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.

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 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.

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.

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．

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．