Special Issue:
Challenges and Opportunities in Hepatocellular Carcinoma
Ana Catarina Viana Valle
Department of Research, Idis Lamasson Institute, Ribeirao Preto, Sao Paulo, Brazil
Aloíso Cunha de Carvalho
Department of Research, Idis Lamasson Institute, Ribeirao Preto, Sao Paulo, Brazil
Samir Wady Rahme
Department of Research, Idis Lamasson Institute, Ribeirao Preto, Sao Paulo, Brazil
Andrêssa de Rezende Bastos Araújo
BioInnova Laboratory, Brasilia, Distrito Federal, Brazil
Patrícia Furtado Malard
BioInnova Laboratory, Brasilia, Distrito Federal, Brazil
Hilana S. Sena Brunel
BioInnova Laboratory, Brasilia, Distrito Federal, Brazil
Abstract
Hepatocellular carcinoma (HCC) is a type of neoplasm of high-frequency occurrence and late diagnosis. Therefore, medicine must act in a multidisciplinary and preventive manner to give patients a better prognosis. Homeopathy appears as a possible therapeutic tool to treat these patients, emphasizing significant results regarding quality of life and longevity. This article aimed to evaluate the effect of homeopathic dilutions of Ruta graveolens in the D35 potency on the in vitro cell viability and nitric oxide quantification of hepatocellular carcinoma cells (HepG2). The results showed a critical cytotoxic activity and high production of nitric oxide of the cells when the medicine to the culture. These results indicate that Ruta D35 has action potential in inhibiting HepG2 tumor cell growth, being an important and promising therapeutic tool for treating patients diagnosed with hepatocellular carcinoma if these results be confirmed in vivo.
Ana Catarina Viana Valle
Doctor Izao Soares Institute, Integrative Medicine, Ribeirao Preto, SP, Brazil.
Aloísio Cunha Cunha de Carvalho
Doctor Izao Soares Institute, Integrative Medicine, Ribeirao Preto, SP, Brazil.
Abstract
Hepatocellular carcinoma is the most common liver neoplasm in dogs and can be treated by the Viscum album therapy in a curative or palliative way. The objective is to report a hepatocellular carcinoma case in a dog treated by homeopathic therapy, extending to Palliative Care, with a 24-month survival. A 12-year-old Schnauzer male with a history of a liver nodule was treated by intravenous and subcutaneous applications of V. album in different dynamization and combinations, chromotherapy, and oral homeopathic medicines. The tumor growth was controlled, and the health condition of the patient was stable while the medication was given as prescribed. However, as application frequency was reduced, tumor growth increased, and health deterioration was verified. Nevertheless and contrary to expectations, the patient had a 24-month survival. Therefore, these findings point to the potential of V. album on enhancing the quality of life, controlling tumor growth, and prolonging survival in patients with hepatocellular carcinoma. Patients under continuous treatment would benefit better from these properties.
Ana Catarina Viana Valle
Department of Research, Idis Lamasson Institute, Ribeirao Preto, Sao Paulo, Brazil.
Aloiso Cunha de Carvalho
Department of Research, Idis Lamasson Institute, Ribeirao Preto, Sao Paulo, Brazil.
Samir Wady Rahme
Department of Research, Idis Lamasson Institute, Ribeirao Preto, Sao Paulo, Brazil.
Andressa de Rezende Bastos Araujo
BioInnova Laboratory, Brasilia, Distrito Federal, Brazil.
Patrícia Furtado Malard
BioInnova Laboratory, Brasilia, Distrito Federal, Brazil.
Hilana S. Sena Brunel
BioInnova Laboratory, Brasilia, Distrito Federal, Brazil.
Abstract
Viscum album (VA), also known as Mistletoe, has various therapeutic properties, including analgesic, anti-inflammatory, and anticancer effects. It has been used for treating different types of cancer, exhibiting proven efficacy against breast cancer, glioblastoma, carcinoma, and other advanced-stage tumor types. Besides promoting improvements in the clinical condition, VA also helps reduce the side effects caused by conventional treatment, thereby offering patients a better quality of life. Hence, the objective of this study was to assess the effects of the homeopathic dilution of VA at the potency of D30 (1×10-30) (VA D30) on human mesenchymal stem cells (MSCs) and hepatocellular carcinoma cells (HepG2). The cells were grown in 75 cm² flasks until they reached approximately 80% confluence. Subsequently, they were trypsinized and plated in 96-well plates at 10,000 cells/well. After 24 hours of incubation in an oven, VA was added at 30 and 40 µL/mL concentrations. The cells were further incubated for an additional 48 hours. After the treatment, the cells underwent a cell viability test using MTT. The results indicated a decrease in HepG2 viability, while no damage to normal cells (MSCs) was detected. The findings suggest that VAD30 holds promise as a potential therapeutic agent in treating hepatocellular carcinoma due to its observed cytotoxicity towards HepG2 cells while exhibiting no adverse effects on mesenchymal stem cells at the equivalent concentration.
