Induction of Hepatocellular Carcinoma in Conventional Domestic Swine Using N-Diethylnitrosamine and Phenobarbital.

Purpose: Large animal models are still used in many studies because of their likeness to humans. It has not been documented that regular-sized conventional farm-breed pigs, generally bred for meat production, can be used to generate hepatocellular carcinoma (HCC) animal models. The goal of this study was to investigate how N-diethylnitrosamine (DENA) and phenobarbital (PB) together can generate HCC in ordinary farmed pigs. Materials and Methods: Conventional domestic swine (Sus scrofa domesticus) were used. DENA 15 mg/kg was intraperitoneally injected weekly for 12 weeks, while PB tablets (4 mg/kg) were also administered through food for 16 weeks. Blood testing and ultrasonography evaluation were performed to monitor the progress. Subsequently, computed tomography was conducted in cases with suspected nodules, followed by histopathological examination to confirm the diagnosis. Results: Ten swine (seven males, three females; age: 2 months; weight: 9-15 kg) were included in the study and followed up for 25 months; nine were experimental, and one was control for ethical considerations. The maximum weight of animals during this study reached 162-228 kg. The weight gain seen in the intervention swine was predominantly lower than that documented in the control. The laboratory analysis revealed no notable abnormalities in liver function markers but did demonstrate statistically significant changes in urea (p = 0.028) and creatinine (p = 0.003) levels. Ultrasonography and computed tomography showed multiple liver nodules with characteristics resembling HCC. Serial imaging screening and more extended observations revealed that all animals eventually developed tumors. Histopathological confirmation at 15-22 weeks post-induction revealed that all intervened swine developed multiple nodules of well-differentiated HCC and some with hepatic angiosarcoma. Conclusion: This study successfully generated HCC in conventional domestic swine with a DENA and PB combination. This investigation required at least 15 months to develop tumors. This model will be beneficial for future investigations of HCC in large animals.

Inventing Engineered Organoids for end-stage liver failure patients.

End-stage liver disease (ESLD) is a term used clinically in reference to a group of liver diseases with liver transplantation as the choice of treatment. Due to the limitations of liver transplantation, alternative treatments are needed. The use of primary human hepatocytes represents a valid alternative treatment, but the limitations related to hepatocyte quality, viability, function, conservation, and storage need to be overcome. Transplanted hepatocytes have only been followed for 6-9 months. Therefore, long-term causes of failures are not yet established, including rejection, apoptosis, or other causes. Other alternative therapies to replace liver transplantation include plasmapheresis, hemodiafiltration, and artificial livers. Unfortunately, these methods are highly limited due to availability, high cost, anaphylaxis reaction, development-deposition of immune-complexes, and restricted functionality. Liver organoids, which utilize stem cells instead of 'impractical' adult hepatocytes, may be a solution for the development of a complex bioartificial liver. Recent studies have explored the benefits of differentiating mature hepatocytes from stem cells inside a bioreactor. When the use of human-induced Hepatocytes (hiHeps) was investigated in mouse and pig models of liver failure, liver failure markers were decreased, hepatocyte function indicated by albumin synthesis improved, and survival time increased. Bioartificial liver treatment may decrease the infiltration of inflammatory cells into liver tissue by down-regulating pro-inflammatory cytokines.

Multinational Study to Assess Stress Levels Among the Health Care Workers of Radiation Oncology Community at the Outset of the COVID-19 Pandemic.

PURPOSE: To evaluate stress levels among the health care workers (HCWs) of the radiation oncology community in Asian countries. METHODS: HCWs of the radiation oncology departments from 29 tertiary cancer care centers of Bangladesh, India, Indonesia and Nepal were studied from May 2020 to July 2020. A total of 758 eligible HCWs were identified. The 7-Item Generalized Anxiety Disorder, 9-Item Patient Health Questionnaire, and 22-Item Impact of Events Scale-Revised were used for assessing anxiety, depression, and post-traumatic stress disorder. Univariate and multivariate analysis was done to identify the causative factors affecting mental health. RESULTS: A total of 758 participants from 794 HCWs were analyzed. The median age was 31 years (IQR, 27-28). The incidence of moderate to severe levels of anxiety, depression, and stress was 34.8%, 31.2%, and 18.2%, respectively. Severe personal concerns were noticed by 60.9% of the staff. On multivariate analysis, the presence of commonly reported symptoms of COVID-19 during the previous 2 weeks, contact history (harzard ratio [HR], 2.04; CI, 1.15 to 3.63), and compliance with precautionary measures (HR, 1.69; CI, 1.19 to 2.45) for COVID-19 significantly predicted for increasing anxiety (HR, 2.67; CI, 1.93 to 3.70), depression (HR, 3.38; CI 2.36 to 4.84), and stress (HR, 2.89; CI, 1.88 to 4.43) (P < .001). A significant regional variation was also noticed for anxiety, stress, and personal concerns. CONCLUSION: This survey conducted during the COVID-19 pandemic revealed that a significant proportion of HCWs in the radiation oncology community experiences moderate to severe levels of anxiety, depression, and stress. This trend is alarming and it is important to identify and intervene at the right time to improve the mental health of HCWs to avoid any long-term impacts.

