Relapse and side effects of steroid therapy beyond 3 years in autoimmune pancreatitis: A multicenter retrospective study.

BACKGROUND: The impact of extended steroid administration on patients with autoimmune pancreatitis after a 3-year maintenance period remains poorly understood. This study analyzed the advantage and disadvantage of continuing steroid therapy beyond 3 years. METHODS: In this retrospective multicenter study across 17 institutions, patients who successfully completed 3 years of maintenance therapy without experiencing relapse were categorized into two groups: the maintenance therapy discontinuation group, who discontinued steroid therapy after the initial 3-year period, and maintenance therapy continuation group, who continued steroid therapy beyond 3 years. The cumulative relapse rate after 3 years of maintenance therapy was the primary outcome. Relapse predictors were compared using the Gray test for cumulative relapse incidence by specific factor. RESULTS: Of 211 patients, 105 experienced no relapse during the 3-year maintenance therapy and were divided into two groups: 69 in the maintenance therapy discontinuation group and 36 in the maintenance therapy continuation group. The relapse rate was lower in the maintenance therapy continuation group than in the maintenance therapy discontinuation group (P = 0.035). Predictors of relapse after 3 years included cessation of maintenance therapy (hazard ratio [HR] = 3.76; 95 % confidence interval [CI] = 1.07-13.3, P = 0.040) and renal involvement (HR = 2.88; 95 % CI = 1.04-7.99, P = 0.042). The maintenance therapy continuation group showed a significantly higher prevalence of macrovascular complications, compared with the maintenance therapy discontinuation group (P = 0.005). CONCLUSIONS: Cessation of steroid maintenance therapy and renal involvement were predictors of relapse after 3 years of maintenance therapy. However, the long-term use of steroids may increase the risk of macrovascular complications.

Adverse events of self-expandable metal stent placement for malignant distal biliary obstruction: a large multicenter study.

BACKGROUND AND AIMS: Endoscopic placement of self-expandable metal stents (SEMSs) for malignant distal biliary obstruction (MDBO) may be accompanied by several types of adverse events. The present study analyzed the adverse events occurring after SEMS placement for MDBO. METHODS: The present study retrospectively investigated the incidence and types of adverse events in patients who underwent SEMS placement for MDBO between April 2018 and March 2021 at 26 hospitals. Risk factors for acute pancreatitis, cholecystitis, and recurrent biliary obstruction (RBO) were evaluated by univariate and multivariate analyses. RESULTS: Of the 1425 patients implanted with SEMSs for MDBO, 228 (16.0%) and 393 (27.6%) experienced early adverse events and RBO, respectively. Pancreatic duct without tumor involvement (P = .023), intact papilla (P = .025), and SEMS placement across the papilla (P = .037) were independent risk factors for acute pancreatitis. Tumor involvement in the orifice of the cystic duct was an independent risk factor for cholecystitis (P < .001). Use of fully and partially covered SEMSs was an independent risk factor for food impaction and/or sludge. Use of fully covered SEMSs was an independent risk factor for stent migration. Use of uncovered SEMSs and laser-cut SEMSs was an independent risk factor for tumor ingrowth. CONCLUSIONS: Pancreatic duct without tumor involvement, intact papilla, and SEMS placement across the papilla were independent risk factors for acute pancreatitis, and tumor involvement in the orifice of the cystic duct was an independent risk factor for cholecystitis. The risk factors for food impaction and/or sludge, stent migration, and tumor ingrowth differed among types of SEMSs.

Comparison of 22-gauge standard and Franseen needles in EUS-guided tissue acquisition for diagnosing solid pancreatic lesions: a multicenter randomized controlled trial.