Ana Catarina Viana Valle
Department of Research, Idis Lamasson Institute, Ribeirao Preto, Sao Paulo, Brazil
Aloíso Cunha de Carvalho
Department of Research, Idis Lamasson Institute, Ribeirao Preto, Sao Paulo, Brazil
Samir Wady Rahme
Department of Research, Idis Lamasson Institute, Ribeirao Preto, Sao Paulo, Brazil
Andrêssa de Rezende Bastos Araújo
BioInnova Laboratory, Brasilia, Distrito Federal, Brazil
Patrícia Furtado Malard
BioInnova Laboratory, Brasilia, Distrito Federal, Brazil
Hilana S. Sena Brunel
BioInnova Laboratory, Brasilia, Distrito Federal, Brazil
Abstract
Homeopathy has become increasingly known and used in various treatments, showing excellent clinical results. One of its most common indications is to help treat chronic diseases, directly improving patients’ quality of life, especially those with cancer. Hepatocellular carcinoma is a disease that depends on different factors for its development and the success of its treatment. In this context, searching for new therapeutic tools is essential, and homeopathy seems promising. Therefore, Anonna muricata (soursop/graviola) and Handroanthus impetiginosus (purple ipe) have been studied due to their action potential against tumor cells. This study aimed to evaluate the effect of these medicines combined in 1.1mL ampoules, in homeopathic dilutions, on HepG2 (hepatocellular carcinoma) cells through in vitro tests. Cells were cultivated in 75 cm² culture bottles in an oven with controlled temperature and CO2 quantity (37 ºC, 5% CO2). Then, cells were plated in 96-well plates where treatment was performed using the products at different concentrations. After 48 hours of treatment, cell viability analyses were performed by MTT and quantification of the nitric oxide released using the Griess reaction. Treatment with the Anonna muricata D5 (1×10-5) + Handroanthus impetiginosus D5 (1×10-5) formulation resulted in decreased cell viability and increased nitric oxide production by these cells. These findings indicate that this medicine showed an antitumor effect and can be an ally in treating this type of pathology.
Ana Catarina Viana Valle
Department of Research, Idis Lamasson Institute, Ribeirao Preto, Sao Paulo, Brazil
Aloíso Cunha de Carvalho
Department of Research, Idis Lamasson Institute, Ribeirao Preto, Sao Paulo, Brazil
Samir Wady Rahme
Department of Research, Idis Lamasson Institute, Ribeirao Preto, Sao Paulo, Brazil
Andrêssa de Rezende Bastos Araujo
BioInnova Laboratory, Brasilia, Distrito Federal, Brazil
Patrícia Furtado Malard
BioInnova Laboratory, Brasilia, Distrito Federal, Brazil
Hilana S. Sena Brunel
BioInnova Laboratory, Brasilia, Distrito Federal, Brazil
Abstract
Hepatocellular carcinoma is a type of cancer with a high mortality rate since it is primarily diagnosed in an advanced stage. Therefore, searching for therapies that help in this treatment becomes increasingly important. Therapies comprising Complementary Medicine have become more popular and have shown beneficial effects in treating various types of cancer. Homeopathy, a therapy established for more than 200 years to treat various diseases, has become the target of several studies, especially regarding chronic diseases, which are difficult to control by conventional medicine. This study evaluated the effect of the homeopathic dilution of Chelidonium majus D35 (1×10-35) in hepatocellular carcinoma cells (HepG2). Cells were cultivated in an oven at 37 ºC, 5% CO2, and then trypsinized and plated in 96-well plates for product addition. Chelidonium majus D35 was added in triplicate to each well at three different concentrations. The concentrations tested were 20, 40, and 60 µL/mL. After 48 hours of incubation with the product, cell viability was measured by MTT, and it was possible to observe a decrease in the groups that received the treatment compared to the control.
A decrease in cell viability was recorded compared to the control of cells without treatment, indicating a cytotoxic effect of Chelidonium majus D35 on tumor cells. Different studies confirm this result due to the evaluation of biologically active compounds present in extracts of Chelidonium majus D35 that control cell proliferation and induce apoptosis. The results of the in vitro tests performed were satisfactory.
