Chronological Course and Clinical Features after Denver Peritoneovenous Shunt Placement in Decompensated Liver Cirrhosis.

BACKGROUND: Refractory ascites affects the prognosis and quality of life in patients with liver cirrhosis. Peritoneovenous shunt (PVS) is a treatment procedure of palliative interventional radiology for refractory ascites. Although it is reportedly associated with serious complications (e.g., heart failure, thrombotic disease), the clinical course of PVS has not been thoroughly evaluated. OBJECTIVES: To evaluate the relationship between chronological course and complications after PVS for refractory ascites in liver cirrhosis patients. MATERIALS AND METHODS: This was a retrospective study of 14 patients with refractory ascites associated with decompensated cirrhosis who underwent PVS placement between June 2011 and June 2023. The clinical characteristics, changes in cardiothoracic ratio (CTR), and laboratory data (i.e., brain natriuretic peptide (BNP), D-dimer, platelet) were evaluated. Follow-up CT images in eight patients were also evaluated for ascites and complications. RESULTS: No serious complication associated with the procedure occurred in any case. Transient increases in BNP and D-dimer levels, decreased platelet counts, and the worsening of CTR were observed in the 2 days after PVS; however, they were improved in 7 days in all cases except one. In the follow-up CT, the amount of ascites decreased in all patients, but one patient with a continuous increase in D-dimer 2 and 7 days after PVS had thrombotic disease (renal and splenic infarction). The mean PVS patency was 345.4 days, and the median survival after PVS placement was 474.4 days. CONCLUSIONS: PVS placement for refractory ascites is a technically feasible palliative therapy. The combined evaluation of chronological changes in BNP, D-dimer, platelet count and CTR, and follow-up CT images may be useful for the early prediction of the efficacy and complications of PVS.

Elderly Woman With No Autoimmune Disease With Aseptic Meningitis Caused by Celecoxib.

Nonsteroidal anti-inflammatory drug (NSAID)-induced aseptic meningitis (NIAM) is frequently reported in patients with autoimmune disease. Ibuprofen-induced NIAM is the most common case report of NIAM. We report a patient without autoimmune disease who developed NIAM following oral celecoxib administration. A literature review and survey of cases registered in the Japanese Adverse Drug Event Report (JADER) database is also provided. A 73-year-old woman with no autoimmune disease developed a headache the day after taking celecoxib, and NIAM was suspected. The headache resolved quickly following celecoxib discontinuation. Although lumbar puncture was not available in this case, bacterial or viral meningitis was negative, and NIAM could not be ruled out. This case involved an older adult patient without an autoimmune disease, with celecoxib as the causative NSAID. A literature review found numerous cases of autoimmune diseases in younger patients. To date, only one case of celecoxib-induced NIAM has been reported. Analysis of NIAM cases in JADER revealed an onset time of approximately three days. JADER analysis indicated that NIAM tended to occur immediately after administration, although the onset with cyclooxygenase-2 selective agents might be slower.

Early and late outcomes of congenital biliary dilatation in pediatric patients.

BACKGROUND: This study aimed to reveal the early and late postoperative complications and outcomes after surgery for congenital biliary dilatation (CBD) by reviewing cases over the past 40 years. METHODS: We retrospectively evaluated 59 patients with CBD who underwent radical surgery for complications and outcomes, based on medical records. Early complications were defined as those requiring treatment within 5 years of the initial operation. Late complications were defined as those treated more than 5 years later. RESULTS: The median age at the first surgery was 37 months. Regarding biliary reconstruction, 54 of the 59 patients (91.5%) underwent hepaticojejunostomy. Although three patients underwent cholecystoduodenostomy and one patient underwent hepaticoduodenostomy, all were converted to hepaticojejunostomy after a median of 12.5 years. One patient developed synchronous biliary carcinoma and underwent pancreaticoduodenectomy. Early complications occurred in seven patients with 10 events (surgical site infection, n = 3 bile leakage, n = 3; ileus, n = 3; bile duct obstruction, n = 1 and intussusception, n = 1). Late complications occurred in nine patients with 12 events (ileus, n = 3; anastomotic stricture, n = 3; hepatolithiasis, n = 3; asynchronous biliary carcinoma, n = 2; pancreatolithiasis, n = 1). Two of the three patients with hepatolithiasis underwent hepatectomy refractory to the endoscopic approach. Two patients developed asynchronous biliary carcinoma at 34 and 13 years after last operation; both ultimately died of the carcinoma. Only 35 patients (61.4%) underwent a follow-up examination. A total of 11 female patients (45.8%) eventually married, and all successfully gave birth. CONCLUSION: Although the long-term prognosis is excellent with complete cyst excision and hepaticojejunostomy, we emphasize the importance of long-term follow-up.

