VEGF-C and COX-2 expression in papillary thyroid cancer.

In papillary thyroid cancer (PTC), age appears to be the most important single prognostic factor. Another characteristic feature is the lack of association between survival and lymph node metastases. Earlier, we found that expression of cyclooxygenase-2 (COX-2) is higher in older PTC patients, in agreement with the finding that older patients have a worse prognosis. Recent findings suggest that COX-2 can up-regulate vascular endothelial growth factor-C (VEGF-C) expression. Here, we investigated whether expression of VEGF-C differs between young and older PTC patients and whether expression of VEGF-C and COX-2 are correlated. Our retrospective study comprised 106 PTC patients selected by age: those under 35 or over 55 at diagnosis. Paraffin-embedded tissue samples were analysed by immunohistochemistry for VEGF-C protein expression. Furthermore, we investigated by quantitative RT-PCR and enzyme immunoassay the relationship between VEGF-C and COX-2 expression in papillary thyroid cancer cells (NPA cells). VEGF-C expression was significantly increased with age. In the tumours from older lymph node-positive (N1) patients, VEGF-C expression was significantly higher than in the tumours from young N1 patients. Moreover, all patients who died of cancer or who developed distant metastases were old, and most tumours from these patients (4 of 5) expressed VEGF-C and had had nodal metastases at the time of primary operation. Immunohistochemically, expression of COX-2 and VEGF-C correlated strongly. In cell culture, this correlation was not so clear, because the COX-2 selective inhibitor, NS-398, did not reduce VEGF-C expression. However, as both COX-2 and VEGF-C were induced by the tumour promoter phorbol 12-myristate 13-acetate (PMA), the same factors may control them both.

Upregulated but insufficient generation of activated protein C is associated with development of multiorgan failure in severe acute pancreatitis.

INTRODUCTION: Disturbed protein C (PC) pathway homeostasis might contribute to the development of multiple organ failure (MOF) in acute pancreatitis (AP). We therefore evaluated circulating levels of PC and activated protein C (APC), evaluated monocyte deactivation in AP patients, and determined the relationship of these parameters to MOF. PATIENTS AND METHODS: Thirty-one patients in the intensive care unit were categorized as cases (n = 13, severe AP with MOF) or controls (n = 18, severe AP without MOF). Blood samples were drawn every second day to determine the platelet count, the levels of APC, PC, and D-dimer, and the monocyte HLA-DR expression using flow cytometry. The APC/PC ratio was used to evaluate turnover of PC to APC. RESULTS: During the initial two weeks of hospitalization, low PC levels (<70% of the adult mean) occurred in 92% of cases and 44% of controls (P = 0.008). The minimum APC level was lower in cases than in controls (median 85% versus 97%, P = 0.009). Using 87% as the cut-off value, 8/13 (62%) cases and 3/18 (17%) controls showed reduced APC levels (P = 0.021). A total of 92% of cases and 50% of controls had APC/PC ratios exceeding the upper normal limit (P = 0.013). Plasma samples drawn before MOF showed low PC levels and high APC/PC ratios. HLA-DR-positive monocytes correlated with PC levels (r = 0.38, P < 0.001) and APC levels (r = 0.27, P < 0.001), indicating that the PC pathway was associated with systemic inflammation-triggered immune suppression. CONCLUSION: PC deficiency and decreased APC generation in severe AP probably contributed to a compromised anticoagulant and anti-inflammatory defence. The PC pathway defects were associated with the development of MOF. The data support feasibility of testing the use of APC or PC to improve the clinical outcome in AP.

Spontaneous disappearance of Helicobacter pylori antibodies in patients with advanced atrophic corpus gastritis.

Background. Only a few reported studies focus on the natural history and course of advanced and severe chronic atrophic gastritis. Methods. In this study we followed 47 men (mean age 62 years) with advanced (moderate or severe) Helicobacter pylori-positive atrophic corpus gastritis. Duration of endoscopic follow-up was 6 years and follow-up based on serum levels of pepsinogen I and antibodies to H. pylori covered a period of 10 years. None of the patients was treated for H. pylori infection prior to end of follow-up. Results. The median H. pylori antibody titre declined (IgG from 4000 to 1300; IgA from 200 to 50) in the study population, and 11 men (23%) converted to seronegative (p=0.0005, Fisher's exact test). There was a small but significant (p=0.0004, Page's test) declining trend in mean atrophy score of the corpus during follow-up (from 2.5 to 2.2). However, no significant changes were observed in grade of atrophy or intestinal metaplasia of the antral mucosa or in grade of intestinal metaplasia in the corpus. The mean SPGI level remained at the initial low level during the entire follow-up. Conclusions. H. pylori antibodies disappear spontaneously within 10 years in almost one fourth of patients with advanced atrophic corpus gastritis. The disappearance of H. pylori antibodies is accompanied by no or more than a mild improvement of the gastric mucosa.