Linda Ding, PhD
Department of Radiation Oncology, UMass Chan Medical School, Worcester, MA 01655, USA; Department of Radiation Oncology, UMass Memorial Health, Worcester, MA 01655 USA
Shirin Sioshansi, MD
Department of Radiation Oncology, UMass Chan Medical School, Worcester, MA 01655, USA; Department of Radiation Oncology, UMass Memorial Health, Worcester, MA 01655 USA
Hesham Malik, MD
Department of Radiology, UMass Chan Medical School, Worcester, MA 01655, USA; Department of Radiology, UMass Memorial Health, Worcester, MA 01655, USA
Elisa Franquet-Elia, MD
Department of Radiology, UMass Chan Medical School, Worcester, MA 01655, USA; Department of Radiology, UMass Memorial Health, Worcester, MA 01655, USA
Lacey McIntosh, DO, MPH
Department of Radiology, UMass Chan Medical School, Worcester, MA 01655, USA; Department of Radiology, UMass Memorial Health, Worcester, MA 01655, USA
Evan Ruppell, DO
Department of Radiology, UMass Chan Medical School, Worcester, MA 01655, USA, Department of Radiology, UMass Memorial Health, Worcester, MA 01655, USA
Robert Licho, MD
Department of Radiology, UMass Chan Medical School, Worcester, MA 01655, USA, Department of Radiology, UMass Memorial Health, Worcester, MA 01655, USA
Young Kim, MD
Department of Radiology, UMass Chan Medical School, Worcester, MA 01655, USA, Department of Radiology, UMass Memorial Health, Worcester, MA 01655, USA
Alan Goldstein, MD
Department of Radiology, UMass Chan Medical School, Worcester, MA 01655, USA, Department of Radiology, UMass Memorial Health, Worcester, MA 01655, USA
Kriti Mittal, MD
Department of Medicine, UMass Chan Medical School, Worcester, MA 01655, USA, Department of Medicine, UMass Memorial Health, Worcester, MA 01655 USA
Ming-Jin Wang, MD
Department of Medicine, UMass Chan Medical School, Worcester, MA 01655, USA, Department of Medicine, UMass Memorial Health, Worcester, MA 01655 USA
Patan Gultawatvichai, MD
Department of Medicine, UMass Chan Medical School, Worcester, MA 01655, USA, Department of Medicine, UMass Memorial Health, Worcester, MA 01655 USA
Savant Mehta, MD
Department of Medicine, UMass Chan Medical School, Worcester, MA 01655, USA, Department of Medicine, UMass Memorial Health, Worcester, MA 01655 USA
Kimberly Foley, NP
Department of Medicine, UMass Memorial Health, Worcester, MA 01655 USA
Sean Wilson, MD
Department of Radiology, UMass Chan Medical School, Worcester, MA 01655, USA, Department of Radiology, UMass Memorial Health, Worcester, MA 01655, USA
Maryann L Bishop-Jodoin, MEd
Department of Radiation Oncology, UMass Chan Medical School, Worcester, MA 01655, USA
Thomas J FitzGerald, MD
Department of Radiation Oncology, UMass Chan Medical School, Worcester, MA 01655, USA Department of Radiation Oncology, UMass Memorial Health, Worcester, MA 01655 USA
Abstract
Yttrium-90 (Y-90) therapy has become an important component to the care of patients with primary hepatic malignancies and lesions that have metastasized to the liver. Therapy is administered through an intra-arterial procedure after an interventional procedure is performed using an albumin labeled product to ensure therapy will be delivered to the target volume of interest with minimal migration from the target of choice. In the past, dose to target has been measured by activity delivered and qualitative deposition of dose on metabolic imaging post application. Imaging tools such as single positron emission computer tomography (SPECT) and digital positron emission tomography have given us insight into quantitative dose to volumetric tumor target and dose to normal tissue. Recent validation of computational software has provided voxel-based dosimetry similar to applied processes established in radiation oncology planning systems. This development presents an opportunity to create dose volume analysis similar to teletherapy and brachytherapy dose delivery for Y-90 therapy. In this case report, we review Y-90 dosimetry on a patient with dual diagnosis of a locally advanced high-risk adenocarcinoma of the prostate which required treatment to the para-aortic lymph nodes located in the same axial plane with renal parenchyma. Although not clinically anticipated, hepatocellular carcinoma was serendipitously discovered at the time of staging for prostate cancer. Treatment dosimetry of the hepatocellular carcinoma is reviewed in retrospect with voxel-based commercial software. Same day SPECT study suggested dose localized to the liver, however voxel planning software confirmed unintentional dose to additional structures including the right kidney and uninvolved liver which influenced radiation therapy treatment planning for prostate carcinoma. With modern available tools, post therapy dosimetry for Y-90 can be performed in a manner similar to volumetric dosimetry used in radiation oncology and provide valuable dose volume analysis of dose delivered to target and additional tissue.
Farshid Gheisari
Ionizing and Non-ionizing Radiation Protection Research Center (INIRPRC), Shiraz University of Medical Sciences, Shiraz, Iran
Reza Vali
Diagnostic Imaging, Nuclear Medicine Division, The Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada
Abstract
Hepatocellular Carcinoma (HCC) is a growing global health burden with high incidence and mortality rates. Despite advances in surgical techniques and perioperative care, outcomes after surgical treatment have not improved over the past three decades. Molecular imaging is an emerging field that enables researchers to study diseases at the molecular and cellular levels, enabling the detection of elevated serum α-fetoprotein (AFP) and abnormal expressions of various HCC-specific and nonspecific cell surface antigens and intracellular targets. Molecular imaging techniques detect liver lesions at the molecular and cellular level, allowing early detection and accurate staging of HCC. Positron emission tomography (PET) imaging offers greater sensitivity and specificity, while hepatobiliary-specific radiotracers with SPECT imaging provide insights into benign and malignant lesion differentiation. Radiomics and artificial intelligence are vital in deciphering molecular imaging data, with machine learning algorithms boosting diagnostic gains and predicting treatment response. Theranostics, a state-of-the-art application, provides diagnostic and therapeutic leverage following a single imaging agent. By understanding tumor biology in real time, radiopharmaceuticals can be transformed into personalized radiotherapies, enabling clinicians to make science-driven decisions throughout the illness. Future directions include developing novel radiotracers and integrating AI into clinical decision-making. Collaboration between academic researchers, clinicians, and industry colleagues is crucial to converting exciting advances into improved clinical outcomes for HCC patients.
Ana Catarina Viana Valle
Department of Research, Idis Lamasson Institute, Ribeirao Preto, Sao Paulo, Brazil.
Aloiso Cunha de Carvalho
Department of Research, Idis Lamasson Institute, Ribeirao Preto, Sao Paulo, Brazil.
Samir Wady Rahme
Department of Research, Idis Lamasson Institute, Ribeirao Preto, Sao Paulo, Brazil.
