scholarly journals Case Report: Nivolumab-Induced Autoimmune Pancreatitis

2021 ◽  
Author(s):  
Preeya Goyal ◽  
Justin T. Moyers ◽  
Bassem G. Elgohary ◽  
Muhammad B. Hammami
Keyword(s):  
Autoimmune Pancreatitis ◽  
Clinical Course ◽  
Checkpoint Inhibitors ◽  
Extrahepatic Bile Duct ◽  
Magnetic Resonance Cholangiopancreatography ◽  
Pancreatic Injury ◽  
Cholestatic Liver Disease ◽  
Positron Emission ◽  
Clinically Significant ◽  
Cell Death Protein

ABSTRACT Nivolumab is an anti-programmed cell death protein 1 monoclonal antibody. While an effective treatment for a variety of tumors, immune checkpoint inhibitors (ICI) can cause immune-related adverse events such as ICI-pancreatic injury (ICI-PI). Here we present a case of a 60-year-old man with metastatic acral melanoma treated with nivolumab and ipilimumab who developed ICI-PI. Changes in positron emission tomography images preceded symptom onset. However, this case is unique in that the patient presented with cholestatic liver disease. Magnetic resonance cholangiopancreatography showed a dilated extrahepatic bile duct that resolved with steroid therapy, similar to the clinical course of autoimmune pancreatitis. ICI-PI has variable presentations including obstructive jaundice with a clinical course mimicking autoimmune pancreatitis and prompt awareness and treatment of ICI-PI is clinically significant given increasing use of ICIs.

scholarly journals PD-L1 Targeting Immune-Microbubble Complex Enhances Therapeutic Index in Murine Colon Cancer Models

2020 ◽  
Vol 14 (1) ◽  
pp. 6
Author(s):  
Daehyun Kim ◽  
Seung Soo Lee ◽  
Hyungwon Moon ◽  
So Yeon Park ◽  
Hak Jong Lee
Keyword(s):  
Cancer Immunotherapy ◽  
Focused Ultrasound ◽  
Therapeutic Potential ◽  
Checkpoint Inhibitors ◽  
Therapeutic Index ◽  
Treatment Regimens ◽  
Cancer Models ◽  
Programmed Death ◽  
Murine Colon ◽  
Cell Death Protein

Cancer immunotherapy has revolutionized the way different neoplasms are treated. Among the different variations of cancer immunotherapy, the checkpoint inhibitors targeting the programmed cell death protein 1 (PD-1)/programmed death-ligand 1 (PD-L1) axis have been validated and are currently used in the clinics. Nevertheless, these therapeutic antibodies are associated with significant side effects and are known to induce immune-related toxicities. To address these issues, we have developed an immune-microbubble complex (IMC) which not only reduces the toxicities associated with the antibodies but also enhances the therapeutic efficacy when combined with focused ultrasound. The concept of IMCs could be applied to any type of antibody-based treatment regimens to maximize their therapeutic potential.

scholarly journals Diffuse Cystic Metastases in the Lung after Nivolumab Treatment in a Patient with Non-Small Cell Lung Cancer: A Case Report

2021 ◽  
pp. 34-38
Author(s):  
Satoshi Muto ◽  
Yuki Ozaki ◽  
Takuya Inoue ◽  
Naoyuki Okabe ◽  
Yuki Matsumura ◽  
...  
Keyword(s):  
Lung Adenocarcinoma ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Lung Metastases ◽  
Sialyl Lewis X ◽  
Ground Glass ◽  
Cystic Lesions ◽  
Positron Emission ◽  
Ground Glass Nodules

Although diffuse cysts in the lung can be found in many diseases, they are uncommon in metastatic lung adenocarcinoma. They are even more unusual after the administration of immune checkpoint inhibitors. A case of lung adenocarcinoma that developed diffuse cysts in the lungs during treatment with nivolumab is reported. The patient was a 60-year-old woman with postoperative recurrent lung adenocarcinoma in mediastinal lymph nodes and pleural dissemination. After first-line treatment with cisplatin, pemetrexed, and bevacizumab, computed tomography (CT) showed disease progression. Treatment was then switched to nivolumab. After 5 courses of nivolumab, CT showed multiple ground-glass nodules in her lungs. After 4 more courses of nivolumab, the ground-glass nodules increased in size, and cystic air spaces appeared in their centers. The patient did not have any symptoms. Laboratory tests showed no evidence of infection or nivolumab-induced pneumonitis. Sialyl Lewis X-i antigen increased, and positron emission tomography showed abnormal uptake of 18F-fluorodeoxyglucose in these lesions. Considering this evidence, the cystic lesions were diagnosed as multiple lung metastases. Various differential diagnoses should be considered when diffuse cystic lesions are found in the lungs after the administration of immune checkpoint inhibitors.

