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1.
Pediatric Oncology Patients With Vincristine-Induced Recurrent Laryngeal Nerve Palsy: Two Case Reports and a Brief Review of Literature.
Tay, SY, Foster, J, Heczey, A, Sitton, M
Ear, nose, & throat journal. 2021;(10):NP459-NP463
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Abstract
INTRODUCTION Vincristine (VCR) is a chemotherapeutic agent used widely in the treatment of hematologic and solid tumors, known to result in neurotoxicity, especially with cumulative administrations. Bilateral vocal fold palsy (VFP) is a rare but life-threatening complication of VCR. We report 2 patients with hepatoblastoma presenting with stridor following VCR treatment and propose a management plan. METHODS Electronic medical records of oncology patients treated at a tertiary hospital with VCR-induced VFP were reviewed. Literature review was performed in PubMed using the terms: hoarseness, VFP, stridor, vincristine. RESULTS A total of 23 children with VCR-induced VFP were identified from the literature review and adding on our 2 cases. Seventeen (77.3%) were male and 5 (22.7%) were female. The median presenting age was 36.0 months (5-204 months). Acute lymphoblastic leukemia, 15 of 23 (65.2%), was the most common malignancy. Eighteen patients (78.3%) had bilateral VFP and 5 (21.7%) had unilateral VFP. The mean time to VF function recovery was 167.3 days (median: 200.5 days, range: 7-270 days) in the intervention group versus 72.1 days (median: 31.5 days, range: 3-240 days) in the conservative group. One patient in the intervention group had persistent VFP. Sixteen patients (69.6%) were observed, 4 (17.4%) underwent tracheostomy, 1 (4.35%) was intubated, 1 (4.35%) underwent cordectomy, and 1 (4.35%) required positive pressure support. Vincristine was restarted in 12 patients (54.5%), of which 4 developed recurrence of airway symptoms and had to stop VCR. CONCLUSION A new-onset hoarseness or stridor in a child on VCR should raise the suspicions of VFP. The assumption of an upper respiratory-induced hoarseness or stridor should be avoided. Decisions regarding readministration of VCR and possible airway interventions should be made via a multidisciplinary team approach.
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Nutritional considerations for the management of the older person with hepato-pancreatico-biliary malignancy.
Bibby, N, Griffin, O
European journal of surgical oncology : the journal of the European Society of Surgical Oncology and the British Association of Surgical Oncology. 2021;(3 Pt A):533-538
Abstract
Malnutrition and cancer cachexia are prevalent in older people with hepato-pancreatico-biliary (HPB) malignancy, with the resultant loss of muscle mass and function accelerating normal age-associated losses. Unintentional weight loss may be missed in patients with pre-illness obesity, delaying diagnosis and limiting treatment potential and access. Sarcopenia and/or sarcopenic obesity increase the risk of dose-limiting chemotherapy toxicity, post-operative mortality and overall survival. The aetiology of malnutrition and weight loss is multi-factorial in patients with HPB malignancy, necessitating systematic evaluation of endocrine and exocrine function, and multi-modal therapeutic strategies. Prehabilitation aims to reduce the complications and side effects associated with treatment, aid recovery and improve quality of life, with the greatest benefits potentially being seen in high risk groups, such as people who are older and frail. Post-operatively, individualised nutritional support therapies targeting the preservation of weight and muscle indices are required to improve post-operative morbidity, and avoid delay or early cessation of any necessary adjuvant therapy.
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The use of nanotechnology to combat liver cancer: Progress and perspectives.
Mintz, KJ, Leblanc, RM
Biochimica et biophysica acta. Reviews on cancer. 2021;(2):188621
Abstract
Liver cancer is one of the most common cancers worldwide and is also one of the most difficult cancers to treat, resulting in almost one million deaths per year, and the danger of this cancer is compounded when the tumor is nonresectable. Hepatocellular carcinoma (HCC) is the most common type of liver cancer and has the third highest mortality rate worldwide. Considering the morbid statistics surrounding this cancer it is a popular research topic to target for better therapy practices. This review summarizes the role of nanotechnology in these endeavors. Nanoparticles (NPs) are a very broad class of material and many different kinds have been used to potentially combat liver cancer. Gold, silver, platinum, metal oxide, calcium, and selenium NPs as well as less common materials are all inorganic NPs that have been used as a therapeutic, carrier, or imaging agent in drug delivery systems (DDS) and these efforts are described. Carbon-based NPs, including polymeric, polysaccharide, and lipid NPs as well as carbon dots, have also been widely studied for this purpose and the role they play in DDS for the treatment of liver cancer is illustrated in this review. The multifunctional nature of many NPs described herein, allows these systems to display high anticancer activity in vitro and in vivo and highlights the advantage of and need for combinatorial therapy in treating this difficult cancer. These works are summarized, and future directions are presented for this promising field.
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Obesity and Liver Cancer in Japan: A Comprehensive Review.