Long-term health-related quality of life in survivors of severe acute pancreatitis.

OBJECTIVE: To evaluate the health-related quality of life (HRQL) and postdischarge outcome after severe acute pancreatitis. DESIGN AND SETTING: Observational study in a department of surgery (surgical and general intensive care unit) in a tertiary care hospital. PATIENTS AND PARTICIPANTS: Of 283 patients with severe acute pancreatitis 211 survived; during a follow-up period an additional 27 died. The Rand 36-item Health Survey with accessory question was mailed to 174 eligible patients. The final study population comprised 145 patients (83% response rate). Age- and sex-matched Finnish population scores were compared with the study population; accessory questions were analyzed separately. RESULTS: No clinically significant differences were found in long-term HRQL between study patients and the general population. Of the 145 patients 87% returned to work, 27% suffered recurrent pancreatitis, and 43% developed diabetes. Of 113 patients with alcohol-induced severe acute pancreatitis 30% were abstinent and 28% problem drinkers, alcohol-dependent, or alcoholics. CONCLUSIONS: Up to 13% of severe acute pancreatitis patients surviving initial hospitalization die within a few years. Among the survivors long-term HRQL is comparable to that of the normal population. The majority return to work and reduce their alcohol consumption markedly.

AMES, MACIS and TNM prognostic classifications in papillary thyroid carcinoma.

The need for total thyroidectomy and extended for lymphadenectomy and the need for postoperative radioiodine ablation in the treatment of papillary thyroid carcinoma is continuously debated. Since less aggressive treatment in low-risk patients has been suggested, several scoring systems have been developed to identify low-risk patients. In the current study, we compared the AMES, MACIS and TNM staging systems in predicting carcinoma-specific mortality in papillary thyroid carcinoma. Between 1967 and 1994, 495 patients with papillary thyroid carcinoma were treated at the Department of Surgery, Helsinki University Central Hospital. Carcinoma-specific mortality in the AMES low-risk group, comprising 89.7% of these patients, was 2.4%. Corresponding figures for the MACIS were 89.9%, and 2.4%, and for the TNM 85.9% and 1.2%. The mortality ratio, at 10 years, between low-risk and high-risk patients was 22.2 for the AMES, 25.0 for the MACIS and 41.8 for the TNM system. The proportion of explained variance in the Cox model was 16.3 for the AMES, 30.0 for the MACIS taken as a conitinuous variable and 28.9 for the TNM stage. The TNM stage was on average superior to the MACIS or AMES score in predicting cancer-specific mortality of patients with papillary thyroid carcinoma. This may be explained by the fact that the TNM system includes the prognostic effect of nodal metastases, which is included in neither the MACIS nor AMES systems.

Elevated levels of the complement regulator protein CD59 in severe acute pancreatitis.

OBJECTIVE: Complement activation occurs in patients with acute pancreatitis (AP) and may contribute to the development of organ failure. Because a number of enzymes are released during AP that could influence the complement inhibitor CD59, the purpose of this study was to examine serum levels of CD59 in relation to severity of AP. MATERIAL AND METHODS: Twelve patients with severe AP had organ failure (referred to as the grade 2 group). For each of them, we found 2-3 age-matched AP patients who served as controls (n=27). Of these, a total of 13 had mild AP (grade 0 group) and 14 severe AP without organ failure (grade 1 group). Blood samples were collected at admission and on days 1 and 3-7 post-admission. Grade 2 patients were compared with grade 0 and grade 1 patients. CD59 levels were measured by a sandwich enzyme immunoassay. RESULTS: At admission, median CD59 levels were significantly higher (p = 0.002) in grade 2 patients (median 104.2 ng/ml, range 26.1-186.3) than in grade 0 patients (37.3, range 30.3-75.9) and grade 1 patients (38.6, range 19.9 96.1). CD59 levels remained higher in grade 2 patients than in grade 0 and 1 patients on day 1 (p = 0.001) and days 3-7 (p = 0.002). The CD59 levels correlated significantly (p < 0.05) with C-reactive protein (CRP) levels (R = 0.40) and APACHE II scores (R = 0.32) on admission. CONCLUSIONS: Organ failure and severity of AP are associated with elevated serum levels of CD59.

