic invasion are important factors in predicting lymph node metastases. Thus, the ability to perform gastrectomy with dissection of lymph nodes is a basic requirement for gastric cancer surgeons.

The role of leukocytes during acute phase inflammation in crystalline silica-induced lung injury.

Silicosis is characterized by progressive granulomatous and fibrogenic response in the lung. Inhaled crystalline silica (Qt) induces activation of pulmonary macrophages and leukocyte infiltration in the lung of Qt-treated animals. We investigated the role of leukocyte infiltration and L-selectin during the acute phase of inflammation in developing chronic lung injury in Qt-treated rats. Seventy Wistar male rats were treated with a single transtracheal instillation of Qt (25 mg/kg). Rats were treated intraperitoneally with anti L-selectin monoclonal antibody (mAb), F(ab')2 HRL-3 (HRL-3, a blocking mAb), or RF(ab')2 HRL-2 (HRL-2, a non-blocking mAb)for 4 days before and after Qt injection. Administration of HRL-3 reduced approximately 50% of leukocyte infiltration in the BAL, whereas HRL-2 treatment prior to Qt stimulation showed time-dependent increase of BAL leukocytes. CINC and GRO levels as well as peripheral blood cell counts were similar in HRL-2- or HRL-3-treated animals in the first 4 days of the study. Three months after Qt treatment, extensive granuloma-containing macrophages and leukocytes developed in the lung of the HRL-3-treated rats as compared with the HRL-2-treated rats. Ratio of CD4+ to CD8+ T cells in granulomas did not differ between the HRL-3 and HRL-2 groups. Results suggest that an early phase of leukocyte activation was diminished by blocking L-selectin with the antibody, but treatment with anti-L-selectin increased the formation of granulomas in the Qt-treated rats.

Serological diagnosis of equine influenza using the hemagglutinin protein produced in a baculovirus expression system.

The hemagglutinin (HA) protein of an equine influenza strain, A/equine/La Plata/1/93 (LP/93), was produced using a baculovirus expression system. Silkworm larvae inoculated with recombinant baculovirus expressed high quantities of the HA protein which was then purified to greater than 95% purity by fetuin-affinity chromatography. Purified HA protein was used subsequently in an ELISA for detection of antibodies in horse sera. Two hundred serum samples from vaccinated racehorses were reacted on ELISA plates coated with 40.0 ng/ml of purified HA protein. Subsequent optical density (OD) levels revealed titers which correlated highly with respective hemagglutinin inhibition (HI) antibody titers which ranged from <1:8 to 1:256 (correlation coefficient among them was 0.850). ELISA OD levels and HI titers increased at 5 and 7 days post-inoculation, respectively, in a horse inoculated intranasally with LP/93. Respective antibody levels were observed to change in an essentially parallel manner during a period of 1 month. Similarly, ELISA OD levels correlated with HI titers in horses during a period of 6 weeks following intramuscular inoculation with inactivated single-strain vaccines containing LP/93, A/equine/Kentucky/1/81 (H3N8) or A/equine/Rome/5/91 (H3N8). A similar pattern was also observed in eight horses throughout a 10-week period following inoculation with a commercially available inactivated trivalent vaccine containing A/equine/Newmarket/1/77(H7N7), A/equine/Kentucky/81 and LP/93. From these results, it is suggested that this ELISA system could be used for disease diagnosis and surveillance of HI antibody titers among vaccinated horses.

[Visual memory impairment during postpartum].

Using a visual memory test we studied memory in pregnant women. Benton's Visual Retention Test was used with 54 pregnant women three times: at term, 3-4 days post-partum, and one month after birth. There was a significant decline in visual memory at 3-4 days post-partum (p < 0.01). There was no interaction between hours of sleep and memory of pregnant women at any period. Although memory declined at 3-4 days, there was no interaction between this decline and duration of labor, intra-partum hemorrhage, or memory at one month post-partum. It is not yet clear why visual memory declined shortly after birth. Further studies on post-partum memory decline as well as the possible relationship to hormonal and mood changes are necessary.

Macrophage inflammatory protein-1alpha relates to the recruitment of inflammatory cells in myosin-induced autoimmune myocarditis in rats.