Nishikawa, H, Fukunishi, S, Asai, A, Nishiguchi, S, Higuchi, K
Anticancer research. 2021;(5):2227-2237
Abstract
Lifestyle-related factors play a major role in the development of cancer. In recent years, obesity has become widespread in the world and has attracted attention not only as a cause of diabetes mellitus and atherosclerotic diseases but also as a factor in carcinogenesis. In Japan, the number of obesity-related malignancies has been increasing with the westernization of lifestyle. On the other hand, it is estimated that there are more than 10 million nonalcoholic fatty liver disease (NAFLD) patients in Japan. NAFLD is classified into simple fatty liver and nonalcoholic steatohepatitis (NASH), and 10-20% of NASH patients will progress to liver cirrhosis and 2-3% of them will develop hepatocellular carcinoma (HCC) per year. Research interest in metabolism-associated liver cancer has been increasing in recent years. Here in this review, we will comprehensively summarize the current knowledge with regard to the relationship between obesity and HCC in Japan.
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Frailty assessment tools and geriatric assessment in older patients with hepatobiliary and pancreatic malignancies.
Rostoft, S, van Leeuwen, B
European journal of surgical oncology : the journal of the European Society of Surgical Oncology and the British Association of Surgical Oncology. 2021;(3 Pt A):514-518
Abstract
BACKGROUND The majority of patients with hepatobiliary and pancreatic (HBP) malignancies are older than 65 years. Due to the heterogeneity of this older population, decisions regarding surgical treatment cannot rely solely on treatment guidelines, but have to take into account patient frailty, geriatric impairments and resilience as well as patient preferences. In the few studies of older patients with HBP malignancies that have included a preoperative geriatric assessment (GA), frailty and elements from the GA such as reduced functional status have emerged as powerful predictors of postoperative morbidity and mortality, length of stay, type of treatment received and survival. A GA is a systematic evaluation of functional status, comorbidities, polypharmacy, cognition, nutritional status, emotional status, and social support. MATERIALS AND METHODS A Pubmed search identifying clinical studies investigating the association between frailty, GA and outcomes in patients with HBP malignancies. RESULTS A total of 20 studies were included in this review. For HBP malignancies, the evidence linking frailty and GA variables to negative outcomes is limited, but generally shows that frailty, functional dependency, comorbidity, and sarcopenia predict postoperative complications and survival. CONCLUSION Although scarcely investigated, frailty and elements from a GA seem to be associated with negative short- and long-term treatment outcomes in older patients with HBP malignancies. Future studies should investigate the impact of geriatric interventions and prehabilitation on outcomes.
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Gut microbiota alterations are distinct for primary colorectal cancer and hepatocellular carcinoma.
Jia, W, Rajani, C, Xu, H, Zheng, X
Protein & cell. 2021;(5):374-393
Abstract
Colorectal cancer (CRC) and hepatocellular carcinoma (HCC) are the second and third most common causes of death by cancer, respectively. The etiologies of the two cancers are either infectious insult or due to chronic use of alcohol, smoking, diet, obesity and diabetes. Pathological changes in the composition of the gut microbiota that lead to intestinal inflammation are a common factor for both HCC and CRC. However, the gut microbiota of the cancer patient evolves with disease pathogenesis in unique ways that are affected by etiologies and environmental factors. In this review, we examine the changes that occur in the composition of the gut microbiota across the stages of the HCC and CRC. Based on the idea that the gut microbiota are an additional "lifeline" and contribute to the tumor microenvironment, we can observe from previously published literature how the microbiota can cause a shift in the balance from normal → inflammation → diminished inflammation from early to later disease stages. This pattern leads to the hypothesis that tumor survival depends on a less pro-inflammatory tumor microenvironment. The differences observed in the gut microbiota composition between different disease etiologies as well as between HCC and CRC suggest that the tumor microenvironment is unique for each case.
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Enhanced recovery after surgery programmes in older patients undergoing hepatopancreatobiliary surgery: what benefits might prehabilitation have?
Bongers, BC, Dejong, CHC, den Dulk, M
European journal of surgical oncology : the journal of the European Society of Surgical Oncology and the British Association of Surgical Oncology. 2021;(3 Pt A):551-559
Abstract
Due to an aging population and the related growing number of less physically fit patients with multiple comorbidities, adequate perioperative care is a new and rapidly developing clinical science that is becoming increasingly important. This narrative review focuses on enhanced recovery after surgery (ERAS®) programmes and the growing interest in prehabilitation programmes to improve patient- and treatment-related outcomes in older patients undergoing hepatopancreatobiliary (HPB) surgery. Future steps required in the further development of optimal perioperative care in HPB surgery are also discussed. Multidisciplinary preoperative risk assessment in multiple domains should be performed to identify, discuss, and reduce risks for optimal outcomes, or to consider alternative treatment options. Prehabilitation should focus on high-risk patients based on evidence-based cut-off values and should aim for (partly) supervised multimodal prehabilitation tailored to the individual patient's risk factors. The program should be executed in the living context of these high-risk patients to improve the participation rate and adherence, as well as to involve the patient's informal support system. Developing tailored (multimodal) prehabilitation programmes for the right patients, in the right context, and using the right outcome measures is important to demonstrate its potential to further improve patient- and treatment-related outcomes following HPB surgery.
