US drug approvals rise in 2020 over previous year

Several medicines were approved as first treatments, including Gilead Sciences' Veklury (remdesivir) for patients with COVID-19 who require hospitalization (4);Amivas' artesunate for injection for severe malaria (5);Horizon Therapeutics Ireland DAC's Tepezza (teprotumumab-trbw), an antibody drug conjugate (ADC) for treating thyroid eye disease (6);and Ultragenyx Pharmaceutical's Dojolvi (triheptanoin) and Alnylam Pharmaceuticals' Oxlumo (lumasiran), both first treatments for metabolic disorders-Dojolvi for treating paediatric and adult patients with molecularly confirmed long-chain fatty acid oxidation disorders (7) and Oxlumo (lumasiran) for treating the rare genetic disorder, primary hyperoxaluria type 1 (8). Blueprint Medicines Corporation) for treating unresectable or metastatic gastrointestinal stromal tumours harboring a platelet-derived growth factor receptor alpha exon 18 mutation (9);Koselugo (selumetinib, AstraZeneca Pharmaceuticals), for neurofibromatosis type 1 (10);Pemazyre (pemigatinib, Incyte Corporation), for certain types of previously treated, advanced bile duct cancer (cholangiocarcinoma) (11);Tabrecta (capmatinib, Novartis) for non-small cell lung cancer that has spread to other parts of the body and whose tumours have mutations that lead to MET exon 14 skipping (12);and Retevmo (selpercatinib, Loxo Oncology, a subsidiary of Eli Lilly and Company) for treating three types of tumours with alterations of the "rearranged during transfection" gene (13). Gilead, "U.S. FDA Approves Kite's Tecartus, the First and Only CAR T Treatment for Relapsed or Refractory Mantle Cell Lymphoma," Press Release, 24 July 2020.

Post-COVID-19 syndrome mimicking cholangiocarcinoma: A case report.

Key Clinical Message: The differential diagnosis of post-COVID-19 syndrome is important in patients with symptoms of biliary obstruction. This patient had severe COVID-19 who underwent ERCP and mimicked cholangiocarcinoma. Abstract: Patients with severe coronavirus disease 2019 (COVID-19) manifest liver injuries with pathological changes because of lowered blood oxygen saturation, cardiac malfunction, hepatotoxic drugs during treatment, and cellular injury. This paper reports a patient with a history of severe COVID-19 who mimics cholangiocarcinoma after undergoing endoscopic retrograde cholangiopancreatography (ERCP). It was shown that differential diagnosis of post-COVID-19 syndrome is greatly important mostly in patients with symptoms of biliary obstruction.

Comprehensive analysis of the novel omicron receptor AXL in cancers.

The SARS-CoV-2 is constantly mutating, and the new coronavirus such as Omicron has spread to many countries around the world. Anexelekto (AXL) is a transmembrane protein with biological functions such as promoting cell growth, migration, aggregation, metastasis and adhesion, and plays an important role in cancers and coronavirus disease 2019 (COVID-19). Unlike angiotensin-converting enzyme 2 (ACE2), AXL was highly expressed in respiratory system cells. In this study, we verified the AXL expression in cancer and normal tissues and found AXL expression was strongly correlated with cancer prognosis, tumor mutation burden (TMB), the microsatellite instability (MSI) in most tumor types. Immune infiltration analysis also demonstrated that there was an inextricable link between AXL expression and immune scores in cancer patients, especially in BLCA, BRCA and CESC. The NK-cells, plasmacytoid dendritic cells, myeloid dendritic cells, as one of the important components of the tumor microenvironment, were highly expressed AXL. In addition, AXL-related tumor neoantigens were identified and might provide the novel potential targets for tumor vaccines or SARS-Cov-2 vaccines research in cancer patients.

Improved Survival and Quality of Life Through an Integrative, Multidisciplinary Oncological Approach: Pathophysiological Analysis of Four Clinical Cancer Cases and Review of the Literature.

