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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.

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. 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. 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. We reported here the essence of the clinical practice guideline for PEP.

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.

ERCP後膵炎の腹痛 (膵性疼痛) の発生機序について考察した. 診断的ERCP19,815例に偶発した膵炎23例をもとに, 多変量解析した結果, 性と年齢, 年齢と死亡率, SIRS項目の有無と硬膜外ブロック施行, systemic inflammatory response syndrome (SIRS) 項目の有無と重症度, 重症度と死亡率にそれぞれ有意差を認めた. すなわち, SIRS項目陽性例は有意に“強い腹痛”を訴える例が多く, 重症化しやすいことが判明した.膵性疼痛はトリプシン, サイトカイン (TNF-α), PAR-2, アラキドン酸カスケード, polymodal-nociceptorのカスケード反応により惹起される. 我々は, 発症時に痛みを伴わないERCP後膵炎は経験していない. “強い腹痛 (膵性疼痛)”を訴える例で, とくにSIRSを発症している例には, NSAIDやオピオイドの漫然投与を避けて, 持続動注療法を含むプロテアーゼインヒビターの投与を発症早期より施行することで, 膵性疼痛のカスケード反応を早期に制御すれば, ペインコントロールとSIRSの治療が同時に可能であり, 結果的にERCP後膵炎の重症化を阻止出来る可能性が高い.

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. (Gastrointest Endosc 2002;55:50-4.)

A 76-year-old woman was admitted with obstructive jaundice. US and MR cholangiopancreatography (MRCP) revealed an inoperative cholangiocarcinoma, 3 cm in diameter at the hilum of the liver, the obstruction of the hepatic duct bifurcation and the separation of bilateral hepatic bile ducts. Percutaneous transhepatic biliary drainage (PTBD) was performed from bilateral hepatic bile ducts. The right PTBD tube was spontaneously extubated. We could not succeed in performing internal biliary drainage across the hilar malignant stricture from a left hepatic bile duct, because of bad angulation. Transpapillary insertion into the common bile duct (CBD) was extremely difficult due to the collapse of the CBD. Endoscopic sphincterotomy (EST) after precutting method was performed. Although we performed the ballooned dilatation of malignant stricture and the insertion of a self-expandable metallic stent (EMS) into a right hepatic bile duct transpapillary. After dilatation of the hilar malignant stricture by the initial EMS, we inserted a guidewire into the CBD through the wire mesh of a stent from the left PTBD tube. We could insert the second EMS from a left hepatic bile duct to the CBD transhepatically, using a dilator and a dilating balloon. Finally, we performed the ballooned dilatation from bilateral hepatic bile ducts to the CBD transpapillary. She was discharged after bilateral internal biliary drainages, successfully.

It was very difficult to treat a 90-year-old woman for choledocholithiasis with acute obstructive suppurative cholangitis, gallbladder perforation, and a pool of bile in the right perirenal spase. Extracorporeal shockwave lithotripsy (ESWL) was performed after emergency percutaneous transhepatic biliary drainage (PTBD), but we could not perform lithotripsy successfully because of large and hard stones. Although Endoscopic sphincterotomy (EST) was performed using an ultratome by rendezvous method. Lithotripsy was finally successful, after three times endoscopic mechanical lithotripsy (EML) and procedure using an endotriptor for basket impaction. It is very important in advanced aged patients that endoscopic treatment should be performed step by step.

A 74-year-old woman was admitted to the hospital because of constipation and marked abdominal distension. She had become to be bedridden after cerebral infarction 10 years previously, and was tabescent due to vomiting. A left hemicolectomy and colostomy were performed because conservative therapy seemed to be ineffective. The postoperative course was good and her nutritional status improved.

Early duodenal cancer has been detected with increasing frequency of endoscopy and the advent of an aging society. Aged patients, however, are often inoperable because of complications due to various underlying diseases. The authors report a case of early duodenal cancer curatively operated by endoscopic polypectomy and refer to related cases in the literature.

We have been performing bile duct lithotripsy by EST at Kumamoto Regional Medical Center since January 1982. A balloon catheter is the method of choice for performing lithotripsy. For stone removal, a conventional FG-22Q basket catheter was used from January 1982 to June 1984 (extraction rate: 88.5%), and a prototype EML BML-1Q basket catheter was used with a FG-22Q basket catheter from July 1984 to April 1990 (extraction rate: 91.5%). Since May 1990, lithotripsy has been performed in the following sequence with excellent results (extraction rate: 97.0%): EST-balloon catheter, slide-type EML BML-3Q-balloon catheter. Although the difference between the extraction rates for BML-1Q and BML-3Q basket catheters were only marginally significant, the difference between the conventional basket FG-22Q and BML-3Q was clearly significant. Lithotomy using the procedure employed since May 1990 is therefore recommended as a highly effective means of extracting gallstones and is considered to be superior to conventional methods.

