Primary sclerosing cholangitis with partial steroid responsiveness: a case report.

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.

Large or multiple pseudocysts can impede or complicate the nonsurgical treatment of pancreatolithiasis.

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.

B-mode ultrasonographic diagnosis in gallbladder wall thickening.

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.

Recent innovations in therapeutic endoscopy for pancreatobiliary diseases.

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.

Diagnostic performance of real-time tissue elastography in chronic hepatitis C patients with sustained virological response.

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.

Management of Pancreatolithiasis: A Nationwide Survey in Japan.

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.

Long-term outcomes in patients with gallstones detected by mass screening.

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.

New developments in diagnosis and non-surgical treatment of chronic pancreatitis.

Chronic pancreatitis is progressive and irreversible, leading to digestive and absorptive disorders by destruction of the exocrine pancreas and to diabetes mellitus by destruction of the endocrine pancreas. When complications such as pancreatolithiasis and pseudocyst occur, elevated pancreatic ductal pressure exacerbates pain and induces other complications, worsening the patient's general condition. Combined treatment with extracorporeal shock-wave lithotripsy and endoscopic lithotripsy is a useful, minimally invasive, first-line treatment approach that can preserve pancreatic exocrine function. Pancreatic duct stenosis elevates intraductal pressure and favor both pancreatolithiasis and pseudocyst formation, making effective treatment vitally important. Endoscopic treatment of benign pancreatic duct stenosis stenting frequently decreases pain in chronic pancreatitis. Importantly, stenosis of the main pancreatic duct increases risk of stone recurrence after treatment of pancreatolithiasis. Recently, good results were reported in treating pancreatic duct stricture with a fully covered self-expandable metallic stent, which shows promise for preventing stone recurrence after lithotripsy in patients with pancreatic stricture. Chronic pancreatitis has many complications including pancreatic carcinoma, pancreatic atrophy, and loss of exocrine and endocrine function, as well as frequent recurrence of stones after treatment of pancreatolithiasis. As early treatment of chronic pancreatitis is essential, the new concept of early chronic pancreatitis, including characteristics findings in endoscopic ultrasonograms, is presented.

Clinical features of eosinophilic esophagitis: ten Japanese cases.

AIM: We studied eosinophilic esophagitis (EE) to clarify the clinical and endoscopic features of a Japanese case series. METHODS: Records of 10 patients diagnosed with EE at our hospital between May 2010 and December 2011 were examined for age, sex, symptoms, allergic disorder, endoscopic findings, and treatment received. Esophageal wall thickness was measured by endoscopic ultrasonography (EUS). RESULTS: Patients were seven males and three females with a mean age of 48 years. Symptoms included dysphagia, heartburn, food impaction, and chest pain. Nine patients had a history of allergic diseases. Increased peripheral eosinophil count was observed in one patient whereas increased immunoglobulin E level was observed in eight patients. Endoscopic findings included longitudinal furrows in all patients, mucosal edema in nine patients, loss of vascular pattern in nine patients, white exudates in six patients, cobblestone-like appearance in five patients, and concentric rings in three patients. EUS revealed thickening of the esophageal wall in one patient. Histopathological examination revealed eosinophilic infiltration (≥15 eosinophils/high-powered field) in the esophageal epithelium of all patients. Treatment was required in six patients. Proton pump inhibitor (PPI) therapy was given as the first-line treatment but was ineffective in four patients and effective in two patients. Steroid therapy was given to three patients unresponsive to PPI therapy and was effective. CONCLUSIONS: EE was common among relatively young men and was associated with allergic diseases. Longitudinal furrows were observed as the most characteristic endoscopic finding. Esophageal wall thickening was not commonly observed by EUS.

Air in the main pancreatic duct associated with a pancreatic intraductal papillary mucinous neoplasm.

A 62-year-old man was referred to our hospital after ultrasonographic mass screening detected a pancreatic cyst that proved to be an intraductal papillary mucinous neoplasm. Computed tomography additionally demonstrated air in the main pancreatic duct. Magnetic resonance cholangiopancreatography and endoscopic retrograde cholangiopancreatography delineated a filling defect in the main pancreatic duct in the body of the pancreas. The sphincter of Oddi was open. The main pancreatic duct was dilated by viscous mucin; air in the duct was attributed to consequent dysfunction of the sphincter. Laboratory findings included no significant abnormality. The patient has remained asymptomatic during follow-up. Of 25 previously reported cases with air in the duct, only 1 involved an intraductal papillary mucinous neoplasm.

[Diagnosis of the depth of gastric cancer invasion by endoscopic ultrasonography].

