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.

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.

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.

Tissue harmonic versus contrast-enhanced harmonic endoscopic ultrasonography for the diagnosis of pancreatic tumors: Prospective multicenter study.

OBJECTIVES: This prospective multicenter study aimed to assess and compare the accuracy of tissue harmonic endoscopic ultrasonography (TH-EUS) and contrast-enhanced harmonic endoscopic ultrasonography (CH-EUS) for differentiating pancreatic carcinoma from other pancreatic tumors. METHODS: Consecutive patients with solid pancreatic tumors were prospectively enrolled between August 2013 and December 2014. To assess the accuracy of TH-EUS and CH-EUS, we compared four parameters of TH-EUS (fuzzy edge, irregular periphery, hypoechogenicity, and heterogeneous internal echogenicity) and four parameters of CH-EUS (hypoenhancement and heterogeneous enhancement in the early and late phases, respectively) to investigate which parameter of each method was most suitable to diagnose pancreatic carcinomas. Interobserver agreement and the diagnostic ability of pancreatic carcinoma using TH-EUS and CH-EUS were assessed and compared. RESULTS: A total of 204 patients were enrolled. For the diagnosis of pancreatic carcinoma, interobserver agreement by experts and nonexperts was 0.33-0.50 and 0.35-0.50 for TH-EUS, respectively, and 0.72-0.74 and 0.20-0.54 for CH-EUS, respectively. Irregular periphery was the most accurate diagnostic parameter among TH-EUS findings for differentiating pancreatic carcinomas, with sensitivity, specificity, and accuracy of 95.0%, 42.9%, and 78.9%, respectively. Late phase hypoenhancement was the most accurate diagnostic parameter among CH-EUS findings for differentiating pancreatic carcinomas, with sensitivity, specificity, and accuracy of 90.8%, 74.6%, and 85.8%, respectively. The accuracy of CH-EUS (late phase hypoenhancement) for diagnosis of pancreatic carcinoma was significantly higher than that of TH-EUS (irregular periphery) (p < 0.001). CONCLUSION: In comparison with TH-EUS, CH-EUS increased the diagnostic ability and reproducibility for the diagnosis of pancreatic carcinoma. UMIN (000011124).

Type 1 Autoimmune Pancreatitis with Imaging Appearance Similar to That of Malignant Cystic Tumor.

A 79-year-old man was admitted with asymptomatic elevation of liver enzymes and tumor markers. Abdominal contrast-enhanced computed tomography demonstrated swelling of the pancreatic head, and additional blood test showed raised IgG4 levels. Histological examination by endoscopic ultrasonography (EUS)-guided fine needle aspiration for pancreatic head mass revealed storiform fibrosis and IgG4-positive plasma cell infiltration. We diagnosed this case as type 1 autoimmune pancreatitis (AIP). In addition, there was a cystic lesion in the pancreatic body apart from the pancreatic head mass. A mural nodule in the multilocular cyst was detected by EUS, and there was positive uptake of fluorodeoxyglucose in positron emission tomography/magnetic resonance imaging. The preoperative diagnosis of this cystic lesion was intraductal papillary mucinous carcinoma, and distal pancreatomy was performed. Histopathological findings showed various sizes of retention cysts caused by IgG4-positive plasma cell infiltration around the pancreatic branch ducts. The mural nodule was a fibrotic mass with diffuse infiltration of IgG4-positive cells. This cystic lesion mimicking malignant cystic neoplasm occurred in relation to AIP. This case provided important information helping to understand the mechanism of formation of mural nodules in multilocular cysts in patients with type 1 AIP.

[Diagnostic utility of endoscopic ultrasonography elastography and contrast-enhanced harmonic endoscopic ultrasonography in a patient with type 2 autoimmune pancreatitis].

A referring hospital diagnosed a 57-year-old man with a pancreatic head mass. The initial endoscopic ultrasonography-guided fine needle aspiration (EUS-FNA) was inconclusive because of the small sample size. Endoscopic ultrasonography elastography (EUS-EG) and contrast-enhanced harmonic endoscopic ultrasonography (CE-EUS), conducted at our institute, raised the possibility of mass-forming pancreatitis or autoimmune pancreatitis (AIP). A repeat EUS-FNA revealed inflammatory changes, including a neutrophilic duct injury suggestive of type 2 AIP. The pancreatic lesion responded well to the steroid therapy. The present case suggests that EUS-EG and CE-EUS may be useful for diagnostic exclusion of pancreatic cancers, and the combined use of EUS-EG and CE-EUS, with EUS-FNA, may help characterize inflammatory pancreatic lesions.

Metabolomics for the early detection of cisplatin-induced nephrotoxicity.

Cisplatin, which is an inorganic molecule containing a platinum ion, is an antineoplastic agent that has been used to treat various solid tumors. However, its side effects include nephrotoxicity, neurotoxicity, bone marrow toxicity, gastrointestinal toxicity, and ototoxicity, which can limit its use. In this study, nephrotoxicity was caused by the intraperitoneal injection of cisplatin into rats, and then metabolome analysis was performed using gas chromatography/mass spectrometry (GC/MS) and liquid chromatography/mass spectrometry (LC/MS) to find plasma metabolite biomarker candidates that would facilitate the early detection of cisplatin-induced nephrotoxicity. As a result, chronological changes were detected in the plasma levels of cysteine-cystine and 3-hydroxy-butyrate in the GC/MS-based metabolomics study. In the LC/MS-based metabolomics study, 3 acylcarnitines and a phosphatidylethanolamine with C18:2-C18:2 were identified as potential plasma biomarkers of cisplatin-induced nephrotoxicity. The plasma levels of these 6 metabolites altered significantly after the administration of cisplatin, and these alterations occurred quicker than the equivalent changes in the plasma levels of creatinine and blood urea nitrogen, which are usually used as indicators of renal dysfunction. These results indicate that the abovementioned metabolites might be reliable biomarkers that would allow the earlier detection of cisplatin-induced nephrotoxicity and that metabolomics is a useful tool for discovering biomarkers that could be used to predict the side effects of cancer therapy.