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Biomedical subjects

Sonshin Takao

Publications and source records attributed to Sonshin Takao.

At least 19 recordsLinked to original sources

Impact of lymph node micrometastasis in patients with pancreatic head cancer.

PURPOSE: The purpose of this study was to investigate the clinical significance of nodal micrometastasis in patients who underwent a curative operation for pancreatic cancer. EXPERIMENTAL DESIGN: Fifty-eight patients underwent a macroscopically curative resection with extended lymph node dissection for pancreatic cancer. The total number of resected lymph nodes was 1,058, and 944 histologically negative lymph nodes were subjected to immunohistochemical staining to detect occult micrometastases. RESULTS: Nodal micrometastases were detected immunohistochemically in 147 out of 944 resected histologically negative lymph nodes (15.6%). Forty-four of all 58 patients (75.9%) and 13 of the 23 histologically node-negative patients (56.5%) had nodal micrometastases. Nodal micrometastases existed in the N1 lymph node area most frequently, followed by the N2 and N3 lymph node areas. The distribution was similar to that of histologically metastatic lymph nodes. Ten out of 16 patients (62.5%) with histological N1, and 5 out of 16 patients (31.3%) with histological N2 had nodal micrometastases beyond the histological lymph node status. Three and 5-year survival rates of pN0 patients without lymph node nodal micrometastases were both 60.0%, while those with nodal micrometastases were 19.2% and 0%, respectively. There was statistically significant difference between the both groups (P = 0.041). CONCLUSIONS: Nodal micrometastasis in pancreatic cancer existed in wider and more distant areas than histological lymph node status, and it was an unfavorable predictive factor, even in N0 patients.

Adenocarcinoma↗

Carcinoembryonic antigen messenger RNA expression in blood predicts recurrence in esophageal cancer.

PURPOSE: The clinical significance of isolated tumor cells (ITC) in blood has not been clearly established, particularly during follow-up in cancer patients. We conducted a longitudinal analysis of the relationship between ITC in blood during follow-up and clinicopathologic findings in patients with esophageal squamous cell carcinoma. EXPERIMENTAL DESIGN: Blood samples obtained from 106 patients were examined by real-time RT-PCR assay targeting carcinoembryonic antigen (CEA) mRNA. Follow-up examination every 3 months after surgery included testing for CEA mRNA and tumor markers, as well as imaging. RESULTS: Thirty-nine (36.8%) patients were positive for CEA mRNA expression. CEA mRNA positivity significantly correlated with tumor depth, lymph node metastasis, stage, and venous invasion. Recurrent disease was found in 34 of 106 (32.1%) cases. CEA mRNA was found in 28 (76.5%) patients experiencing relapse. Of these 28 patients, the number positive of CEA mRNA before detection by imaging, at the same time of detection by imaging, and after detection by imaging was 18 (52.9%), 8 (23.5%), and 2 (5.9%), respectively. The sensitivity, specificity, positive predictive value, and negative predictive value for CEA mRNA were higher than those for serum CEA or squamous cell carcinoma. Patients positive for CEA mRNA experienced significantly shorter disease-free interval than those with negative CEA mRNA (P < 0.001). According to multivariate analysis, CEA mRNA positivity was an independent factor for disease-free interval. CONCLUSIONS: Examination of CEA mRNA in peripheral blood during follow-up is useful for early detection of occult recurrence. We believe that CEA mRNA in blood will be a new marker for recurrence in esophageal squamous cell carcinoma.

Adult↗

A new technique for pancreaticogastrostomy for the soft pancreas: the transfixing suture method.