scholarly journals The Diagnostic Yield of Magnetic Resonance Cholangiopancreatography in the Setting of Acute Pancreaticobiliary Disease — A Single Center Experience

2021 ◽  
pp. 084653712110137
Author(s):  
Sultan Yahya ◽  
Abdullah Alabousi ◽  
Peri Abdullah ◽  
Milita Ramonas
Keyword(s):  
Magnetic Resonance ◽  
Diagnostic Yield ◽  
Binary Logistic Regression ◽  
Magnetic Resonance Cholangiopancreatography ◽  
Significant Discrepancy ◽  
Logistic Regression Models ◽  
Single Center Experience ◽  
New Information ◽  
Clinically Significant ◽  
Enzyme Elevation

Purpose: To discern whether preceding ultrasound (US) results, patient demographics and biochemical markers can be implemented as predictors of an abnormal Magnetic Resonance Cholangiopancreatography (MRCP) study in the context of acute pancreaticobiliary disease. Methods: A retrospective study was performed assessing US results, age, gender, elevated lipase and biliary enzymes for consecutive patients who underwent an urgent MRCP following an initial US for acute pancreaticobiliary disease between January 2017-December 2018. Multivariable binary logistic regression models were constructed to assess for predictors of clinically significant MRCPs, and discrepant US/MRCP results. Results: A total of 155 patients (mean age 56, 111 females) were included. Age (OR 1.03, P < 0.05), hyperlipasemia (OR 5.33, P < 0.05) and a positive US (OR 40.75, P < 0.05) were found to be independent predictors for a subsequent abnormal MRCP. Contrarily, gender and elevated biliary enzymes were not reliable predictors of an abnormal MRCP, or significant MRCP/US discrepancies. Of 66 cases (43%) of discordant US/MRCPs, half had clinically significant discrepant findings such as newly discovered choledocholithiasis and pancreaticobiliary neoplasia. Age was the sole predictor for a significant US/MRCP discrepancy, with 2% increase in the odds of a significant discrepancy per year of increase in age. Conclusion: An abnormal US, hyperlipasemia and increased age serve as predictors for a subsequent abnormal MRCP, as opposed to gender and biliary enzyme elevation. Age was the sole predictor of a significant US/MRCP discrepancy that provided new information which significantly impacted subsequent management. In the remaining cases, however, MRCP proved useful in reaffirming the clinical diagnosis and avoiding further investigations.

scholarly journals Clinical Applications of Immunotherapy Combination Methods and New Opportunities for the Future

2017 ◽  
Vol 2017 ◽  
pp. 1-10 ◽  
Author(s):  
Ece Esin
Keyword(s):  
Cell Death ◽  
Programmed Cell Death ◽  
Checkpoint Inhibitors ◽  
Innate Immune ◽  
Small Subset ◽  
New Class ◽  
Combination Strategies ◽  
Combination Methods ◽  
Immune Editing ◽  
Cell Death Protein

In the last decade, we have gained a deeper understanding of innate immune system. The mechanism of the continuous guarding of progressive mutations happening in a single cell was discovered and the production and the recognition of tumor associated antigens by the T-cells and elimination of numerous tumors by immune-editing were further understood. The new discoveries on immune mechanisms and its relation with carcinogenesis have led to development of a new class of drugs called immunotherapeutics. T lymphocyte-associated antigen 4, programmed cell death protein 1, and programmed cell death protein ligand 1 are the classes drugs based on immunologic manipulation and are collectively known as the “checkpoint inhibitors.” Checkpoint inhibitors have shown remarkable antitumor efficacy in a broad spectrum of malignancies; however, the strongest and most durable immune responses do not last long and the more durable responses only occur in a small subset of patients. One of the solutions which have been put forth to overcome these challenges is combination strategies. Among the dual use of methods, a backbone with either PD-1 or PD-L1 antagonist drugs alongside with certain cytotoxic chemotherapies, radiation, targeted drugs, and novel checkpoint stimulators is the most promising approach and will be on stage in forthcoming years.

scholarly journals A Resected Case of Mucinous Adenocarcinoma of the Duodenum, Mimicking Intraductal Papillary Neoplasm of the Bile Duct

2015 ◽  
Vol 100 (11-12) ◽  
pp. 1443-1448
Author(s):  
Norio Kubo ◽  
Hideki Suzuki ◽  
Norihiro Ishii ◽  
Mariko Tsukagoshi ◽  
Akira Watanabe ◽  
...  
Keyword(s):  
Bile Duct ◽  
Common Bile Duct ◽  
Transverse Colon ◽  
Extrahepatic Bile Duct ◽  
Magnetic Resonance Cholangiopancreatography ◽  
Mucinous Carcinoma ◽  
Villous Tumor ◽  
Intraductal Papillary Neoplasm ◽  
The Common ◽  
Papillary Neoplasm

