Posterior Reversible Encephalopathy Syndrome (PRES) Following Bevacizumab and Atezolizumab Therapy in Hepatocellular Carcinoma (HCC)

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Background

Bevacizumab, an anti-vascular endothelial growth factor monoclonal antibody, is known to inhibit angiogenesis and prevent carcinogenesis. Recent evidence from the IMbrave050 trial indicates that combining bevacizumab with atezolizumab enhances recurrence-free survival (RFS) in high-risk HCC patients undergoing curative treatments. Bevacizumab is notorious for causing endothelial dysfunction that may provoke vasospasm, leading to central hypoperfusion, hypertension, and, albeit rarely, PRES. Similarly, immunotherapy, including atezolizumab, has been implicated in PRES, underscoring a potential risk when these therapies are administered concurrently.

Case Presentation

A 64-year-old woman with a history of hepatitis C and alcoholic cirrhosis was diagnosed with stage II (T2 N0 M0) HCC. Following partial hepatectomy, we proceeded with adjuvant systemic therapy with atezolizumab and bevacizumab (per the IMbrave050 trial). After her 2nd treatment, she developed altered mental status, seizures, and severe hypertension. Labs revealed acute kidney injury and elevated creatinine kinase levels suggesting rhabdomyolysis. Computed tomography head showed no acute findings, but magnetic resonance imaging of the brain identified increased flair attenuated inversion recovery (FLAIR) signal in the brain’s posterior regions, indicating PRES. Symptomatic management with anti-hypertensives and intravenous fluids led to the recovery of mental status to baseline. Further therapy with bevacizumab and atezolizumab was then held off.

Discussion

Therapeutic advances in HCC management through the IMbrave050 trial demonstrate the efficacy of bevacizumab and atezolizumab in reducing RFS, without highlighting the serious side effects like PRES. To our knowledge, this is the first case reported where PRES occurred with the simultaneous use of atezolizumab and bevacizumab. Since both drugs can individually cause PRES, there might be a heightened risk with the co-administration, signaling a critical need for vigilant monitoring and further research into this treatment modality’s long-term safety profile.

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Background

Bevacizumab, an anti-vascular endothelial growth factor monoclonal antibody, is known to inhibit angiogenesis and prevent carcinogenesis. Recent evidence from the IMbrave050 trial indicates that combining bevacizumab with atezolizumab enhances recurrence-free survival (RFS) in high-risk HCC patients undergoing curative treatments. Bevacizumab is notorious for causing endothelial dysfunction that may provoke vasospasm, leading to central hypoperfusion, hypertension, and, albeit rarely, PRES. Similarly, immunotherapy, including atezolizumab, has been implicated in PRES, underscoring a potential risk when these therapies are administered concurrently.

Case Presentation

A 64-year-old woman with a history of hepatitis C and alcoholic cirrhosis was diagnosed with stage II (T2 N0 M0) HCC. Following partial hepatectomy, we proceeded with adjuvant systemic therapy with atezolizumab and bevacizumab (per the IMbrave050 trial). After her 2nd treatment, she developed altered mental status, seizures, and severe hypertension. Labs revealed acute kidney injury and elevated creatinine kinase levels suggesting rhabdomyolysis. Computed tomography head showed no acute findings, but magnetic resonance imaging of the brain identified increased flair attenuated inversion recovery (FLAIR) signal in the brain’s posterior regions, indicating PRES. Symptomatic management with anti-hypertensives and intravenous fluids led to the recovery of mental status to baseline. Further therapy with bevacizumab and atezolizumab was then held off.

Discussion

Therapeutic advances in HCC management through the IMbrave050 trial demonstrate the efficacy of bevacizumab and atezolizumab in reducing RFS, without highlighting the serious side effects like PRES. To our knowledge, this is the first case reported where PRES occurred with the simultaneous use of atezolizumab and bevacizumab. Since both drugs can individually cause PRES, there might be a heightened risk with the co-administration, signaling a critical need for vigilant monitoring and further research into this treatment modality’s long-term safety profile.