Polymorphisms of the TNF, CD14, and HSPA1B genes in patients with acute alcohol-induced pancreatitis.

OBJECTIVES: Genotype assessment has been suggested to be a tool for predicting disease severity in acute pancreatitis (AP). To study this hypothesis, we performed genotype analysis of tumor necrosis factor (TNF) -308 A/G, CD14 -159C/T, and HSPA1B +1267 A/G polymorphisms. METHODS: This is a case-control association study of 397 patients with AP (214 of whom had an alcohol-induced AP) and 300 controls. The control group comprised 218 subjects with detailed data of alcohol consumption, 70 of whom were heavy drinkers (daily alcohol intake >40 g), and 92 blood donors. The severity of AP was determined according to the Atlanta classification. Genotyping was performed by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry-assisted genotyping method. RESULTS: Major allele frequency in TNF gene was 0.87 for patients with AP and 0.86 for controls. For CD14, the gene major allele frequency was 0.60 for patients and 0.63 for controls. For HSPA1B, the major allele frequencies were 0.52 for patients and 0.49 for controls, respectively. The allele frequencies did not differ significantly between AP patients with organ failure and those with mild disease, patients with alcohol-induced AP, or those with biliary AP. The patients with septic infectious complications (n = 47) had genotype distribution no different from those with mild, uncomplicated disease (n = 245). CONCLUSIONS: The TNF, CD14, and HSPA1B polymorphisms studied seem not to play a role in determining the severity of AP or the risk of alcohol-induced AP and thus do not serve as a tool for predicting disease severity.

Treatment of bleeding pseudoaneurysms in patients with chronic pancreatitis.

BACKGROUND: In patients with chronic pancreatitis, an actively bleeding pseudoaneurysm can be life-threatening. Angioembolization is an attractive alternative to often complex operative management, and its feasibility was assessed in a retrospective analysis. METHODS: During 1993-2005, 33 patients (27 males, median age 51 years) with bleeding pancreatic pseudoaneurysms underwent urgent angiographic evaluation followed by angioembolization if possible. Angioembolization was performed in 23 patients, whereas 10 patients required hemostatic surgery, including 6 distal pancreatectomies and 3 vessel ligations. RESULTS: Between 1993 and 2005 33 out of 745 patients (4.4%) admitted for chronic pancreatitis had bleeding pancreatic pseudoaneurysms. The proportion of bleeders out of the total number of hospital admissions for chronic pancreatitis was 33 out of 1,892 (1.7%). The overall success rate of angioembolization was 22 out of 33 (67%) including 3 patients requiring re-embolization for recurrent bleeding. The success rate was 16 out of 20 (80%) when the pseudocyst was in the head of the pancreas, and only 50% when the splenic artery was the source of bleeding. Four of the 5 cases with free bleeding into the peritoneal cavity required operative intervention. The overall mortality and morbidity rates were 2 out of 33 (6%) and 7 out of 33 (21%) respectively, with no significant differences between embolized and operated patients. Angioembolization was associated with a significantly lower need for total blood transfusions and length of hospital stay. During the years 2000-2005, the overall success rate of angioembolization was 95%. CONCLUSIONS: All hemodynamically stable patients with chronic pancreatitis and bleeding pseudoaneurysms should undergo prompt initial angiographic evaluation and embolization if possible. Repeated angioembolization is feasible in patients with recurrent bleeding, whether initially embolized or operated. Patients with unsuccessful embolization should undergo emergency hemostatic surgery with ligation of the bleeding vessel in the head of the pancreas and distal resection in patients bleeding from the splenic artery or its branch. The combination of angioembolization and later endoscopic drainage of the pseudocyst via endoscopic retrograde cholangiopancreatography (ERCP) is effective in the majority of the cases of pseudoaneurysms in chronic pancreatitis.

Disialotransferrin, determined by capillary electrophoresis, is an accurate biomarker for alcoholic cause of acute pancreatitis.

