三好 広尚

OBJECTIVES: We set out to predict whether nonsurgical treatment is likely to succeed in removing pancreatic stones in a given patient and also to determine an optimal maximal number of extracorporeal shock wave lithotripsy (ESWL) sessions for treatment of pancreatolithiasis in that patient. MATERIALS AND METHODS: We ascertained the number of ESWL sessions for each of 164 patients undergoing that treatment for pancreatolithiasis between 1992 and 2020. Median follow-up duration was 31 months (range, 0-239), median age was 58 years (22-83), and the male to female ratio was 5.1:1.0. Patients were divided into 2 groups based upon an optimal maximal number of ESWL sessions determined by receiver operating characteristic analysis. RESULTS: Total stone clearance was achieved in 130 of 164 patients (79%). The median number of ESWL sessions was 3 (1-61). Receiver operating characteristic analysis determined 7 to be the optimal maximal number of sessions. Complete clearance was more frequent (87%) among the 131 patients requiring 7 or fewer ESWL sessions than among the 33 undergoing more (48%, P < 0.001). Seventeen patients (52%) undergoing 8 or more sessions still had residual stones. CONCLUSIONS: If any pancreatic stones persist after 7 ESWL sessions, we recommend transition to medical or surgical treatments.

A 69-year-old woman suspected to have IgG4-related sclerosing cholangitis causing bile duct stenosis was transferred from another hospital after diarrhea, eosinophilia, and eosinophilic infiltration were detected and prednisolone was prescribed. Additional biliary imaging suggested primary sclerosing cholangitis, but the IgG4 level and inferior bile duct stenosis were alleviated by steroid therapy, suggesting IgG4-related sclerosing cholangitis. Therefore, prednisolone was continued. Bile duct biopsy findings suggesting adenocarcinoma led to a diagnosis of pancreatoduodenectomy. The latter specimen only displayed evidence of primary sclerosing cholangitis, and prednisolone was discontinued. Intractable cholangitis necessitated left hepatectomy, after which serum alkaline phosphatase levels increased and eosinophilic colitis recurred. The reintroduction of prednisolone effectively managed the diarrhea but only temporarily reversed the alkaline phosphatase elevation. When histologic sections from resection specimens were compared, the hepatectomy specimen exhibited greater eosinophil infiltration than the earlier pancreatoduodenectomy specimen, suggesting eosinophilic cholangiopathy superimposed on primary sclerosing cholangitis.

OBJECTIVES: We aimed to determine when a coexisting pseudocyst was likely to complicate the nonsurgical treatment of pancreatolithiasis. METHODS: We treated 165 patients with pancreatolithiasis nonsurgically between 1992 and 2020, including 21 with pseudocysts. Twelve patients had a single pseudocyst less than 60 mm in diameter. Pseudocysts in the other nine patients had diameters of at least 60 mm or were multiple. The locations of pseudocysts along the length of the pancreas varied from the area with stone involvement to the pancreatic tail. We compared the outcomes in these groups. RESULTS: We found no significant differences in pain relief, stone clearance, stone recurrence, or the likelihood of adverse events between pseudocyst groups or between patients with vs without pseudocysts. However, 4 of 9 patients with large or multiple pseudocysts required transition to surgical treatment (44%) compared with 13 of 144 patients with pancreatolithiasis and no pseudocyst (9.0%) (P=0.006). CONCLUSIONS: Patients with smaller pseudocysts typically underwent nonsurgical stone clearance successfully with few adverse events, similar to findings in patients with pancreatolithiasis and no pseudocysts. Pancreatolithiasis complicated by large or multiple pseudocysts did not cause more adverse events but was more likely to require transition to surgery compared with pancreatolithiasis without pseudocysts. In patients with large or multiple pseudocysts, early transition to surgery should be considered when nonsurgical treatment is ineffective.

BACKGROUND: Many guidelines for nonsurgical treatment of pancreatolithiasis suggest little guidance for patients with pancreatolithiasis who do not have abdominal pain. Some patients with pancreatolithiasis whom we have treated nonsurgically with extracorporeal shock-wave lithotripsy did not have abdominal pain, and we describe one of them here. METHODS AND RESULTS: A 42-year-old man complaining of an 8-kg weight loss over 6 months was admitted to a nearby hospital, where fasting blood sugar and hemoglobin A1c values were 500 mg/dL and 11.8%. Computed tomography showed stones in the head of the pancreas and dilation of the main pancreatic duct. He was referred to our hospital to be considered for nonsurgical treatment of pancreatolithiasis. His height and weight were 160 cm and 52 kg (body mass index, 20.31). No tenderness or other abdominal findings were evident. After obtaining informed consent for nonsurgical treatment despite absence of abdominal pain, we performed extracorporeal shock wave lithotripsy. Computed tomography showed disappearance of stones from the pancreatic head. At discharge, his weight had increased to 62 kg and hemoglobin A1c was 6.8%, though antidiabetic medication has since become necessary. CONCLUSION: We believe that nonsurgical treatment of pancreatolithiasis was helpful for this patient, and could improve exocrine and endocrine function in other patients without abdominal pain.