Background

Bevacizumab, an anti-vascular endothelial growth factor monoclonal antibody, is known to inhibit angiogenesis and prevent carcinogenesis. Recent evidence from the IMbrave050 trial indicates that combining bevacizumab with atezolizumab enhances recurrence-free survival (RFS) in high-risk HCC patients undergoing curative treatments. Bevacizumab is notorious for causing endothelial dysfunction that may provoke vasospasm, leading to central hypoperfusion, hypertension, and, albeit rarely, PRES. Similarly, immunotherapy, including atezolizumab, has been implicated in PRES, underscoring a potential risk when these therapies are administered concurrently.

Case Presentation

A 64-year-old woman with a history of hepatitis C and alcoholic cirrhosis was diagnosed with stage II (T2 N0 M0) HCC. Following partial hepatectomy, we proceeded with adjuvant systemic therapy with atezolizumab and bevacizumab (per the IMbrave050 trial). After her 2nd treatment, she developed altered mental status, seizures, and severe hypertension. Labs revealed acute kidney injury and elevated creatinine kinase levels suggesting rhabdomyolysis. Computed tomography head showed no acute findings, but magnetic resonance imaging of the brain identified increased flair attenuated inversion recovery (FLAIR) signal in the brain’s posterior regions, indicating PRES. Symptomatic management with anti-hypertensives and intravenous fluids led to the recovery of mental status to baseline. Further therapy with bevacizumab and atezolizumab was then held off.

Discussion

Therapeutic advances in HCC management through the IMbrave050 trial demonstrate the efficacy of bevacizumab and atezolizumab in reducing RFS, without highlighting the serious side effects like PRES. To our knowledge, this is the first case reported where PRES occurred with the simultaneous use of atezolizumab and bevacizumab. Since both drugs can individually cause PRES, there might be a heightened risk with the co-administration, signaling a critical need for vigilant monitoring and further research into this treatment modality’s long-term safety profile.

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Cholangioblastic Intrahepatic Cholangiocarcinoma: A Rare Case of an Inhibin-Positive Variant Mimicking Neuroendocrine Tumors

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Background

Cholangiocarcinoma (CCA) is a rare and aggressive cancer of the biliary system, accounting for 15% of primary liver cancers. Most CCAs arise spontaneously, with risk factors including primary biliary cirrhosis, liver fluke infection, and biliary malformations. A newly described variant, Inhibin-positive Cholangioblastic (solid-tubulocystic) intrahepatic cholangiocarcinoma (iCCA), mimics neuroendocrine tumors (NET). This report presents a case of this new variant.

Case Presentation

A 53-year-old female with a history of alcohol use disorder and no family history of liver cancer presented with watery diarrhea for a month. Blood tests, including tumor markers, were normal. An ultrasound revealed a large mass in the right hepatic lobe. CT and MRI scans suggested a hemangioma. Due to the mass’s size and spontaneous bleeding risk, she underwent surgical resection. The mass was initially thought to be a hemangioma but was later identified as poorly differentiated intrahepatic CCA with a solid and tubulocystic structure. Pathology showed strong staining for Cytokeratin (CK) 7, CK-19, and Inhibin, and weak staining for synaptophysin, confirming a diagnosis of cholangioblastic iCCA. Genetic testing revealed no actionable variations. She was started on capecitabine for 8 cycles. Follow-up imaging showed no disease recurrence or metastasis.