OBJECTIVES: Serum disialotransferrin is a specific marker of heavy alcohol consumption. We tested its accuracy and probability in detecting alcoholic cause of acute pancreatitis (AP). METHODS: Blood samples from 271 consecutive AP patients, admitted to the Helsinki University Central Hospital emergency unit, were analyzed. RESULTS: The median (range) disialotransferrin value was significantly higher (P = 0.001) in AP patients with alcoholic (n = 172) 1.6% (0.3%-14.4) than with biliary (n = 60) 0.7% (0.3%-1.3%) or other causes (n = 39) 0.8% (0.3%-4.1%). In receiver operating curve analysis, disialotransferrin, as a single analyte, was significantly (P = 0.001-0.0001) more accurate (area under the curve [AUC], 0.88; 95% confidence interval [CI], 0.84-0.92) in detecting alcoholic AP as compared with glutamyl transferase (AUC, 0.51; 95% CI, 0.45-0.57), aspartate aminotransferase (AUC, 0.57; 95% CI, 0.51-0.63), alanine aminotransferase (AUC, 0.63; 95% CI, 0.57-0.69), erythrocyte mean cell volume (AUC, 0.72; 95% CI, 0.67-0.78), amylase (AUC, 0.74; 95% CI, 0.67-0.78), C-reactive protein (AUC, 0.65; 95% CI, 0.59-0.71), and bilirubin (AUC, 0.55; 95% CI, 0.49-0.62). At a disialotransferrin cutoff of 1.2%, giving an 8% false-positive rate, the positive likelihood ratio was 8.47. Thus, a positive disialotransferrin test result, performed within 24 hours of admission, increased the probability of alcoholic AP from pretest 64% to posttest 94%. CONCLUSIONS: Disialotransferrin, determined by capillary electrophoresis, is accurate, simple, and a rapid single biomarker of the alcoholic cause of AP.

Immunohistochemical expression of Bcl-2, Ki-67, and p21 in patients with papillary thyroid cancer.

Papillary thyroid cancer (PTC) is a slow-growing tumor with a favorable outcome. Still, some low-risk patients develop local or distant metastases and eventually die from their disease. Many molecular markers are involved in proliferation and apoptosis, including Bcl-2, Ki-67, and p21. Because age over 45 is the most important determinant of a poor survival, we analyzed whether the expression of these tumor proliferation markers differs between young and older PTC patients. Our study comprised 108 PTC patients retrospectively selected by age, i.e. those younger than 35 or older than 55 at diagnosis. Formalin-fixed, paraffin-embedded archival tissue blocks were analyzed for Bcl-2, Ki-67, and p21 protein expression by immunohistochemistry. We showed that expression of Ki-67 increases significantly with age, indicating that tumors in older patients may grow faster. This higher proliferative activity may explain the worse prognosis in these patients. Expression of p21 was higher in large tumors and in tumors extending beyond the thyroid capsule. Expression of Bcl-2 did not correlate with clinical parameters.

Prognostic factors in papillary thyroid cancer: an evaluation of 601 consecutive patients.

BACKGROUND: Although papillary thyroid cancer (PTC) is among the most curable cancer types, it can be a distressing disease for those patients suffering from frequent recurrences or even distant metastases leading to death. Age over 45 years is the most important indicator of poor prognosis. Our aim was to evaluate markers which might predict the outcome of an individual patient better than does TNM classification alone. MATERIALS AND METHODS: Of 601 consecutive patients who underwent surgery for PTC, retrospectively we selected 36 patient pairs in which one recovered completely after primary surgery, and the other suffered from aggressive disease. Formalin-fixed, paraffin-embedded tumor samples from these 72 patients were analyzed by immunohistochemistry for COX-2, MMP-2, VEGF-C, Bcl-2, Ki-67, and p21 expression. RESULTS AND CONCLUSIONS: None of the markers we studied showed a superiority over TNM classification in selecting patients likely to progress to aggressive disease. However, the expression of COX-2 and VEGF-C seemed to be increased in patients over 45, which could explain the more aggressive behavior of these tumors. Moreover, we found that age over 45, tumor size over 4 cm, extrathyroidal extension of tumor, nodal metastases, distant metastases, and stage IV had an unfavorable effect on survival.

Early sequential changes in serum markers of acute pancreatitis induced by endoscopic retrograde cholangiopancreatography.