Duodenum mucinous carcinoma is very rare, and the prognosis of the patient is very bad, especially when the tumor is invasive to other organs. In this case, duodenum carcinoma was invasive to common bile duct and transverse colon. Mucinous fluid, which was secreted from a duodenum tumor, was found in the dilatated bile duct. The intraductal papillary neoplasm of the bile duct was considered a differential diagnosis. We performed aggressive resection and had a good prognosis. A 74-year-old woman received a diagnosis of cholangitis and was treated with antibiotic drugs. Endoscopic retrograde cholangiopancreatography revealed a defect in the lower common bile duct with the mucoid fluid. We suspected intraductal papillary neoplasm of the bile duct, but no malignant cells were detected. One year later, gastrointestinal fiberscopy revealed a villous tumor in the postbulbar portion of the duodenum; adenocarcinoma was detected in biopsy specimens. Computed tomography revealed dilatation of the duodenum with an enhanced tumor, and dilatation of both the common and intrahepatic bile ducts. Magnetic resonance cholangiopancreatography revealed that the duodenum was connected with the common bile duct and ascending colon. We resected the segmental duodenum, extrahepatic bile duct, left lobe of liver, a partial of the transverse colon, and associated lymph nodes. Although the advanced duodenal carcinoma had poor prognosis, the patient was alive, without recurrence, 5 years after the operation.

18 F-Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography imaging for the diagnosis of immune checkpoint inhibitors associated myocarditis

2021 ◽  
Author(s):  
Stéphane Ederhy ◽  
Perrine Devos ◽  
Bruno Pinna ◽  
Elisa Funck-Brentano ◽  
Baptiste Abbar ◽  
...  
Keyword(s):  
Immune Checkpoint ◽  
Fdg Pet ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Diagnostic Value ◽  
Predictive Values ◽  
Fdg Uptake ◽  
Positron Emission ◽  
Medicine Physician ◽  
Oncology Unit

Abstract Immune-checkpoint inhibitors (ICI) have profoundly improved the prognosis of cancer patients but are associated with life-threatening myocarditis (incidence≤1%).The diagnosis of ICI-myocarditis remains challenging necessitating the need for novel diagnostic strategies.This single center cohort included 61 consecutive patients referred to our cardio-oncology unit for a suspicion of ICI-myocarditis with a positive troponin, between March 2019 and March 2021. In the 31 patients with suspected ICI-myocarditis with available FDG-PET, the median delay between admission and the first available FDG-PET performed was 12 days [interquartile-range:9-30]. Patients received ICI (ICI-monotherapy: 24/31, 77% and ICI-combination therapy: 7/31, 23%), mainly for lung cancer (n=10), melanoma (n=5), and kidney cancer (n=3). FDG-PET was performed using a standardized protocol involving dietary measures prior to PET, including fasting of at least 6h and a fat enriched diet without carbohydrates for 24h. FDG-PET platforms included Biograph-mCT-Flow Siemens (n=9/34, 26%) or Discovery-MI-5-Ring General Electric (n=25/34, 74%) devices and analysed using Singo.via Workstation (Siemens) by a nuclear medicine physician blinded to patients’ medical records. Interpretation of FDG-PET was based on the following classification: 1/No FDG uptake, 2/Diffuse FDG uptake, 3/Focal FDG uptake, 4/Focal on diffuse FDG uptake.An abnormal cardiac fixation on FDG-PET suggestive of myocarditis was observed in only 2/21 (9.5%) patients with otherwise definite ICI-myocarditis (1 diffuse, 1 focal), not different in proportion versus 1/7 (14.3%, 1 focal) patient without ICI-myocarditis (p>0.99). The sensitivity, specificity, positive predictive and negative predictive values (with their 95% confidence-interval) of FDG-PET for ICI-myocarditis was 9.5% (1.2-30.4%), 85.7% (42.1-99.6%), 66% (17.5-95%), 24% (18.5-30.6%), respectively. Only 2/14(14.2%) FDG-PET were positive despite being performed at a time in which ICI-myocarditis was fully active with troponin levels over ten-times the normal values versus 0/6(0%,p>0.99) for FDG-PET performed when troponin levels were abnormal but below ten-times the upper limit. Similarly, there was no difference in FDG-PET positivity rate for exams performed within 14 days (1/7, 14.3%; plus 3 inconclusive exams) versus those performed after 14 days (1/14, 7.2%; no inconclusive exams; p>0.99) of hospital admission.Altogether, our study suggests that FDG-PET has a limited diagnostic value for the diagnosis of ICI-Myocarditis.

