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Makoto Shinzeki,
Takashi Ueda,
Yoshifumi Takeyama,
Takeo Yasuda, Naoki Matsumura,
Hidehiro Sawa,
Takahiro Nakajima,
Ippei Matsumoto,
Tsunenori Fujita,
Tetsuo Ajiki,
Yasuhiro Fujino,
Yoshikazu Kuroda
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ABSTRACT: In severe acute pancreatitis (SAP), it is clinically important at the time of admission to predict the likelihood of early death. This investigation aimed to clarify the factors predicting early death in SAP.
Early death was defined as death within 10 days after disease onset. Prediction factors for early death were evaluated from data obtained on admission from 93 patients with SAP, and the characteristics of patients who died early were analyzed.
Between the early-death and early-survival groups, significant factors were base excess (BE), serum creatinine (Cr), blood sugar, serum glutamate oxaloacetic transaminase, and serum calcium. Multivariate analysis revealed that BE was an independent prediction factor for early death. The early-death rate in patients with BE < -5.5 mEq/l and Cr >or= 3.0 mg/dl was 31% and 36%, respectively. The combination of BE and Cr raised the positive predictive value to 50%, and was equally able to predict early death as the Japanese Severity Score (JSS), which was the most useful of the three conventional scoring systems used. All early-death patients had pancreatic necrosis, and their JSS was >or= 15 (stage 4). Characteristically, early-death patients had lactate dehydrogenase (LDH)>1300 IU/l, or they had serious preexisting comorbidities.
As a single parameter, BE was most useful for predicting early death. The combination of BE and Cr could predict early death as well as the JSS. An extreme rise of LDH and serious preexisting comorbidity may also be risk factors for early death.
Journal of Gastroenterology 01/2008; 43(2):152-8. · 4.16 Impact Factor
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Hidehiro Sawa,
Takashi Ueda,
Yoshifumi Takeyama,
Takeo Yasuda,
Makoto Shinzeki, Naoki Matsumura,
Takahiro Nakajima,
Ippei Matsumoto,
Tsunenori Fujita,
Tetsuo Ajiki,
Yasuhiro Fujino,
Yoshikazu Kuroda
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ABSTRACT: Sepsis due to infected pancreatic necrosis is the most serious complication in the late phase of severe acute pancreatitis (SAP). Bacterial translocation from the gut is thought to be the main cause of pancreatic infection. The possibility has recently been reported that selective digestive decontamination (SDD) and enteral nutrition (EN) may alleviate the complications and reduce the mortality rate in patients with SAP. We analyzed the treatment outcome of SDD and EN in patients with SAP.
We divided 90 patients with SAP into three groups: SDD(-)EN(-),group A; SDD(+)EN(-), group B; and SDD(+)EN(+), group C. Clinical outcome was analyzed retrospectively. The effect of SDD was compared in groups A and B, and the effect of EN was compared in groups B and C.
The background of patients was not significantly different between the groups. SDD reduced the incidence of organ dysfunction (from 70% to 59%) and the mortality rate (from 40% to 28%), but the differences were not significant. EN reduced the incidence of infected pancreatic necrosis (from 31% to 24%) and the frequency of surgery for pancreas (from 28% to 18%), and further reduced the mortality rate (from 28% for SDD to 16%), but the differences were not significant. The peripheral lymphocyte count was significantly increased in patients with EN.
SDD and EN did not significantly affect the treatment outcome in SAP. However, the results in this study raise the possibility that SDD and EN may decrease the complications and reduce the mortality rate in SAP. The efficacy of SDD and EN for SAP should be evaluated in a randomized controlled trial.