Objectives: According to the National Cancer Institute, the integrative medicine (IM) approach to medical care combines standard medicine with complementary and alternative medicine practices that have proved safe and effective. Methods: We describe the clinical cases of four patients with malignant pleural mesothelioma (MPM), diffuse malignant peritoneal mesothelioma (DMPM), intrahepatic cholangiocarcinoma, and breast cancer (BC) who received supportive treatment (ST) according to an IM approach after the failure of standard cancer treatments or the appearance of serious adverse events caused by antiblastic chemotherapy. The critical role of complementary drugs in reducing the side effects of cancer treatments and normalizing the white cell count is especially apparent in the case of the patient with metastatic BC, who experienced prolonged neutropenia. Results: The IM approach was well-tolerated and had no adverse side effects. It improved the quality of life (QoL) of all patients and in two cases extended overall survival. Conclusion: The extended clinical and instrumental response to IM of the patients with malignant mesothelioma and the improved health-related QoL and good tolerance of the ST demonstrated in all cases support the value of this approach in patients whose cancer therapies have failed but who show a good performance status. Our data require confirmation in a well-designed prospective clinical trial.

Impact of the COVID-19 Pandemic on Liver Cancer Staging at a Multidisciplinary Liver Cancer Clinic.

To compare liver cancer resectability rates before and during the COVID-19 pandemic. Background: Liver cancers usually present with nonspecific symptoms or are diagnosed through screening programs for at-risk patients, and early detection can improve patient outcomes. In 2020, the COVID-19 pandemic upended medical care across all specialties, but whether the pandemic was associated with delays in liver cancer diagnosis is not known. Methods: We performed a retrospective review of all patients evaluated at the Johns Hopkins Multidisciplinary Liver Cancer Clinic from January 2019 to June 2021 with a new diagnosis of suspected or confirmed hepatocellular carcinoma (HCC) or biliary tract cancer (BTC). Results: There were 456 liver cancer patients (258 HCC and 198 BTC). From January 2019 to March 2020 (pre-pandemic), the surgical resectability rate was 20%. The subsequent 6 months (early pandemic), the resectability rate decreased to 11%. Afterward from October 2020 to June 2021 (late pandemic), the resectability rate increased to 27%. The resectability rate early pandemic was significantly lower than that for pre-pandemic and later pandemic combined (11% lower; 95% confidence interval [CI], 2%-20%). There was no significant difference in resectability rates pre-pandemic and later pandemic (7% difference; 95% CI, -3% to 16%). In subgroup analyses, the early pandemic was associated with a larger impact in BTC resectability rates than HCC resectability rates. Time from BTC symptom onset until Multidisciplinary Liver Clinic evaluation increased by over 6 weeks early pandemic versus pre-pandemic (Hazard Ratio, 0.63; 95% CI, 0.44-0.91). Conclusions: During the early COVID-19 pandemic, we observed a drop in the percentage of patients presenting with curable liver cancers. This may reflect delays in liver cancer diagnosis and contribute to excess mortality related to the COVID-19 pandemic.

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.

Multi-target endoscopic ultrasound EUS-M guided biopsy is superior to pet scan for staging for malignancies

BackgroundPET scan is widely used not only to diagnose malignancy and its staging, but a small proportion of patients do have false-positive results. EUS now is a well-established modality to get tissue diagnosis, and with multi-target approach can help stage disease more accurately with histopathological results. We share our experience with EUS-M cases with different variety of malignancies.MethodsA total of 25 cases underwent EUS-M from June 2020 till June 2022. Informed consent was obtained, and with Covid screen test with PCR was performed before the procedure. Procedures were done with all SOPs as per institutional guidelines. 22G FNB needle was used in 24 cases, 25G needle in 01 case;Franseen design with the capillary suction method was used to obtain visible core samples for histopathology without ROSE. All cases have confirmed the histopathological diagnosis with the same pathology from other site of Biopsy. Order of Biopsy was Nodes→ Liver metastatic lesion→ Primary Tumour. In cases of nodes mediastinal→ porta-hepatis/pancreatic→ Para-aortic. All samples were adequate for making a confirmatory diagnosis on the tissue sample.ResultsAmong total of 25 cases, Age 54 Mean (22–77) with 16 Males. Duration of procedure 38 Minutes Mean (20–85). Cases with multiple lymphadenopathy from different anatomical regions were 09, while other sites included Liver for metastasis and Primary tumour from pancreas/CBD/GB in 16 cases. Multiple site single pass was performed in 24 cases. 19 cases had malignant pathologies. Final diagnosis of the Disease was pancreatic adenocarcinoma 07, NETs 02, Lymphoma 04, GB Adenocarcinoma/Cholangiocarcinoma 06 and metastatic RCC 01, TB 01. 04 cases had benign disease. All procedures were done under Conscious sedation as day care procedure. There were no immediate or early complications in all cases.ConclusionsEUS-M is a safe and accurate modality to stage malignancy with superiority over PET Scan to obtain a histological diagnosis.