BACKGROUND/AIMS: Trypsinogen activation is thought to play a crucial role in the pathogenesis of acute pancreatitis (AP). Our aim was to characterize the very early sequential changes of trypsinogen-1, trypsinogen-2, the trypsin-2-alpha1-antitrypsin complex (T2-AAT), and pancreatic secretory trypsin inhibitor (PSTI) in serum from patients with pancreatitis induced by endoscopic retrograde cholangiopancreatography (ERCP), a model for studying the early phase of the disease in humans. PATIENTS AND METHODS: The study population consisted of 659 consecutive patients with 897 ERCP procedures. Blood samples were obtained before and at different time points after the procedure. The serum concentrations of trypsinogen-1 and trypsinogen-2, PSTI and T2-AAT were determined by time-resolved immunofluorometric assays. RESULTS: ERCP-induced pancreatitis developed after 50 of the 897 ERCP procedures (5.6%). Sixty-one randomly selected ERCP patients without post-ERCP pancreatitis served as controls. Trypsinogen-1 and trypsinogen-2 showed an equally steep increase during the two first hours after ERCP in patients developing AP, but trypsinogen-1 decreased more rapidly than trypsinogen-2, which remained elevated during the 5-day study period. Serum PSTI also increased rapidly whereas T2-AAT increased more slowly peaking at 24 h. In patients developing post-ERCP pancreatitis the median concentration of trypsinogen-1 was markedly higher than in the controls already before the ERCP procedure. In the control group the concentrations of trypsinogen-1, trypsinogen-2, PSTI and T2-AAT did not change significantly. CONCLUSIONS: The rapid increase of trypsinogen-1 and trypsinogen-2 and PSTI in the early phase of AP suggests that release of pancreatic enzymes is the initial event while the delayed increase of T2-AAT may reflect that the capacity of the intrapancreatic PSTI-based inhibitory mechanism has been exhausted.

Monocyte anergy is present in patients with severe acute pancreatitis and is significantly alleviated by granulocyte-macrophage colony-stimulating factor and interferon-gamma in vitro.

OBJECTIVES: Severe acute pancreatitis (AP) is frequently associated with immune suppression, which increases the risk of infections, organ failure, and death. Our aims were to measure monocyte function (ie, HLA-DR expression and tumor necrosis factor-alpha [TNF-alpha] production as markers of immune suppression) in patients with severe AP and to determine whether treatment of blood samples with granulocyte-macrophage colony-stimulating factor (GM-CSF) and/or interferon-gamma (IFN-gamma) corrected the functional defects of monocytes in vitro. METHODS: The study consisted of 28 patients with severe AP who were treated at intensive care unit and in whom the proportion of HLA-DR-positive monocytes in the circulation was less than 70%, and 28 matched control subjects who were selected from healthy laboratory personnel. HLA-DR density was determined by whole blood flow cytometry. Monocyte TNF-alpha production in response to bacterial lipopolysaccharides (LPSs) was studied in a whole blood assay. Aliquots of blood were supplemented with IFN-gamma (all 28 patients), GM-CSF (the last 24 patients), or both (the last 12 patients). RESULTS: The median proportion of HLA-DR-positive monocytes was 45% in patients (range, 18%-73%) and was 98% in controls (range, 86%-100%; P < 0.001). TNF-alpha levels in response to LPSs were lower in patients (545 pg/mL; range, 84-1990 pg/mL) than in controls (1415 pg/mL; range, 660-5490 pg/mL; P < 0.001). The proportion of HLA-DR-positive cells correlated positively with TNF-alpha levels (r = 0.56; P < 0.01). Both GM-CSF and IFN-gamma increased HLA-DR expression of monocytes in patients (98%; range, 74%-100% for GM-CSF; 99%; range, 86%-100% for IFN-gamma; both P < 0.001). The combination restored monocyte HLA-DR expression (99%; range, 96%-100%; P = 0.002). Compared with basal levels, GM-CSF increased TNF-alpha production of monocytes both in blood samples from patients (median, 1320 pg/mL; range, 35-8015 pg/mL) and controls (median, 3450 pg/mL; range, 1040-9835 pg/mL; both P < 0.001). IFN-gamma increased TNF-alpha production by monocytes in patients (683 pg/mL; range, 186-2705 pg/mL; P < 0.05) but not in controls (1658 pg/mL; range, 765-4755 pg/mL; P = 0.31). With the combination of GM-CSF and IFN-gamma, the TNF-alpha levels of monocytes in patients (3185 pg/mL; range, 545-8280 pg/mL) and in controls (2800 pg/mL; range, 1080-6860 pg/mL) were comparable. CONCLUSIONS: The proportion of HLA-DR-positive monocytes correlates with TNF-alpha production, and they both reflect the degree of immune suppression. The low proportion of HLA-DR-positive monocytes in AP can be reversed in vitro by GM-CSF and/or IFN-gamma. The GM-CSF and IFN-gamma treatments also increase LPS-induced TNF-alpha production. By the combination of GM-CSF and IFN-gamma, but not by either agent alone, LPS-induced TNF-alpha production of monocytes was equally high in patients and in controls.