In experimental autoimmune myocarditis (EAM) there is a characteristic initial focal inflammatory response in the myocardium, induced mainly by CD4(+) T cells and macrophages, which leads to massive myocardial damage. Macrophage inflammatory protein-1alpha (MIP-1alpha) induces chemotaxis in lymphocytes, eosinophils, basophils, and macrophages. We assessed the potential role of MIP-1alpha in the pathogenesis of EAM in rats immunized with porcine myosin. Following immunization, the levels of MIP-1alpha mRNA in EAM showed an increase on Day 11 and peaked on Day 17. MIP-1alpha-positive cells were predominantly immunoreactive to OX6 antibody (dendritic cells) and ED2 antibody (resident macrophages) by Day 14. Marked cellular infiltration was seen on Day 17 with the major population of MIP-1alpha-positive cells also positive for ED1 (inflammatory macrophages). We then examined the association of MIP-1alpha with the development of myocardial inflammation. Rats were divided into three groups: Group A consisted of EAM rats (n = 10); Group B consisted of EAM rats treated with anti-MIP-1alpha (1 mg/kg) on Days 11, 13, and 15, before the onset of initial inflammation (n = 5); and Group C consisted of EAM rats treated with anti-MIP-1alpha from the start of the initial inflammation on Days 14, 16, and 18 (n = 5). Rats were euthanized on Day 21 and three transverse sections of the heart were prepared to determine the percentage of the area affected by inflammatory lesions. This area of inflammation was significantly smaller in Group B (27 +/- 4%) than in Groups A (51 +/- 6%) or C (50 +/- 6%) (p < 0.01), indicating that the administration of antibody before the initiation of inflammation, in part, will inhibit myocardial inflammation. These data suggest that MIP-1alpha may play an important role in the recruitment of inflammatory cells in the early stages of EAM.

Tenascin-C modulates adhesion of cardiomyocytes to extracellular matrix during tissue remodeling after myocardial infarction.

Tenascin-C (TNC), an extracellular matrix glycoprotein, plays important roles in tissue remodeling. TNC is not normally expressed in adults but reappears under pathologic conditions. The present study was designed to clarify the contribution of TNC to ventricular remodeling after myocardial infarction. We examined the expression of TNC after experimental myocardial infarction in the rat by immunohistochemistry and in situ hybridization. Within 24 hours of permanent coronary ligation, interstitial fibroblasts in the border zone started to express TNC mRNA. The expression of TNC was down-regulated on Day 7 and was no longer apparent by Day 14 after infarction. During the healing process, TNC protein and TNC-producing cells were found at the edges of the residual myocardium. Some of the TNC-producing cells were immunoreactive for alpha-smooth muscle actin. In culture, TNC increased the number of cardiomyocytes attached to laminin but inhibited the formation of focal contacts at costameres. The results indicate that during the acute phase after myocardial infarction, interstitial cells in the border zone synthesize TNC, which may loosen the strong adhesion of surviving cardiomyocytes to connective tissue and thereby facilitate tissue reorganization.

Primary sclerosing cholangitis successfully treated by resection of the confluence of the hepatic duct.

Primary sclerosing cholangitis (PSC) is a cholestatic disease characterized by chronic inflammatory fibrosis of the extra- and intrahepatic bile ducts. Although the prognosis of patients with PSC was believed to be poor, some patients have not experienced the expected rapid clinical progression. A 51-year-old man with PSC was initially hospitalized for jaundice. Laboratory data showed low levels of the complement components C3, C4, and CH50. Percutaneous transhepatic biliary drainage was performed. Cholangiography revealed complete obstruction of the common bile duct below the confluence of the cystic duct. The confluence of the hepatic duct was resected and it was reconstructed by hepaticojejunostomy for palliation of the obstructive jaundice. Increased thickness of the walls of the common bile duct, right hepatic bile duct, and gallbladder was observed. Histopathological examination of the resected specimen revealed periductal fibrosis, with an onion-skin-like appearance. The patient is currently doing well, approximately 7 years after the surgery, without any signs of PSC recurrence. In this extraordinary patient, the laboratory data for C3, C4, and CH50 showed a complete return to normal levels. The positive results in this patient suggest that resection of the confluence of the hepatic duct may be an effective surgical treatment for noncirrhotic PSC patients who have dominant extrahepatic strictures.

Activated human T cells directly induce osteoclastogenesis from human monocytes: possible role of T cells in bone destruction in rheumatoid arthritis patients.