Hybrid endoscopic ultrasound in the covid-19 era for the tissue diagnosis of solid lesions;an initial experience from a tertiary care centre from Pakistan

BackgroundEndoscopic Ultrasound (EUS) is a well-established mode of intervention for tissue acquisition in solid organs with rapid on-site evaluation (ROSE). In the Covid-19 era, the implementation of infection control mechanisms has led to modified hybrid techniques to get high diagnostic yield for tissue sampling. Combination of Covid-19 SOPs and tissue acquisition method outline this hybrid technique to get a high diagnostic Yield. We share our initial experience of EUS cases performed with this approach without ROSE.MethodsAll 125 cases who underwent EUS-guided biopsy from June 2020 till June 2022 were included. The Procedure was done in a negative pressure room with all SOPs as per institutional guidelines for patient and staff safety with a minimum number of persons during the procedure.ResultsAmong these cases, 85 were male, mean age of 56 years (range 22–90), Mean duration of procedure 28 minutes mean (10–90 min). 91 cases for organs targeted for malignant pathology include pancreas 53, liver 03, lymph nodes 22, subepithelial lesions 10, mediastinal lesions 15, common-bile duct/gall bladder 07, gastric and retroperitoneal 01 case, 13 cases had a multi-targeted biopsy for the additional staging of disease. The number of ‘passes’ with the needle was average 02 with single pass 20, two pass 60, three passes 20, multitarget single pass in 25. Needle size (Franseen design) used for procedures was 22G in 115 cases and 25G in 10. Common tissue diagnoses include pancreatic adenocarcinoma 38, neuroendocrine tumours 06, tuberculosis 07, gastrointestinal stromal tumours 03, leiomyoma 05, lymphoma 06, metastatic renal cell carcinoma 05, squamous cell carcinoma 05, cholangiocarcinoma/gall bladder adenocarcinoma 13, Sarcoma 03, solid pseudopapillary epithelial neoplasm of pancreas (SPEN) 03 and one case for Schwannoma, breast metastasis, accessory spleen, ectopic pancreas, sarcoidosis There were no immediate or early complications in all cases.ConclusionsHybrid EUS in Covid 19 Era has emerged as a useful/cost-effective and safe approach to get tissue yield without the need for ROSE.

COVID-19 and liver cancer: lost patients and larger tumours.

BACKGROUND: Northern England has been experiencing a persistent rise in the number of primary liver cancers, largely driven by an increasing incidence of hepatocellular carcinoma (HCC) secondary to alcohol-related liver disease and non-alcoholic fatty liver disease. Here we review the effect of the COVID-19 pandemic on primary liver cancer services and patients in our region. OBJECTIVE: To assess the impact of the COVID-19 pandemic on patients with newly diagnosed liver cancer in our region. DESIGN: We prospectively audited our service for the first year of the pandemic (March 2020-February 2021), comparing mode of presentation, disease stage, treatments and outcomes to a retrospective observational consecutive cohort immediately prepandemic (March 2019-February 2020). RESULTS: We observed a marked decrease in HCC referrals compared with previous years, falling from 190 confirmed new cases to 120 (37%). Symptomatic became the the most common mode of presentation, with fewer tumours detected by surveillance or incidentally (% surveillance/incidental/symptomatic; 34/42/24 prepandemic vs 27/33/40 in the pandemic, p=0.013). HCC tumour size was larger in the pandemic year (60±4.6 mm vs 48±2.6 mm, p=0.017), with a higher incidence of spontaneous tumour haemorrhage. The number of new cases of intrahepatic cholangiocarcinoma (ICC) fell only slightly, with symptomatic presentation typical. Patients received treatment appropriate for their cancer stage, with waiting times shorter for patients with HCC and unchanged for patients with ICC. Survival was associated with stage both before and during the pandemic. 9% acquired COVID-19 infection. CONCLUSION: The pandemic-associated reduction in referred patients in our region was attributed to the disruption of routine healthcare. For those referred, treatments and survival were appropriate for their stage at presentation. Non-referred or missing patients are expected to present with more advanced disease, with poorer outcomes. While protective measures are necessary during the pandemic, we recommend routine healthcare services continue, with patients encouraged to engage.

