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Background: Pancreatic cancer is among the malignancies with the poorest prognosis, largely due to its aggressive nature and resistance to conventional therapies. Case Summary: This report describes the case of a 69-year-old male patient with stage IV primary lung adenocarcinoma presenting with high levels of programmed death-ligand 1 (PD-L1). Simultaneously, abdominal computed tomography (CT) showed a dilated pancreatic duct at the level of the pancreatic head and a hypodense lesion in the uncinate process involving the superior mesenteric artery. Fine-needle aspiration (FNA) of the pancreatic lesions was negative. After three cycles of chemoimmunotherapy, positron emission tomography–computed tomography (PET-CT) showed complete remission of the lung nodules, lymphadenopathy, and pleural thickening, as well as a decrease in the size of the pancreatic lesion. After another six months, a PET-CT scan showed a focal increased uptake in the pancreatic mass in the same location, indicating disease progression. A core biopsy of the pancreatic tumor showed atypical spindle cell morphology with positive staining for vimentin, characteristic of mesenchymal differentiation with no apparent epithelial features. Comprehensive molecular profiling through Caris Molecular Intelligence® revealed four genes with actionable mutations in the pancreatic tissue, including KRAS (p.G12D) and TP53 (p.R175H). These molecular findings suggested the diagnoses of sarcomatoid carcinoma and conventional pancreatic ductal adenocarcinoma with epithelial–mesenchymal transition. Primary mesenchymal tumors and neuroendocrine neoplasms were excluded because immunohistochemistry was negative for anaplastic lymphoma kinase (ALK), smooth muscle actin (SMA), desmin, CD34, signal transducer and activator of transcription 6 (STAT6), S100, HMB45, CD117, discovered on GIST-1 (DOG1), CD56, progesterone, and synaptophysin. However, despite multiple rounds of systemic chemotherapy, immunotherapy, and radiation, his pancreatic disease rapidly deteriorated and metastasized to the liver and bone. Conclusions: Despite multiple lines of treatment, the patient's condition worsened and he succumbed to his pancreatic malignancy. This study highlights the clinical characteristics, diagnosis, and treatment of rare pancreatic cancer, emphasizing the importance of molecular testing and histopathological biomarkers in personalizing treatment. It also provides insights into promising therapeutic approaches for similar cases with an unusual presentation. [ABSTRACT FROM AUTHOR]

Bladder cancer (BC) poses a significant health challenge, particularly in metastatic cases, where the prognosis is unfavorable and therapeutic options are limited. Poly ADP-ribose polymerase (PARP) inhibitors have gained approval for use in various cancer types, but their application in BC remains controversial, despite the notable prevalence of DNA damage response alterations in advanced or metastatic urothelial carcinomas. In this report, we describe a 66-year-old heavy-smoking female diagnosed with muscle-invasive BC. She underwent multiple rounds of chemotherapy and radiation, yet her disease remained poorly controlled, leading to metastasis in the left obturator internus muscle. Comprehensive genomic profiling through FoundationOne® Liquid CDx, examining a 324-gene panel using circulating tumor DNA from blood samples, revealed a pathogenic ATM gene alteration (p.Q654fs*10, c.1960delC), suggesting potential eligibility for PARP inhibitor therapy. Remarkably, the patient achieved a complete response to talazoparib, prompting an optimal investigation into BC candidates for this promising therapy. Plain language summary: A new hope for advanced bladder cancer treatment: a case study on the success of PARP inhibitors Bladder cancer is a significant health problem, particularly when it spreads to other parts of the body. The outcome for these advanced cases is often poor and treatment options are limited. One type of treatment, called PARP inhibitors, has shown success in treating other types of cancer, but its use in bladder cancer is still under investigation. This article presents the case of a 66-year-old heavy-smoker woman who was diagnosed with an aggressive form of bladder cancer. Despite several rounds of chemotherapy and radiation, her cancer was not well-controlled and spread to a hip muscle. A detailed genetic analysis revealed specific alterations that suggested she might benefit from treatment with a PARP inhibitor. This type of treatment works by blocking a protein that cancer cells need to repair their DNA, causing the cancer cells to die. The patient was treated with a PARP inhibitor called talazoparib and her cancer completely disappeared with this treatment. This positive response highlights the potential of PARP inhibitors as a promising treatment for bladder cancer, especially in patients who don't respond to conventional treatments and whose cancer has specific genetic changes. Our study also provides an overview of clinical trials evaluating PARP inhibitors in bladder cancer and summaries reported bladder cancer cases in the literature showing a good response to PARP inhibitors, along with their respective genetic alterations. In conclusion, this case study contributes to the growing understanding of personalized medicine, where treatment is tailored to the specific genetic mutations of each patient's cancer. It emphasizes the importance of identifying bladder cancer patients who could benefit most from PARP inhibitor therapy, offering a potential lifeline for those who haven't responded to initial treatment. [ABSTRACT FROM AUTHOR]

Background: Hepatocellular carcinoma (HCC) is a significant health problem associated with several risk factors, increasingly driven by non-alcoholic steatohepatitis and metabolic syndrome. This association poses a challenge for the primary treatments of HCC, which may include immune checkpoint inhibitors and vascular endothelial growth factor inhibitors, due to their potential cardiotoxic effect. Therefore, it is imperative to balance the therapeutic effects of these agents with their potential cardiovascular adverse events., Case Description: We describe the case of a man in his seventies with advanced HCC and significant cardiovascular comorbidities who was treated with atezolizumab and bevacizumab. Despite achieving a clinical and radiologic complete response, the patient experienced a deterioration in cardiac function after 16 months, necessitating the discontinuation of bevacizumab. The patient continued to respond well to atezolizumab, but unfortunately, he passed away due to a cardiac event after 4 years of follow-up., Conclusions: Careful risk stratification and optimization of modifiable risk factors is of uttermost importance in management of HCC. Close monitoring, comprehensive patient management in a cardio-oncology clinic is also vital, particularly for patients at high risk of developing cardiovascular adverse events. The delicate balance between the efficacy of cancer treatments and their potential cardiotoxicity is one of the principal determinants of outcomes of patients diagnosed with HCC., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://jgo.amegroups.com/article/view/10.21037/jgo-24-359/coif). P.S. reports that he is the owner of Ladprao General Hospital with stock less than 5%. J.S. reports receiving consulting fee from Paige AI and having professional activities in Paige AI. G.K.A.A. reports receiving research grant support from Agenus, Arcus, Astra Zeneca, BioNtech, BMS, Elicio, Genentech/Roche, Helsinn, Parker Institute, Pertzye, Puma, QED, Servier, and Yiviva, and consulting support from Abbvie, Alligator Astra Zeneca, Autem, Berry Genomics, BioNtech, Boehringer Ingelheim, BMS, Eisai, Exelixis, Genentech/Roche, Incyte, Ipsen, J-Pharma, Merck, Merus, Neogene, Novartis, Servier, Tango, Tempus, Vector, and Yiviva. The other authors have no conflicts of interest to declare., (2024 AME Publishing Company. All rights reserved.)