BACKGROUND AND AIMS: This large multicenter randomized controlled trial compared the diagnostic yields of 22-gauge standard and 22-gauge Franseen needles for EUS-guided tissue acquisition (EUS-TA) of solid pancreatic lesions. METHODS: Consecutive patients with solid pancreatic lesions were prospectively randomized to EUS-TA using standard or Franseen needles. Samples obtained with the first needle pass and with second and subsequent passes were evaluated separately. The primary endpoint was the rate of accuracy for diagnosis of malignancy. Other endpoints were technical success rate, sample cellularity, adverse events, diagnostic accuracy in patient subgroups, and the diagnostic accuracy and numbers of second and subsequent needle passes. RESULTS: Of 523 patients undergoing EUS-TA, 260 were randomized to using standard 22-gauge needles and 263 to 22-gauge Franseen needles. The technical success rate in each group was 99.6%, with similar adverse event rates in the standard (1.5%) and Franseen (.8%) needle groups. First-pass EUS-TA using the Franseen needle resulted in significantly greater diagnostic accuracy (84.0% vs 71.2%, P < .001) and sensitivity (82.4% vs 66.7%, P < .001) than first-pass EUS-TA using a standard needle and also resulted in superior diagnostic accuracy in patients requiring immunostaining. Second and subsequent EUS-TA using Franseen needles showed significantly greater accuracy (94.7% vs 90.0%, P = .049) and sensitivity (94.0% vs 88.6%, P = .047) and required fewer needle passes (1.81 vs 2.03, P = .008) than using standard needles. CONCLUSIONS: EUS-TA with the Franseen needle is superior to EUS-TA with a standard needle with respect to diagnostic accuracy per pass, particularly in patients who require immunostaining, and number of passes when using macroscopic on-site evaluation. (Clinical trial registration numbers: UMIN000030634 and jRCTs052180062.).

Endoscopic placement of covered versus uncovered self-expandable metal stents for palliation of malignant gastric outlet obstruction.

OBJECTIVE: Stenting is an established endoscopic therapy for malignant gastric outlet obstruction (mGOO). The choice of stent (covered vs uncovered) has been examined in prior randomised studies without clear results. DESIGN: In a multicentre randomised prospective study, we compared covered (CSEMS) with uncovered self-expandable metal stents (UCSEMS) in patients with mGOO; main outcomes were stent dysfunction and patient survival, with subgroup analyses of patients with extrinsic and intrinsic tumours. RESULTS: Overall survival was poor with no difference between groups (probability at 3 months 49.7% for covered vs 48.4% for uncovered stents; log-rank for overall survival p=0.26). Within that setting of short survival, the proportion of stent dysfunction was significantly higher for uncovered stents (35.2% vs 23.4%, p=0.01) with significantly shorter time to stent dysfunction. This was mainly relevant for patients with extrinsic tumours (stent dysfunction rates for uncovered stents 35.6% vs 17.5%, p<0.01). Subgrouping was also relevant with respect to tumour ingrowth (lower with covered stents for intrinsic tumours; 1.6% vs 27.7%, p<0.01) and stent migration (higher with covered stents for extrinsic tumours: 15.3% vs 2.5%, p<0.01). CONCLUSIONS: Due to poor patient survival, minor differences between covered and uncovered stents may be less relevant even if statistically significant; however, subgroup analysis would suggest to use covered stents for intrinsic and uncovered stents for extrinsic malignancies.

[An autopsy case of anaplastic pancreatic carcinoma with diffuse liver metastases in acute hepatic failure].

A 76-year-old man presented to our hospital with continuous abdominal pain and vomiting. The results of the computed tomography indicated a pancreatic head mass with multiple liver metastatic tumors. Multiple liver tumors progressed rapidly, and the patient died of the resulting acute hepatic failure approximately 1 month after the onset of symptoms. The results of the postmortem examination indicated anaplastic pancreatic carcinoma (pleomorphic type) with multiple liver metastases. The tumor cells in the primary pancreatic lesion and liver metastases were replaced with normal tissue, and they showed a decrease in stainability by E-cadherin staining. Overall, the pathological findings suggested that the inhibition of E-cadherin may be related to the proliferation and infiltration of anaplastic cancer cells.

Utility and Safety of a Novel Fully Covered Metal Stent in Unresectable Distal Malignant Biliary Obstruction.

