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.

Pancreatic injury in patients treated with immune checkpoint inhibitors: a retrospective multicenterstudy.

BACKGROUND: Immune checkpoint inhibitor-related pancreatic injury (ICI-PI) is a rare occurrence, which has not been reported in detail. We conducted a retrospective multicenter study to determine the clinical characteristics, risk factors, and treatment of ICI-PI. METHODS: We reviewed the medical records of patients who received ICIs for malignant tumors between April 2014 and April 2019 at 16 participating hospitals. Patients with elevated pancreatic enzymes or pancreatitis were identified and classified using the Common terminology Criteria for Adverse Events (CTCAE) ver.5.0). The number of patients with pancreatic enzyme elevation was determined and those with pancreatic enzyme elevation of ≥ grade 3 according to CTCAE ver.5.0, or pancreatitis underwent detailed analysis for ICI-PI. RESULTS: The study enrolled 1069 patients. Nineteen patients (1.8%) had ICI-PI, 5 (0.5%) of whom also had pancreatitis. Four patients had mild pancreatitis, whereas 1 patient had severe pancreatitis, culminating in death. Steroid therapy was administered to 7 of 19 patients, which led to ICI-PI improvement in 5 patients. On the other hand, ICI-PI improved in 9 of 12 patients who were not administered steroid therapy. Six of the 14 patients with ICI-PI improvement were rechallenged with ICI, and ICI-PI relapse occurred in only 1 patient (16.7%), which improved with ICI discontinuation and steroid therapy. CONCLUSIONS: ICI-PI is a rare occurrence, with a low incidence of pancreatitis, which followed a very serious course in one patient. Although the benefit of steroid therapy for ICI-PI is unclear, ICI rechallenge is acceptable after improvement of ICI-PI without pancreatitis.

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.

Double balloon enteroscopy in the detection and removal of jejunal anisakiasis: Case report.

A 53-year-old Japanese man presented to the emergency department with epigastric pain and bloating. Computed tomography revealed a thickening of the jejunal wall and proximal dilation. Double-balloon enteroscopy was performed to investigate the jejunal thickening, which revealed an anisakis larva in the jejunum with an associated ulcer. The larva was removed using endoscopic forceps, after which there was immediate improvement of symptoms. Further patient interview determined that he had consumed marinated mackerel the day before the onset of symptoms. After diagnosis of small intestinal anisakiasis, he was successfully treated using double-balloon enteroscopy. Its use for small intestinal anisakiasis is rare, and this case may be the first instance in the jejunum. Removal of the anisakis larva led to a clear diagnosis and a quick resolution of symptoms. A history of raw fish consumption a few days before the onset of abdominal symptoms and abnormal findings on computed tomography scans are key to the diagnosis of small intestinal anisakiasis. Double-balloon enteroscopy was thought to be a safe means of making accurate diagnoses and appropriate treatment of our patients.

A novel fully covered metal stent for unresectable malignant distal biliary obstruction: results of a multicenter prospective study.

Background/Aims: Endoscopic self-expandable metal stent (SEMS) placement is currently the standard technique for treating unresectable malignant distal biliary obstructions (MDBO). Therefore, covered SEMS with longer stent patency and fewer migrations are required. This study aimed to assess the clinical performance of a novel, fully covered SEMS for unresectable MDBO. Methods: This was a multicenter single-arm prospective study. The primary outcome was a non-obstruction rate at 6 months. The secondary outcomes were overall survival (OS), recurrent biliary obstruction (RBO), time to RBO (TRBO), technical and clinical success, and adverse events. Results: A total of 73 patients were enrolled in this study. The non-obstruction rate at 6 months was 61%. The median OS and TRBO were 233 and 216 days, respectively. The technical and clinical success rates were 100% and 97%, respectively. Furthermore, the rate of occurrence of RBO and adverse events was 49% and 21%, respectively. The length of bile duct stenosis (<2.2 cm) was the only significant risk factor for stent migration. Conclusions: The non-obstruction rate of a novel fully covered SEMS for MDBO is comparable to that reported earlier but shorter than expected. Short bile duct stenosis is a significant risk factor for stent migration.

Clinical outcome of conservatively managed pancreatic intraductal papillary mucinous neoplasms with mural nodules and main duct dilation.