Efficient synthesis of rare sugars from galactose in hot compressed water using eggshells as an environmentally friendly catalyst.

Aqueous galactose solutions containing eggshell was heated at 120 °C to produce calcium supplements containing rare sugars. Galactose was isomerized to rare sugars with improving rare sugar yields compared to those without eggshell. Organic acids were also formed as byproducts during the reaction. These acids were neutralized by dissolving eggshells with increasing the calcium ion concentration in the solution. When eggshell components (calcium carbonate, magnesium carbonate, or calcium phosphate) were used for the treatment, rare sugars were also formed. Especially, addition of magnesium carbonate improved rare sugar yield, but byproduct formation became more pronounced. Eggshells used in the treatment were used for repeated treatments. When eggshells were used three times, rare sugar yield changed only slightly but the selectivity of rare sugars improved significantly. By these processes, we obtained an aqueous solution of rare sugars containing calcium ion at 295 mg/L, which has potential as ingredients for dietary supplements.

Conditional deficiency of Rho-associated kinases disrupts endothelial cell junctions and impairs respiratory function in adult mice.

The Ras homology (Rho) family of GTPases serves various functions, including promotion of cell migration, adhesion, and transcription, through activation of effector molecule targets. One such pair of effectors, the Rho-associated coiled-coil kinases (ROCK1 and ROCK2), induce reorganization of actin cytoskeleton and focal adhesion through substrate phosphorylation. Studies on ROCK knockout mice have confirmed that ROCK proteins are essential for embryonic development, but their physiological functions in adult mice remain unknown. In this study, we aimed to examine the roles of ROCK1 and ROCK2 proteins in normal adult mice. Tamoxifen (TAM)-inducible ROCK1 and ROCK2 single and double knockout mice (ROCK1flox/flox and/or ROCK2flox/flox;Ubc-CreERT2) were generated and administered a 5-day course of TAM. No deaths occurred in either of the single knockout strains, whereas all of the ROCK1/ROCK2 double conditional knockout mice (DcKO) had died by Day 11 following the TAM course. DcKO mice exhibited increased lung tissue vascular permeability, thickening of alveolar walls, and a decrease in percutaneous oxygen saturation compared with noninducible ROCK1/ROCK2 double-floxed control mice. On Day 3 post-TAM, there was a decrease in phalloidin staining in the lungs in DcKO mice. On Day 5 post-TAM, immunohistochemical analysis also revealed reduced staining for vascular endothelial (VE)-cadherin, ß-catenin, and p120-catenin at cell-cell contact sites in vascular endothelial cells in DcKO mice. Additionally, VE-cadherin/ß-catenin complexes were decreased in DcKO mice, indicating that ROCK proteins play a crucial role in maintaining lung function by regulating cell-cell adhesion.

Tapeworm Infection Diagnosed after Campylobacter jejuni-induced Enteritis.

A 35-year-old man with fever and diarrhea visited our hospital because of white string-like fecal excretion. Based on a morphological examination of the excreted object, a Diphyllobothrium infection was suspected. Additionally, Gram staining of a fecal sample revealed Campylobacter infection. After the intraduodenal administration of meglumine/diatrizoate sodium, the tapeworm was excreted. A polymerase chain reaction-based DNA sequence analysis demonstrated that the tapeworm excreted in this case was Diphyllobothrium nihonkaiensis. This report presents a rare case of coinfection with Diphyllobothrium nihonkaiensis and Campylobacter jejuni. Therefore, it is important to consider the coexistence of other intestinal infections when diagnosing parasitic infections in patients with fever.

Effects of thienopyridine class antiplatelets on bleeding outcomes following robot-assisted radical prostatectomy.