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Is transcatheter arterial chemoembolization plus sorafenib better than chemoembolization plus placebo in the treatment of hepatocellular carcinoma?
Xie, Y, Tian, H, Xiang, H
Tumori. 2021;(4):292-303
Abstract
OBJECTIVE To evaluate the efficacy and safety of transcatheter arterial chemoembolization (TACE) plus sorafenib compared with TACE plus placebo for hepatocellular carcinoma (HCC) using meta-analytical techniques. METHODS A search of PubMed, EMBASE, and Cochrane Library databases were done from inception to December 27, 2019. Published trials including a treatment group receiving TACE + sorafenib and a control group receiving TACE + placebo with data for at least 1-year survival or tumor response or time to progression were included. RESULTS Our study suggested that there was no evidence that TACE plus sorafenib was associated with a lower risk of disease progression compared with TACE plus placebo for treatment of HCC (hazard ratio 0.94 [95% confidence interval (CI), 0.84-1.05]), and no significant difference for treatment of HCC compared with TACE plus placebo in terms of 0.5-, 1-, 1.5-, and 2-year survival rates (risk ratio [RR] 1.01 [95% CI, 0.97-1.05]; RR 1.00 [95% CI, 0.92-1.08], RR 1.04 [95% CI, 0.89-1.23], RR 0.98 [95% CI, 0.72-1.34], respectively). The meta-analysis also showed that TACE + sorafenib seemed to have no significant difference for treatment of HCC compared with TACE + placebo in terms of complete response, partial response, stable disease, progressive disease, overall response rate, and disease control rate. There was an increased incidence of fatigue of grade 3/4 and elevation of aspartate aminotransferase and alanine aminotransferase of grade 3/4 in patients receiving TACE plus sorafenib compared with those receiving TACE plus placebo. CONCLUSIONS There is no additive benefit of TACE plus sorafenib compared to TACE plus placebo for HCC.
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Molecular therapies for HCC: Looking outside the box.
Faivre, S, Rimassa, L, Finn, RS
Journal of hepatology. 2020;(2):342-352
Abstract
Over the past decade, sorafenib has been the only systemic agent with proven clinical efficacy for patients with unresectable hepatocellular carcinoma (HCC). Recently, lenvatinib was shown to be non-inferior to sorafenib, while regorafenib, cabozantinib, and ramucirumab were shown to be superior to placebo in patients failing sorafenib. In addition, trials of immune checkpoint inhibitors reported encouraging efficacy signals. However, apart from alpha-fetoprotein, which is used to select patients for ramucirumab, no biomarkers are available to identify patients that may respond to a specific treatment. Different synergisms have been postulated based on the potential interplay between antiangiogenic drugs and immunotherapy, with several clinical trials currently testing this hypothesis. Indeed, encouraging preliminary results of phase I studies of bevacizumab plus atezolizumab and lenvatinib plus pembrolizumab have led to the design of ongoing phase III trials, including both antiangiogenics and immune checkpoint inhibitors in the front-line setting. Other important phase II studies have tested molecular therapies directed against different novel targets, such as transforming growth factor-beta, MET (hepatocyte growth factor receptor), and fibroblast growth factor receptor 4. These studies integrated translational research with the aim of better defining the biological tumour profile and identifying tumour and blood biomarkers that select patients who may really benefit from a specific molecular therapy. Importantly, good safety profiles make these drugs suitable for future combinations. In this review, we discuss the most recent data on novel combination strategies and targets, as well as looking ahead to the future role of molecular therapies in the treatment of patients with advanced HCC.
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Targeted Molecular Therapeutic Options for Hepatocellular Carcinoma.
Sridhar, S, Sharma, I, Sankpal, UT, Ghabach, B, Narra, K, Neerukonda, L, Basha, R
Critical reviews in oncogenesis. 2020;(1):47-55
Abstract
Liver cancer is the 6th leading cause of cancer related deaths in the US even though it ranks 14th in incidence. More men are diagnosed with liver cancer than women, and the number of projected deaths among men (20,020) is almost double that among women (10,140) in the US. Infections like hepatitis and metabolic conditions like obesity are believed to be major risk factors for the onset of liver cancer. Hepatocellular carcinoma (HCC), the most common type of liver cancer, accounts for 75% of all cases. Chemotherapy has not been effective in treating HCC. Targeted therapies are being used in advanced HCC patients due to a better survival and less side effects when compared to traditional chemotherapy. Therapeutic agents targeting the regulators of growth factor signaling pathways and the mediators of downstream signaling-for example, inhibitors of the tyrosine kinase receptor-are used as targeted molecular therapies. Kinase inhibitors that modulate growth signals, such as sorafenib and lenvatinib, are commonly employed in targeted molecular therapy for HCC patients. This review covers these agents, highlighting modes of action and providing details on clinical trials.