OBJECTIVE: Clinical guidelines consider abdominal pain an indication for nonsurgical treatment of pancreatolithiasis. We examined benefit from nonsurgically treating asymptomatic pancreatolithiasis. METHODS: We retrospectively reviewed 165 patients with pancreatolithiasis who underwent nonsurgical treatment between 1992 and 2020. Symptoms were absent in 41, while 124 had abdominal pain. In the asymptomatic group, the median follow-up duration was 8 months (range, 0-166 months), and the median age was 61 years (range, 32-80 years). In patients with pain, the median follow-up duration was 43 months (range, 0-293 months), while the median age was 57 years (range, 22-80 years). The male:female ratio was 3.6:1 for asymptomatic patients and 5.9:1 for those with pain. We compared treatment outcome, stone recurrence rate, and changes in pancreatic exocrine function (bentiromide- p -aminobenzoic acid test results) between groups. RESULTS: Nonsurgical treatment for patients with asymptomatic pancreatolithiasis had a 63% stone clearance rate, lower than 84% for symptomatic pancreatolithiasis but comparable to outcomes at other institutions. Pancreatic exocrine function values during the year after treatment were mean, 52% (standard deviation, 16%) in the asymptomatic group, similar to mean, 57% (standard deviation, 17%) in the symptomatic group. CONCLUSIONS: Nonsurgical treatment in asymptomatic pancreatolithiasis may preserve pancreatic exocrine function as well as in symptomatic pancreatolithiasis.

OBJECTIVES: While chronic pancreatitis associated with pancreatolithiasis presents with pain, exocrine and endocrine pancreatic functions worsen with time. We examined outcomes of nonsurgical treatment. METHODS: Between 1992 and 2020, we treated pancreatolithiasis nonsurgically in 165 patients with chronic pancreatitis using extracorporeal shock wave lithotripsy alone or followed by endoscopic procedures. The mean follow-up duration was 49 months (standard deviation, 56 months) and the age was 56 years (standard deviation, 13 years). The male:female ratio was 5.1:1 (138 men, 27 women). We followed treatment results including relief of abdominal pain, stone clearance and recurrence, and pancreatic exocrine function (bentiromide-p-aminobenzoic acid testing). RESULTS: Treatment relieved pain in 117 of 124 patients (94%). The overall stone clearance was achieved in 130 of 165 patients (79%). Stones recurred during follow-up in 50 of 130 patients (38%). One fifth of recurrences were early, often involving stricture of the main pancreatic duct. After 1 year, 65% of the patients had improved or stable exocrine function. CONCLUSIONS: Nonsurgical stone removal usually improved symptoms and preserved pancreatic exocrine function. Nonsurgical treatment with extracorporeal shock wave lithotripsy followed by endoscopic treatment if needed is useful as initial management for pancreatolithiasis.

Diseases associated with gallbladder wall thickening include benign entities such as adenomyomatosis of the gallbladder, acute and chronic cholecystitis, and hyperplasia associated with pancreaticobiliary maljunction, and also cancer. Unique conditions such as sclerosing cholecystitis and cholecystitis associated with immune checkpoint inhibitor treatment can also manifest as wall thickening, as in some systemic inflammatory conditions. Gallbladder cancer, the most serious disease that can show wall thickening, can be difficult to diagnose early and to distinguish from benign causes of wall thickening, contributing to a poor prognosis. Differentiating between xanthogranulomatous cholecystitis and gallbladder cancer with wall thickening can be particularly problematic. Cancers that thicken the wall while coexisting with benign lesions that cause wall thickening represent another potential pitfall. In contrast, some benign gallbladder lesions that can cause wall thickening, such as adenomyomatosis and acute cholecystitis, typically show characteristic ultrasonographic features that, together with clinical findings, permit easier diagnosis. In this review of the literature, we describe B-mode abdominal ultrasonographic diagnosis of gallbladder lesions showing wall thickening.