This study aimed to assess the effects of thienopyridine-class antiplatelet agents (including ticlopidine, clopidogrel, and prasugrel) on bleeding complications in patients who underwent robot-assisted radical prostatectomy. This cohort study used a database for robot-assisted radical prostatectomy at 23 tertiary centers nationwide between 2011 and 2022. Patients who received thienopyridines (thienopyridine group) were compared with those who received aspirin monotherapy (aspirin group). The primary outcome was the incidence of bleeding complications. High-grade complications were defined as Clavien-Dindo grade III or higher. The risks of these outcomes were evaluated using inverse probability of treatment weighted regression models. The study results demonstrated that thienopyridine therapy was associated with a higher risk of overall bleeding complications (OR: 3.62, 95%CI 1.54-8.49). The increased risks of the thienopyridine group were detected for low-grade bleeding complications (OR: 3.20, 95%CI 1.23-8.30) but not for high-grade bleeding complications (OR: 5.23, 95%CI 0.78-34.9). The increased risk of bleeding complications was not observed when thienopyridine was discontinued (OR: 2.52, 95%CI 0.83-7.70); however, it became apparent when it was continued perioperatively (OR: 4.35, 95%CI 1.14-16.61). In conclusion, thienopyridine increased the incidence of bleeding complications, particularly low-grade bleeding complications, following robot-assisted radical prostatectomy. These bleeding effects emerged when thienopyridine was continued perioperatively.

Prostate cancer and liquid biopsies: Clinical applications and challenges.

Liquid biopsy has emerged as a valuable and minimally invasive tool for real-time detection of clinically actionable abnormalities across various cancer types. Its applicability is particularly compelling in the realm of prostate cancer, where novel therapeutic agents, including those targeting DNA repair systems, are under development. Despite these advancements, challenges persist in effectively screening for prostate cancer, enhancing risk stratification, and determining optimal approaches for treating advanced disease. Consequently, there is a pressing need for improved biomarkers to aid clinicians in decision-making within these contexts. Cell-free DNA and extracellular vesicle analysis have demonstrated promise in diagnosis, prognostication, assessment of treatment responses, and identification of emerging mechanisms of resistance. Nevertheless, obstacles must be addressed before liquid biopsies can be integrated into routine clinical practice. These challenges encompass preanalytical considerations such as sample collection and storage, methods of extracellular vesicle isolation and enrichment, and the need for enhanced interpretation of generated sequencing data. This review provides a comprehensive overview of current clinical opportunities in managing prostate cancer through blood-based liquid biopsy, highlighting the progress made, and acknowledging the challenges that remain. Additionally, we discuss the next steps required for the effective implementation of liquid biopsies in guiding personalized treatment strategies for prostate cancer.

Malignancy After Living Donor Liver Transplantation.

OBJECTIVES: De novo malignancy (DNM) is a major cause of death in long-term recipients of liver transplantation (LT). We herein report our experience with DNM after living-donor LT (LDLT). PATIENTS AND METHODS: A total of 111 LDLT procedures were performed in our institute from 1999 to 2022. Among them, 70 adult (>13 years old) LDLT recipients who survived for more than 1 year were included in this study. RESULTS: During a median follow-up of 146 (range, 12-285) months, 7 out of 70 recipients developed 8 DNMs, including lung cancer in 4, post-transplant lymphoproliferative disease in 3, and skin cancer in 1. One patient developed metachronal skin cancer and post-transplant lymphoproliferative disease. The pre-LT smoking history rate in patients with DNM was higher than in patients without DNM (P = .004). The survival time after DNM was 6 (1-166) months. Only 2 patients underwent R0 resection. DNM did not recur during follow-up. Other patients who underwent R1 resection and/or chemotherapy and/or radiotherapy all died due to DNMs during the follow-up. The cumulative DNM incidence was 3.5% at 10 years and 18.4% at 20 years after LDLT. The cumulative survival rate in patients with DNM was significantly worse than that in patients without DNM after LDLT (P = .049). CONCLUSION: The survival rate of patients with DNM was lower than that of those without DNM. A pre-LT smoking history is a risk factor for DNM. R0 resection is effective for improving the prognosis of patients with DNM. Regular cancer screening is important for detecting DNM early after LDLT.