[Synchronous Double Primary Non-B, and Non-C Intrahepatic Cholangiocarcinoma and Hepatocellular Carcinoma-A Case Report]

A 78-year-old man without hepatitis virus B or C underwent right hemi-hepatectomy and lymph node dissection for a tumor 5 cm in diameter located in the hepatic hilum of the posterior segment of the liver with portal vein thrombi extending into the main portal trunk and a tumor 1.5 cm in diameter in the peripheral side of segment 5 of the liver. Histopathologically, the former was diagnosed as intrahepatic cholangiocarcinoma and the latter as hepatocellular carcinoma(HCC). Five months after the surgery, intrahepatic and lymph node metastases were diagnosed based on computed tomography(CT);therefore, chemotherapy with S-1 for 3 months and gemcitabine and cisplatin(GC)for 5 months was administered, after which the metastatic lesions were not detected. Nineteen months after the surgery, partial resection of segment 2 of the liver was performed for a tumor 3 cm in diameter, which was diagnosed as HCC histopathologically. Two years after the second surgery, 2 recurrent nodules in the liver in segments 3 and 4 were detected on CT. Platinum-based hepatic arterial infusion chemotherapy(HAIC)and transcatheter arterial chemoembolization(TACE)were performed, and chemotherapy with GC was then administered for 7 months. For a new tumor detected in segment 1 in the liver, TACE was performed 17 months after initial HAIC. Seventy-four months after the initial surgery, 5 new nodules less than 1 cm in diameter were detected, and chemotherapy with sorafenib was administered for 5 months, after which the patient died of coronavirus disease 2019.

The Implications of Treatment Delays in Adjuvant Therapy for Resected Cholangiocarcinoma Patients.

PURPOSE: The purpose of this study is to understand factors associated with timing of adjuvant therapy for cholangiocarcinoma and the impact of delays on overall survival (OS). METHODS: Data from the National Cancer Database (NCDB) for patients with non-metastatic bile duct cancer from 2004 to 2015 were analyzed. Patients were included only if they underwent surgery and adjuvant chemotherapy and/or radiotherapy (RT). Patients who underwent neoadjuvant or palliative treatments were excluded. Pearson's chi-squared test and multivariate logistic regression analyses were used to assess the distribution of demographic, clinical, and treatment factors. After propensity score matching with inverse probability of treatment weighting, OS was compared between patients initiating therapy past various time points using Kaplan Meier analyses and doubly robust estimation with multivariate Cox proportional hazards modeling. RESULTS: In total, 7,733 of 17,363 (45%) patients underwent adjuvant treatment. The median time to adjuvant therapy initiation was 59 days (interquartile range 45-78 days). Age over 65, black and Hispanic race, and treatment with RT alone were associated with later initiation of adjuvant treatment. Patients with larger tumors and high-grade disease were more likely to initiate treatment early. After propensity score weighting, there was an OS decrement to initiation of treatment beyond the median of 59 days after surgery. CONCLUSIONS: We identified characteristics that are related to the timing of adjuvant therapy in patients with biliary cancers. There was an OS decrement associated with delays beyond the median time point of 59 days. This finding may be especially relevant given the treatment delays seen as a result of COVID-19.

Management of Liver Tumors during the COVID-19 Pandemic: The Added Value of Selective Internal Radiation Therapy (SIRT).

BACKGROUND: In the context of the coronavirus disease 2019 (COVID-19) pandemic, liver-directed therapies (LDTs) may offer minimally invasive integrative tools for tumor control. Among them, selective internal radiation therapy (SIRT) represents a safe, flexible and effective treatment. Purpose of this study is to present our experience with SIRT during the first wave of COVID-19 pandemic and provide an overview of the indications and challenges of SIRT in this scenario. METHODS: We retrospectively analyzed the number of patients evaluated by Multidisciplinary Liver Tumor Board (MLTB) and who were undergoing LDTs between March and July 2020 and compared it with 2019. For patients treated with SIRT, clinical data, treatment details and the best radiological response were collected. RESULTS: Compared to 2019, we observed a 27.5% reduction in the number of patients referred to MLTB and a 28.3% decrease in percutaneous ablations; transarterial chemoembolizations were stable, while SIRT increased by 64%. The majority of SIRT patients (75%) had primary tumors, mostly HCC. The best objective response and disease control rates were 56.7% and 72.2%, respectively. CONCLUSION: The first wave of the COVID-19 pandemic was characterized by an increased demand for SIRT, which represents a safe, flexible and effective treatment, whose manageability will further improve by simplifying the treatment workflow, developing user-friendly and reliable tools for personalized dosimetry and improving interdisciplinary communication.