Journal of Hepato-Biliary-Pancreatic Surgery 02/2007; 14(5):503-8. · 1.60 Impact Factor
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ABSTRACT: In severe acute pancreatitis (SAP), immunologic impairment in the early phase may be linked to subsequent infectious complications that are main contributor to the high mortality. Toll-like receptors (TLRs) recognize microorganisms as the innate immune system, and are involved in host defense mechanism. TLR2 recognizes lipoteichoic acid (LTA) of gram-positive bacteria, and TLR4 recognizes lipopolysaccharide (LPS) of gram-negative bacilli. This study aimed to investigate the expression of TLRs on macrophages and their TLRs-mediated cytokine production in rat SAP. SAP was induced by retrograde injection of 3% sodium deoxycholate into the biliopancreatic duct in male Wistar rats. Macrophages were isolated from bronchoalveolar lavage fluid 6 hours after induction of SAP. The expression of TLR2 and TLR4 was analyzed by real-time RT-PCR and western blotting. TNF-alpha release from macrophages was estimated after 4-hour stimulation of LTA or LPS. Endotoxin/bacterial translocation (E/BT) was also evaluated in this model. The expression of TLR2 (mRNA and protein) and LTA-mediated TNF-alpha production were significantly decreased in SAP compared with control. The expression of TLR4 (mRNA and protein) and LPS-mediated TNF-alpha production was also significantly decreased in SAP compared with control. E/BT occurred 18 hours after induction of SAP. These results suggest that the impaired responsiveness to LTA and LPS of macrophages is derived from decreased expression of TLR2 and TLR4, respectively. This suppression of immune response in the early phase may be implicated in the mechanism of infectious complications.
The Kobe journal of medical sciences 02/2007; 53(5):219-27.
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ABSTRACT: In severe acute pancreatitis (SAP), it is important clinically to predict the prognosis at the time of admission. Most scoring systems for severity of acute pancreatitis consist of multiple factors and are complicated. This investigation aimed to propose a simple scoring system for the prediction of the prognosis of SAP.
Prognostic factors were evaluated by receiver operator characteristic curve analyses and multivariate analysis from data that were obtained on admission of 137 patients with SAP. A simple scoring system with 3 most useful factors was made, and its usefulness was investigated in comparison with conventional scoring systems.
Three prognostic factors were selected: serum blood urea nitrogen > or = 25 mg/dL, serum lactate dehydrogenase > or = 900 IU/L, and contrast-enhanced computed tomography finding with pancreatic necrosis. On admission, 137 patients were classified from 0 to 3 by the number of positive items (simple prognostic score [SPS]). Mortality rates for patients whose SPS was 0, 1, 2, and 3 were 2% (1/42 patients), 18% (7/40 patients), 48% (12/25 patients), and 67% (20/30 patients), respectively. Furthermore, when usefulness of SPS was compared with conventional scoring systems, the area under the curve by receiver operator characteristic curve analyses in SPS was 0.83; the Ranson score was 0.83; the Japanese severity score was 0.83; the Acute Physiology and Chronic Health Evaluation II score was 0.81, and the Glasgow score was 0.75. After onset, SPS kept almost same levels from day 2 to day 6, and a significant difference was observed between survivors and nonsurvivors from day 1 to day 6.
This scoring system that comprised 3 items is simple, is feasible for the prediction of prognosis and conventional scoring systems, and is useful for the selection of the extremely severe patients with SAP on admission.
Surgery 01/2007; 141(1):51-8. · 3.10 Impact Factor
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ABSTRACT: We have demonstrated that apoptosis was detected in liver and kidney cells in severe acute pancreatitis and that cellular injury because of apoptosis may be involved in the mechanism of multiple organ dysfunction syndrome. Vascular endothelial growth factor (VEGF) is a glycoprotein with potent angiogenic, mitogenic, and vascular permeability-enhancing activities specific for endothelial cells. It has been reported that VEGF is implicated in many diseases such as cancer and inflammation.
Serum VEGF concentrations were determined in patients with acute pancreatitis at the time of admission, and the relationships with severity, blood biochemical parameters on admission, organ dysfunction during the clinical course, and prognosis were analyzed. Moreover, to clarify the role of VEGF in acute pancreatitis, effects of VEGF were investigated in experimental severe acute pancreatitis.
Serum VEGF levels were significantly elevated in patients with acute pancreatitis. Serum VEGF levels were not related to severity or prognosis. In male patients, among the various blood biochemical parameters, serum lactate dehydrogenase, and blood urea nitrogen levels were positively correlated with serum VEGF levels. Serum VEGF levels with organ dysfunction (liver and kidney) were higher than those without organ dysfunction. In rat experimental severe acute pancreatitis, serum VEGF levels were significantly elevated. Recombinant VEGF did not affect the lung water content, volume of ascitic fluid, hematocrit, or serum amylase, but improved the hepatic and renal dysfunctions. Apoptosis of liver and kidney was significantly inhibited by the administration of VEGF.