Emerging drugs for the treatment of hepatic fibrosis on nonalcoholic steatohepatitis.

INTRODUCTION: Approved drug therapies for nonalcoholic steatohepatitis (NASH) are lacking, for which various agents are currently being tested in clinical trials. Effective drugs for liver fibrosis, the factor most associated with prognosis in NASH, are important. AREAS COVERED: This study reviewed the treatment of NASH with a focus on the effects of existing drugs and new drugs on liver fibrosis. EXPERT OPINION: Considering the complex pathophysiology of fibrosis in NASH, drug therapy may target multiple pathways. The method of assessing fibrosis is important when considering treatment for liver fibrosis in NASH. The Food and Drug Administration considers an important fibrosis endpoint to be histological improvement in at least one fibrosis stage while preventing worsening of fatty hepatitis. To obtain approval as a drug for NASH, efficacy needs to be demonstrated on endpoints such as liver-related events and myocardial infarction. Among the current therapeutic agents for NASH, thiazolidinedione, sodium-glucose co-transporter 2, and selective peroxisome proliferator-activated receptors α modulator have been reported to be effective against fibrosis, although further evidence is required. The effects of pan-peroxisome proliferator-activated receptors, obeticholic acid, and fibroblast growth factor-21 analogs on liver fibrosis in the development stage therapeutics for NASH are of particular interest.

Treatment patterns and prognosis in patients with Bacillus Calmette-Guérin-exposed high-risk non-muscle invasive bladder cancer: a real-world data analysis.

PURPOSE: The International Bladder Cancer Group designated the subgroup that is resistant to Bacillus Calmette-Guérin (BCG) but does not meet the criteria for BCG-unresponsive NMIBC as "BCG-exposed high-risk NMIBC" to guide optimal trial design. We aimed to investigate the treatment patterns and prognoses of patients with BCG-exposed NMIBC. METHODS: We conducted a retrospective chart review of 3283 patients who received intravesical BCG therapy for NMIBC at 14 participating institutions between January 2000 and December 2019. Patients meeting the criteria for BCG-exposed and BCG-unresponsive NMIBC, as defined by the Food and Drug Administration and International Bladder Cancer Group, were selected. To compare treatment patterns and outcomes, high-risk recurrence occurring more than 24 months after the last dose of BCG was defined as "BCG-treated NMIBC." In addition, we compared prognoses between BCG rechallenge and early cystectomy in patients with BCG-exposed NMIBC. RESULTS: Of 3283 patients, 108 (3.3%), 150 (4.6%), and 391 (11.9%) were classified as having BCG-exposed, unresponsive, and treated NMIBC, respectively. BCG-exposed NMIBC demonstrated intermediate survival curves for intravesical recurrence-free and progression-free survival, falling between those of BCG-unresponsive and treated NMIBC. Among patients with BCG-exposed NMIBC, 48 (44.4%) received BCG rechallenge, which was the most commonly performed treatment, and 19 (17.6%) underwent early cystectomy. No significant differences were observed between BCG rechallenge and early cystectomy in patients with BCG-exposed NMIBC. CONCLUSIONS: The newly proposed definition of BCG-exposed NMIBC may serve as a valuable disease subgroup for distinguishing significant gray areas, except in cases of BCG-unresponsive NMIBC.

Dysphagia Secondary to Myotonic Dystrophy Unveiled in a Case of Destructive Spondylitis With Synovitis, Acne, Pustulosis, Hyperostosis, Osteitis (SAPHO) Syndrome Presenting As Torticollis.