BACKGROUND AND AIMS: Real-time tissue elastography is a non-invasive method for measuring liver elasticity. However, there are no reports evaluating the value of real-time tissue elastography for liver fibrosis in hepatitis C virus-infected patients with sustained virological response. The aim of this study is to clarify the diagnostic performance of real-time tissue elastography in patients with sustained virological response. METHODS: In this prospective study, we enrolled 425 chronic hepatitis C patients who underwent liver biopsy: 118 patients with sustained virological response (45.8% women) and 307 patients with hepatitis C virus (51.1% women). The post-sustained virological response biopsy was performed 5.9 ± 1.8 years after the therapy. Liver fibrosis index measurements as assessed using real-time tissue elastography were performed on the same day of biopsy. RESULTS: The respective mean liver fibrosis index values for fibrosis stages F0, F1, F2, F3, and F4 were 2.82 ± 0.33, 2.90 ± 0.51, 3.06 ± 0.58, 3.65 ± 0.24, and 3.83 ± 0.65, respectively, in patients with sustained virological response. The diagnostic accuracies expressed as areas under the receiver operating characteristic curves in patients with sustained virological response were 0.776 for the diagnosis of significant fibrosis (≥F2), 0.885 for severe fibrosis (≥F3), and 0.860 for cirrhosis (F4), respectively. The optimum cut-off values liver fibrosis index were 3.14 for ≥F2, 3.24 for ≥F3, and 3.30 for F4 in patients with sustained virological response. CONCLUSION: Real-time tissue elastography is an acceptable method for predicting the severity of fibrosis in hepatitis C virus patients with sustained virological response.

膵管内乳頭粘液性腫瘍(IPMN)に対する腹部超音波(US)と磁気共鳴胆道膵管造影(MRCP)の描出能を比較し、最終的なIPMNの外科的切除の必要性に関連する要因を特定した。IPMN患者170例(男性85例、女性85例、平均66±11歳)を対象に、USにより検出した病変を部位および嚢胞サイズにより評価した。さらに、フォローアップ期間中の手術の必要性に関連する臨床および画像の特徴を調べた。全嚢胞サイズに対して、MRCPと比較したUSによる検出率は膵頭部で60.8%、膵体部で79.8%、膵尾部で32.8%であった。170例の患者のうち、12例(7.1%)が追跡期間に外科的切除を実施した。主膵管の拡大(直径拡大≧0.2mm/年)および高齢(70歳以上)は外科的切除の必要性と独立して有意に関連することが示された。膵頭部および膵尾部におけるUSの嚢胞検出能は特に膵尾部において限定的であった。これらの領域では相対的に複数の嚢胞が頻発することから、USにより膵体部に嚢胞を検出した際はMRCPを実施すべきであることが示された。

The development of endoscopic treatment for pancreatobiliary diseases in recent years is remarkable. In addition to conventional transpapillary treatments under endoscopic retrograde cholangiopancreatography (ERCP), new endoscopic ultrasound-guided therapy is being developed and implemented. On the other hand, due to the development/improvement of various devices such as new metal stents, a new therapeutic strategy under ERCP is also advocated. The present review focuses on recent advances in the endoscopic treatment of pancreatic pseudocysts, walled-off necrosis, malignant biliary strictures, and benign biliary/pancreatic duct strictures.

OBJECTIVES: The aim of this study was to assess prevailing treatment of pancreatolithiasis in Japan. METHODS: We surveyed clinical data from 1834 patients (1479 men and 355 women) at 125 hospitals. RESULTS: Extracorporeal shock-wave lithotripsy (ESWL) was performed alone in 103 patients (5.6%), ESWL plus an endoscopic procedure in 446 (24.3%), endoscopic treatment alone in 261 (14.2%), and surgery in 167 (9.1%). Other treatments were given to 358 (19.5%), whereas 499 (27.2%) received no treatment. Symptoms were relieved in 85.7% after ESWL, 80.8% after endoscopic treatment alone, and 92.8% after surgery. Early complication rates within 3 months after ESWL, endoscopic treatment alone, and surgery were 8%, 4.5%, and 27.1%, respectively. Late complications after ESWL, endoscopic procedures alone, and surgery were 1.7%, 2.5%, and 8.2%, respectively. Symptom relief but also early and late complications were greater after surgery than after ESWL and endoscopic treatment. Among 417 patients undergoing ESWL, 61 (14.6%) required surgery, as did 32 (16%) of 200 patients treated endoscopically. Surgery was required less frequently following initial operative treatment (11/164 patients [6.7%]). Nonsurgical initial treatments were chosen more frequently. CONCLUSIONS: First-line treatment of pancreatolithiasis should be ESWL with or without endoscopy because of minimal invasiveness and fewer complications.