BACKGROUND: Self-expandable metal stents (SEMSs) are widely used in patients with distal malignant biliary obstruction. A SEMS that can avoid occlusion as much as possible is desirable. AIMS: The aim of this multicenter single-arm prospective study was to assess the clinical effectiveness and safety of a novel fully covered braided SEMS. METHODS: We enrolled consecutive patients with distal malignant biliary obstruction between February 2016 and November 2017 at ten tertiary-care medical centers. RESULTS: We included 79 patients with a median age of 76 years; 47 (59.5%) patients were men. The technical and clinical success rate was 98.7% and 93.6%, respectively. Recurrent biliary obstruction occurred in 14 patients (17.9%); stent ingrowth, overgrowth, migration, and other occurred in five (6.4%), four (5.1%), four (5.1%), and one (1.3%) patients, respectively. All reinterventions in patients with recurrent biliary obstruction were successful via the transpapillary approach. Adverse events occurred in 15 patients (19.2%); cholangitis, pancreatitis, and others occurred in ten (12.8%), three (3.8%), and two (2.6%) patients, respectively. The stent patency probability at 6 months was 48.5%. Median time to stent patency was 171 days, median time to recurrent biliary obstruction was 536 days, and median survival time was 195 days. CONCLUSIONS: We confirmed the utility and safety of a novel fully covered braided SEMS with low axial force and high radial force in patients with malignance biliary obstruction. This novel SEMS is recommended in patients with distal malignant biliary obstruction.

[A case of intracholecystic papillary neoplasm of the gallbladder (ICPN) examined using contrast-enhanced endoscopic ultrasonography].

A 78-year-old woman was found to have gallbladder wall thickening on ultrasonography during a routine health check-up and was referred to our clinic. On contrast-enhanced endoscopic ultrasonography, a papillary lesion measuring 14mm was detected in the fundus, which showed a heterogeneous enhancement at the early phase. She underwent cholecystectomy and gallbladder bed resection. Histological examination revealed that the tumor consisted of mucinous atypical cells, regularly arranged in a high-papillary architecture with delicate fibrovascular cores, which led to the diagnosis of intracholecystic papillary neoplasm of the gallbladder.

Double immunostaining for maspin and p53 on cell blocks increases the diagnostic value of biliary brushing cytology.

Our objective is to elucidate the usefulness of maspin/p53 double immunostaining on biliary brushing cytology specimens. We first examined the expression of maspin in the biliary epithelium with variable degrees of dysplasia using surgically resected specimens (n = 56). Maspin appeared to be overexpressed in a stepwise manner from benign to malignant cholangiocytes: the reactive epithelium (20%), biliary intraepithelial neoplasia (~50%), and invasive cholangiocarcinomas (>90%). Next, an automated sequential double immunostaining protocol for maspin and p53 was applied to paraffin-embedded cell blocks of the biliary brushing cytology specimens obtained from 58 consecutive patients. Cell block preparation was successful in 44 cases (76%), which were morphologically diagnosed as adenocarcinoma (n = 16), atypical cells not diagnostic for malignancy (n = 10), and benign (n = 18). Double positive cells were observed in 14/16 (88%) morphologically malignant, 6/10 (60%) borderline, and 0/18 benign cases. All 20 positive cases were proven to have pancreatobiliary malignancies by subsequent imaging or pathological analyses. A similar staining protocol for S100P and p53 was also applied to the same cohort; however, the positive frequency was slightly lower than those of maspin and p53 (36% vs. 45%). In conclusion, Maspin/p53 double immunostaining on cell blocks contributes to the detection of malignant cells in biliary brushing cytology specimens.

A case of esophageal mucosa-associated lymphoid tissue lymphoma diagnosed using endoscopic ultrasound-guided fine-needle aspiration.

A 65-year-old man presenting with an esophageal lesion underwent esophagogastroduodenoscopy and computed tomography and an upper esophageal submucosal mass was found. Endoscopic ultrasound-guided fine-needle aspiration led to the diagnosis of mucosa-associated lymphoid tissue lymphoma of the esophagus. Positron emission tomography showed abnormal uptake in the internal iliac lymph nodes, and laparoscopic biopsy findings confirmed the diagnosis of esophageal cancer. The patient declined treatment of any kind and has been followed up for 39 months with no progression of the lymphoma.

[A case of pancreatic mixed acinar-endocrine carcinoma suggested by preoperative ultrasound-guided fine needle aspiration].

A 73-year-old man visited our hospital for consultation regarding a pancreatic tumor. Abdominal computed tomography, magnetic resonance imaging, and endoscopic ultrasound scan (EUS) revealed tumor 2 cm in diameter located in the pancreatic tail. EUS-guided fine needle aspiration (EUS-FNA) suggested pancreatic mixed acinar-endocrine carcinoma, and he underwent distal pancreatectomy. Few reports exist where preoperative EUS-FNA suggested pancreatic mixed acinar-endocrine carcinoma; thus, we report this case.