BACKGROUND/PURPOSE: Pancreatic anastomotic leakage remains a persistent problem after pancreaticoduodenectomy (PD). The presence of soft, nonfibrotic pancreatic tissue is one of the most important risk factors for pancreatic leakage. Accordingly, we devised a pancreas-transfixing suture method for pancreaticogastrostomies in patients with a soft, nonfibrotic pancreatic remnant. METHODS: The pancreas-transfixing method was applied in 103 consecutive patients after either standard PD (49 patients) or pylorus-preserving pancreaticoduodenectomy (PPPD) (54 patients) for malignant or benign disease. Of these 103 patients, 65 had a soft, nonfibrotic pancreatic remnant. For the pancreaticogastrostomy technique, an ultrasonically activated scalpel was used for transecting the pancreas. The inner layer involves a duct-to-mucosa anastomosis with an internal stent and the outer layer involves a single row of pancreas-transfixing sutures between the pancreatic remnant and the posterior gastric wall. RESULTS: Operative mortality was zero and morbidity was 22%. Only two patients (2%) developed pancreatic leaks; both resolved nonoperatively with the continuation of closed drainage. CONCLUSIONS: This technique is simple and appears to reduce the risk of pancreatic leakage, possibly by decreasing the risk of suture injury of the pancreas and by embedding the transected stump into the wall of the stomach. This novel pancreaticogastrostomy technique is an effective reconstructive procedure, especially for patients with a soft, nonfibrotic pancreas.

Adult↗

Role of positron emission tomography in decisions on treatment strategies for pancreatic cancer.

BACKGROUND/PURPOSE: The purpose of this study was to estimate the usefulness of positron emission tomography (PET) in deciding on strategies for the treatment of pancreatic cancer. The following two parameters were evaluated: the ability of PET to provide an estimation of the progression of pancreatic cancer, and the ability of PET to predict survival and the effect of chemoradiotherapy. METHODS: Forty-two patients underwent PET as part of the procedure for making a diagnosis of pancreatic tumors. The maximum standardized uptake value (SUVmax) levels were compared with clinicopathological factors and analyzed. RESULTS: PET provided a sensitivity of 87%, a specificity of 67%, and an overall accuracy of 85% for the diagnosis of pancreatic malignancy. Tumors with distant metastases showed significantly higher SUV levels than tumors without metastasis. In the patients who received chemoradiotherapy, the overall survival of the group in which SUVmax was less than 7.0 was better than that of the group in which SUVmax was more than 7.0. CONCLUSIONS: We conclude that PET is a useful tool for determining pathological status and distant metastasis in pancreatic cancer, and for predicting the prognosis of patients receiving chemoradiotherapy.

Adult↗

Gene transfer to corneal epithelium and keratocytes mediated by ultrasound with microbubbles.

PURPOSE: The cornea is an ideal organ for evaluating gene transfer because it can be treated noninvasively and monitored easily. The present study was performed to investigate the practical efficacy and safety of ultrasound (US) plus microbubble (MB)-mediated gene transfer to cornea. METHODS: Cultured rabbit corneal epithelial (RC-1) cells were incubated in 24-well dishes with plasmid DNA having a green fluorescent protein (GFP) gene under a cytomegalovirus promoter. The cells were exposed to US under different intensities (1 MHz; power, 0.5 approximately 2 W/cm2; duration, 15-120 seconds; duty cycle, 20%-100%). The effect of simultaneous stimulation with MBs was also examined. Gene transfer was quantified by counting the number of GFP-positive cells under microscopy. Furthermore, in vivo gene transfer was examined by GFP plasmid injection into rabbit cornea and US exposure with MBs. RESULTS: In the in vitro study, DNA exposure alone could not transfer gene into cultured RC-1 cells; US enhanced gene transfer slightly. Coexposure with MBs significantly increased gene transfer efficiency. In the in vivo study, DNA injection alone could transfer the gene to a limited degree, but plasmid injection plus US with MBs strongly increased gene transfer efficiency without apparent tissue damage, and gene transfer was achieved two dimensionally. CONCLUSIONS: US with MBs greatly increases gene transfer to in vivo and in vitro corneal cells. This noninvasive gene transfer method may be a useful tool for clinical gene therapy.

Animals↗

[A case of gemcitabine-based chemo-radiation therapy for locally advanced unresectable pancreatic cancer].