Background Gallstones are detected in about 5% of healthy Japanese. We followed up individuals showing gallstones upon screening, investigating features of those requiring surgery. Methods In 2002 we performed health evaluations for 21,550 persons (13,986 men and 7,564 women), detecting gallstones ultrasonographically in 837 or 3.9% (561 men, or 4.0%; 276 women, or 3.6%). Up until 2012, we followed up 720 of the 837 persons with gallstones (86.0%) and compared individuals requiring or not requiring cholecystectomy as to age, gender, body mass index, diabetes, liver function, lifestyle, abdominal symptoms, and ultrasonographic findings. We also compared laboratory data obtained before and after surgery. The study was reviewed and approved by our institutional review board, and registered on UMIN-CTR (ID: UMIN000021995). Results Among 720 persons with gallstones, 55 (7.6%) were treated by surgery. Men tended to undergo surgery more frequently than women (P = 0.086, 43 of 488, or 8%, vs. 12 of 232, or 5.2%). Need for cholecystectomy was significantly more likely among ethanol drinkers (P = 0.008). Gallstone diameters between 6 to 15 mm were more frequent in the surgical group (51.5%) than in subjects requiring only observation (29.5%; P = 0.002). Adenomyomatosis or gallbladder wall thickening was more frequent in the surgical group (P = 0.002), as was presence of abdominal symptoms (P = 0.0002). Hemoglobin A1c was significantly higher after surgery (5.4 +/- 0.6) than before (5.3 +/- 0.5; P = 0.001). Conclusions Among persons with gallstones detected by screening, men who drank, had abdominal symptoms, and showed gallbladder wall thickening or adenomyomatosis were more likely to require surgery within 4 years.

Objective Pancreatolithiasis is often treated by fragmentation of stones by extracorporeal shock wave lithotripsy, followed by additional endoscopic treatments, such as endoscopic pancreatic sphincterotomy. However, it is difficult to remove minute fragments or protein plugs using the conventional basket catheter. We recently used a newly developed nitinol basket catheter, for endoscopic removal of pancreatic stones. We report the results of our study on the usefulness of this catheter. Patients and methods The subjects were 8 patients with pancreatolithiasis treated by extracorporeal shock wave lithotripsy plus endoscopic treatment at our department between July 2014 and January 2015. There were 7 men and 1 woman, ranging in age from 26 to 86 years (median 46 years). Endoscopic removal of pancreatic stones using the nitinol basket catheter was performed a total of 15 times, and the insertability, success rate of pancreatic stone removal, complications, and pancreatic stone recurrence rate were examined. Results The nitinol basket catheter was easily inserted in 12 (80%) of the 15 sessions. In the remaining 3 sessions, it was difficult to insert the catheter because of narrowing of the main pancreatic duct in the pancreatic head, kinking of the pancreatic duct in the pancreatic head and body, and edema around the papilla present immediately after pancreatic sphincterotomy. The success rate of endoscopic removal of pancreatic stones was 87.5% (7/8 patients), 73% (11/15 sessions). As for complications, mild pancreatitis occurred in 1 session, and mild transient abdominal pain in 2; both complications resolved with conservative treatment. Recurrence of the pancreatolithiasis was found after 8 months in 1 (12.5%) of the 8 patients, who had narrowing of the main pancreatic duct in the pancreatic head. Conclusion The nitinol basket catheter is advantageous for the removal of small pancreatic stones and protein plugs, which are difficult to visualize by pancreatography, and may be useful for preventing recurrence of pancreatolithiasis.

Adaptations of endoscopic treatment of the minor papilla are performed in patients with main pancreatic duct stricture in the head of the pancreas in those with chronic pancreatitis, chronic pancreatitis patients who are difficult to treat because of extensive flexure in the head of the pancreas, patients with a pancreatic stone in the accessory pancreatic duct region, and patients with pancreatic divisum. In such patients, we perform endoscopic minor papilla sphincterotomy (EMPST) to cut the minor papilla up to the superior border in the direction of 12 to 1 o'clock. Bleeding, acute pancreatitis, and perforation are reported as complications of EMPST. In endoscopic pancreatic stone removal via the minor papilla, we insert a basket catheter along with a guidewire, and open the basket catheter while being careful not to injure the pancreatic duct wall, and remove stones that had been fragmented to a size of 5~6mm by extracorporeal shockwave lithotripsy. Acute pancreatitis, basket impaction, and pancreatic juice outflow disorders with minor papilla edema are reported as complications of endoscopic pancreatic stone removal via the minor papilla. We perform endoscopic stent placement via the minor papilla to insert a stent of 5 Fr along with a guidewire in patients who do not undergo EMPST, or a stent of 5∼7 Fr along with a guidewire in patients in whom we perform EMPST. Stent obstruction, migration, and transformation of the pancreatic duct are reported as complications of endoscopic stent placement via the minor papilla. We review the procedures of these endoscopic treatments by describing cases that we have treated.