A case of acute recurrent pancreatitis caused by biliopancreatic reflux without pancreaticobiliary maljunction.

Acute recurrent pancreatitis (ARP) is a clinical condition characterized by repeated episodes of acute pancreatitis. In this case study, a 62-year-old man was diagnosed with mild pancreatitis five years ago, with alcohol intake initially considered the cause. Since then, he experienced three episodes of pancreatitis despite ceasing alcohol consumption completely. Consequently, the patient was diagnosed with ARP. Various diagnostic and imaging tests were performed to determine the etiology of his condition, including blood tests, magnetic resonance cholangiopancreatography, endoscopic ultrasonography, and contrast-enhanced computed tomography. The results were inconclusive; however, endoscopic retrograde cholangiopancreatography revealed the reflux of bile and pancreatic juice into the alternative ducts, despite the absence of anatomical abnormalities in the biliary tract or pancreatic duct. These findings subsequently led to the diagnosis of biliopancreatic reflux, which activated pancreatic enzymes causing ARP. Endoscopic biliary sphincterotomy was performed to alleviate the patient's symptoms. One year later, the patient remained symptom-free. This case highlights the importance of examining bile and pancreatic juice components before considering endoscopic sphincterotomy in patients with unexplained ARP.

Factors Associated with Overlap between Functional Dyspepsia and Nonerosive Reflux Disease in Endoscopy-based Helicobacter pylori-uninfected Japanese Health Checkup Participants: A Prospective, Multicenter Cross-sectional Study.

Objective We assessed the factors associated with overlap between functional dyspepsia (FD) and nonerosive reflux disease (NERD) in endoscopy-based Helicobacter pylori-uninfected Japanese health checkup participants. Methods We utilized baseline data from 3,085 individuals who underwent upper endoscopy for health screening in a prospective, multicenter cohort study. The participants were asked to complete a questionnaire detailing their upper abdominal symptoms and lifestyle. Anxiety was assessed using the State-Trait Anxiety Inventory (STAI) score. FD, postprandial distress syndrome (PDS), and epigastric pain syndrome (EPS) were defined according to the Rome III criteria. NERD was defined as heartburn or regurgitation ≥1 day/week without erosive esophagitis. Results Of the 3,085 participants, 73 (2.4%), 97 (3.1%), and 84 (2.7%) had FD alone, NERD alone, and FD-NERD overlap, respectively. Factors associated with FD-NERD-overlap participants compared with participants with neither FD nor NERD were women [odds ratio (OR): 2.08, 95% confidence interval (CI): 1.24-3.52], body mass index (BMI) <18.5 (OR: 2.87, 95% CI: 1.56-5.07), alcohol consumption ≥20 g/day (OR: 1.85, 95% CI: 1.06-3.15), and a high STAI score (OR: 2.53, 95% CI: 1.62-4.00). Increasing age (OR: 1.06, 95% CI: 1.01-1.11) and EPS symptoms [pure EPS (OR: 3.67, 95% CI: 1.65-8.51) and PDS-EPS overlap (OR: 11.6, 95% CI: 4.09-37.2)] were associated with FD-NERD overlap vs. FD alone. Women (OR: 3.17, 95% CI: 1.47-7.04), BMI <18.5 (OR: 3.03, 95% CI: 1.04-9.90), and acid reflux symptoms ≥2 days a week (OR: 3.57, 95% CI: 1.83-7.14) were associated with FD-NERD overlap vs. NERD alone. Conclusion Understanding the clinical features of overlap between FD and NERD will lead to better management.

Temporal progression of pancreatic cancer computed tomography findings until diagnosis: A large-scale multicenter study.