Diagnostic laparoscopy in abdominal stab wounds: a prospective, randomized study.

BACKGROUND: The optimal strategy for identifying patients with abdominal stab wounds requiring surgical repair has not been defined. The potential benefits of diagnostic laparoscopy by incorporating it into the routine diagnostic workup of patients with anterior abdominal stab wounds was evaluated in a two-layer, randomized study. METHODS: From May 1997 through January 2002, stable patients without peritonitis but with demonstrated peritoneal violation were randomized (A) to exploratory laparotomy (AEL) (n = 23) or diagnostic laparoscopy (ADL) (n = 20). Simultaneously, patients with equivocal peritoneal violation on local wound exploration were randomized (B) to diagnostic laparoscopy (BDL) (n = 28) or expectant nonoperative management (BNOM) (n = 31). Hospital morbidity, length of stay, and costs were primary endpoints, with postdischarge disability being a secondary endpoint. RESULTS: In patients with peritoneal penetration (AEL vs. ADL), there were minimal differences in the therapeutic operation rate (8 of 23 [AEL] vs. 8 of 20 [ADL], p = 0.761), mortality (none), morbidity (3 of 23 vs. 2 of 20, p = 0.999), hospital stay (mean +/- SD) (5.7 +/- 2.5 vs. 5.1 +/- 4.0 days, p = 0.049), hospital costs (4.6 +/- 1.3 vs. 4.8 +/- 1.9 x 1,000 EUR, p = 0.576), and length of sick leave (34 +/- 12 vs. 29 +/- 11 days, p = 0.305). In patients with equivocal peritoneal penetration (BDL vs. BNOM), laparoscopy found more mostly minor organ injuries (7 of 28 [BDL] vs. 1 of 31 [BNOM], p = 0.022) with no significant difference in therapeutic operations (3 of 28 vs. 1 of 31, p = 0.337) or morbidity (3 of 28 vs. 0 of 31, p = 0.101), but was associated with increased length of stay (2.6 +/- 2.1 vs. 1.9 +/- 1.8 days, p = 0.022), hospital costs (4.2 +/- 1.3 vs. 1.5 +/- 1.1 x 1,000 EUR, p = 0.000), and sick leave requirements (18 of 23 vs. 8 of 28 of eligible patients, p = 0.001). CONCLUSION: In patients with demonstrated peritoneal violation, laparoscopy offers little benefit over exploratory laparotomy. In patients with equivocal peritoneal penetration on local wound exploration, laparoscopy detects more mostly minor organ injuries than expectant nonoperative management but is associated with increased hospital stay, costs, and sick leave requirements. Overall, diagnostic laparoscopy cannot be recommended as a routine diagnostic tool in anterolateral abdominal and thoracoabdominal stab wounds.

Occult diaphragmatic injuries caused by stab wounds.

BACKGROUND: Missed diaphragmatic perforation caused by penetrating trauma can lead to subsequent strangulation of a hollow viscus, which has prompted the use of invasive diagnostic procedures to exclude occult diaphragmatic injuries in asymptomatic, high-risk patients. The objective of this study was to determine the incidence of occult diaphragmatic injuries caused by stab wounds of the lower chest and upper abdomen, and to examine the natural history and consequences of missed diaphragmatic injuries. METHODS: On the basis of patient data from two previous randomized studies from our institution, a retrospective analysis was performed on 97 patients treated for anterior stab wounds located between the nipple line, the umbilical level, and the posterior axillary lines not having indications for immediate surgical exploration. The patients were divided into two groups on the basis of their initial randomized management (open or laparoscopic exploration vs. expectant observation). RESULTS: In the exploration group (n = 47), four diaphragmatic injuries (9%) were detected (three left-sided and one right-sided). Excluding patients with associated injuries requiring surgical repair, the incidence of occult diaphragmatic injuries was 3 of 43 (7%). In the observation group (n = 50), there were two patients (4%) with delayed presentation of missed left-sided diaphragmatic injury 2 and 23 months later, respectively. Both injuries resulted from stab wounds of the left flank and presented with herniation of the stomach or small bowel and colon. The overall incidence of occult diaphragmatic injuries in left-sided thoracoabdominal stab wounds was 4 of 24 (17%), and was much lower after stab wounds of left epigastrium (0%), right lower chest (0%), and right epigastrium (4%). CONCLUSION: In asymptomatic patients with anterior or flank stab wounds of the lower chest or upper abdominal area, the risk of an occult diaphragmatic injury is approximately 7% which, if undetected, is associated with a high risk of subsequent hollow viscus herniation. Exclusion of an occult diaphragmatic injury with invasive diagnostic methods, such as laparoscopy or thoracoscopy, should be considered at least in left-sided stab wounds of the lower chest.