Endoscopic ultrasonography (EUS) is useful to diagnose the depth of invasion because of obtaining tomographic image of gastric cancer. Stomach layer has a 5-layer structure. Gastric cancer is visualized as low echoic tumor image by EUS. Massive invasion of gastric cancer is viewed as low echoic and clear boundary image. Diffuse invasion is imaged unclear boundary echo and visualized thick layer with remaining layer structure. Invasion depth of gastric cancer by EUS is diagnosed according to level of wall destruction. When depressed type cancer has ulceration in cancer nest, echoic image is modified with fibrous tissue. The diagnostic criteria of depressed type cancer classified into EUS imaging of cancer in consideration for image modified by fibrous tissue accompanied ulceration.

We have performed three-dimensional intraductal ultrasonography (3D-IDUS) since 1995. 3D-IDUS is useful for evaluation of bile duct carcinoma because it has a comprehensive image display. We can produce longitudinal reconstruction images with using the functions of the 3D-IDUS systems, dual-plane reconstruction images, including radial and longitudinal reconstruction images and oblique reconstruction images. The advantage of 3D-IDUS is that the time required for the examination is reduced compared with that required for conventional IDUS. We Studied the results of 3D-lDUS and pathological findings for tumor extension in 25 patients with bile duct carcinoma. Overall accuracy for depth of tumor invasion was 88%, for tumor invasion to the portal vein 92%, and for tumor invasion to the pancreas was 84%. 3D-IDUS clearly demonstrates invasion of the pancreas or portal vein. However, intraductal spreading of the tumor is difficult to diagnose precisely. Diagnostic accuracy for intraductal spreading was only 70.0%, sensitivity 60%, and specificity 80%. 3D-IDUS could not detect subsequently demonstrated histological infiltration of the fibrous layer of perimuscular loose connective tissue. Another problem of 3D-IDUS is the limitation in diagnosis of lymph node metastasis. We have to continue to study the development 3D-IDUS systems to resolve these problems.

We investigated the usefulness of contrast-enhanced ultrasonography for differential diagnosis of polypoid gallbladder lesions in 60 patients, consisting of gallbladder carcinoma in 20, adenoma in 2, benign polyp in 29, and adenomyomatosis in 9, comparing contrast enhancement patterns with pathologic findings. We monitored vascular flow for 120 sec, constructing a time intensity curve (TIC) by flash-echo imaging. We compared the number of vessels and vessel diameter determined by contrast enhancement patterns and by pathologic examination. Contrast enhancement patterns were classified as linear, scattered, diffuse, or branched. When diffuse type and branched type were considered as indicative of cancer, accuracy was 84.5%, sensitivity 100%, and specificity 76.9%. In gallbladder carcinoma, the TIC rose from no contrast to early-phase contrast sooner than in other diseases. In adenocarcinoma, high-intensity values persisted at 120 sec. With an intensity of 90 or greater at 120 sec taken as indicating cancer, accuracy was 89.7%, sensitivity 89.5%, and specificity 89.7%; Vessels were significantly more numerous in diffuse type cases than in those with other patterns. Vessel diameter was greatest in the diffuse type and the branched type patterns, both differing significantly from the linear type. Ultrasonographic contrast enhancement patterns show characteristic associations with pathologic findings and serve as valuable adjuncts in the diagnosis of gallbladder diseases.

This study was undertaken to clarify the importance of nutritional status in patients with acute cholecystitis, and also evaluate whether they benefited from enteral nutrition supplementation, including medium-chain triglycerides (MCT), during the convalescent stage. Patients with acute cholecystitis admitted to our hospital between April 1994 and March 2002 were classified into a poor nutrition group (n = 40 total serum protein&lt 5.0g/d/) or a fair nutrition group (n = 71 &gt 5.0g/df). Patients with poor nutrition were significantly more elderly than those with fair nutrition, and had significantly higher serum C-reactive protein (CRP) concentrations. The two groups did not differ significantly with respect to other laboratory data, gender distribution, or medical treatment. We supplemented ordinary meals with enteral nutrition including MCT in 16 patients during the convalescent stage (MCT group). We compared their length of hospital stay and days required to recovery to pre-admission functional status for activities of daily living (ADL) with the same intervals in 16 patients without supplementation (non-MCT group) selected to match for age, gender, and fair or poor nutritional status from among 111 patients. Hospitalizations were significantly longer in the poor nutrition group (43.0 ± 2.2 days) than in the fair nutrition group (27.0 ± 8.2 days). Significantly more days were required to recover ADL status in the poor nutrition group (12.0 ± 7.2 days) than in the fair group (9.4 ± 5.2 days). Hospitalizations were significantly shorter in the MCT group (20.1 ± 15 days) than in the non-MCT group (35.4 ± 12.8 days). Significantly fewer days were required to recover ADL status in the MCT group (10.9 ± 7 days) than in the non-MCT group (13.1 ± 6.8 days). Administration of enteral nutrition including MCT during convalescence from acute cholecystitis thus appears to promote functional recovery shorten hospital stay.