OBJECTIVE: To elucidate the direct role of human T cells in the induction of osteoclastogenesis in rheumatoid arthritis (RA), by studying human monocytes and the pathogenetic roles of receptor activator of nuclear factor kappaB ligand (RANKL), RANK, and osteoprotegerin (OPG). METHODS: Synovial tissue obtained at total knee replacement was stained immunohistologically using anti-RANKL, CD3, and CD4 antibodies. Synovial fluid was obtained from patients with RA, osteoarthritis (OA), gout, or trauma. Concentrations of the soluble form of RANKL (sRANKL) and OPG in the synovial fluid were measured by enzyme-linked immunosorbent assay. Activated T cells from peripheral blood mononuclear cells (PBMC) of healthy volunteers were cultured with human monocytes from PBMC. RESULTS: Immunostaining of the synovial tissue of RA patients demonstrated that RANKL-positive cells were detected in a subset of fibroblast-like synoviocytes and infiltrating mononuclear cells. Double immunostaining revealed that RANKL-positive cells were detected in a subset of CD3+ cells and CD4+ cells. An increased concentration of sRANKL and a decreased concentration of OPG were detected in synovial fluid from RA patients. The ratio of the concentration of sRANKL to that of OPG was significantly higher in synovial fluid of RA patients than in synovial fluid of patients with OA or gout. The activated T cells expressing RANKL induced osteoclastogenesis from autologous peripheral monocytes. The role of RANKL in this osteoclastogenetic process was confirmed by dose-dependent inhibition by OPG. CONCLUSION: The present study is the first to demonstrate osteoclastogenesis using human-derived T cells and monocytes. In addition, the present findings suggest that excess production of RANKL by activated T cells increases the level of sRANKL in synovial fluid and may contribute to osteoclastic bone resorption in RA patients.

Production of biologically active recombinant bovine interferon-gamma by two different baculovirus gene expression systems using insect cells and silkworm larvae.

The full-length bovine interferon-gamma (bIFN-gamma) cDNA, including the secretion signal peptide coding region was recloned into baculovirus transfer vectors pAcYM1 and pBm050. These vectors were co-transfected with Autographa californica nuclear polyhedrosis virus (AcNPV) or Bombyx mori nuclear polyhedrosis virus (BmNPV) DNA into Spodoptera frugiperda cells (SF21AE) and Bombyx mori cells (BmN), respectively. The recombinant viruses, named AcBIFN-gamma and BmBIFN-gamma, were then recovered. Recombinant bIFN-gamma (rbIFN-gamma) was accumulated in the culture fluid of AcBIFN-gamma-infected Trichoplusia ni cells and BmBIFN-gamma-infected silkworm larvae. These rbIFN-gamma forms were shown to be glycosylated 20 and 22 kDa proteins as confirmed by SDS-PAGE and tunicamycin treatment. These products were sensitive to cystein proteinase. Both rbIFN-gamma proteins, showed high-level biological activities by plaque reduction assay using vesicular stomatitis virus, and MHC class II antigen induction on bovine macrophage cells.

Probability of lymph node metastasis in small gastric cancer tumor: is it an indication for limited surgery?

The purpose of this study was to determine the factors that are predictive of lymph node metastasis in a small gastric cancer tumor <2 cm in diameter. The clinicopathological features of 17 patients with node-positive small gastric cancer were reviewed from the database of gastric cancer at the Department of Surgery, Sendai National Hospital, Sendai, Japan, and they were compared with those of 131 patients with node-negative cancer. The independent risk factors influencing the lymph node metastasis were determined by multiple logistic regression analysis. Depth of invasion, macroscopic appearance, cancer-stromal relationship, and lymphatic microinvasion were found to be associated with lymph node metastasis. The variables found to be significant risk factors for lymph node metastasis were depth of invasion (P = 0.0250) and lymphatic microinvasion (P = 0.0028). It is possible for even a small gastric cancer tumor to have lymph node metastasis. A surgeon treating a small gastric cancer tumor must consider that although the cure rate is high, >10% of these tumors have lymph node metastases. Because of the possibility of lymph node metastasis, even with accurate knowledge of the depth of cancer invasion, selective performance of local resection or limited surgery with incomplete lymph node dissection is not justified. Accurate preoperative diagnosis and the appropriate decision for surgical indication are important. Large-scale randomized, controlled trials should be performed to show the advantage of limited surgery for gastric cancer.

[Primary endocardial fibroelastosis].

Endocardial fibroelastosis is a disease characterized by a prominent proliferation of dense collagenous and elastic tissue in the endocardium with the occurrence of congestive heart failure and death in early life. There are, however, many recorded instances of infants surviving the initial illness and living up to or beyond puberty. The clinicopathological factors for good prognosis include the increase in myocardial mass of ventricle evaluated by ventriculography and the histopathologic evidence for compensatory myocardial cell hypertrophy in the biopsied myocardium.