Andressa de Rezende Bastos Araujo
BioInnova Laboratory, Brasilia, Distrito Federal, Brazil.
Patricia Furtado Malard
BioInnova Laboratory, Brasilia, Distrito Federal, Brazil.
Hilana S. Sena Brunel
BioInnova Laboratory, Brasilia, Distrito Federal, Brazil.
Abstract
Homeopathy has been increasingly standing out for its proven clinical benefits and for providing a course of treatment with fewer side effects to patients, thus promoting a better quality of life for them. Homeopathic therapy can be used in different contexts and is an additional alternative for treating cancer patients in Integrative Medicine. Within this context, hepatocellular carcinoma has a high mortality rate and, in most cases, is diagnosed in advanced cases. Therefore, this study evaluated the in vitro efficacy of the association of the homeopathic medicines Taraxacum officinale and Lycopodium clavatum against HepG2 cells. For this purpose, cells were grown in 75 cm² flasks and then plated in 96-well plates. The treatment with Taraxacum D4 + Taraxacum D8 + Taraxacum D12 and Taraxacum D5 + Lycopodium D6 at concentrations of 20, 40, and 60 µL/mL was added to each well. After 48 hours of incubation in an oven at 37ºC, 5% CO2, cells were subjected to the cell viability test by MTT. A decrease in viability was observed compared to the control group (cells without treatment). In addition, the medicine Taraxacum officinale was more effective in decreasing cell viability than the other medicines in the three conditions tested. In conclusion, the homeopathic medicine Taraxacum D4 + Taraxacum D8 + Taraxacum D12, in accord of potencies, is promising against hepatocellular carcinoma cells and can be used to aid in the treatment of this type of cancer.
Rana Rabei
UCSF
Nicholas Fidelman, MD
Abstract
The aim of this review is to explore the implications of frailty in the treatment of patients with hepatocellular carcinoma (HCC). Frailty, a multidimensional geriatric syndrome, has been increasingly recognized as an important predictor of adverse outcomes and mortality in various patient populations. This review specifically focuses on the prevalence of frailty in the cirrhotic population and its role as a prognostic tool for procedural and surgical outcomes of transplantation, hepatectomy and liver-directed therapies. Understanding the impact of frailty on HCC treatment can help guide clinicians in optimizing management strategies and improving patient outcomes.
Regis Otaviano Franca Bezerra
Departamento de Radiologia, Instituto do Cancer do Estado de São Paulo, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo, SP BR.
Rafael Soares Pinheiro
Disciplina de Transplante de Figado e Orgaos do Aparelho Digestivo, Departamento de Gastroenterologia, Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo, SP, BR.
Tiago M. Magalhães
Departamento de Estatistica, Instituto de Ciencias Exatas, Universidade Federal de Juiz de Fora, Juiz de Fora, MG, BR.
Allana Christina Fortunato
Disciplina de Transplante de Figado e Orgaos do Aparelho Digestivo, Departamento de Gastroenterologia, Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo, SP, BR.
Liege Tambelini
Departamento de Radiologia, Instituto do Cancer do Estado de São Paulo, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo, SP BR.
Gustavo Conti
Departamento de Radiologia, Instituto do Cancer do Estado de São Paulo, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo, SP BR.
Matheus F. F. Aguiar
Disciplina de Transplante de Figado e Orgaos do Aparelho Digestivo, Departamento de Gastroenterologia, Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo, SP, BR.
Vinicius Rocha-Santos
Disciplina de Transplante de Figado e Orgaos do Aparelho Digestivo, Departamento de Gastroenterologia, Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo, SP, BR.
Daniel R. Waisberg
Disciplina de Transplante de Figado e Orgaos do Aparelho Digestivo, Departamento de Gastroenterologia, Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo, SP, BR.
Manoel de Souza Rocha
Departamento de Radiologia, Instituto do Cancer do Estado de São Paulo, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo, SP BR.
Giovanni Guido Cerri
Departamento de Radiologia, Instituto do Cancer do Estado de São Paulo, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo, SP BR.
Luis Augusto Carneiro D’Albuquerque
Disciplina de Transplante de Figado e Orgaos do Aparelho Digestivo, Departamento de Gastroenterologia, Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo, SP, BR.
Wellinton Andraus
Disciplina de Transplante de Figado e Orgaos do Aparelho Digestivo, Departamento de Gastroenterologia, Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo, SP, BR.
Abstract
INTRODUCTION: Sarcopenia is defined as loss of muscle mass. Besides, myosteatosis is characterized by increased proportion of intermuscular and intramuscular fat. We aimed evaluate the impact of sarcopenia and myosteatosis in hepatocellular carcinoma (HCC) recurrence after liver transplantation.
METHODS: Retrospective study of consecutive patients with HCC who underwent liver transplantation in a single institution. Right psoas attenuation (PAt) was measured in Hounsfield units at the level of the third lumbar vertebra. Partial volume of the right psoas (PV) was measured up to the level of the iliac crest. Sarcopenia was defined based on the median values found in each measured parameter.