Background: Stricture of the main pancreatic duct associated with chronic pancreatitis is a cause of pain due to ductal high pressure and the formation of pancreatic stones, but there is no established non-surgical therapeutic procedure. We attemped a new method for treating this condition, called short-term metal stenting. Methods: In three patients who had experienced recurrent stones and pancreatitis attacks several times after extracorporeal shock wave lithotripsy, a self-expandable metal stent was placed into the pancreatic duct for 2-7 days. Results: Dilatation was successful in all cases. Over observation periods of 18-25 months (mean, 22 months) following stent withdrawal, no recurrence of stones or attacks of pancreatitis was observed. Conclusion: Short-term metal stenting is an effective procedure for dilating stricture of the main pancreatic duct. It is also promising as a method for preventing recurrence of stones or episodes of pancreatitis.

We inserted a metallic stent into the strictures of the main pancreatic duct in two patients with calcified chronic pancreatitis and severe abdominal pain not to be relieved using narcotics. One patient was a 39-year- old male, and the other was 49-year-old male. Their etiology of chronic pancreatitis was alcoholism. We inserted a Strecker stent, 7 mm in diameter and 6 cm in length, for achieving long-term patency than plastic stent. In one patient, the stent was obstructed half a year after the first treatment and pancreatic calculi recurred with abdominal pain. After endoscopic extraction of pancreatic stone and balloon dilatation of the stent was performed three times, a plastic stent was inserted in the metallic stent twice. Even if he was performed nerve block twice, he was administered narcotics for treatment of continuous abdominal pain. In the other patient, the stent was obstructed 1.5 years after insertion and pancreatic calculi recurred with abdominal pain. He was treated with extracorporeal shock-wave lithotripsy for pancreatic stone, abdominal pain continued. He underwent pylorus preserving pancreato-duodenectomy 6 years after the first stenting, because the obstructed metallic stent could not be removed. Metallic stent should not be chosen for treatment of pancreatic duct stricture.

Actual age and biological age are not always proportional. To find out indices of aging, other than actual age, we investigated relationship between aging and four hepatic fibrosis markers: hyaluronates, type IV collagen, type IV collagen 7s and P III P. The subject of this study were 78 patients of inpatients and outpatients of our hospital. They were divided into four groups of very elderly (over 80-year-old), elderly (70-79-year-old), non-elderly (50-69-year-old), and non-elderly (20-49-year-old), and these four groups were compared. The results were as follows: regarding hyaluronates value were 86.3 +/- 46.7 ng/ml in the patients in the very elderly group, 58.9 +/- 37.4 ng/ml in the elderly group, 48.7 +/- 71.9 ng/ml in patients aged between 50 and 69 years old, and 22.6 +/- 26.1 ng/ml in patients aged between 20 and 49 years old. Regarding type IV collagen value were 134.6 +/- 27.8 ng/ml in the very elderly group, 131.1 +/- 46.5 ng/ml in the elderly group, 135.1 +/- 102.1 ng/ml in patients aged between 50 and 69 years old and 92.8 +/- 21.8 ng/ml in patients aged between 20 and 49 years old. Type IV collagen 7s value were 4.4 +/- 0.9 ng/ml in the very elderly group, 4.4 +/- 0.6 ng/ml in the elderly group, 4.8 +/- 1.6 ng/ml in patients of between 50 and 69 years old, and 4.3 +/- 0.6 ng/ml in patients between 20 and 49 years old. P III P value were 0.70 +/- 0.31 U/ml in the very elderly group, 0.64 +/- 0.34 U/ml in the elderly group, 0.59 +/- 0.43 U/ml in patients aged between 50 and 69 years old, and 0.46 +/- 0.14 U/ml in patients aged between 20 and 49 years old. The results indicated that three markers: hyaluronates, type IV collagen, P III P increased with the aging. Especially, hyaluronates were remarkably increased. Next, we studied 159 patients (78 patients added to 81 patients who visited our hospital for health checkup), and investigated the fluctuation of hyaluronate values by the aging. The results showed a definite increase of hyaluronate values with age. A correlation was recognized between ages and hyaluronate values (correlation coefficient: r = 0.64, p < 0.001). Furthermore we investigated effect on aging of various items including fibrosis markers, immunoglobulin or serum albumin by using multiple factor analysis, and found that hyaluronates influenced most strongly on aging (p < 0.0002, p < 0.00002). Thus, hyaluronates could be considered to be an index other than actual ages to evaluate progress of aging.

