New Model of Colon Interposition Following Distal Gastrectomy in Rats

An interposed colon segment has been clinicallyused as a gastric substitute following anesophagogastric resection for benign or malignantesophageal and gastric cardia disease. The purpose ofthis study is to establish a rat model of colonicinterposition following distal gastrectomy and toinvestigate its serial mucosal changes. About 80% of theglandular stomach was resected, and a 3-cm segment ofthe transverse colon interposed isoperistalticallybetween the remnant stomach and duodenum. Epithelialproliferation and aberrant crypt foci in the interposedcolon segment were investigated serially. Crypt lengths in the interposed colon increasedsignificantly (P < 0.05) compared to the remnantcolon. The number of goblet cells per crypt per 1 mm inthe interposed colon also decreased significantly (P< 0.05) compared to the remnant colon. A PCNA labelingindex (LI) of the remnant colon was almost 30%. A PCNALI in the interposed colon at 4, 8, and 12 months aftersurgery was 30.8%, 31.8%, and 47.8%, respectively. The PCNA LI in the interposed colon increasedsignificantly (P < 0.05) 12 months after surgerycompared to the remnant colon at 4, 8, and 12 monthsafter surgery. Aberrant crypt foci were not detected in the interposed colon segment. In conclusion, weestablished a rat model of colonic interpositionfollowing distal gastrectomy. The interposed colonmucosa adapted well. Long-term mucosal changes of the interposed colon segment should now bestudied.     

Intraoperative massive pulmonary tumor embolism from clear cell sarcoma in the retroperitoneum: successful treatment using cardiopulmonary bypass

Malignant neoplasms rarely extend into the inferior vena cava and up to the right side of the heart. Although massive pulmonary tumor embolism occurs relatively rarely, it can be a catastrophic problem. Intraoperative pulmonary tumor embolism and cardiac arrest occurred in a 68-year-old woman while dissecting the inferior vena cava to resect a pararenal tumor extending into the retrohepatic inferior vena cava. Abrupt arterial hypotension, tachycardia, and increased central venous pressure lead to the diagnosis of massive pulmonary tumor embolism. Emergency cardiopulmonary bypass was commenced under profound hypothermia and cardiac arrest. The tumors in the main pulmonary artery were extracted, and fragments of remnant tumor were retrieved by a vascular endoscope, a Fogarty catheter, and milking of the lung. Following embolectomy, the tumor in the retrohepatic to infrarenal inferior vena cava was removed and the primary tumor together with the infrarenal inferior vena cava was resected under hepatic vascular exclusion and partial cardiopulmonary bypass. The inferior vena cava below the renal veins was not reconstructed. The patient recovered with slight retrograde amnesia. A postoperative pulmonary perfusion scintigram showed no defect in the pulmonary circulation. She is well now 8 months after surgery. Safe prevention measures should be accomplished as a part of the perioperative management of patients with inferior vena cava tumor thrombus that may be fragile, and cardiopulmonary bypass should always be stand-by on surgery.     

Omentoplasty for cervical esophagogastrostomy following radical esophagectomy with three-field dissection

BACKGROUND/AIMS: Anastomotic leakage is the main cause of postoperative mortality and incidence of which, following three-field lymph node dissection, is around 30%. The study was undertaken to investigate the role of omentoplasty to reinforce cervical esophagogastrostomy with the expectation of lowering the rate of anastomotic leakage after radical esophagectomy with three-field lymph node dissection. METHODOLOGY: Between July 1995 and Dec 1997, a total of 32 patients underwent total thoracic esophagectomy with three-field lymph node dissection and cervical esophagogastrostomy. Eleven patients were stage IIA, 3 stage IIB, 5 stage III and 13 stage IV. After radical esophagectomy and lymph node dissection, several omental branches of the gastroepiploic vessels remained to supply a gastric tube. An end-to-side cervical esophagogastrostomy was performed on the posterior wall of the gastric tube using a circular stapler. The omentoplasty--wrapping the esophagogastrostomy--was performed. A retrosternal route for reconstruction was used in 23 patients and a posterior mediastinal route in 9 patients. RESULTS: Esophageal anastomotic leakage occurred in only 1 patient, 3.1% overall. There was neither pyothorax nor mediastinitis. There was no lethal anastomotic leakage. Later, 2 patients (6.2%) developed an anastomotic stricture that required balloon dilatation. CONCLUSIONS: Omentoplasty to reinforce cervical esophagogastrostomy decreases anastomotic failure following radical esophagectomy with three-field lymph node dissection.     