These results suggest that VEGF is closely related to organ dysfunction in severe acute pancreatitis, and that VEGF may function as not a vascular permeability factor, but a protective factor via the anti-apoptotic effect against the organ injuries in this disease.
Journal of Surgical Research 09/2006; 134(2):223-30. · 2.25 Impact Factor
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ABSTRACT: Coagulative disorders are known to occur in severe acute pancreatitis (SAP), and they are related to its severity and organ dysfunctions. Tissue factor (TF) is a transmembrane glycoprotein that activates the extrinsic pathway of the blood coagulation cascade. Plasma TF levels increase in patients with sepsis and acute coronary syndrome. However, plasma TF levels in SAP have not yet been reported.
We measured plasma TF antigen levels by enzyme-linked immunosorbent assay in 36 patients with acute pancreatitis at the time of admission. The relationships between their plasma TF levels and various factors (severity, etiology, pancreatic necrosis, organ dysfunction, and prognosis) were analyzed. The utility of plasma TF as a clinical marker was evaluated.
Plasma TF levels significantly increased in patients with SAP compared with healthy volunteers and drinkers, respectively. Plasma TF level in alcoholic SAP with pancreatic necrosis was significantly higher than that in alcoholic SAP without pancreatic necrosis or that in nonalcoholic SAP with pancreatic necrosis. The incidence of an abnormally high level of plasma TF was 63.6% in alcoholic SAP with pancreatic necrosis. The area under the ROC curve of plasma TF for detection of pancreatic necrosis in alcoholic SAP was 0.773 and was superior to those of Japanese severity score and lactate dehydrogenase.
Plasma TF levels were elevated in patients with SAP, particularly in those with alcoholic SAP with pancreatic necrosis, suggesting that TF may be closely related to the development of pancreatic necrosis in alcoholic SAP and that the plasma TF level may be a useful marker for it.
Journal of Gastroenterology 07/2006; 41(6):575-81. · 4.16 Impact Factor
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ABSTRACT: We have reported that peripheral lymphocyte reduction due to apoptosis is linked to the development of subsequent infectious complications in patients with severe acute pancreatitis and that Th1 (helper T cell type 1)/Th2 (helper T cell type 2) balance tends to cause Th1 suppression in experimental severe acute pancreatitis. It has been reported that interleukin (IL)-18 is a cytokine produced from Kupffer cells and activated macrophages, and that IL-18 acts on Th1 cells and in combination with IL-12 strongly induces production of interferon-gamma. However, the role of IL-18 in acute pancreatitis has not yet been fully understood.
Serum IL-18 concentrations were determined by an enzyme-linked immunosorbent assay in 43 patients with acute pancreatitis at the time of admission. The relationships with etiology, pancreatic necrosis, severity, blood biochemical parameters on admission, infection, and organ dysfunction during the clinical course and prognosis were analyzed.
Serum IL-18 levels in patients with acute pancreatitis (656+/- 11pg/ml) were significantly higher than those in healthy volunteers (126+/- pg/ml). Serum IL-18 levels were significantly positively correlated with the Ranson score and Japanese severity score. Among the blood biochemical parameters on admission, base excess and total protein were significantly negatively correlated with serum IL-18 levels. Moreover, the CD4/CD8 rate of lymphocytes, serum IL-6 levels, and serum IL-8 levels were significantly positively correlated with serum IL-18 levels. On day 7 after admission, the CD4/CD8 rate of lymphocytes and the rate of CD4-positive lymphocytes were significantly positively correlated with serum IL-18 levels. Furthermore, serum IL-18 levels in patients with hepatic dysfunction (980+/- 25pg/ml) were significantly higher than those without hepatic dysfunction (464+/- 8pg/ml). Serum IL-18 levels were not related to infection or prognosis. Elevation of serum IL-18 levels continued during 4 weeks after admission.
These results suggest that serum IL-18 levels are significantly elevated and are correlated with severity in patients with acute pancreatitis and that IL-18 may be closely related to helper T cell response and hepatic dysfunction in this disease.