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.

Development of pancreatic ductal adenocarcinoma associated with intraductal papillary mucinous neoplasia.

We retrospectively investigated the incidence of pancreatic ductal adenocarcinoma among patients with intraductal papillary mucinous neoplasms of the pancreas. Based on imaging in 195 such patients, we chose surgery as initial treatment for 54, and periodic evaluation over 6 to 192 months (mean, 52) for 141. In 6 of the 141 patients observed for intraductal papillary mucinous neoplasm (4.2%), pancreatic ductal adenocarcinoma developed. Further, careful monitoring for cancer occurrence in the remnant pancreas proved essential in the surgical resection group; 2 of 26 patients (7.7%) subsequently developed pancreatic ductal adenocarcinoma in the remnant pancreas, at 41 months and 137 months after surgery. Serial observation of patients with intraductal papillary mucinous neoplasms by contrast-enhanced computed tomography or magnetic resonance cholangiopancreatography therefore is critical, whether or not surgical treatment initially was performed.

Diagnosis of gallbladder tumors.

Gallbladder cancer is among the organs examined in mass screening for cancer using ultrasonography; the reported prevalence of gallbladder cancer in such screening of a general population was 0.011%, while the prevalence of gallbladder polyps was reported as 4.3 to 6.9%. Endoscopic ultrasonography is useful for the differential diagnosis of gallbladder tumors detected by mass screening, as well as for estimating the depth of tumor invasion and detecting abnormal connections between pancreatobiliary ducts. While a systematic approach leading to diagnosis by endoscopic ultrasonography is useful, recent advances of contrast-enhanced ultrasonography are expected to establish it as a new modality for early detection. At our hospital, 7 of 26 patients with abnormal connections between pancreatobiliary ducts developed gallbladder carcinoma (23.1%), and 7 of 48 patients with gallbladder carcinoma had abnormal connections between pancreatobiliary ducts (12.5%). Serial observation in patients with gallstones and prophylactic surgery in patients with abnormal connections between pancreatobiliary ducts are necessary.

Endoscopic approach via the minor duodenal papilla.

BACKGROUND/AIMS: We describe procedures for endoscopic approach via the minor papilla in symptomatic patients with pancreas divisum, pancreatic stones, and stricture of the Santorini's duct, and neoplasms of the minor papilla: endoscopic minor papilla sphincterotomy, endoscopic pancreatic stone removal, endoscopic stent placement in Santorini's duct, and resection of minor papilla neoplasms. METHODS: The most important procedural detail was insertion of a guide wire into Santorini's duct via the minor papilla, requiring gentle manipulation of both the cannula and guide wire to avoid subsequent complications such as pancreatitis. RESULTS: Minor papilla sphincterotomy was most effective in the treatment of patients with pancreas divisum and associated with acute recurrent pancreatitis; these patients are the best candidates for endoscopic dorsal duct decompression including minor papilla sphincterotomy and stenting. Endoscopic treatment via the minor duodenal papilla was the only useful method for patients whose lesions could not be approached via the major papilla. It is a safe procedure to relieve pain. Long-term results of dorsal ductal stenting were satisfactory in 76 and 90% of patients (19/25 and 9/10, respectively). CONCLUSION: The high level of endoscopic skills necessary and the small number of patients who need these procedures should limit this approach to select institutions with appropriate endoscopic expertise.

Differential diagnosis and treatment of biliary strictures.

Biliary tract strictures present both diagnostic and therapeutic challenges to clinicians. Advances in imaging and endoscopic techniques have improved our ability to differentiate between benign and malignant lesions. Intraductal ultrasonography (IDUS), using an endoscopic approach, has the potential to aid in separating benign and malignant biliary lesions. In a series of 93 patients, a majority of whom had cancer, we found that IDUS had a sensitivity and specificity of 89.7% and 84%, respectively, for diagnosing biliary strictures. However, benign strictures associated with untreated autoimmune pancreatitis and/or the intrapancreatic portion of the distal common bile duct could not be easily distinguished from malignant strictures. Direct visualization of biliary mucosa using a percutaneous transhepatic endoscopic approach also helps separate benign from malignant biliary strictures. Further, the ability to obtain multiple directed biopsies using a percutaneous approach also increases diagnostic accuracy. A final advantage of the percutaneous approach is that once a suitable sized tract has been established, biliary strictures and stents can be placed. IDUS and percutaneous biliary endoscopy are promising new modalities for the diagnosis and treatment of biliary strictures.

[Usefulness of contrast-enhanced ultrasonography in the differential diagnosis of polypoid gallbladder lesions].

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.