To report an instructive case involving destructive spondylitis and synovitis-acne-pustulosis-hyperostosis-osteitis (SAPHO) syndrome, presenting with torticollis and postoperative dysphagia without hoarseness, attributed to hidden myotonic dystrophy (DM). A 51-year-old male patient with a cervical deformity, who was previously managed conservatively for a metastatic tumor, underwent reconstruction surgery and subsequently experienced postoperative dysphagia. The presence of destructive spondylitis with torticollis, warranting prompt assessment to prevent paralysis, adds complexity to the delayed identification of DM. Given the rarity of DM, peculiar neurological symptoms and other systemic comorbidities did not lead to a preoperative diagnosis without prior knowledge. The patient's dysphagia induced respiratory arrest and required reintubation. Challenges in extubation and ventilator weaning arose due to hypercapnia. Superimposed COVID-19 infection elongated the duration of intubation. Extubation failed due to aspiration pneumonia and required a tracheotomy. Despite laryngeal elevation and preservation of the relaxation of the oesophageal entrance, the sensation and movement of the tracheopharynx were disturbed. The patient exhibited an oropharyngeal propulsive disorder, predominantly indicative of motor neuron disease. The patient's mother stated that his brother had been hospitalized for a long time after abdominal surgery. Finally, the patient was diagnosed with DM, which is known to cause post-anesthetic dysphagia. Recognizing the existence of severe destructive cervical spondylitis associated with SAPHO is crucial. Although DM is not very common, it is not classified as extremely rare. Therefore, surgeons should be mindful of the potential risks associated with general anesthesia in patients with DM. The complexity of preoperative conditions may hinder an accurate diagnosis. Recognizing and establishing preoperative expectations can assist surgeons in preventing complications, even if complex spinal surgery is required for patients with DM.

Multicomponent Intervention for Overactive Bladder in Women: A Randomized Clinical Trial.

Importance: Although the cognitive components of behavioral therapy for overactive bladder (OAB) are widely recognized, there is a lack of studies evaluating the effectiveness of multicomponent interventions that include cognitive components as a treatment for OAB. Objective: To examine the efficacy of a multicomponent intervention in improving health-related quality of life (HRQOL) for women with moderate to severe OAB. Design, Setting, and Participants: This multicenter, open-label, randomized clinical trial was conducted in Japan among women aged 20 to 80 years who had moderate to severe OAB. Participants were recruited from 4 institutions between January 16, 2020, and December 31, 2022, through self-referral via advertisement or referral from the participating institutions. Interventions: Participants were randomized 1:1 by minimization algorithm using an internet-based central cloud system to four 30-minute weekly sessions of a multicomponent intervention or waiting list. Both groups continued to receive baseline treatment throughout the study period. Main Outcomes and Measures: The primary outcome was the least-squares mean changes from baseline through week 13 in HRQOL total scores of the OAB questionnaire between 2 groups. Secondary outcomes included OAB symptom score and frequency volume chart. Results: A total of 79 women were randomized to either the intervention group (39 participants; mean [SD] age, 63.5 [14.6] years) or the waiting list control group (40 participants; mean [SD] age, 63.5 [12.9] years). One participant from each group dropped out from the allocated intervention, while 5 participants in the intervention group and 2 in the control group dropped out from the primary outcome assessment at week 13. Thirty-six participants (92.3%) in the intervention group and 35 (87.5%) in the control group had moderate OAB. The change in HRQOL total score from baseline to week 13 was 23.9 points (95% CI, 18.4-29.5 points) in the intervention group and 11.3 points (95% CI, 6.2-16.4 points) in the waiting list group, a significant difference of 12.6 points (95% CI, 6.6-18.6 points; P < .001). Similar superiority of the intervention was confirmed for frequency of micturition and urgency but not for OAB symptom score. Conclusions and Relevance: These findings demonstrate that a multicomponent intervention improves HRQOL for women with moderate to severe OAB and suggest that the cognitive component may be an effective treatment option for women with OAB. Trial Registration: UMIN Clinical Trials Registry Identifier: UMIN000038513.

Post-treatment Neutrophil/Lymphocyte Ratio Is a Prognostic Factor in Head and Neck Cancers Treated With Nivolumab.