BACKGROUND: Focal parenchymal atrophy and main pancreatic duct (MPD) dilatation have been identified as early signs of pancreatic ductal adenocarcinoma. However, limited evidence exists regarding their temporal progression due to previous study limitations with restricted case numbers. OBJECTIVE: To ascertain a more precise frequency assessment of suspicious pancreatic ductal adenocarcinoma findings as well as delineate the temporal progression of them. METHODS: A multicenter retrospective study was conducted on patients diagnosed with pancreatic ductal adenocarcinoma between 2015 and 2021. We included patients who had undergone at least one computed tomography (CT) scan ≥6 months before diagnosing pancreatic ductal adenocarcinoma. The temporal progression of suspicious pancreatic ductal adenocarcinoma findings on CT was investigated. RESULTS: Out of 1832 patients diagnosed with pancreatic ductal adenocarcinoma, 320 had a previous CT before their diagnosis. Suspicious pancreatic ductal adenocarcinoma findings were detected in 153 cases (47.8%), with focal parenchymal atrophy (26.6%) being the most common followed by MPD dilatation (11.3%). Focal parenchymal atrophy was the earliest detectable sign among all suspicious findings and became visible on average 2.7 years before diagnosis, and the next most common, MPD dilatation, 1.1 years before diagnosis. Other findings, such as retention cysts, were less frequent and appeared around 1 year before diagnosis. Focal parenchymal atrophy followed by MPD dilatation was observed in 10 patients but not in reverse order. Focal parenchymal atrophy was more frequently detected in the pancreatic body/tail. No significant relationship was found between the pathological pancreatic ductal adenocarcinoma differentiation or tumor stage and the time course of the CT findings. All cases of focal parenchymal atrophy progressed just prior to diagnosis, and the atrophic area was occupied by tumor at diagnosis. Main pancreatic duct dilatation continued to progress until diagnosis. CONCLUSION: This large-scale study revealed that the temporal progression of focal parenchymal atrophy is the earliest detectable sign indicating pancreatic ductal adenocarcinoma. These results provide crucial insights for early pancreatic ductal adenocarcinoma detection.

Covered self-expandable metal stents with an anti-migration system improve patency duration without increased complications compared with uncovered stents for distal biliary obstruction caused by pancreatic carcinoma: a randomized multicenter trial.

OBJECTIVES: The requirements of biliary stents used in the palliation of malignant biliary obstruction are a long duration of patency and minimal adverse effects. Covered self-expandable metal stents (SEMSs) have been shown to prevent tumor ingrowth, which is the most frequent complication of uncovered SEMSs. However, because they are prone to migration, the superiority of covered SEMS has yet to be convincingly demonstrated. The aim of this study was to evaluate the superiority of covered over uncovered SEMSs in the palliation of distal biliary obstruction due to unresectable pancreatic carcinoma, using both stent types with relatively low axial force and uncovered flared ends to prevent their migration. METHODS: From April 2009 to December 2010, 120 patients who were admitted to 22 tertiary-care centers because of distal biliary obstruction from unresectable pancreatic carcinomas were enrolled in this prospective randomized multicenter study. Patients were randomly assigned to receive a covered or uncovered SEMS deployed at the site of the biliary stricture during endoscopic retrograde cholangiopancreatography. Stent patency time, patient survival time, patient survival time without stent dysfunction (time to stent dysfunction or patient death), cause of stent dysfunction (ingrowth, overgrowth, migration, or sludge formation), and serious adverse events were compared between covered and uncovered SEMS groups. RESULTS: Patient survival time in the two groups did not significantly differ (median: 285 and 223 days, respectively; P=0.68). Patient survival time without stent dysfunction was significantly longer in the covered than in the uncovered SEMS group (median: 187 vs. 132 days; P=0.043). Stent patency was also significantly longer in the covered than in the uncovered SEMS group (mean±s.d.: 219.3±159.1 vs. 166.9±124.9 days; P=0.047). Reintervention for stent dysfunction was performed in 14 of 60 patients with covered SEMSs (23%) and in 22 of 60 patients with uncovered SEMSs (37%; P=0.08). Stent dysfunction was caused by tumor ingrowth, tumor overgrowth, and sludge formation in 0 (0%), 3 (5%), and 11 (18%) patients in the covered SEMSs group, and in 15 (25%), 2 (3%), and 6 (10%) patients in the uncovered SEMSs group, respectively. Stent migration was not observed in either group. Rates of tumor overgrowth and sludge formation did not significantly differ between the two groups, whereas the rate of tumor ingrowth was significantly lower in the covered than in the uncovered SEMS group (P<0.01). Acute pancreatitis occurred in only one patient in the covered SEMS group. Acute cholecystitis occurred in one patient in the covered SEMS group and in two patients in the uncovered SEMS group. There was no significant difference between the two groups in the incidence of serious adverse events. CONCLUSIONS: By preventing tumor ingrowth and migration, covered SEMSs with an anti-migration system had a longer duration of patency than uncovered SEMSs, which recommends their use in the palliative treatment of patients with biliary obstruction due to pancreatic carcinomas.