Discussion

CCA often presents at advanced stages with symptoms like weight loss and jaundice. Diagnosis involves clinical assessment, lab work, and imaging, particularly MRI. Cholangioblastic Intrahepatic CCA (iCCA) is a newly described variant of cholangiocarcinoma. There have been 16 reported cases of the disease. Initially, it was thought to be a NET as it expressed Chromogranin, insulinoma-associated protein-1, and Synaptophysin. Almost half of the reported cases were diagnosed as NET initially. One tool clinicians can use to differentiate them is inhibin. Inhibin has been documented in all of the reported cases of Cholangioblastic iCCA. A novel inhibin-positive cholangioblastic iCCA variant with a Nipped-B-like protein and nucleus accumbens associated-1 (NIPBL-NACC1) fusion transcript has been reported recently, further helping differentiate the two. There is no standard of therapy for this variant. It’s managed similarly to CCAs, relying on surgical resection as the primary treatment. Limited data shows varied responses to neoadjuvant and adjuvant therapy.

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Background

Cholangiocarcinoma (CCA) is a rare and aggressive cancer of the biliary system, accounting for 15% of primary liver cancers. Most CCAs arise spontaneously, with risk factors including primary biliary cirrhosis, liver fluke infection, and biliary malformations. A newly described variant, Inhibin-positive Cholangioblastic (solid-tubulocystic) intrahepatic cholangiocarcinoma (iCCA), mimics neuroendocrine tumors (NET). This report presents a case of this new variant.

Case Presentation

A 53-year-old female with a history of alcohol use disorder and no family history of liver cancer presented with watery diarrhea for a month. Blood tests, including tumor markers, were normal. An ultrasound revealed a large mass in the right hepatic lobe. CT and MRI scans suggested a hemangioma. Due to the mass’s size and spontaneous bleeding risk, she underwent surgical resection. The mass was initially thought to be a hemangioma but was later identified as poorly differentiated intrahepatic CCA with a solid and tubulocystic structure. Pathology showed strong staining for Cytokeratin (CK) 7, CK-19, and Inhibin, and weak staining for synaptophysin, confirming a diagnosis of cholangioblastic iCCA. Genetic testing revealed no actionable variations. She was started on capecitabine for 8 cycles. Follow-up imaging showed no disease recurrence or metastasis.

Discussion

CCA often presents at advanced stages with symptoms like weight loss and jaundice. Diagnosis involves clinical assessment, lab work, and imaging, particularly MRI. Cholangioblastic Intrahepatic CCA (iCCA) is a newly described variant of cholangiocarcinoma. There have been 16 reported cases of the disease. Initially, it was thought to be a NET as it expressed Chromogranin, insulinoma-associated protein-1, and Synaptophysin. Almost half of the reported cases were diagnosed as NET initially. One tool clinicians can use to differentiate them is inhibin. Inhibin has been documented in all of the reported cases of Cholangioblastic iCCA. A novel inhibin-positive cholangioblastic iCCA variant with a Nipped-B-like protein and nucleus accumbens associated-1 (NIPBL-NACC1) fusion transcript has been reported recently, further helping differentiate the two. There is no standard of therapy for this variant. It’s managed similarly to CCAs, relying on surgical resection as the primary treatment. Limited data shows varied responses to neoadjuvant and adjuvant therapy.

Background

Cholangiocarcinoma (CCA) is a rare and aggressive cancer of the biliary system, accounting for 15% of primary liver cancers. Most CCAs arise spontaneously, with risk factors including primary biliary cirrhosis, liver fluke infection, and biliary malformations. A newly described variant, Inhibin-positive Cholangioblastic (solid-tubulocystic) intrahepatic cholangiocarcinoma (iCCA), mimics neuroendocrine tumors (NET). This report presents a case of this new variant.

Case Presentation

A 53-year-old female with a history of alcohol use disorder and no family history of liver cancer presented with watery diarrhea for a month. Blood tests, including tumor markers, were normal. An ultrasound revealed a large mass in the right hepatic lobe. CT and MRI scans suggested a hemangioma. Due to the mass’s size and spontaneous bleeding risk, she underwent surgical resection. The mass was initially thought to be a hemangioma but was later identified as poorly differentiated intrahepatic CCA with a solid and tubulocystic structure. Pathology showed strong staining for Cytokeratin (CK) 7, CK-19, and Inhibin, and weak staining for synaptophysin, confirming a diagnosis of cholangioblastic iCCA. Genetic testing revealed no actionable variations. She was started on capecitabine for 8 cycles. Follow-up imaging showed no disease recurrence or metastasis.