A 49-year-old man was admitted to our hospital with vomiting. Abdominal CT revealed an avascular tumor at the uncinate process of the pancreas measuring 36x30 mm. Preoperative serum CA 19-9 was 361 U/ml. During laparotomy,the tumor was deemed unresectable (T4NXM0, Stage IVa),and duodenojejunostomy was performed. External-beam radiotherapy (EBRT) (50.4 Gy/28Fr) with concurrent twice-weekly gemcitabine (GEM) (40 mg/m(2)/day) was delivered. In the outpatient setting, and 1,000 mg/m(2) of GEM was administered intravenously on days 1, 8, and 15. Cycles were repeated every 28 days. The patient received 13 cycles of GEM chemotherapy until the appearance of a grade 2 facial rash. A decrease in tumor size was observed, and the serum CA 19-9 level dropped to 16 U/ml. He remained well without any symptoms and pursued normal activity for 33 months. He died of peritoneal dissemination 43 months after diagnosis. Gemcitabine-based chemo-radiation seems to be a safe and effective regimen for unresectable pancreatic cancer.

Adenocarcinoma↗

A phase I combination chemotherapy study of biweekly paclitaxel and S-1 administration in patients with advanced gastric cancer.

The aim of the current study was to determine the maximum tolerated dose (MTD) and the dose limiting toxicity (DLT) of a combination of paclitaxel and S-1 in patients with advanced gastric cancer. Fifteen patients were enrolled. The dose for S-1 was set at 80 mg/m2/day (days 1-14), while the dose for paclitaxel increased by 10 mg/m2 for every three patients, with a starting dose of 100 mg/m2 and was given biweekly on day 1 and 15. There was no severe toxicity (grade 4) recorded in patients receiving up to 120 mg/m2 of paclitaxel. Leukopenia/neutrophilia with grade 1 to 3 occurred in six patients up to level 3. At 130 mg/m2 of paclitaxel, grade 4 leukocytopenia and neutropenia events and grade 3 diarrhea developed in one out of three patients. One patient in another group of three patients that were enrolled at level 3, developed grade 4 granulocytopenia with fever (a body temperature higher than 38 degrees C) and grade 3 leukocytopenia. Eight patients, out of a total of 15, showed a partial response, resulting in an objective response rate of 53%. Five patients received gastrectomy. Median survival time was 428 days and the 1 year survival rate was 53%. Biweekly paclitaxel/S-1 combination chemotherapy could be safely used for the treatment of advanced gastric cancer. The recommended doses for a phase II study with paclitaxel and S-1 are 120 mg/m2 and 80 mg/m2, respectively.

Adult↗

Predictive value of p53 and 14-3-3sigma for the effect of chemoradiation therapy on esophageal squamous cell carcinoma.

BACKGROUND AND OBJECTIVES: The p53 family regulates cell-cycle arrest, triggers apoptosis, repairs DNA damage caused by various genotoxic stresses, and protects cells from death upon irradiation. The purpose of the present study was to examine the expressions of p53 and one of the p53 family proteins, 14-3-3sigma, in biopsy specimens and to predict the clinical and histological responses to chemoradiation therapy (CRT) in patients with esophageal squamous cell carcinoma (ESCC). METHODS: We investigated with the relationship between p53 and 14-3-3sigma expressions in biopsy specimens obtained from 62 patients with ESCC and analyzed these patients' clinical and histological responses to CRT. Chemoradiation therapy consisted of 5-fluorouracil plus cisplatin and 40 Gy of radiation. RESULTS: Following CRT, 71.0% of patients showed a positive clinical response and 52.8% showed a positive histological response. The rate of positive expression was 43.5% for p53 and 58.1% for 14-3-3sigma. Statistically significant correlations were found between p53 expression and clinical response to CRT (P = 0.001) and histological response to CRT (P = 0.041), and between 14-3-3sigma expression and histological response to CRT (P = 0.01). Furthermore, in p53-positive tumors, CRT was more effective in tumors with 14-3-3sigma-positive expressions than those with 14-3-3sigma-negative expressions (P = 0.037). The survival rate of the patients with 14-3-3sigma-positive tumors was better than those with 14-3-3sigma-negative tumors in patients with p53-positive tumors (P = 0.047). CONCLUSIONS: We demonstrated that p53-negative or 14-3-3sigma-positive expressions were closely related to the response to CRT. It is clinically useful to examine the expression of these genes in biopsy specimens for predicting the CRT outcomes in patients with ESCC.

