Congenital cardiac liver cirrhosis with combined hepatocellular-cholangiocarcinoma-a case report.

Background: Cardiac liver cirrhosis secondary to Fontan procedure has been associated with hepatocellular carcinoma at a younger age. However, Fontan associated liver disease and combined hepatocellular-cholangiocarcinoma has not been previously reported. Combined hepatocellular-cholangiocarcinoma is a rare cancer that accounts for 2-5% of primary liver tumors and poses significant diagnostic and treatment challenges. This case highlights these needs and potential screening and treatment considerations. Herein we describe a case of combined hepatocellular-cholangiocarcinoma in a patient with autism, congenital heart disease, and Fontan procedure. Case Description: The patient is a 27-year-old male who presented with a liver mass detected on MRI performed in the context of a rising alpha-fetoprotein during a screening visit. Biopsy of the mass revealed a combined hepatocellular-cholangiocarcinoma which was staged as localized. Due to the COVID-19 pandemic and subsequent halt of all elective surgeries, the patient received local therapy with chemoembolization followed by pembrolizumab. The disease progressed though, and therapy was changed to gemcitabine plus cisplatin. Patient received 2 cycles of therapy, after which he and his family decided to transfer medical care to Memorial Sloan Kettering. Next generation sequencing of the tumor revealed TP53 and FGFR2 mutations. By then patient was also found to have lung metastasis. To help address the hepatocellular carcinoma, lenvatinib was added. Patient had sustainable disease control for about a year, yet eventually developed thrombocytopenia complicated by an episode of gastrointestinal bleeding. With a worsening performance status, adverse events of the treatment, and recurrent hospitalizations, a goals of care discussion with his family led to the discontinuation of active cancer therapy and patient was started on best supportive care. Patient remained in active follow-up until the time of this report and passed away less than a year from initiating best supportive care alone. Conclusions: This challenging case raises awareness towards screening and monitoring all patients with Fontan procedure for Fontan associated liver disease and liver cancers, including combined hepatocellular-cholangiocarcinoma. To the best of our knowledge, this is the first description of combined hepatocellular-cholangiocarcinoma occurring in the context of cardiac cirrhosis. The management difficulties that led to altering the goals of care, is another reminder of the dynamic nature of the care oncologists would provide.

Drug Development in Low- and Middle-Income Countries: Opportunity or Exploitation?

Low- and middle-income countries (LMICs) represent a diverse group of regions with varied cancer presentation. Drug development and accessibility across these regions have primarily been dependent on the trials initiated and conducted across high-income countries. Representation of LMIC regions in these trials in terms of study population has been minimal, leading to inequitable distribution of optimal and affordable cancer care. In spite of many challenges, LMICs have now increasingly been able to contribute to anticancer drug development. The opportunities present in LMICs must be explored and used in conjunction with due collaborative efforts from high-income countries, health care planners, and regulatory agencies. Global drug development trials should not only factor in suitable representation of LMICs but also design studies with pragmatic objectives and endpoints so that the trial results lead to equitable and affordable cancer care. Strengthening collaboration between cancer researchers from LMICs and high-income countries and empowering the local investigator with adequate resources will help remove current disparities.

Oncofertility and COVID-19-cancer does not wait.

The current pandemic due to the coronavirus disease 2019 (COVID-19) outbreak has forced physicians to review their current clinical practice and guidelines. Although elective procedures using assisted reproductive technologies (ART) should be preferably canceled or postponed at this time, this does not always apply to urgent procedures such as those in patients with cancer. A complete oncofertility counseling balancing the benefits and risks of undergoing fertility preservation before commencing gonadotoxic therapies (chemotherapy and/or radiotherapy) should also be provided during the COVID-19 outbreak. This article briefly highlights what patients, oncologists and fertility specialists need to keep in mind during oncofertility counseling at the time of the COVID-19 outbreak.