Background/Aim: Inflammation and nutrition-based biomarkers, such as the neutrophil/lymphocyte ratio (NLR), platelet/lymphocyte ratio (PLR), lymphocyte/monocyte ratio (LMR), C-reactive protein/albumin ratio (CAR), prognostic nutritional index (PNI), systemic immune inflammation index (SII), and systemic inflammation response index (SIRI), have prognostic value for several types of malignancies. Markers that precisely reflect the prognosis of patients with head and neck cancers (HNCs) treated with immune-checkpoint inhibitors remain unclear. This retrospective study aimed to investigate the prognostic value of hematological markers before and after treatment with nivolumab in patients with recurrent or metastatic HNC (RM-HNC). Patients and Methods: We evaluated the clinical data of 44 patients with recurrent/metastatic head and neck squamous cell carcinoma treated with nivolumab between April 2017 and April 2023 at Shinshu University Hospital. Values of hematological biomarkers (NLR, LMR, PLR, CAR, PNI, SII, and SIRI) were calculated before and 4-6 weeks after nivolumab initiation. Receiver operating characteristic curves were constructed to determine the cutoff values of pre- and post-treatment markers for overall survival (OS) and progression-free survival (PFS). Results: Among all pre- and post-treatment markers, post-treatment NLR showed the highest area under the curve (AUC=0.702). A high post-treatment NLR (cutoff value, 4.01) was associated with a poor OS (p=0.027) and a tendency for shorter PFS (p=0.117). Multivariate analysis showed that a high post-treatment NLR was significantly associated with poor OS (p=0.026). Conclusion: A high post-treatment NLR was associated with poor response to nivolumab in head and neck cancers.

Renal cell carcinoma with multiple bone metastases effectively treated by a combination of tyrosine kinase inhibitor, robot-assisted partial nephrectomy, and metastasectomy.

Key Clinical Message: Maintaining a disease-free status for a long time in cases of renal cell carcinoma with multiple bone metastases and repeated recurrences is challenging. What matters most in the multidisciplinary approach is the treatment strategy. Although this is a case where multidisciplinary treatment resulted in long-term CR during the TKI era, the treatment strategy is still relevant now that treatment options have increased. Abstract: Recent advances in medications, such as immune checkpoint inhibitors (ICIs) and tyrosine kinase inhibitors (TKIs), have improved metastatic renal cell carcinoma (mRCC) outcomes. We report a case of mRCC with bone metastasis that was successfully treated using a multidisciplinary approach. Here, we present a case of a 56-year-old man with left renal cancer and large and painful bone metastases at the 11th thoracic vertebrae (Th11). Therefore, a metastasectomy of Th11 was performed. Systemic treatment with TKI, robot-assisted partial nephrectomy, and metastasectomy were then administered. No recurrence was observed in >2 years. Long-term disease-free survival with the TKI-era multidisciplinary approach in a patient with mRCC remains significant when considering treatment sequences, especially now that drug treatment options-including ICIs-have increased. Treatment strategy and indication and timing of resection of the primary lesion and metastasectomy should be carefully considered in each case.

Surgical Outcomes of Ipsilateral Inguinal Hernia After Kidney Transplantation.

OBJECTIVES: We aimed to clarify the clinical features and outcomes of ipsilateral inguinal hernias after kidney transplantation. PATIENTS AND METHODS: Eleven patients diagnosed with inguinal hernia on the ipsilateral side after kidney transplantation between 2011 and 2022 were analyzed. Clinical data were retrospectively reviewed from the medical records. RESULT: Eleven patients were included in the analysis (median age, 68 [range, 28-75] years, male, n = 11). The time from kidney transplantation to hernia surgery was 107 (6-393) months. Eight patients had direct-type inguinal hernias. Three had indirect-type inguinal hernias. Hernia contents included the small intestine (n = 5), transplanted ureter and bladder (n = 2), only bladder (n = 1), transplanted kidney, ureter, and small intestine (n = 1), transplanted kidney and small intestine (n = 1), and transplanted ureter (n = 1). Six patients (55%) were diagnosed with urinary tract obstruction due to inguinal hernia. All hernias were repaired using mesh. The plug method was used in 9 cases. The Lichtenstein method was used in 2 cases. The median operative time was 110 (73-155) minutes, and the median blood loss was 3 (1-85) mL. The median postoperative hospital stay was 4 (2-7) days. In the 6 patients with urinary obstruction, the serum creatinine levels improved (P = .028), and the transplanted urinary tract obstruction disappeared after surgery. There was no recurrence of inguinal hernia. One patient experienced chronic pain in the groin area (Clavien-Dindo grade II) during follow-up. CONCLUSION: Surgical intervention for inguinal hernia after kidney transplantation is safe and effective for preventing worsening of the kidney graft function.

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.

A Predictive Strategy for Nonsurgical Management of Pancreatic Stones.

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.