RESULTS: Our study sample included 206 patients. The median follow-up was 4.83 years (IQR 2.35–7.82 years). Overall survival was 84% at 1 year and 75% at 3 years. There were 16 patients (7.76%) with HCC recurrence. Sarcopenia had no impact on overall survival (p<0.68) or disease-free survival (p<0.679). The continuous value of psoas attenuation was negatively associated with the risk of HCC recurrence (p=0.017). Univariate analysis for HCC recurrence identified micro- and macrovascular invasion, preoperative AFP greater than 200, pathological staging beyond Milan Criteria and presence of myosteatosis as significant risk factors. Multivariate analysis only confirmed myosteatosis as an independent risk factor for recurrence (HH 5.88, 95% CI 1.52; 25, and p=0.005).
CONCLUSIONS: Myosteatosis was associated with HCC recurrence after liver transplantation.
Dhineshreddy Gurala, MD
Gastroenterology and Hepatology, Staten Island University Hospital, Northwell Health, Staten Island, New York, USA
Ravindran Nishal, MD
Gastroenterology and Hepatology, Staten Island University Hospital, Northwell Health, Staten Island, New York, USA
Jobin Philipose, MD
Gastroenterology and Hepatology, Mountain View Medical Center, Las Cruces, New Mexico, USA
Abstract
Obesity is a chronic, preventable condition, and has a significant public health concern. Its implications extend beyond metabolic syndrome, casting a shadow over the development and prognosis of various cancers, with a particularly strong tie to hepatocellular carcinoma (HCC) among all cancer types. Non-Alcoholic Fatty Liver Disease (NAFLD) is now a leading cause of liver cancer, along with the treatment of hepatitis B and C. Liver cancer is the fourth most common cause of cancer related deaths worldwide, with obesity, exacerbating the risk especially two times higher in Body Mass Index (BMI) above 30 and four times higher in BMI above 35. Visceral adiposity, measured by waist circumference, is considered more important risk factor than general adiposity. Several mechanisms have been proposed to explain the pathophysiology of how obesity can trigger HCC, but the precise mechanisms that control the progression from steatosis to steatohepatitis and tumor initiation remain unclear. Hepatocellular cancer may occur in patients with NAFLD without cirrhosis. The diagnosis of HCC in NAFLD can be challenging due to an increase in poor-quality ultrasound in obese individuals, which necessitates a more accurate and cost-effective surveillance strategy for early detection. The delay in diagnosis, older age, and the presence of relevant comorbidities limit the possibility of therapeutic intervention. Weight management through lifestyle changes and surgical interventions like bariatric surgery offers promise in mitigating both metabolic syndrome and the risk of HCC. Diagnosis hinges on advanced imaging techniques like multiphase Magnetic Resonance Imaging or Computed Tomography scan using specific criteria. Treatment modalities for HCC are multifaceted, depends upon tumor characteristics, metastasis, cirrhosis, and overall liver function. However, despite advancements, there remains a pressing need for more efficacious interventions to combat obesity and curb the trajectory of HCC, given its persistently high mortality rate. Surveillance protocols for HCC in cirrhotic patients entail regular abdominal ultrasounds with or without Alpha Fetoprotein testing at six-month intervals. However, there is a need for cost effective surveillance strategies for HCC in non-cirrhotic NAFLD.
Anjum Siddiqui
Dr. Anjum Siddiqui, Senior Resident, Department of Medicine, LHMC & Smt.SK Hospital, New Delhi
Aparna Agrawal
Director Professor, Department of Medicine, LHMC& Smt S.K Hospital, New Delhi
Praveen Kumar
Director Professor, Department of Paediatrics, LHMC& Kalawati Saran Children’s Hospital, New Delhi
Lekhraj Hemraj Ghotekar
Head of Department and Director Professor, Department of Medicine, LHMC& Smt S.K Hospital, New Delhi
Sanjana Taneja
MBBS, Lady Hardinge Medical College and associated Hospitals, New Delhi
Abstract
Gluten, in genetically susceptible individuals induces an immune mediated enteropathy called Celiac disease (CD). It is an established cause of malabsorption, with the worldwide prevalence being 1% in the general population. It is found across all age groups, from infants to the elderly with 20% patients being diagnosed in the seventh decade of life. It has varying clinical presentations ranging from silent asymptomatic forms which are diagnosed during screening to life threatening forms with severe malabsorption to atypical presentations, with the symptom spectrum extending beyond the gastrointestinal tract which are more common in adults. High index of suspicion, robust screening and testing, followed by strict adherence to gluten free diet is a must to curb and cure the disease. Patients tend to face difficulties not only during diagnosis, but also with compliance and availability of a gluten free diet, in addition to significant economic and psychosocial burden, which is more predominant in developing countries. Screening of high-risk groups like first-degree relatives of celiac disease, patients with severe malnutrition, other autoimmune diseases, refractory anaemia and irritable bowel syndrome should be done to enhance case detection. In low middle income countries, judicious resource utilisation takes precedence, hence, tackling a multifactorial disease such as celiac disease becomes challenging. Repeated follow ups, awareness among patients and doctors, encouragement, availability of testing and dietary counselling is necessary for management of the disease in such settings. Improving sanitation and feeding practices may also play role in decreasing incidence, considering childhood GI infections are a well-established risk factor. Increased availability of serological tests (IgA/IgG anti-tTG, anti -EMA and anti-DGP), biopsy, genetic testing and other newer modalities under research have improved the diagnostic accuracy. Poor compliance increases the risk of GI malignancy, non-Hodgkin’s lymphoma, Hepatocellular carcinoma and MALToma. Hence adherence is a must to prevent complications. A wide variety of treatment modalities are being evaluated to bring into force alternative strategies for management. Only providing gluten free diet is often not sufficient for improvement of nutritional status in patients with CD. Hence, micronutrient supplementation should also be encouraged to meet the unmet needs.