Non-Operative Management of Bronchobiliary Fistula Due to Proximal Migration of Biliary Stent in a Patient With Unresectable Klatskin Tumor.

INTRODUCTION: One of the methods for the biliary tree decompression in the case of Klatskin tumor is transpapillary stenting, which could be completed by stent migration in 4% to 10% of cases. Approximately half of the stent migrations are in the proximal direction. In this study, we reported a rare case of proximal trans-diaphragmatic stent migration to the lower lobe of the right lung with the formation of a biliary-bronchial fistula (BBF). CASE PRESENTATION: A 60-year-old woman was diagnosed with hilar cholangiocarcinoma (type 3B by Bismuth-Corlette) complicated by posthepatic jaundice. To relieve jaundice there were performed endoscopic retrograde cholangiopancreatography, endoscopic sphincterotomy, endobiliary stent placement (10 Fr, 150 mm). A restenting (11.5 Fr, 130 mm) was performed in 2.5 months due to endobiliary tube occlusion. In the next 2 months, coughing attacks and biliptysis have appeared in the patient. A CT scan showed penetration of the liver, diaphragm, and lower lobe of the right lung with the proximal part of the stent and caused BBF formation. Anti-inflammatory and antibacterial therapy was administrated for 14 days and BBF was closed. Stent retrieval from the right hemithorax and endobiliary restenting was performed in 9 months after primary stenting. During follow-up, appropriate positioning and functioning of the stent were observed. CONCLUSION: BBF formation is a rare complication of endobiliary stenting, which can be successfully treated by anti-inflammatory and antibiotic therapy, followed by transpapillary stent retrieval.

Complicated course of biliary inflammatory myofibroblastic tumor mimicking hilar cholangiocarcinoma: A case report and literature review.

BACKGROUND: The inflammatory myofibroblastic tumor (IMT) is a rare, idiopathic, usually benign, mass-forming disease with myofibroblastic proliferation and a varying amount of inflammatory cells. Although it can affect various organs, the biliary tract is a rare localization of primary IMT, clinically, endoscopically and radiologically imitating cholangiocarcinoma. The treatment options are based only on clinical practice experience. CASE SUMMARY: A 70-year-old woman was referred to our center due to progressive fatigue, weight loss, abdominal pain, night sweats, and elevated liver enzymes. Magnetic resonance cholangiopancreatography and endoscopic retrograde cholangiopancreatography (ERCP) revealed proximal common hepatic duct and hilar biliary strictures extending bilaterally to lobular bile ducts. Although initial clinical, endoscopic and radiological signs were typical for hilar cholangiocarcinoma, histological examination showed no signs of malignancy. In total, 8 biopsies using different approaches were performed (several biopsies from dominant stricture during ERCP and direct cholangioscopy; ultrasound-guided liver biopsy; diagnostic laparoscopy with liver and lymph node biopsies). Histological examination revealed signs of IMT, and the final diagnosis of biliary IMT was stated. Although IMT is usually a benign disease, in our case, it was complicated. All pharmacological treatment measures were ineffective. The patient still needs permanent stenting, suffers from recurrent infections and mechanical jaundice. Despite that, the patient already survived 24 mo. CONCLUSION: IMT presenting with hilar biliary strictures is a unique diagnostic and clinical challenge as it is indistinguishable from cholangiocarcinoma, and there are no evidence-based treatment options. Our goal is to increase the understanding of this rare disease and its possible course.

Thrombotic Microangiopathy in a Patient With COVID-19 Infection and Metastatic Cholangiocarcinoma.

This is a case report of a 63-year-old African American female with a past medical history most significant for metastatic cholangiocarcinoma that presented for evaluation of persistent shortness of breath. Initial workup was remarkable for refractory anemia, moderate schistocytes on peripheral smear and lab work suggestive of a hemolytic anemia. Due to concern for thrombotic thrombocytopenic purpura (TTP), she subsequently underwent several rounds of plasma exchange without significant improvement. Secondary to progressive renal failure, patient eventually had a renal biopsy with findings remarkable for thrombotic microangiopathy (TMA). Simultaneously, patient was also diagnosed with coronavirus disease 2019 (COVID-19) infection. After a few weeks of supportive care, she was stable for discharge. Unfortunately, she did become dialysis dependent. Prior to hospital admission, she was being treated for metastatic cholangiocarcinoma and had received chemotherapy with gemcitabine. Her last chemotherapy session was approximately 3 weeks prior to her first hospitalization. Furthermore, although her hemolytic work did suggest TMA, it was not consistent with the diagnosis of TTP. She was transferred to a tertiary care center where hemolytic labs were trended, and supportive care was maximized. In light of the current COVID-19 pandemic, it is crucial to further investigate the pathophysiology of TMA in patients with active malignancies and COVID-19 infections. To our knowledge, this is the first case of TMA in a patient with both metastatic cholangiocarcinoma and COVID-19 infection.