Background: EUS-guided drainage has been recognized as a nonsurgical treatment for pancreatic pseudocysts. Bleeding at the puncture site is a known complication of this procedure. This is a report of the use of new equipment for one-step drainage without the use of an electrosurgical needle. Methods: EUS-guided cystoenterostomy was performed in 3 patients. The mean size of the pseudocysts was 8 cm (head = 1, body = 2). A needle and drainage tube were inserted in a one-step procedure into the cyst through the accessory channel of an echoendoscope under EUS. The drainage tube was released immediately after insertion. Observations: All 3 patients were treated successfully without complication. A drainage tube was inserted through the duodenal bulb (n = 1) and the body of the stomach (n = 2).The drain was removed after 1 month in all patients. Two of the 3 drains were obstructed by sludge. One pseudocyst recurrence was observed at a mean follow-up of 3.6 months (range 2-6 months). Conclusions:The EUS-guided one-step system is simple to use and suitable for drainage of pancreatic pseudocysts. It appears to minimize the risk of hemorrhage.

BACKGROUND/AIMS: Many patients with mucin-producing pancreatic tumor, characterized by dilatation of the pancreatic duct, are diagnosed by conventional ultrasonography in a mass ultrasonographic survey in Japan. It is a necessary and reliable method for making a precise diagnosis and for deciding on the treatment approach. Endoscopic ultrasonography (EUS) is appreciated as a useful method for precise diagnosis of pancreatic tumors. Intraductal ultrasonography (IDUS) is expected to be a new modality for the more detailed diagnosis of pancreatic tumors. METHODOLOGY: Endoscopic ultrasonography and intraductal ultrasonography were performed in 23 patients with mucin-producing pancreatic tumor. The differences in ultrasonographic findings between benign and malignant tumors were studied. RESULTS: Ultrasonographic findings of mucin-producing pancreatic tumor revealed by EUS and IDUS were: cystic lesion, mural nodule in the cystic lesion, wall thickness of the cyst, mucus echoes, and solid tumor with a mixed echo pattern. Seven out of 11 patients with mural nodule were diagnosed as carcinomas and another 4 patients had adenoma. Seven of 8 patients with mucus echoes were diagnosed as carcinoma. Three of 4 patients with solid tumor were diagnosed as invasive carcinoma. The ultrasonographic findings suggesting malignancy were: mural nodule, irregular wall thickness, mucus echoes, and solid tumor with a mixed pattern. Solid tumor indicated invasive carcinoma exclusively. CONCLUSIONS: Intraluminal ultrasonography, EUS and IDUS are very useful in making a differential diagnosis between benign and malignant tumors in mucin-producing pancreatic tumors.

主膵管内結石症の30例に対して，E(P)STなしでESWLを第一選択の治療法とした22例のうち18例に結石が自然消失し，残る4例は内視鏡的に結石を除去した。内視鏡的除去を第一選択とし結石除去が困難であった8例はESWLの併用で結石は消失した．治療後には疼痛，高アミラーゼ血症，主膵管拡張が改善した．膵内外分泌機能は経過観察後はほぼ不変，あるいは一部で改善する症例があり，結石除去により膵機能が保持される可能性が示唆された．経過観察中に膵癌と膵管内乳頭状腫瘍が各1例発見された．膵石治療にはESWLを第一選択とし，結石除去後も慎重な経過観察が必要である．副膵管ドレナージ優位例，多発結石例，主膵管狭窄例では治療後の膵炎の発症や治療期間，結石再発の点からEPSTや膵管内ステント留置などの補助療法が必要と考えられた．

Background/Aims: The present study was undertaken to investigate possible changes in the K-ras oncogene in patients with gallbladder lesions (carcinoma, adenoma or hyperplasia) in relation to the presence or absence of an anomalous connection of pancreatobiliary ducts (ACPBD). Methodology: Gallbladder specimens were obtained from 44 patients with lesions that were either with or without ACPBD, and DNA samples were analyzed using PCR-SSCP. Point mutations in codons 12, 13 and 61 were analyzed by direct sequencing methods with oligonucleotide primers. Results: The K-ras codon 12 was detected in 83.3% (5/6) of carcinomas, the one adenoma tested and in 35.7% (5/14) of hyperplastic lesions with ACPBD, as opposed to only 36.4% (4/11) of carcinomas without ACPBD. The one case of gallbladder adenoma and 11 cases of normal gallbladder without ACPBD studied demonstrated no point mutations in the K-ras oncogene. Conclusions: Alteration of the K-ras oncogene appears to be involved in the early stages of gallbladder carcinogenesis when in association with ACPBD. The results further suggest that hyperplasia in cases with ACPBD may be a significant pre-cancerous lesion.