Discussion

CCA often presents at advanced stages with symptoms like weight loss and jaundice. Diagnosis involves clinical assessment, lab work, and imaging, particularly MRI. Cholangioblastic Intrahepatic CCA (iCCA) is a newly described variant of cholangiocarcinoma. There have been 16 reported cases of the disease. Initially, it was thought to be a NET as it expressed Chromogranin, insulinoma-associated protein-1, and Synaptophysin. Almost half of the reported cases were diagnosed as NET initially. One tool clinicians can use to differentiate them is inhibin. Inhibin has been documented in all of the reported cases of Cholangioblastic iCCA. A novel inhibin-positive cholangioblastic iCCA variant with a Nipped-B-like protein and nucleus accumbens associated-1 (NIPBL-NACC1) fusion transcript has been reported recently, further helping differentiate the two. There is no standard of therapy for this variant. It’s managed similarly to CCAs, relying on surgical resection as the primary treatment. Limited data shows varied responses to neoadjuvant and adjuvant therapy.

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Chronic Myeloid Leukemia Presenting as Priapism: A Rare and Acute Initial Presentation in a Young Male

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Introduction

Priapism, defined as a prolonged and often painful penile erection without sexual arousal, constitutes a urological emergency requiring immediate intervention. While commonly associated with conditions like sickle cell anemia and certain medications, malignancy-related priapism is rare and frequently overlooked. Herein, we present a unique case of a 31-year-old male with no significant medical history, who developed persistent priapism as the initial presentation of chronic myeloid leukemia (CML).

Case Presentation

A 31-year-old male without significant medical history, presented to the emergency department with painless priapism, was evaluated by urology and discharged home with precautions. He returned the following day with persistent, now painful priapism. Upon examination, his vital signs were stable. Urology performed aspiration and injection with Sudafed, resulting in mild symptom improvement. Laboratory findings revealed elevated white blood cell count (563.64 k/mcL), anemia (hemoglobin 8.4 g/dL), and a peripheral blood smear showed immature circulating cells with blast forms. He was transferred to a tertiary care center where conservative management addressed bleeding from the penile injection site, with subsequent treatment including leukapheresis and hydroxyurea for cytoreduction. Imaging revealed severe splenomegaly (36 cm) with abdominal mass effect. Peripheral flow cytometry didn’t show malignancy, but cytogenetic analysis showed a BCR/ABL1 fusion gene, confirming chronic myeloid leukemia (CML). Bone marrow biopsy showed hypercellularity without increased blasts. Treatment with dasatinib reduced the white count to 52,000 k/mcL, and was discharged home.

Discussion

Priapism is a urological emergency necessitating immediate intervention to prevent erectile dysfunction and permanent impotence. Management aims to achieve detumescence and typically involves methods such as irrigation or injection of vasoconstrictors into the penis. Malignancy-associated priapism (MAP) often results from venous obstruction due to hyperviscosity. Studies show that CML accounts for approximately 50% cases presenting with MAP, predominantly affecting younger individuals with a mean onset around 27 years of age. Priapism can occur before, during, or after treatment initiation or splenectomy in these patients. Providers should keep a high threshold of suspicion for MAP in patients with no other risk factors as prompt identification and treatment are needed to avoid permanent injury.

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Introduction

Priapism, defined as a prolonged and often painful penile erection without sexual arousal, constitutes a urological emergency requiring immediate intervention. While commonly associated with conditions like sickle cell anemia and certain medications, malignancy-related priapism is rare and frequently overlooked. Herein, we present a unique case of a 31-year-old male with no significant medical history, who developed persistent priapism as the initial presentation of chronic myeloid leukemia (CML).