Eron G Manusov
Department of Human Genetics, The University of Texas Rio Grande Valley, Brownsville, TX, United States; South Texas Diabetes and Obesity Institute, The University of Texas Rio Grande Valley, Brownsville, TX, United States
Vincent P. Diego
Department of Human Genetics, The University of Texas Rio Grande Valley, Brownsville, TX, United States; South Texas Diabetes and Obesity Institute, The University of Texas Rio Grande Valley, Brownsville, TX, United States
Edward Abrego
The University of Texas Rio Grande Valley, School of Medicine, Edinburg Texas
Kathryn Herklotz
The University of Texas Rio Grande Valley, School of Medicine, Edinburg Texas
Marcio Almeida
Department of Human Genetics, The University of Texas Rio Grande Valley, Brownsville, TX, United States; South Texas Diabetes and Obesity Institute, The University of Texas Rio Grande Valley, Brownsville, TX, United States
Xi Mao
Department of Economics, University of Texas Rio Grande Valley, Brownsville, TX 78520
Sandra Laston
Department of Human Genetics, The University of Texas Rio Grande Valley, Brownsville, TX, United States; South Texas Diabetes and Obesity Institute, The University of Texas Rio Grande Valley, Brownsville, TX, United States
John Blangero
Department of Human Genetics, The University of Texas Rio Grande Valley, Brownsville, TX, United States; South Texas Diabetes and Obesity Institute, The University of Texas Rio Grande Valley, Brownsville, TX, United States
Sarah Williams-Blangero
Department of Human Genetics, The University of Texas Rio Grande Valley, Brownsville, TX, United States; South Texas Diabetes and Obesity Institute, The University of Texas Rio Grande Valley, Brownsville, TX, United States
Abstract
Non-alcoholic fatty liver disease (NAFLD) encompasses a range of liver conditions, from benign fatty accumulation to severe fibrosis. The global prevalence of NAFLD has risen to 25-30%, with variations across ethnic groups. NAFLD may advance to hepatocellular carcinoma, increases cardiovascular risk, is associated with chronic kidney disease, and is an independent metabolic disease risk factor. Assessment methods for liver health include liver biopsy, magnetic resonance imaging, ultrasound, and vibration-controlled transient elastography (VCTE by FibroScan). Hepatic transaminases are cost-effective and minimally invasive liver health assessment methods options.
This study focuses on the interaction between genetic factors underlying the traits (hepatic transaminases and the FibroScan results) on the one hand and the environment (depression) on the other. We examined 525 individuals at risk for metabolic disorders. We utilized variance components models and likelihood-based statistical inference to examine potential GxE interactions in markers of NAFLD, including aspartate aminotransferase (AST), alanine aminotransferase (ALT), and the AST/ALT ratio, and Vibration-Controlled Transient Elastography (VCTE by FibroScan). We calculated the Fibroscan-AST (FAST) score (a score that identifies the risk of progressive non-alcoholic steatohepatitis (NASH) and screened for depression using the Beck Depression Inventory-II (BDI-II). We identified significant G x E interactions for AST/ALT ratio x BDI-II, but not AST, ALT, or the FAST score. Our findings support that genetic factors play a role in hepatic transaminases, especially the AST/ALT ratio, with depression influencing this relationship. These insights contribute to understanding the complex interplay of genetics, environment, and liver health, potentially guiding future personalized interventions.
Priya Hays
Hays Documentation Specialists, LLC, San Mateo, CA USA
Abstract
Cancer stems cells are cells in tumors that have self-renewing capabilities and proliferation, and are partly responsible for tumor growth, metastasis and drug resistance, and have been associated with multidrug resistance and epithelial-mesenchymal transition. mRNA stemness index or mRNAsi is a machine learning tool that uses the application of algorithms to find associations between cancer stemness and tumor prognostic signatures. mRNAsi predicts gene mutation status and identifies tumor signaling pathways. Clinical tier grading is a common feature for stratifying the presenting features and symptoms of patients in several diseases. This study is a review article that summarizes studies in lung cancer, gastric cancer, hepatocellular carcinoma and glioblastoma that use mRNA stemness index machine learning tools to identify differentially expressed genes, characterize the tumor microenvironment and tumor mutational burden, and determine clinical endpoints. A prognostic signature is shown in this paper as determined by mRNAsi high and low values, and a clinical tier grading system is proposed that categorizes cancer stemness presenting characteristics. This clinical grading tier system demonstrates a relationship between cancer stemness and immune checkpoint inhibitor efficacy. This type of tiered system for cancer patients and the accompanying workflow proposed may prove useful to oncologists, and has not been performed before, and is unique in the literature.