14-3-3 Proteins↗

Initial metastatic, including micrometastatic, sites of lymph nodes in esophageal squamous cell carcinoma.

BACKGROUND AND OBJECTIVES: It is important to identify the initial lymph node metastasis when performing less invasive surgery. The purpose of the present study was to analyze locations of solitary lymph node metastasis and micrometastasis in esophageal carcinoma. METHODS: We retrospectively analyzed the initial sites of lymph node metastasis in esophageal cancer. Sixty-five consecutive patients with solitary lymph node metastasis, and 33 pN0 patients with only lymph node micrometastasis detected by immunohistochemistry, were classified according to tumor location and tumor depth. RESULTS: The location of lymph node metastasis in the 22 patients with superficial cancer was limited to recurrent nerve nodes (RN) in the upper thoracic esophagus; RN, paraesophageal nodes (PE), or perigastric nodes (PG) in the middle or lower thoracic esophagus. Thirty-six patients with advanced cancer had lymph node metastasis at RN, PE, or PG locations, while in the remaining seven, lymph node metastasis was found in areas far from the primary tumor. Regarding the 33 patients with lymph node micrometastasis, the locations of micrometastasis were similar to those of solitary metastasis. CONCLUSIONS: Although less invasive surgery, such as reduction of lymphadenectomy, may be suitable for superficial cancer, it should be performed with special care in advanced cancer.

Aged↗

Multiple primary carcinomas with esophageal squamous cell cancer: clinicopathologic outcome.

The incidence of multiple primary carcinomas (MPCs) associated with esophageal cancer has increased. The purpose of this study was to analyze clinicopathologic findings for MPC and for only esophageal cancer (OEC). Of 157 patients with MPCs, 60 had synchronous cancer and 97 metachronous cancer. Another 42 patients had antecedent esophageal cancer (AEC), and 55 patients had subsequent esophageal cancer (SEC). We retrospectively analyzed the clincopathologic findings for patients in these categories. The incidence of early-stage carcinoma was higher in patients with MPCs than in those with an OEC. Of patients with MPCs, those with metachronous cancer had a higher rate of early-stage carcinoma than those with synchronous cancer. The 5-year survival rates were not significantly different for MPC and OEC patients. Patients with metachronous cancer had a significantly better prognosis than those with synchronous cancer (p = 0.017); and in the metachronous cancer group the prognosis was significantly better for patients with AEC than for those with SEC (p = 0.0005). Meticulous follow-up after treatment of a first cancer should be required to detect other early-stage carcinomas.

Aged↗

A case of leptomeningeal carcinomatosis from esophageal basaloid carcinoma diagnosed by quantitative reverse transcription-polymerase chain reaction for carcinoembryonic antigen.

We describe herein the case of a 68-year-old man who experienced leptomeningitis after esophagectomy from an esophageal basaloid carcinoma. Although the patient had a good operative course for the first 10 days after surgery, he suddenly had general convulsions with unconsciousness. He was placed on mechanical ventilation in an intensive care unit. Computed tomography and magnetic imaging resonance did not reveal any abnormal findings. No abnormal data in the cerebrospinal fluid were found by biochemical, virological, and cytological examination. The positive expression of carcinoembryonic antigen messenger ribonucleic acid in cerebrospinal fluid was detected by a quantitative reverse transcription-polymerase chain reaction method. Immunohistochemical staining using an anticytokeratin antibody confirmed the presence of tumor cells in the cerebrospinal fluid. Spontaneous breathing was recovered after treatment with systemic chemotherapy. Six months after surgery, computed tomography revealed multiple brain metastases. This case demonstrates that the quantitative reverse transcription-polymerase chain reaction method of analyzing carcinoembryonic antigen messenger ribonucleic acid may be a sensitive and useful method for determining leptomeningeal metastasis before the detection of tumors by cytological and imaging examinations in patients with cancer.