Liver Toxicity with Cancer Checkpoint Inhibitor Therapy

2018 ◽  
Vol 38 (04) ◽  
pp. 366-378 ◽  
Author(s):  
Brian Nadeau ◽  
Leslie Fecher ◽  
Scott Owens ◽  
Nataliya Razumilava
Keyword(s):  
Liver Toxicity ◽  
Cytotoxic T Lymphocyte ◽  
Checkpoint Inhibitor ◽  
Checkpoint Inhibitors ◽  
Immunosuppressive Agents ◽  
Inhibitor Therapy ◽  
Significant Survival ◽  
The Us ◽  
Checkpoint Inhibitor Therapy ◽  
Clinically Significant

AbstractImmune checkpoint inhibition targeted against cytotoxic T-lymphocyte–associated antigen 4 (CTLA-4) and programmed cell death protein 1 (PD-1) has shown clinically significant survival benefit when used to treat multiple types of advanced cancer. These drugs have gained approval by the US Food and Drug Administration and their indications continue to increase. Checkpoint inhibitor therapy is associated with a unique side-effect profile characterized as immune-related adverse events (irAEs), which can result in significant morbidity and rarely mortality. Hepatotoxicity from checkpoint inhibitors is a less common irAE and often mild, while its incidence and severity vary based on the class and dose of checkpoint inhibitor, monotherapy versus combination therapy, and the type of cancer. Histological assessment of suspected irAEs is nonspecific and can show a variety of features. Hepatic irAEs can require discontinuation of checkpoint inhibitor therapy and treatment with immunosuppressive agents.

scholarly journals Metabolomic adaptations and correlates of survival to immune checkpoint blockade

2019 ◽  
Vol 10 (1) ◽  
Author(s):  
Haoxin Li ◽  
Kevin Bullock ◽  
Carino Gurjao ◽  
David Braun ◽  
Sachet A. Shukla ◽  
...  
Keyword(s):  
Immune Checkpoint ◽  
Checkpoint Inhibitors ◽  
Resistance Mechanism ◽  
Immune Checkpoint Blockade ◽  
Checkpoint Blockade ◽  
Adaptive Resistance ◽  
Metabolic Monitoring ◽  
Pd1 Blockade ◽  
To Receive ◽  
Cell Death Protein

Abstract Despite remarkable success of immune checkpoint inhibitors, the majority of cancer patients have yet to receive durable benefits. Here, in order to investigate the metabolic alterations in response to immune checkpoint blockade, we comprehensively profile serum metabolites in advanced melanoma and renal cell carcinoma patients treated with nivolumab, an antibody against programmed cell death protein 1 (PD1). We identify serum kynurenine/tryptophan ratio increases as an adaptive resistance mechanism associated with worse overall survival. This advocates for patient stratification and metabolic monitoring in immunotherapy clinical trials including those combining PD1 blockade with indoleamine 2,3-dioxygenase/tryptophan 2,3-dioxygenase   (IDO/TDO) inhibitors.

scholarly journals Evaluation of response to immune checkpoint inhibitors: Is there a role for positron emission tomography?

2017 ◽  
Vol 9 (2) ◽  
pp. 27 ◽  
Author(s):  
Matteo Bauckneht ◽  
Roberta Piva ◽  
Gianmario Sambuceti ◽  
Francesco Grossi ◽  
Silvia Morbelli
Keyword(s):  
Positron Emission Tomography ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Emission Tomography ◽  
Positron Emission

scholarly journals Rheumatic immune-related adverse events from checkpoint inhibitor therapy: a case series

2021 ◽  
Vol 3 (2) ◽  
Author(s):  
Antonella Laria ◽  
Alfredomaria Lurati ◽  
Laura Castelnovo ◽  
Antonio Tamburello ◽  
Paola Maria Faggioli ◽  
...  
Keyword(s):  
Adverse Events ◽  
T Lymphocyte ◽  
Cytotoxic T Lymphocyte ◽  
Checkpoint Inhibitor ◽  
Checkpoint Inhibitors ◽  
Case Series ◽  
Hematologic Malignancies ◽  
Checkpoint Inhibitor Therapy ◽  
Cancer Immunotherapies ◽  
Cell Death Protein

Immune checkpoint inhibitors (ICIs) targeting cytotoxic T-lymphocyte associated protein-4 (CTLA-4), programmed cell death protein-1 (PD-1), and its ligand PD-L1 are established cancer immunotherapies for solid tumor and hematologic malignancies. These therapies are involved in immune-related adverse events (irAE), both general and rheumatic ones. In general, immune-related adverse events (irAE) management includes drug-holding, tapering doses of corticosteroids, and specific immunosuppression for clinically severe cases, such as infliximab or mycophenolate.

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