Development and evaluation of FSSG: frequency scale for the symptoms of GERD

Background The aim of this study was to produce a simplified questionnaire for evaluation of the symptoms of gastroesophageal reflux disease (GERD).Methods A total of 124 patients with an endoscopic diagnosis of GERD completed a 50-part questionnaire, requiring only yes or no answers, that covered various symptoms related to the upper gastrointestinal tract, as well as psychosomatic symptoms. The 12 questions to which patients most often answered yes were selected, and were assigned scores (never = 0; occasionally = 1; sometimes = 2; often = 3; and always = 4) to produce a frequency scale for symptoms of GERD (FSSG). Sensitivity, specificity, and accuracy of the FSSG questionnaire were evaluated in another group of patients with GERD and non-GERD. The usefulness of this questionnaire was evaluated in 26 other GERD patients who were treated with proton pump inhibitors for 8 weeks.Results When the cutoff score was set at 8 points, the FSSG showed a sensitivity of 62%, a specificity of 59%, and an accuracy of 60%, whereas a cutoff score of 10 points altered these values to 55%, 69%, and 63%. The score obtained using the questionnaire correlated well with the extent of endoscopic improvement in patients with mild or severe GERD.Conclusions This new questionnaire is useful for the objective evaluation of symptoms in GERD patients.     

Omentoplasty versus no omentoplasty for cervical esophagogastrostomy following radical esophagectomy

BACKGROUND/AIMS: Omentoplasty--wrapping the omentum around the alimentary tract anastomosis is thought to lower the rate of anastomotic leakage. We evaluated the role of omentoplasty to reinforce cervical esophagogastrostomy after radical esophagectomy. METHODOLOGY: We compared anastomotic leakage, stricture formation, and related deaths in 63 patients who underwent radical esophagectomy and cervical esophagogastrostomy, with (n = 48) or without (n = 15) omentoplasty, between 1995 and 1999. RESULTS: An esophageal anastomotic leakage was diagnosed in 1 of the 48 patients (2.1%) with omentoplasty versus 3 of the 15 patients (20.0%) without omentoplasty (P < 0.01). Anastomotic stricture occurred in 2 (4.2%) of the omentoplasty group and 1 (6.7%) of the no omentoplasty group (P < 0.01). Death within 1 month was zero in the omentoplasty group and one (6.7%) in the no-omentoplasty group, despite no differences in lethal anastomotic leakage. CONCLUSIONS: Omentoplasty of cervical esophagogastrostomy reduced anastomotic leakage. Although promising, these observations require confirmation with a randomized prospective study.     

Immunobiotic Lactobacillus jensenii Modulates the Toll-Like Receptor 4-Induced Inflammatory Response via Negative Regulation in Porcine Antigen-Presenting Cells