Case Presentation

A 31-year-old male without significant medical history, presented to the emergency department with painless priapism, was evaluated by urology and discharged home with precautions. He returned the following day with persistent, now painful priapism. Upon examination, his vital signs were stable. Urology performed aspiration and injection with Sudafed, resulting in mild symptom improvement. Laboratory findings revealed elevated white blood cell count (563.64 k/mcL), anemia (hemoglobin 8.4 g/dL), and a peripheral blood smear showed immature circulating cells with blast forms. He was transferred to a tertiary care center where conservative management addressed bleeding from the penile injection site, with subsequent treatment including leukapheresis and hydroxyurea for cytoreduction. Imaging revealed severe splenomegaly (36 cm) with abdominal mass effect. Peripheral flow cytometry didn’t show malignancy, but cytogenetic analysis showed a BCR/ABL1 fusion gene, confirming chronic myeloid leukemia (CML). Bone marrow biopsy showed hypercellularity without increased blasts. Treatment with dasatinib reduced the white count to 52,000 k/mcL, and was discharged home.

Discussion

Priapism is a urological emergency necessitating immediate intervention to prevent erectile dysfunction and permanent impotence. Management aims to achieve detumescence and typically involves methods such as irrigation or injection of vasoconstrictors into the penis. Malignancy-associated priapism (MAP) often results from venous obstruction due to hyperviscosity. Studies show that CML accounts for approximately 50% cases presenting with MAP, predominantly affecting younger individuals with a mean onset around 27 years of age. Priapism can occur before, during, or after treatment initiation or splenectomy in these patients. Providers should keep a high threshold of suspicion for MAP in patients with no other risk factors as prompt identification and treatment are needed to avoid permanent injury.

Introduction

Priapism, defined as a prolonged and often painful penile erection without sexual arousal, constitutes a urological emergency requiring immediate intervention. While commonly associated with conditions like sickle cell anemia and certain medications, malignancy-related priapism is rare and frequently overlooked. Herein, we present a unique case of a 31-year-old male with no significant medical history, who developed persistent priapism as the initial presentation of chronic myeloid leukemia (CML).

Case Presentation

A 31-year-old male without significant medical history, presented to the emergency department with painless priapism, was evaluated by urology and discharged home with precautions. He returned the following day with persistent, now painful priapism. Upon examination, his vital signs were stable. Urology performed aspiration and injection with Sudafed, resulting in mild symptom improvement. Laboratory findings revealed elevated white blood cell count (563.64 k/mcL), anemia (hemoglobin 8.4 g/dL), and a peripheral blood smear showed immature circulating cells with blast forms. He was transferred to a tertiary care center where conservative management addressed bleeding from the penile injection site, with subsequent treatment including leukapheresis and hydroxyurea for cytoreduction. Imaging revealed severe splenomegaly (36 cm) with abdominal mass effect. Peripheral flow cytometry didn’t show malignancy, but cytogenetic analysis showed a BCR/ABL1 fusion gene, confirming chronic myeloid leukemia (CML). Bone marrow biopsy showed hypercellularity without increased blasts. Treatment with dasatinib reduced the white count to 52,000 k/mcL, and was discharged home.

Discussion

Priapism is a urological emergency necessitating immediate intervention to prevent erectile dysfunction and permanent impotence. Management aims to achieve detumescence and typically involves methods such as irrigation or injection of vasoconstrictors into the penis. Malignancy-associated priapism (MAP) often results from venous obstruction due to hyperviscosity. Studies show that CML accounts for approximately 50% cases presenting with MAP, predominantly affecting younger individuals with a mean onset around 27 years of age. Priapism can occur before, during, or after treatment initiation or splenectomy in these patients. Providers should keep a high threshold of suspicion for MAP in patients with no other risk factors as prompt identification and treatment are needed to avoid permanent injury.

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