L Ding
Department of Radiation Oncology, UMass Memorial Health Care, Worcester Ma. 01655 USA; Department of Radiation Oncology, UMass Chan Medical School, Worcester Ma. 01655 USA
S Sioshansi
Department of Radiation Oncology, UMass Memorial Health Care, Worcester Ma. 01655 USA; Department of Radiation Oncology, UMass Chan Medical School, Worcester Ma. 01655 USA
Y Geng
Department of Radiation Oncology, UMass Memorial Health Care, Worcester Ma. 01655 USA
L McIntosh
Department of Radiology, UMass Memorial Health Care, Worcester, Ma. 01655 USA; Department of Radiology, UMass Chan Medical School, Worcester, Ma. 01655 USA
E Ruppell
Department of Radiology, UMass Memorial Health Care, Worcester, Ma. 01655 USA; Department of Radiology, UMass Chan Medical School, Worcester, Ma. 01655 USA
R Licho
Department of Radiology, UMass Memorial Health Care, Worcester, Ma. 01655 USA; Department of Radiology, UMass Chan Medical School, Worcester, Ma. 01655 USA
Y Kim
Department of Radiology, UMass Memorial Health Care, Worcester, Ma. 01655 USA; Department of Radiology, UMass Chan Medical School, Worcester, Ma. 01655 USA
A Goldstein
Department of Radiology, UMass Memorial Health Care, Worcester, Ma. 01655 USA; Department of Radiology, UMass Chan Medical School, Worcester, Ma. 01655 USA
K Mittal
Department of Medicine, UMass Memorial Health Care, Worcester, Ma. 01655 USA; Department of Medicine, UMass Chan Medical School, Worcester, Ma. 01655 USA
M Wang
Department of Medicine, UMass Memorial Health Care, Worcester, Ma. 01655 USA; Department of Medicine, UMass Chan Medical School, Worcester, Ma. 01655 USA
S Mehta
Department of Medicine, UMass Memorial Health Care, Worcester, Ma. 01655 USA; Department of Medicine, UMass Chan Medical School, Worcester, Ma. 01655 USA
K Foley
Department of Medicine, UMass Memorial Health Care, Worcester, Ma. 01655 USA; Department of Medicine, UMass Chan Medical School, Worcester, Ma. 01655 USA
K Smith
Department of Radiation Oncology, UMass Chan Medical School, Worcester Ma. 01655 USA
M Bishop-Jodoin
Department of Radiation Oncology, UMDepartment of Radiation Oncology, UMass Chan Medical School, Worcester Ma. 01655 USA
TJ FitzGerald
Department of Radiation Oncology, UMass Memorial Health Care, Worcester Ma. 01655 USA ; Department of Radiation Oncology, UMass Chan Medical School, Worcester Ma. 01655 USA
Abstract
This paper is a follow-up report concerning a patient treated with Yttrium-90 to a hepatocellular carcinoma. The radiation therapy dose distribution was published as a case report in 2022, https://doi.org/10.18103/mra.v10i11.3379. The hepatic target volume for directed therapy abutted the right kidney and this report provides clinical follow up information on the patient relative to renal function on unintentional radiation renal dose. Yttrium-90 therapy has become an important therapy component for patient care directed to multiple malignancies with emphasis on treating lesions in close proximity to the hepatic parenchyma. The targets are treated with an intra-arterial approach with a goal of applying target directed radiation therapy. Historically, prior to the development of voxel-based dose volume computation software, dose to target was prescribed as activity of isotope delivered with a qualitative assessment of isotope delivery based on images obtained from single positron emission computer tomography. As a qualitative image, single positron emission computer tomography served as an image reference and qualitative surrogate for representing radiation dose. Today, commercial software is available to fuse single positron emission computer tomography images into radiation oncology planning images and calculate dose to volume in a manner similar to how radiation oncology physics dosimetry teams calculate radiation dose to target volume for external therapy and brachytherapy with image guidance. In this particular case, we demonstrated that the proximity of the right kidney to the target resulted in unintentional radiation dose to renal parenchyma evaluated using voxel-based dosimetry. In this report, we review progressive decrease in renal function with blood urea nitrogen/creatinine of 45 and 2.75 respectively with continued normal liver function. Although potentially multi-factorial in origin, the decrease in renal function is at a time point consistent with radiation injury. In this paper we review radiation oncology dose volume constraints for renal tolerance and strategies for patient care moving forward. The goal is to provide additional knowledge of this issue and provide an additional knowledge layer for patient safety with emphasis on improving patient outcomes.
Phillip Huang Chen
Department of Medicine, David Geffen School of Medicine at UCLA, Los Angeles, CA
Steven-Huy Han
Pfleger Liver Institute, UCLA Medical Center, Los Angeles, CA; Greater Los Angeles VA Healthcare System, Los Angeles, CA
Abstract
Hepatitis B (HBV) in special populations within this article is considered as acute on chronic liver failure due to HBV, coinfection with Hepatitis C (HCV), Hepatitis D (HDV), or Human Immunodeficiency Virus (HIV), and HBV infection in patients who are in immunosuppressive states due to specific therapies and liver transplant recipients. Patients within these special populations are at higher risk of liver-related complications such as fibrosis, accelerated cirrhosis, acute on chronic liver failure, and/or development of hepatocellular carcinoma (HCC). Given their respective complex pathophysiology, specific treatment approaches are required for each population. With the introduction of effective antiviral HBV therapies over the past decade and the respective treatment options for the special population diseases, patient outcomes have seen improvement. With the advent of HCV direct antivirals, treatment of HBV-HCV coinfection has been more successful and consistently shown high rates of sustained virologic response. Treatment of HBV-HDV coinfection remains primarily as interferon-based, though new promising therapies have shown greater improvement in viral suppression. HBV-HIV coinfection has also shown promising results given overlapping mechanisms for treatment and specific regimens should be chosen to decrease risk of resistance. HBV reactivation in patients undergoing immunosuppressive therapies have been reported and guidelines recommend close monitoring and in certain cases, HBV antiviral therapy prophylaxis. With the effective HBV therapies, the perception of HBV as a contraindication for liver transplant has been diminishing and prolonged graft survival with effective antiviral therapies have shown promising outcomes.