Background/Aims: It is important to achieve detection of anomalous connections of the pancreatobiliary ducts (ACPBD), because this condition often leads to pancreatobiliary disease. The present prospective investigation focused on revealing the incidence of ACPBD in asymptomatic individuals undergoing medical checkups. Material and Methods: Extracorporeal ultrasonography (US) was performed on all asymptomatic individuals undergoing medical checkups. Identification by abdominal ultrasonography of 3 mm or more gallbladder wall thickening, or 10 mm or more dilatation of the bile duct were considered indicative of ACPBD and endoscopic ultrasonography (EUS) was carried out in selected cases. Endoscopic retrograde cholangiopancreatography (ERCP) was then performed to confirm the existence of ACPBD. Results: The overall incidence of ACPBD was 0.03% (9/27,076 subjects). ACPBD was found in 23% of cases with bile duct dilatation, and in 2.9% with gallbladder wall thickening. Conclusion: ACPBD was not as rare a disease as expected. For early detection of ACPBD, identification by abdominal ultrasonography of gallbladder wall thickening or dilatation of the bile duct are indicative. Patients who are suspected of having this abnormality should then undergo EUS. The final diagnosis should then be made by ERCP.

慢性膵炎確診例24例(ADP18例,MOP6例)を対象に経口的膵管鏡検査(POPS)による慢性膵炎の膵管鏡像について検討した.膵管粘膜面の異常所見はMOP4例,ADP18例で認められ,慢性膵炎全体では24例中22例91.7%であった.MOP4例の異常所見は,粗造粘膜3例75%,発赤2例50%,癩痕2例50%,穎粒状粘膜1例25%であり,ADP18例では粗造粘膜13例72.2%,浮腫状粘膜11例61.1%,発赤7例38.9%,癩痕6例33.3%,穎粒状粘膜4例22.2%,結節状変化2例11.1%であった.膵管内の異常所見は,少量以上の浮遊物がMOPでは6例中2例33.3%,ADP全例で,膵石がADP18例中10例55.6%で認められた.慢性膵炎では膵管像と平行して膵管粘膜面の異常所見や浮遊物の量的増加,結石の出現が認められることより,POPSは慢性膵炎の診断に有用と考えられ,膵管像の変化が比較的軽度であっても内視鏡的に慢性膵炎と診断できる可能性が示唆された.

健常対照(対照)7例，胃潰瘍(GU)19例，十二指腸潰瘍(DU)6例に終夜脳波と胃内pH値の連続測定を行い，睡眠深度に伴う胃内pHの変化を検討した．対照では覚醒期のpH値は睡眠時に比べ低値を示し，特に1期，4期，REM期と比較し有意差が認められた．また，REM期のpH値は他の睡眠段階と比べ高値を示し，1期，2期と有意差がみられた．GUでは覚醒期のpH値は睡眠時より低値を示し，1期，REMと有意差を認めた．またREM期のpH値は他の全睡眠段階と比較し有意に高値を示した．DUでは睡眠段階によるpH値の変動はなかった．睡眠覚醒リズムに伴って対照およびGUでは胃内pHは変動したが，DUでは変動がみられず，DUの発生要因の1つに自律神経の機能異常が考えられた．

A patient with a cholecystocolic fistula, complicating cholecysto‐choledocholithiasis, was treated endoscopically with gallbladder observation by peroral cholecystoscopy (POCCS). The patient was a 71‐year‐old female admitted to our hospital for investigation and treatment of biliary stones and a cholecystocolic fistula. Endoscopic lithotripsy and extracorporeal shock wave lithotripsy (ESWL) were performed after endoscopic sphincterotomy, and the gallbladder was subsequently investigated using a duodenoscope/ cholangioscope of the mother and baby type. Full distension of the gallbladder with saline solution allowed POCCS observation of the entire surface. The gallbladder mucosa was smooth, and neither stones nor tumors were observed. Though the cholecystocolic fistula itself could not be observed, we concluded that it had resulted from cholecystitis. Peroral cholecystoscopy is thus a useful method of investigating the gallbladder in such cases. Copyright © 1995, Wiley Blackwell. All rights reserved