Usefulness of urinary trypsinogen-2 and trypsinogen activation peptide in acute pancreatitis: A multicenter study in Japan.

BACKGROUND: Rapid urinary trypsinogen-2 dipstick test and levels of urinary trypsinogen-2 and trypsinogen activation peptide (TAP) concentration have been reported as prognostic markers for the diagnosis of acute pancreatitis. AIM: To reconfirm the validity of all these markers in the diagnosis of acute pancreatitis by undertaking a multi-center study in Japan. METHODS: Patients with acute abdominal pain were recruited from 17 medical institutions in Japan from April 2009 to December 2012. Urinary and serum samples were collected twice, at enrollment and on the following day for measuring target markers. The diagnosis and severity assessment of acute pancreatitis were assessed based on prognostic factors and computed tomography (CT) Grade of the Japanese Ministry of Health, Labour, and Welfare criteria. RESULTS: A total of 94 patients were enrolled during the study period. The trypsinogen-2 dipstick test was positive in 57 of 78 patients with acute pancreatitis (sensitivity, 73.1%) and in 6 of 16 patients with abdominal pain but without any evidence of acute pancreatitis (specificity, 62.5%). The area under the curve (AUC) score of urinary trypsinogen-2 according to prognostic factors was 0.704, which was highest in all parameter. The AUC scores of urinary trypsinogen-2 and TAP according to CT Grade were 0.701 and 0.692, respectively, which shows higher than other pancreatic enzymes. The levels of urinary trypsinogen-2 and TAP were significantly higher in patients with extended extra-pancreatic inflammation as evaluated by CT Grade. CONCLUSION: We reconfirmed urinary trypsinogen-2 dipstick test is useful as a marker for the diagnosis of acute pancreatitis. Urinary trypsinogen-2 and TAP may be considered as useful markers to determine extra-pancreatic inflammation in acute pancreatitis.

Clinical practice guideline for post-ERCP pancreatitis.

BACKGROUND: Endoscopic retrograde cholangiopancreatography (ERPC) is used for the diagnosis and treatment of pancreatic and biliary diseases. Post-ERCP pancreatitis (PEP) is a complication which needs special care and clinical practice guideline for this morbidity is also needed. METHODS: The key clinical issues of diagnosis and treatment of PEP were listed and checked, and then the clinical questions were formulated. PubMed (MEDLINE) and Ichushi-web (Japanese medical literature) were used as databases. For the study of diagnostic test accuracy, items similar to QUADAS-2, i.e., random selection from a population to which the diagnostic test is applied, blinding of index tests and reference tests, completeness of reference standard, completeness of test implementations, the same timing of tests, and missing data were assessed as well as the indirectness of the study subjects, index tests, reference standard, and outcomes. Grading of recommendations was determined as strong or weak. In clinical practice, the judgment of attending doctors should be more important than recommendations described in clinical practice guidelines. Gastroenterologists are the target users of this clinical practice guideline. General practitioners or general citizens are not supposed to use this guideline. The guideline committee has decided to include wide clinical issues such as etiological information, techniques of ERCP, the diagnosis, treatments, and monitoring of PEP in this guideline. RESULTS: In this concise report, we described ten clinical questions, recommendations, and explanations pertaining to risk factors, diagnosis, prognostic factors, treatments, and preventive interventions in the medical practice for PEP. CONCLUSIONS: We reported here the essence of the clinical practice guideline for PEP.

The proteinase/proteinase-activated receptor-2/transient receptor potential vanilloid-1 cascade impacts pancreatic pain in mice.