Review of Non-Eosinophilic Esophagitis-Eosinophilic Gastrointestinal Disease (Non-EoE-EGID) and a Case Series of Twenty-Eight Affected Patients.

Eosinophilic gastrointestinal disease (EGID) is divided into eosinophilic esophagitis (EoE) and non-eosinophilic esophagitis eosinophilic gastrointestinal disease (non-EoE-EGID) based on the involved gastrointestinal segments. Reports regarding non-EoE-EGID are limited, in part because of its rarity. The present study was performed to review non-EoE-EGID, including its pathogenesis, diagnosis, treatment, and prognosis. Additionally, details regarding 28 cases of non-EoE-EGID recently diagnosed at our Japanese tertial medical center are presented and compared with 20 EoE cases diagnosed during the same period at the same medical center. Comparisons of the two groups clarified differences regarding age- and gender-dependent prevalence between the two conditions, and also showed that systemic involvement and disease severity were greater in the non-EoE-EGID patients. Notably, diagnosis of non-EoE-EGID is difficult because of its lack of specific or characteristic symptoms and endoscopic findings. The clinical characteristics of EoE and non-EoE-EGID differ in many ways, while they also share several genetic, clinical, laboratory, and histopathological features.

Clinicopathological characteristics of abnormal micro-lesions at the oro-hypopharynx detected by a magnifying narrow band imaging system.

BACKGROUND: Narrow band imaging (NBI) with magnifying endoscopy (NBI-ME) allows the detection of abnormal micro-lesions smaller than 5 mm in diameter in the oro-hypopharynx that could not be visualized previously. The purpose of the present study was to clarify the clinicopathological characteristics of abnormal micro-lesions of the oro-hypopharynx detected by NBI-ME. METHODS: Of the 62 lesions detected by NBI-ME, 40 abnormal micro-lesions in 37 patients were removed by endoscopic treatment and were pathologically evaluated. We reviewed the medical records of patients with these lesions and investigated the relationship between NBI-ME findings and pathological findings. RESULTS: Pathological examination revealed the following: high-grade intraepithelial neoplasia (HGIN) in nine (23%) lesions, low-grade intraepithelial neoplasia (LGIN) in 22 (55%), pharyngitis in seven (18%) and papilloma in two (5%). Two NBI-ME findings, high microvascular density (MVD) and a brownish area (BA), were recognized more frequently as the grade of malignancy advanced. The likelihood ratio (confidential interval) for having HGIN in the patients with both MVD and BA was 13 (3.62-127). CONCLUSIONS: The pathological diagnosis of abnormal micro-lesions ranged from pharyngitis to HGIN. High MVD and BA may be important findings for grading the malignancy of abnormal micro-lesions.

A case of COVID-19 diarrhea relieved by bile acid sequestrant administration.

Patients with coronavirus disease 2019 exhibit various gastrointestinal symptoms. Although diarrhea is reported in many cases, the pathophysiology of diarrhea has not been fully clarified. Herein, we report a case of coronavirus disease 2019 with diarrhea that was successfully relieved by the administration of a bile acid sequestrant. The patient was a 59-year-old man whose pneumonia was treated by the administration of glucocorticoids and mechanical ventilation. However, beginning on the 30th hospital day, he developed severe watery diarrhea (up to 10 times a day). Colonoscopy detected ulcers in the terminal ileum and ascending colon. The oral administration of a bile acid sequestrant, colestimide, improved his diarrhea quickly. Ileal inflammation is reported to suppress expression of the gut epithelial apical sodium-dependent bile acid transporter. It decreases bile acid absorption at the distal ileum and increases colonic delivery of bile acids, resulting in bile acid diarrhea. In summary, the clinical course of the case presented in this report suggests that bile acid diarrhea is a possible mechanism of watery diarrhea observed in patients with coronavirus disease 2019.