Previously, we demonstrated that Lactobacillus jensenii TL2937 attenuates the inflammatory response triggered by activation of Toll-like receptor 4 (TLR-4) in porcine intestinal epithelial cells. In view of the critical importance of antigen-presenting cell (APC) polarization in immunoregulation, the objective of the present study was to examine the effect of strain TL2937 on the activation patterns of APCs from swine Peyer''s patches (PPs). We demonstrated that direct exposure of porcine APCs to L. jensenii in the absence of inflammatory signals increased expression of interleukin-10 (IL-10) and transforming growth factor β in CD172a⁺ APCs and caused them to display tolerogenic properties. In addition, pretreatment of CD172a⁺ APCs with L. jensenii resulted in differential modulation of the production of pro- and anti-inflammatory cytokines in response to TLR4 activation. The immunomodulatory effect of strain TL2937 was not related to a downregulation of TLR4 but was related to an upregulation of the expression of three negative regulators of TLRs: single immunoglobulin IL-1-related receptor (SIGIRR), A20, and interleukin-1 receptor-associated kinase M (IRAK-M). Our results also indicated that TLR2 has an important role in the anti-inflammatory activity of L. jensenii TL2937, since anti-TLR2 antibodies blocked the upregulation of SIGIRR and IRAK-M in CD172a⁺ APCs and the production of IL-10 in response to TLR4 activation. We performed, for the first time, a precise functional characterization of porcine APCs from PPs, and we demonstrated that CD172a⁺ cells were tolerogenic. Our findings demonstrate that adherent cells and isolated CD172a⁺ cells harvested from swine PPs were useful for in vitro study of the inflammatory responses in the porcine gut and the immunomodulatory effects of immunobiotic microorganisms.The gut of vertebrates is rich in antigen-presenting cells (APCs), such as macrophages and dendritic cells (DCs). These APCs reside underneath the epithelial cell layer in an immature state and are prepared to recognize foreign antigens or invading pathogens (21). In addition, APCs in gut-associated lymphoid tissues (GALT) persist both in the subepithelial dome region and in the interfollicular regions of Peyer''s patches (PPs). Under steady-state conditions, APCs, together with intestinal epithelial cells, create a tolerogenic environment in response to food antigens and commensal bacteria. However, in the presence of pathogenic microorganisms, APCs undergo a maturation process and the development of adaptive immune responses is initiated (21). These functions of intestinal APCs—specifically, to distinguish between the diverse elements of the intestinal flora and to respond to invading pathogens—are principally determined by pattern recognition receptors (PRRs). Toll-like receptors (TLRs) are an important class of PRRs in innate immunity and play a critical role in pathogen recognition and host defense. However, inappropriate TLR signaling can contribute to loss of tolerance and result in tissue injury (1, 18); for example, the inflammatory response triggered by the interaction between lipopolysaccharide (LPS) and TLR4 can cause serious intestinal damage. LPS present in the outer membrane of Gram-negative bacteria triggers the production of proinflammatory mediators that can contribute to intestinal inflammation and damage during infection. Thus, while TLR4 recognition of LPS is required for clearance of Gram-negative organisms, it is believed that excessive and/or prolonged proinflammatory cytokine secretion can be harmful to the host (1, 18).Lactic acid bacteria (LAB) able to modulate the immune system (immunobiotics) (9) are known to play a beneficial role in the prevention and therapy of a variety of intestinal inflammatory disorders, including atopic and inflammatory bowel diseases (9). In this sense, we have demonstrated that Lactobacillus jensenii TL2937 attenuates the expression of proinflammatory cytokines and chemokines triggered by enterotoxigenic Escherichia coli (ETEC) or by LPS (28). L. jensenii TL2937 attenuates proinflammatory responses in a porcine intestinal epitheliocyte (PIE) cell line by downregulating TLR4-dependent NF-κB and mitogen-activated protein kinase (MAPK) activation. Furthermore, we demonstrated that L. jensenii TL2937 stimulation of PIE cells results in upregulation of three negative regulators of TLRs, A20, B-cell lymphoma 3-encoded protein (Bcl-3), and mitogen-activated protein kinase 1 (MPK-1), and that these effects are partially dependent on the activation of TLR2 (28).Studies on the precise mechanisms of probiotic action indicate that the immunoregulatory mechanisms behind the positive effects of immunobiotics are related to the modulation of immune cells, such as APCs (7, 17, 34). Moreover, different probiotic strains affect APC maturation in different ways since cytokine and surface marker expression in APCs varies with the probiotic strains used (8). L. jensenii TL2937 may be capable of inducing tolerance to LPS in APCs; therefore, studying the effects of this probiotic strain on porcine APCs is important. Most studies addressing the effect of probiotics on APCs have been conducted in mice, and very few studies have investigated these effects in commercially important livestock animals, such as pigs. Recent advances in the characterization of the porcine immune system, particularly in porcine macrophages and DCs, have permitted the use of the porcine model for many immunological studies (2, 38). Although the library of reagents for such studies is still small compared to that for mouse studies, knowledge of porcine immunology is advancing rapidly. Moreover, the porcine immune system has been the focus of increased interest in recent years because of its potential as a suitable model for the study of the human intestinal immune system, since the porcine gastrointestinal tract has many structural aspects that are more similar to those of the human tract than those of the rodent tract are.In view of the critical importance of APC polarization in immunoregulation, the objective of the present study was to examine the effect of L. jensenii TL2937 on activation patterns of APCs from swine PPs. Therefore, in this study, we characterized APCs that were harvested from swine PPs, developed in vitro systems that allowed the evaluation of APC activity, and evaluated the functional consequences of direct exposure of APCs to L. jensenii TL2937 under both inflammatory and noninflammatory conditions.     