AIMS: Proteinase-activated receptor-2 (PAR2) and transient receptor potential vanilloid-1 (TRPV1) are co-localized in the primary afferents, and the trans-activation of TRPV1 by PAR2 activation is involved in processing of somatic pain. Given evidence for contribution of PAR2 to pancreatic pain, the present study aimed at clarifying the involvement of TRPV1 in processing of pancreatic pain by the proteinase/PAR2 pathway in mice. MAIN METHODS: Acute pancreatitis was created by repeated administration of cerulein in conscious mice, and the referred allodynia/hyperalgesia was assessed using von Frey filaments. Injection of PAR2 agonists into the pancreatic duct was achieved in anesthetized mice, and expression of Fos in the spinal cord was determined by immunohistochemistry. KEY FINDINGS: The established referred allodynia/hyperalgesia following cerulein treatment was abolished by post-treatment with nafamostat mesilate, a proteinase inhibitor, and with capsazepine, a TRPV1 antagonist, in mice. Injection of trypsin, an endogenous PAR2 agonist, or SLIGRL-NH(2), a PAR2-activating peptide, into the pancreatic duct caused expression of Fos protein in the spinal superficial layers at T8-T10 levels in the mice. The spinal Fos expression caused by trypsin and by SLIGRL-NH(2) was partially blocked by capsazepine, the former effect abolished by nafamostat mesilate. SIGNIFICANCE: Our data thus suggest that the proteinase/PAR2/TRPV1 cascade might impact pancreatic pain, in addition to somatic pain, and play a role in the maintenance of pancreatitis-related pain in mice.

[Combination of irinotecan and Mitomycin C as second-line chemotherapy for patients with unresectable advanced or recurrent gastric cancer in clinical practice].

BACKGROUND: Recently, combination S-1 and CDDP chemotherapy is considered as a standard regimen for unresectable or recurrent gastric cancer. Second-line chemotherapy is reportedly important to improve survival, and combination of Irinotecan and Mitomycin C as second-line chemotherapy has proven effective in phase II study of JCOG 0109-DI. PURPOSE: We assessed the efficacy of combination of Irinotecan and Mitomycin C as second-line chemotherapy for unresectable and recurrent gastric cancer. PATIENTS AND METHODS: We treated 12 patients receiving combination of Irinotecan and Mitomycin C as second-line chemotherapy between Nov. 2002 and Apr. 2006. RESULTS: The response rate was 42% including 2 complete response. Progression-free survival was 6.1 months, and time to progression was 5.4 months. Median survival time after the start of second-line chemotherapy was 11.2 months, and after first-line treatment 20.5 months. One-year survival rate was 50%, and 2-year survival rate was 33%. CONCLUSION: In our hospital, combination of Irinotecan and Mitomycin C as second-line chemotherapy prolonged median survival time, and seemed to be an effective regimen.

Mechanism of pancreatitis caused by ERCP.

BACKGROUND: Acute pancreatitis can develop after either ERCP or endoscopic sphincterotomy (ES). The pathogenesis of this complication remains poorly understood. METHODS: The frequency and severity of acute pancreatitis were retrospectively evaluated after 17,602 ERCP procedures and 3003 ES procedures. Pancreatitis was diagnosed and evaluated according to the scoring system of Ranson and criteria developed in Japan. RESULTS: Pancreatitis developed after 15 (0.09%) of 17,602 ERCP procedures and 13 (0.43%) of 3003 ES procedures (p = 0.0001, chi-square). The severity of pancreatitis (Ranson score) was less than 3 in 10 cases of ERCP-induced pancreatitis and from 3 to 5 in 5 cases. One (7%) of the 15 patients with ERCP-related pancreatitis died. All 13 patients with ES-induced pancreatitis had a Ranson score of less than 3; none died (p = 0.04, Fisher exact test). The ERCP pancreatitis score (Japanese criteria) beyond 48 hours after the onset of pancreatitis increased in 5 (33%) of the 15 patients with ERCP-induced pancreatitis; the score did not increase in any of the 13 patients with ES-induced pancreatitis (p = 0.04, Fisher exact test). CONCLUSIONS: Although the frequency of ES-induced pancreatitis is significantly higher than that of post-ERCP pancreatitis, the frequency of severe pancreatitis within 48 hours and worsening of pancreatitis after 48 hours is significantly lower with ES-induced pancreatitis. Our hypothesis is that the lowering of pancreatic intraductal pressure after ES mitigates the severity of postprocedure pancreatitis.