Five-Year Cancer Epidemiology at the National Referral Hospital: Hospital-Based Cancer Registry Data in Indonesia.

PURPOSE: In 2016, there were 1,308,061 cases of cancer being treated in Indonesia, with 2.2 trillion rupiahs spent, amounting to $486,960,633 in US dollars (purchasing power parity 2016). The high burden of cancers in Indonesia requires a valid data collection to inform future cancer-related policies. The purpose of this study is to report cancer epidemiological data from 2008 to 2012 based on Hospital-Based Cancer Registry (HBCR) data from Cipto Mangunkusumo Hospital, Indonesia. METHODS: This was a descriptive study with cross-sectional design. Data were collected from Cipto Mangunkusumo Hospital HBCR 2008-2012. Demographical, diagnostic, stages of cancer, and histopathological types of cancer data were extracted. RESULTS: After screening, 18,216 cases were included. A total of 12,438 patients were older than 39 years of age (68.3%), with a female-to-male ratio of 9:5. Most patients have cancers at advanced stages (stages III and IV, 10.2%). The most common sites of cancer were cervix uteri (2,878 cases, 15.8%), breast (2,459 cases, 13.5%), hematopoietic and reticuloendothelial systems (1,422 cases, 7.8%), nasopharynx (1,338 cases, 7.4%), and lymph nodes (1,104 cases, 6.1%). CONCLUSION: From this HBCR, cancer incidence in female was almost twice the incidence in male, largely because of the burden of cervical and breast cancers. The cervix uteri as one of the top five cancer sites based on this HBCR, 2008-2012, are still approximately consistent with Global Cancer Incidence, Mortality and Prevalence 2018, which portrayed that Indonesia has been severely afflicted by cervical cancer cases more than any other Association of Southeast Asian Nations countries. The HBCR could serve as a robust database of epidemiological data for cancer cases in Indonesia.

Regional collaboration to improve quality of radiation therapy in Asia.

In Asia, several challenges hinder the delivery of high-quality cancer treatment, especially radiation therapy (RT). Many Asian countries face large-scale shortage of RT centres and treatment machines. Additionally, there is also a significant technological gap, with many RT centres in Asia still using outdated technology. There is an urgent need to improve radiation treatment quality in Asia. The Federation of Asian Organizations for Radiation Oncology (FARO) was set up to foster regional collaboration, which we believe can help to identify and solve some of these issues collectively. This report describes the background and rationale of starting FARO, and puts forth some of the early achievements of the group, including fact-finding and educational activities. Finally, we discuss future possibilities, including strategic proposals that may benefit the RT community and our patients in Asia.

Tackling Resistance to Cancer Immunotherapy: What Do We Know?

Cancer treatment has evolved tremendously in the last few decades. Immunotherapy has been considered to be the forth pillar in cancer treatment in addition to conventional surgery, radiotherapy, and chemotherapy. Though immunotherapy has resulted in impressive response, it is generally limited to a small subset of patients. Understanding the mechanisms of resistance toward cancer immunotherapy may shed new light to counter that resistance. In this review, we highlighted and summarized two major hurdles (recognition and attack) of cancer elimination by the immune system. The mechanisms of failure of some available immunotherapy strategies were also described. Moreover, the significance role of immune compartment for various established cancer treatments were also elucidated in this review. Then, the mechanisms of combinatorial treatment of various conventional cancer treatment with immunotherapy were discussed. Finally, a strategy to improve immune cancer killing by characterizing cancer immune landscape, then devising treatment based on that cancer immune landscape was put forward.

Ensuring safety and sustainability of radiotherapy services during the COVID-19 pandemic in resources constrain country: An Indonesian experience.

The global COVID-19 pandemic has placed a significant burden on the healthcare sector, overwhelming health services in affected countries worldwide. As healthcare facilities reorganize their services to adapt to this challenging problem, it is important that the sustainability of essential oncology services, including radiotherapy, is maintained. This article describes the Indonesian experience in ensuring sustainability of radiotherapy services during the pandemic, highlighting various important adjustments which were made to allow radiotherapy centers nationwide to continue operating while protecting staff and patients from the risk of disease transmission. As the backlog of patients waiting to start treatment will inevitably grow, some insight on how to proactively manage this issue will also be described.