Aged↗

Endoscopic transgastric drainage of pancreatic pseudocyst with the use of Nd:YAG laser.

Pancreatic pseudocysts have been successfully managed with endoscopic drainage recently. This report describes a case of endoscopic transgastric drainage using endoscopic ultrasonography (EUS) and an Nd:YAG laser. EUS was used to detect an optimal puncture site of the pseudocyst and to reduce the risk of bleeding and perforation. An Nd:YAG laser was used to minimize the risk of bleeding and to penetrate the thick wall of the pseudocyst. After transgastric cystgastrostomy was performed, an internal stent was placed between the pseudocyst and the stomach. There were no complications associated with endoscopic interventions. Complete resolution of the pseudocyst was observed. Endoscopic transgastric drainage of pancreatic pseudocysts is a recommended approach for selected patients with pancreatic pseudocysts that are uncomplicated and are located adjacent to the stomach. Safe and effective drainage can be achieved without hemorrhage and perforation with the use of EUS, an Nd:YAG laser, and a stent. Furthermore, the Nd:YAG laser facilitated passage through a markedly indurated pseudocyst wall and it seemed to be an effective instrument, especially for pseudocysts with a thick wall.

Drainage↗

Reactive oxygen species are essential mediators in antigen presentation by Kupffer cells.

Kupffer cells (KC) act as APC in the liver and play a major role in the clearance of gut-derived antigens and pathogens entering the liver with portal venous blood. Antigen presentation by KC has been implicated in regulation of the local and systemic immune responses. In this study, modulation of KC antigen presentation by antioxidants and the role of reactive oxygen species (ROS) as essential mediators of antigen presentation in KC were investigated. Co-culture of KC with ovalbumin (OVA) antigens resulted in upstream intracellular endogenous ROS generation and increased expression of MHC class II and costimulator molecules, and consequent OVA-specific CD4(+) T-cell proliferation in response to antigen presentation by KC. Scavenging of KC ROS by antioxidants, or blocking of KC ROS generation by specific inhibitors of NADPH oxidase and/or xanthine oxidase, or by specific inhibitors of the mitochondrial electron transport chain, significantly decreased OVA-specific T-cell proliferation in response to antigen presentation by KC. Increased expression of MHC class II and costimulatory molecules in KC pulsed with OVA antigens was blocked by inhibiting ROS generation enzymatically. Intracellular endogenous ROS generation during antigen processing may therefore provide essential secondary signalling for KC antigen presentation.

Animals↗

Impact of vascular endothelial growth factor-C and -D expression in human pancreatic cancer: its relationship to lymph node metastasis.

PURPOSE: The aim of this study was to evaluate the expression of vascular endothelial growth factor (VEGF)-C and -D in pancreatic cancer and to reveal its relation to lymph node metastasis. EXPERIMENTAL DESIGN: Formalin-fixed, paraffin-embedded blocks were obtained from 58 patients with pancreatic head cancer. All of the patients underwent a curative resection. The total number of resected lymph nodes was 1,058. The expressions of VEGF-C and -D were evaluated by immunohistochemical staining. To evaluate the relation to lymph node metastasis, the expressions of VEGF-C and -D between the marginal and central portions in the tumor were compared. When >25% of the tumor cells showed distinct staining, the portion was judged as high expression. RESULTS: The two groups with high expression of VEGF-C (P = 0.015) and VEGF-D (P = 0.020) in the marginal portion had a significantly higher incidence of lymph node metastasis compared with the groups with low expression, respectively. Furthermore, the group with high expression of both VEGF-C and -D in the marginal portion had a higher incidence of lymph node metastasis compared with the group with low expression (P = 0.007). The 5-year survival rate of patients with high expression of both VEGF-C and -D in the marginal portion was significantly lower than that of patients with low expression of both VEGF-C and -D (P = 0.017). CONCLUSIONS: VEGF-C and -D expression in tumor cells in the marginal portion of the tumor significantly associated with lymphatic metastasis and prognosis in patients with pancreatic head cancer.