BACKGROUND: Surgical resection of intraductal papillary mucinous neoplasm (IPMN) is strongly recommended for patients exhibiting high-risk stigmata (HRS). However, determining surgical indications for elderly patients with comorbidities is challenging, as clinical outcomes are not well characterized. This multicenter observational study elucidated the clinical outcomes of patients with IPMN exhibiting HRS who did not undergo surgery. METHODS: This study enrolled 101 IPMN patients exhibiting HRS with follow-up observations at 11 hospitals in Japan (2011-2016). The median observation period was 37 months (maximum: 86 months). Primary outcomes were estimated 5-year overall survival (OS) and disease-specific survival (DSS). Survival was also stratified based on HRS features. RESULTS: Of 101 patients, 32 (31.7%) had the main pancreatic duct (MPD) measuring ≥ 10 mm and 80 (79.2%) had mural nodules measuring ≥ 5 mm. The estimated 5-year OS and DSS were 74% and 91%, respectively. In the stratified analysis, the co-presence of MPD ≥ 10 mm and mural nodules ≥ 5 mm or mural nodule ≥ 10 mm were related to worse 5-year DSS (MPD ≥ 10 mm and mural nodules ≥ 5 mm vs other characteristics: 60% vs 95%, log-rank test: p = 0.049; mural nodules ≥ 10 mm vs < 10 mm: 77% vs 95%, log-rank test: p = 0.003). CONCLUSIONS: The estimated 5-year DSS of conservatively managed IPMN patients with mural nodules and main duct dilation was 91%. Only IPMN patients with plural HRS or large nodule formation might have an increased mortality risk. This is an important insight that can help facilitate appropriate clinical decision-making, especially in the elderly or high-surgical risk IPMN patients.

Sphincter of Oddi manometry using guide-wire-type manometer is feasible for examination of sphincter of Oddi motility.

BACKGROUND: Sphincter of Oddi manometry (SOM) is recognized as the standard diagnostic modality for sphincter of Oddi dysfunction (SOD). However, SOM is not commonly performed because of its technical difficulty and the high incidence of post-procedural pancreatitis. To diminish post-procedural pancreatitis, we tried to develop a new method of SOM. This study examined the feasibility of SOM with a guide-wire-type manometer, which is commonly used to measure the arterial pressure for coronary angiography, for the assessment of SO motility. METHODS: A total of 35 procedures were performed in 8 patients with biliary type III SOD and 14 patients with other disease. We performed SOM using the guide-wire-type manometer on SOD cases and other cases [amplitude, duration, frequency and the area under the curve (AUC) of SO contractions]. RESULTS: The mean time required for the measurement was 7.5 ± 4.1 min. The amplitude, frequency and AUC of SO contractions were significantly larger in the SOD cases than in other diseases (147.2 vs. 92.8 mmHg, p = 0.042; 10 vs. 5/min, p = 0.007; 2,837 vs. 1,122 mmHg s, p = 0.003, respectively). In 6 patients who underwent endoscopic sphincterotomy (EST), the SO amplitude decreased dramatically after EST. In this study, mild pancreatitis was observed in only one patient. CONCLUSIONS: SOM using a guide-wire-type manometer is safe, reliable and easy to apply for the clinical assessment of SO motility. The guide-wire-type manometer may become a new method to measure SO function for the diagnosis of SOD.

A case of lipomatous pseudohypertrophy of the pancreas diagnosed by EUS-FNA.

We report the case of a 56-year-old female with lipomatous hypertrophy of the pancreas. Abdominal CT and MRI showed fatty replacement over the entire pancreas. The pancreatic parenchyma was completely absent. ERCP showed no abnormal findings in the main pancreatic duct. EUS-FNA was performed to achieve a definitive diagnosis. Histological features of the FNA specimens revealed that adipose tissue generally replaced the pancreatic parenchyma, and pancreatic acini were identified with a scattered distribution. To consider the differential diagnosis of lipomatous pseudohypertrophy of the pancreas, it is necessary to distinguish it from obesity, diabetes, and age-related pancreatic fat infiltration and liposarcoma. By performing EUS-FNA, it was possible to obtain a definitive diagnosis in this patient. In conclusion, EUS-FNA may be helpful to make a definitive diagnosis in patients with lipomatous hypertrophy of the pancreas.

Sphincter of Oddi disorder: what is the clinical issue?

Sphincter of Oddi disorder (SOD) is a functional disorder of the sphincter of Oddi (SO) and is pathophysiologically equivalent to functional gastrointestinal disorder (FGID) of the digestive tract. SOD is important as a cause of biliary pain of unknown origin and idiopathic acute recurrent pancreatitis; however, the concept of SOD has not generally spread in the same way as FGID. SOD is diagnosed using ROME III criteria which were revised in 2006 to reduce the number of unnecessary and potentially risky procedures. Many cases of SOD still need SO manometry (SOM) which is performed during endoscopic retrograde cholangiopancreatography (ERCP). It is problematic that SOD patients, who already have a high risk of post-ERCP pancreatitis, require SOM for a definitive diagnosis. SOM is an invasive examination that is accompanied by a high risk of post-procedure pancreatitis and can be performed only at a limited number of institutions because of technical difficulties. In the treatment of SOD, the effectiveness of the drugs is uncertain, and the role of drug therapy in the management of SOD has not yet been established. In recent years, endoscopic sphincterotomy (EST) has been recognized as standard treatment for SOD; however, the effect of EST is not yet clear. The development of less invasive diagnostic techniques is desirable in the future. Furthermore, patient eligibility criteria for EST and the long-term prognosis after EST should be clarified.