Journal of Gastroenterology 03/2006; 41(2):158-65. · 4.16 Impact Factor
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ABSTRACT: We describe a case of intrahepatic cholangiocarcinoma (ICC) in a 50-year-old man. A well-defined, hypoechoic tumor, 3.5 cm in greatest diameter, was detected in the left medial segment of the liver with ultrasonography. Celiac angiography showed staining at the same location. Computed tomography revealed lymph node swelling around the head of the pancreas. On October 10, 1993, the patient underwent partial hepatectomy with pancreatoduodenectomy and lymph node dissection around the hepatoduodenal ligament and along the common hepatic artery. Postoperative histopathological examination showed a moderately differentiated tubular adenocarcinoma which had metastasized to the dissected lymph nodes at the posterior surface of the head of the pancreas and at the root of the middle colic artery. Eight years after surgery, the patient is alive and well with no sign of recurrence. Immunohistochemical staining showed ductal-type mucin core protein-1 expression in the tumor, which indicates more favorable survival after surgery. Patients with ICC and lymph node metastasis are considered to have poor prognosis; however, further study of the characteristics of ICC with lymph node metastasis is needed.
Japanese Journal of Clinical Oncology 07/2002; 32(6):206-9. · 1.78 Impact Factor
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ABSTRACT: It has been reported that MUC1 is an important prognostic factor in several cancers. This study investigated the importance of MUC1 as a prognostic factor in mass-forming intrahepatic cholangiocarcinoma (m-ICC).
In 50 patients with m-ICC who had undergone hepatectomy, expression of MUC1 was investigated. Expression of MUC1 was examined by immunohistochemical staining with monoclonal antibody HMPV, which recognizes the MUC1 core peptide. The immunohistochemical staining patterns of MUC1 were classified into three types: ductal type (the luminal surface membrane of neoplastic cells was stained), cytoplasmic type (the cytoplasm of neoplastic cells was stained dominantly), and negative type.
Expression of MUC1 was detected immunohistochemically in 38 (76%) of 50 cases of m-ICC (ductal type, 18; cytoplasmic type, 20; and negative type, 12). Seventy-five percent of patients with lymph node metastasis had the cytoplasmic type MUC1 expression. Lymph node dissection was performed in only 20 patients, but significant correlation was demonstrated between MUC1 expression and lymph node metastasis (P = 0.0227). The location of MUC1 expression correlated with surgical outcome in m-ICC. Patients with the cytoplasmic type expression showed significantly lower survival rates. Univariate analysis revealed that MUC1 expression was a statistically significant risk factor affecting outcome in m-ICC (P = 0.0028). Furthermore, expression of MUC1 was found to be a statistically significant independent risk factor in multivariate analysis (P = 0.0063).
The results suggest that evaluation of MUC1 expression may be very useful in predicting the surgical outcome in m-ICC.
Cancer 04/2002; 94(6):1770-6. · 4.77 Impact Factor
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ABSTRACT: In severe acute pancreatitis (SAP), endotoxin/bacterial translocation (E/BT) from the gut is main cause of infection, which is contributor to high mortality. Toll-like receptors (TLRs) recognize micro-organisms and are involved in the host defense. This study aimed to investigate the expression of TLR2 and TLR4 in intestinal mucosa in SAP.
SAP was induced by injection of 3% sodium deoxycholate into the biliopancreatic duct in rats. Terminal ileum was removed 2, 6, 12, and 18 hours after the induction. Expression of TLR2/4 was analyzed by western blotting and immunohistochemistry. NF-kappaB activation was assessed by enzyme immunoassay. E/BT was also evaluated.
TLR2/4 proteins were increased 2 and 6 hours, and were decreased 12 and 18 hours after the induction. Immunoreactivities for them were detected at the top of villi and crypt in control rats. They were increased 6 hours, and were diminished 12 hours after the induction. Activated NF-kappaB was increased 6 hours, and was decreased 18 hours after the induction. E/BT occurred 18 hours after the induction.
Intestinal immune response enhances in the early phase and suppresses in the late phase of SAP, and TLRs may be implicated in the mechanism of E/BT.
Hepato-gastroenterology 55(88):2247-51. · 0.66 Impact Factor