Adenocarcinoma↗

The antimetastatic role of thrombomodulin expression in islet cell-derived tumors and its diagnostic value.

Islet cell tumors, endocrine neoplasm arising from pancreatic islets of Langerhans, are histologically difficult to diagnose as benign or malignant. Molecular markers are associated with the clinical characteristics that most of insulinoma are usually benign tumors, whereas other islet cell tumors are malignant but have not been identified. In this context, we newly found that an endothelial anticoagulant thrombomodulin was expressed in the normal islet beta cells and insulinoma, but not of other islet components or noninsulinoma islet cell tumors. Clinically, all of the subjects (n=15) of the insulinoma group showed no metastasis together with thrombomodulin expression in the lesions, whereas the other islet cell tumor groups showed a high incidence of metastasis (82%) and a low expression rate of thrombomodulin (6%). To examine the functional role of thrombomodulin, especially regarding the clinical characteristics of islet cell tumors, we tested the effect of exogenous thrombomodulin overexpression on cell adhesiveness and proliferation using MIN6 insulinoma cell line. In cell-based experiments, thrombomodulin overexpression reduced cell proliferation and enhanced Ca2+-independent cell aggregation, possibly through direct interaction with neural cell adhesion molecule. Taken together, these results are suggesting that thrombomodulin may act as antimetastatic molecule of insulinomas. In addition, thrombomodulin is a clinically useful molecular marker not only for identifying beta-cell-origin islet cell tumors (i.e., insulinomas) but also for predicting disease prognosis of islet cell tumors.

Adolescent↗

Carcinoembryonic antigen messenger RNA expression using nested reverse transcription-PCR in the peripheral blood during follow-up period of patients who underwent curative surgery for biliary-pancreatic cancer: longitudinal analyses.

PURPOSE: Outcome for patients with biliary-pancreatic cancer is still poor, despite curative operation. We investigated the clinical significance of molecular detection of circulating cancer cells in the blood as an early indicator of relapse during follow-up of patients who underwent a curative operation for biliary-pancreatic cancer. PATIENTS AND METHODS: We followed 53 patients who underwent a curative operation for biliary-pancreatic cancer between 1996 and 2001. We used reverse transcription-PCR in the peripheral blood to evaluate carcinoembryonic antigen (CEA) mRNA expression for molecular detection of circulating cancer cells. Follow-up examinations every 3 months after surgery included CEA mRNA expression in the blood, serum CEA, serum carbohydrate antigen 19-9 (CA19-9), and computed tomography or magnetic resonance imaging. RESULTS: Sixteen of 53 patients (30.2%) were diagnosed with a recurrence by imaging studies. The CEA mRNA detection rate in the peripheral blood of these 16 patients was 75% compared with 5.4% in the 37 patients without relapse (P < 0.001). Sensitivity of CEA mRNA, CEA, and CA19-9 serum levels was 75.0%, 50.0%, and 68.8%, respectively. Similarly, specificity was 94.6%, 64.9%, and 81.1%, respectively. CEA mRNA was expressed in the blood, even though tumor markers CEA and CA19-9 were within the normal range in patients with relapse. CEA mRNA expression in the blood, as well as the serum level of CA19-9, tended to be detected a few months earlier than detection by imaging modalities. CONCLUSIONS: During the follow-up of patients who undergo a curative operation for biliary-pancreatic cancer, CEA mRNA expression in the peripheral blood might be a useful and early indicator of relapse.

Adult↗

Value of magnetic resonance cholangiopancreatography with secretin stimulation in the evaluation of pancreatic exocrine function after pancreaticogastrostomy.