Due to increasing number of the elderly, cases of hematemesis and melena in the aged have been increasing. The authors evaluated 69 such cases over 60 years old in whom emergency endoscopy of the upper digestive tract was carried out because of hematemesis and melena. Twenty cases are diagnosed as gastric ulcer (29%), 12 cases as esophageal ulcer and esophageal erosion (17.4%), 9 as duodenal ulcer (13.0%), 7 as gastric cancer (10.1%), 6 as Mallory-Weiss syndrome (8.7%), 6 as esophageal and gastric varices (8.7%), 4 as acute hemorrhagic gastritis (5.8%), 3 as Dieulafoy's ulcer (4.3%), and one case each of chronic pancreatitis (hemosuccus pancreaticus) and hemorrhage due to gastric angiodysplasia (1.4%). Of these cases, blood transfusion was performed in 46 cases (66.7%), and shock occurred in 27 cases (39.1%). The endoscopical hemostatic procedure was effective for detection of underlying diseases in the aged. Surgery was often impossible because of the rapid deterioration of the systemic condition due to the hemorrhage of the digestive tract.

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.We assessed the efficacy of combination of Irinotecan and Mitomycin C as second-line chemotherapy for unresectable and recurrent gastric cancer.We treated 12 patients receiving combination of Irinotecan and Mitomycin C as second-line chemotherapy between Nov. 2002 and Apr. 2006.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%.In our hospital, combination of Irinotecan and Mitomycin C as second-line chemotherapy prolonged median survival time, and seemed to be an effective regimen.

Mortality due to acute cholangitis (AC) has been tremendously reduced by the advent of endoscopic sphincterotomy (EST). This study investigates whether EST is really a curative procedure for the treatment of AC, or not. Diagnosis of AC, in 159 out of 1,061 cases in which EST was performed, had been made by infected bile which was recognized as green or pyobile collected during ERCP. Emergency drainage by EST was performed immediately after AC was diagnosed. The causes of AC were attributable to benign diseases in 128 cases (80.5%) and malignant diseases in the remaining 31 cases. Clinical symptoms included abdominal pain, fever, and obstructive jaundice, but Charcot's triad was noticed in 66 cases (43.3%) and Reynolds pentad in only 7 cases (4.6%). As to the relation between clinical symptoms and properties of bile, pyobile was more likely to be recognized in patients with severe symptoms. Four patients treated at our hospital died of AC (2.5%). All were over 80 years old, and their conditions were already complicated by disseminating intravascular coagulation (DIC) syndrome. Compared with the results obtained in patients treated with percutaneous transhepatic biliary drainage (PTBD), the resulting mortality rate was less. Therefore, we feel the best approach for treating AC, which progresses to acute obstructive suppurative cholangitis (AOSC) in the final stage of the disease, is to diagnose early, by ERCP, and to promptly obtain decompression by subsequent EST, or to perform radical surgery.

In this study the preliminary results on endoscopic clipping for the treatment of bleeding associated with endoscopic sphincterotomy (ES) are reported. Two patients with melena on the 4th and 5th day after ES were treated by this procedure. The sites of bleeding were recognized respectively as being at the posterior and anterior margin of the endoscopic sphincterotomy. One of the two patients had a large exposed vessel clearly situated near to the previous endoscopic incision. Bleeding was immediately stopped in both cases and no early nor late signs of acute pancreatitis were observed. When this procedure is applied special care to avoid ligation of the pancreatic duct is a must. Moreover in order to facilitate endoscopic manouvers and to promote spontaneous expulsion in 2–3 weeks new smaller clips should be developed.

Purpose With spread of laparoscopic surgery for colon, more reliable way to find the lesion from the serosa side during the surgery became more important.We developed new technique to mark the lesion. Marking was usually done by injecting Indian ink with needle through the fiberscope from mucosal side of colon in Japan. But injection not a few failed to limit the ink within the wall of colon. We tried to apply the EMR technique to the marking. Methods The principle is first to inject 2-3ml of saline into submucosal layer with needle device, to make submucosal upheaval of about 1cm and continuously to change saline to ink and inject it. Then we could limit the ink firmly. We modified these methods to find the best way in respects of ink concentration, amount, location and period until the surgery. Baseline conditions were 11% Indian ink, 0.5ml in amount, every 2 points at both oral and anal side at a distance of 5cm from tumor margin and 2days before the surgery. Alternatives were 5%, 0.2ml, 3cm from the margin, respectively. The better conditions were examined. Subjects were 30cases in total, 5cases each in baseline and alternative of concentration, amount and distance. Injection was performed at 2days before surgery in 18cases, 3days before in 4cases and 7days before in 8cases. Results In 30cases, there were no leak of ink into peritoneal cavity, but 20%(4/20) on ordinary methods in the past. In our new technique, 5% in concentration was easier to inject smoothly. 0.2ml in amount was better on the points of size of staining on surgery. There was no difference in local spread of ink among periods from marking until the surgery. Conclusions The principle and details of our new technique for marking on laparoscopic surgery is easy and sure method.