Assessing the impact of COVID-19 on liver cancer management (CERO-19).

BACKGROUND & AIMS: The coronavirus disease 2019 (COVID-19) pandemic has posed unprecedented challenges to healthcare systems and it may have heavily impacted patients with liver cancer (LC). Herein, we evaluated whether the schedule of LC screening or procedures has been interrupted or delayed because of the COVID-19 pandemic. METHODS: An international survey evaluated the impact of the COVID-19 pandemic on clinical practice and clinical trials from March 2020 to June 2020, as the first phase of a multicentre, international, and observational project. The focus was on patients with hepatocellular carcinoma or intrahepatic cholangiocarcinoma, cared for around the world during the first COVID-19 pandemic wave. RESULTS: Ninety-one centres expressed interest to participate and 76 were included in the analysis, from Europe, South America, North America, Asia, and Africa (73.7%, 17.1%, 5.3%, 2.6%, and 1.3% per continent, respectively). Eighty-seven percent of the centres modified their clinical practice: 40.8% the diagnostic procedures, 80.9% the screening programme, 50% cancelled curative and/or palliative treatments for LC, and 41.7% modified the liver transplantation programme. Forty-five out of 69 (65.2%) centres in which clinical trials were running modified their treatments in that setting, but 58.1% were able to recruit new patients. The phone call service was modified in 51.4% of centres which had this service before the COVID-19 pandemic (n = 19/37). CONCLUSIONS: The first wave of the COVID-19 pandemic had a tremendous impact on the routine care of patients with liver cancer. Modifications in screening, diagnostic, and treatment algorithms may have significantly impaired the outcome of patients. Ongoing data collection and future analyses will report the benefits and disadvantages of the strategies implemented, aiding future decision-making. LAY SUMMARY: The coronavirus disease 2019 (COVID-19) pandemic has posed unprecedented challenges to healthcare systems globally. Herein, we assessed the impact of the first wave pandemic on patients with liver cancer and found that routine care for these patients has been majorly disrupted, which could have a significant impact on outcomes.

Strategies for the delay of surgery in the management of resectable hepatobiliary malignancies during the COVID-19 pandemic.

Objective: We aimed to review data about delaying strategies for the management of hepatobiliary cancers requiring surgery during the covid-19 pandemic. Background: Given the covid-19 pandemic, many jurisdictions, to spare resources, have limited access to operating rooms for elective surgical activity, including cancer, thus forcing deferral or cancellation of cancer surgeries. Surgery for hepatobiliary cancer is high-risk and particularly resource-intensive. Surgeons must critically appraise which patients will benefit most from surgery and which ones have other therapeutic options to delay surgery. Little guidance is currently available about potential delaying strategies for hepatobiliary cancers when surgery is not possible. Methods: An international multidisciplinary panel reviewed the available literature to summarize data relating to standard-of-care surgical management and possible mitigating strategies to be used as a bridge to surgery for colorectal liver metastases, hepatocellular carcinoma, gallbladder cancer, intrahepatic cholangiocarcinoma, and hilar cholangiocarcinoma. Results: Outcomes of surgery during the covid-19 pandemic are reviewed. Resource requirements are summarized, including logistics and adverse effects profiles for hepatectomy and delaying strategies using systemic, percutaneous and radiation ablative, and liver embolic therapies. For each cancer type, the long-term oncologic outcomes of hepatectomy and the clinical tools that can be used to prognosticate for individual patients are detailed. Conclusions: There are a variety of delaying strategies to consider if availability of operating rooms decreases. This review summarizes available data to provide guidance about possible delaying strategies depending on patient, resource, institution, and systems factors. Multidisciplinary team discussions should be leveraged to consider patient- and tumour-specific information for each individual case.