BACKGROUND/PURPOSE: The aim of this study was to assess the value of magnetic resonance cholangiopancreatography with secretin stimulation (secretin-MRCP) in evaluating the remnant pancreatic exocrine reserve after pancreaticogastrostomy with pancreaticoduodenectomy. METHODS: Forty-three patients who had undergone pancreaticoduodenectomies and who were given pancreaticogastrostomies for reconstruction were studied. Dynamic MRCPs, using a half-Fourier acquisition single-shot turbo spin-echo (HASTE) sequence were obtained before and up to 10 min after secretin administration. The morphologic features and diameter of the main pancreatic duct were monitored and graded before and after secretin stimulation. The results were compared with those of endoscopic findings, secretin stimulation testing with a collection of pancreatic fluid, N-benzoyl- L-tyrosyl-p-aminobenzoic acid (BT-PABA) excretion testing, and fecal chymotrypsin concentration. RESULTS: The results of secretin-MRCP were classified into three distinct groups: a good-secretion group (group 1; n=22; 51%), a moderate-secretion group (group 2; n=10; 23%), and a poor-secretion group (group 3; n=11; 26%). This MRCP classification correlated significantly with the concentrations of the pancreatic enzymes p-type amylase, lipase, and trypsin in the gastric juice. The BT-PABA test value was 59.8% in group 1, 46.1% in group 2, and 46.5% in group 3, and was significantly higher in group 1 than in groups 2 or 3. The fecal chymotrypsin concentration was 20.5 U/g in group 1, 14.5 U/g in group 2, and 0.7 U/g in group 3, and there was a significant correlation between the MRCP classification and fecal chymotrypsin concentration. CONCLUSIONS: MRCP with secretin stimulation favorably reflected the presence of remnant pancreatic exocrine function. Therefore, secretin-MRCP is a feasible and effective follow-up examination method to evaluate remnant pancreatic exocrine function after pancreaticogastrostomy.

4-Aminobenzoic Acid↗

A potential role of hyperbaric oxygen exposure through intestinal nuclear factor-kappaB.

OBJECTIVE: Recent studies have demonstrated the therapeutic effectiveness and pharmacologic mechanisms of hyperbaric oxygen therapy (HBOT) in the treatment of a systemic shock state. To elucidate the in vivo role of HBOT during sepsis, we evaluated the effects of HBOT on intestinal mucosal injury and bacterial translocation after lipopolysaccharide challenge. DESIGN: Experimental study. SETTING: First Department of Surgery and Division of Emergency Care, Kagoshima University School of Medicine, Kagoshima, Japan. SUBJECTS: : Male rats were treated with lipopolysaccharide by an intraperitoneal route or with lipopolysaccharide and HBOT. INTERVENTIONS: The survival rate, small intestinal tissue damage, and bacterial translocation in the HBOT-treated group were compared with those in the untreated group. Moreover, plasma tumor necrosis factor-alpha and nitrite/nitrate concentrations, inducible nitric oxide synthase and myeloperoxidase activities, and nuclear factor-kappaB in ileal mucosa were investigated. HBOT was initiated 3 hrs after lipopolysaccharide challenge and administered as 100% oxygen, at 2.53 x 10 kPa (2.5 atm absolute), for 60 mins. MEASUREMENTS AND MAIN RESULTS: When a sublethal dose of lipopolysaccharide (24 mg/kg) was given, the survival rate was much better in the HBOT-treated group (75%) than in the untreated group (33%). HBOT given 3 hrs after lipopolysaccharide injection (10 mg/kg) also lessened the histologic tissue damage of the terminal ileum and the incidence and magnitude of bacterial translocation to mesenteric lymph nodes at 24 hrs after the lipopolysaccharide injection. Moreover, HBOT was able to reduce mucosal inducible nitric oxide synthase and myeloperoxidase activities and plasma nitrite/nitrate concentrations but not serum tumor necrosis factor-alpha concentrations. Immunohistochemical examination revealed that HBOT specifically modified the mucosal nuclear factor-kappaB activation within 4-6 hrs after the injection. CONCLUSIONS: HBOT performed 3 hrs after lipopolysaccharide challenge alleviates intestinal barrier dysfunction and improves survival rates. Herein, we propose one possible mechanism for these beneficial effects: HBOT can modify the nuclear factor-kappaB activation in the intestinal mucosa and attenuate the sequential nitric oxide overproduction and myeloperoxidase activation. Consequently, bacterial translocation could be potentially decreased. We believe that the present study should lead to an improved understanding of HBOT's potential role in sepsis.

Animals↗