Proinflammatory effects of pancreatic elastase are mediated through TLR4 and NF-kappaB.

Pancreatic elastase has been implicated in the pathophysiology of severe acute pancreatitis, characterized by systemic inflammatory response, distant organ failure, and high mortality. Here we show that pancreatic elastase activates transcription factors NF-kappaB, AP-1, and NFAT in human myeloid cells (U-937 and THP-1) in culture. Pancreatic elastase also induces TNF-alpha secretion and increased expression of CD11b in THP-1 cells which can be inhibited by neutralizing anti-Toll-like receptor 4 (TLR4) antibodies. NF-kappaB blocking agents (MG-132, PGA1) prevented elastase-induced TNF-alpha secretion from THP-1 cells. Our results suggest that pancreatic elastase-induced proinflammatory effects are mediated by TLR4 and NF-kappaB in human myeloid cells.

Trypsinogen-2 and trypsinogen activation peptide (TAP) in urine of patients with acute pancreatitis.

BACKGROUND AND AIMS: There is an obvious clinical need for a simple test that can identify patients at risk of developing severe acute pancreatitis. In this work we compared urinary trypsinogen-2 with urinary trypsinogen activation peptide (TAP) and serum C-reactive protein (CRP) for early differentiation between mild and severe acute pancreatitis. PATIENTS AND METHODS: The study population consisted of 127 consecutive patients with acute pancreatitis of whom 29 had severe disease. Urinary trypsinogen-2 was measured by a quantitative immunofluorometric assay and TAP by a competitive immunoassay. Serum CRP was determined by immunoturbidimetry. RESULTS: The sensitivity and specificity to identify severe acute pancreatitis on admission was 72% and 81% for urinary trypsinogen-2, 64% and 82% for urinary TAP, and 29% and 93% for serum CRP, respectively. At 24 h after admission, the values were 82% and 78% for urinary trypsinogen-2, 52% and 92% for urinary TAP, and 84% and 72% for serum CRP, respectively. Receiver-operating characteristics curve analysis showed that the area under the curve was larger for urinary trypsinogen-2 than for urinary TAP and serum CRP on admission and 24 h after admission. On admission the positive likelihood ration for urinary trypsiongen-2 was 3.7, for urinary TAP 3.6, and 4.3 for serum CRP, respectively. The corresponding negative likelihood ratios were 0.34, 0.43, and 0.76, respectively. CONCLUSION: Urinary trypsinogen-2 was superior to serum CRP and as god as or even better than urinary TAP and in the early prediction of disease severity in acute pancreatitis. These results suggest that it could be a valuable adjunct in the early assessment of the severity of acute pancreatitis.

Development of Barrett's esophagus after 'spontaneous' healing of atrophic corpus gastritis.

We report here the case of a 58-year-old asymptomatic male smoker who had a gastroscopy performed in 1990 because of a low serum pepsinogen I level (16 microg/l). The patient had severe atrophic corpus gastritis and elevated Helicobacter pylori antibody titers, but no histologic evidence of the bacteria. Additionally, a hiatal hernia without esophagitis was seen. He was followed up endoscopically because of the atypical changes (indefinite for dysplasia) in addition to atrophic gastritis in some of the gastric biopsy samples. During the follow-up period, H. pylori antibody titers declined to normal levels without eradication therapy, and atrophic gastritis healed. The patient developed first erosive esophagitis, and, 5 years later, a 3-cm-long Barrett's esophagus was detected.