Ali Hamdan
Department of Internal Medicine, Faculty of Medicine, University of Balamand, Dekweneh-Beirut, Lebanon
Amir Omar
Department of Internal Medicine, Faculty of Medicine, University of Balamand, Dekweneh-Beirut, Lebanon
Rayane Salameh
Department of Internal Medicine, Faculty of Medicine, University of Balamand, Dekweneh-Beirut, Lebanon
Pierre Hani
Associate professor in Department of Gastroenterology, Faculty of Medicine, University of Balamand, Dekweneh-Beirut, Lebanon
Abstract
Cholangiocarcinoma, an adenocarcinoma arising from the epithelium of biliary ducts, is considered the second most common hepatic malignancy after hepatocellular carcinoma with increasing incidence over the past 3 decades. Many imaging modalities with correlation to clinical presentation are used for the diagnosis and staging of cholangiocarcinoma. However, the diagnosis of cholangiocarcinoma is still challenging due to the presence of some benign and malignant conditions that mimic the clinical presentation and radiological findings of this disease. One of those mimics is the condition of intrabiliary hydatid cyst rupture which can cause biliary obstructive symptoms over weeks with radiological findings that may be indistinguishable from those of cholangiocarcinoma and specifically klatskin tumor when found at the bifurcation of the common hepatic duct. In such a confusing situation, the correct preoperative diagnosis and potential treatment of the disease could both be made possible using Endoscopic Retrograde Cholangiopancreatography avoiding unrequired surgical interventions.
Igor Olegovich Ivanikov, Prof., MD, PhD, DSc
Leading Specialist in Gastroenterology Central Clinical Hospital of Russian Federation Presidential Administration (Moscow, Russia) Professor at Pirogov Russian National Research Medical University (Moscow, Russia)
Mariia Evgenevna Zharova, MD, MSc
Technician at Pirogov Russian National Research Medical University (Moscow, Russia) – Corresponding Author
Natalya Nikolaevna Vinogradova, MD, PhD, DSc
3MD at Cancer Registry Central Clinical Hospital of Russian Federation Presidential Administration (Moscow, Russia)
Julia Vasilevna Grigoreva, MD, PhD
Head of the Gastroenterology Department Central Clinical Hospital of Russian Federation Presidential Administration (Moscow, Russia) Assistant Professor at Pirogov Russian National Research Medical University (Moscow, Russia)
Dmitry Pavlovich Ananyev, MD, PhD
Deputy Chief Physician of Surgery Central Clinical Hospital of Russian Federation Presidential Administration (Moscow, Russia)
Oksana Valentinovna Kryuchkova, MD, PhD
Head of Diagnostic Radiology Central Clinical Hospital of Russian Federation Presidential Administration (Moscow, Russia)
Natalya Vladimirovna Efremova, MD, PhD
Head of the 3rd Internal Medicine Department Central Clinical Hospital of Russian Federation Presidential Administration (Moscow, Russia)
Elena Vladimirovna Myasnikova, MD, PhD
Head of the 2nd Internal Medicine Department Central Clinical Hospital of Russian Federation Presidential Administration (Moscow, Russia)
Evgeniy Leonidovich Nikonov, Prof., MD, PhD, DSc
Head of the Gastroenterology Department Pirogov Russian National Research Medical University (Moscow, Russia)
Abstract
Background: This study aims to analyze liver and bile duct tumors over 35 years in the population of the Main Medical Directorate of the Russian Presidential Administration with a view to identifying epidemiological trends and their possible causes.
Objective: to assess incidence and mortality rates, examine gender-specific patterns, describe histological picture, and evaluate the effectiveness of routine screenings on patient outcomes.
Methods: Retrospective data from the cancer registry of the Main Medical Directorate of the Russian Presidential Administration for 1981-2015 were analyzed. Incidence and mortality rates were assessed with regard to gender distribution, histological confirmation, and survival rates. Standardized indicators were compared with national and international benchmarks.
Results: For a period of 35 years, 227 cases of primary liver and bile duct tumors (ICD-C22) were identified. Of these, males made up 66% (149 cases), whereas for females it was 34% (78 cases). The average age of patients was 71.6 ± 11.4 years. The study reveals a consistent decrease in morbidity and mortality rates for both men and women within the studied population, contrasting with national trends. Study showed 20% increase in the 3-year survival rate for patients diagnosed during routine screenings compared to those presenting with symptoms (p=0.0001). Hepatocellular carcinoma was the most common type of liver cancer in the population. Surgical intervention was utilized in 16% of cases, while chemotherapy was used in 25%. Symptomatic treatment constituted a significant proportion of the treatment modalities.
Conclusion: Our study provides insights into promising epidemiological trends in liver and bile duct tumors. Factors contributing to favorable outcomes include immunization, antiviral treatments, and lower alcohol consumption. Gender-specific patterns highlight the necessity for tailored screening. This study supports the adoption of regular screening efforts to boost early detection rates and enhance patient outcomes. These findings provide significant clinical implications and pave the way for future research.