Immune responses against a single CD8+-T-cell epitope induced by virus vector vaccination can successfully control Trypanosoma cruzi infection

In order to develop CD8+-T-cell-mediated immunotherapy against intracellular infectious agents, vaccination using recombinant virus vectors has become a promising strategy. In this study, we generated recombinant adenoviral and vaccinia virus vectors expressing a single CD8+-T-cell epitope, ANYNFTLV, which is derived from a Trypanosoma cruzi antigen. Immunogenicity of these two recombinant virus vectors was confirmed by the detection of ANYNFTLV-specific CD8+ T cells in the spleens of immunized mice. Priming/boosting immunization using combinations of these two recombinant virus vectors revealed that the adenovirus vector was efficient for priming and the vaccinia virus vector was effective for boosting the CD8+-T-cell responses. Moreover, we also demonstrated that the ANYNFTLV-specific CD8+-T-cell responses were further augmented by coadministration of recombinant vaccinia virus vector expressing the receptor activator of NFkappaB (RANK) ligand as an adjuvant. By priming with the adenovirus vector expressing ANYNFTLV and boosting with the vaccinia virus vectors expressing ANYNFTLV and RANK ligand, the immunized mice were efficiently protected from subsequent challenge with lethal doses of T. cruzi. These results indicated, for the first time, that the induction of immune responses against a single CD8+-T-cell epitope derived from an intrinsic T. cruzi antigen was sufficient to control lethal T. cruzi infection.     

Diagnostic value of measurement of serum type I procollagen carboxy terminal peptides in patients with scirrhous carcinoma of the stomach.

We have evaluated the radioimmunoassay for type I procollagen carboxy terminal peptide (type I C-peptide), which is liberated from type I procollagen during its conversion to collagen, in the serodiagnosis of scirrhous carcinoma of the stomach. The mean (SD) serum concentration of type I C-peptide in 39 normal subjects was 41.7 (19.7) ng/ml. The mean serum values and the positive ratio of type I C-peptide in 11 patients with stages II and III scirrhous carcinoma of the stomach were 91.2 (41.9) ng/ml and 54.5%, respectively. In 10 patients with other types of gastric carcinoma, the mean type I C-peptide values were not significantly different from the normal value. Serum type I C-peptide values reflected the clinical course of scirrhous gastric carcinoma in five patients who underwent either operation or chemotherapy. The measurement of serum type I C-peptide concentrations could provide a useful way of diagnosing and monitoring scirrhous carcinoma of the stomach.     

Blood transfusion causes deterioration in liver regeneration after partial hepatectomy in rats.

BACKGROUND: This study investigated the effects of blood transfusion on liver regeneration and function after hepatectomy in rats. METHODS: Inbred male Sprague-Dawley rats underwent a sham operation or a 70% hepatectomy (PHx) and were randomly divided into seven groups according to transfusion type: groups I and II underwent a sham operation and received saline (I) or whole blood (II). Groups III to VII underwent PHx with saline (III), whole blood (IV), irradiated/leukocyte-depleted whole blood (V), plasma (VI), or autologous blood (VII). The liver regeneration rate, proliferating cell nuclear antigen (PCNA) labeling index, serum aspartate aminotransferase, alanine aminotransferase, purine nucleoside phosphorylase (PNP) activity, hepatocyte growth factor (HGF), and activated transforming growth factor beta1 (TGF-beta(1)) were measured 6 and 24 h and 5 days after PHx. RESULTS: The liver regeneration rate and PCNA labeling index were lower in groups IV and V than in the other groups. Serum liver enzymes 6 h after PHx were worst in groups IV and V. PNP activity increased most in group IV, 6 and 24 h after PHx. The HGF values 6 h after PHx in all the transfused groups were lower than in group III. The activated TGF-beta(1) level 6 h after surgery was highest in group IV. CONCLUSION: Whole blood or irradiated/leukocyte-depleted whole blood impaired liver regeneration after PHx, probably through the production of activated TGF-beta(1) and HGF outside the liver, and plasma or autologous blood reduced the deleterious effects.