Current status of first-line therapy,anti-angiogenic therapy and its combinations of other agents for unresectable hepatocellular carcinoma

Globally, hepatocellular carcinoma (HCC) is a frequently diagnosed malignancy with rapidly increasing incidence and mortality rates. Unfortunately, many of these patients are diagnosed in the advanced stages when locoregional treatments are not appropriate. Before 2008, no effective drug treatments existed to prolong survival, until the breakthrough multi-tyrosine kinase inhibitor (TKI) sorafenib was developed. It remained the standard treatment option for advanced HCC for 10 years, with a battery of other candidate drugs in clinical trials failing to produce similar efficacy results. In 2018, the REFLECT trial introduced another multi-TKI, lenvatinib, which has non-inferior overall survival compared with sorafenib. Thus, offering patients and their treating physicians two effective treatment options. Recently, immunotherapy-based drugs, such as atezolizumab and bevacizumab, have shown promising results in patients with unresectable HCC. This review summarizes clinical trial and real-world data studies of sorafenib and lenvatinib in patients with unresectable HCC. We offer guidance on the optimal choice between the two treatments and discuss the potential of immunotherapy-based combination; when more data become available, this will likely make the choice between sorafenib and lenvatinib somewhat obsolete.     

Impact of overweight and obesity on US renal cell carcinoma incidence trends (1995-2018)

In the United States, renal cell carcinoma (RCC) incidence and the prevalence of obesity, an established risk factor for RCC, have been increasing for several decades. RCC is more common among older individuals. We sought to quantify the contribution of excess adiposity to the rising incidence of RCC among individuals 60 years or older. National Institutes of Health-American Association of Retired Persons Diet and Health Study data (n = 453 859 participants, enrolled in 1995-1996, age at enrollment 50-71 years) were used to estimate multivariable-adjusted hazard ratios (HRs) for RCC across body mass index categories and HRs associated with smoking. Population attributable fractions (PAFs) were calculated using estimated HRs and annual overweight/obesity prevalence from the National Health Interview Survey (1985-2008). PAF estimates were combined with RCC incidence from Surveillance, Epidemiology and End Results-13 to calculate annual percent changes in RCC incidence attributable (and unrelated) to overweight/obesity. We found that between 1995 and 2018, among individuals aged 60 years and older, PAF for overweight/obesity increased from 18% to 29% for all RCCs. In comparison, the PAF for smoking declined from 12% to 9%. RCC incidence increased 1.8% per year (95% confidence interval [CI] 1.5%-2.1%) overall, while RCC incidence attributable to overweight/obesity increased 3.8% per year (95%CI 3.5%-4.2%) and RCC incidence unrelated to overweight/obesity increased 1.2% per year (95% CI 0.9%-1.4%). In conclusion, overweight/obesity appears to have contributed importantly to the rising incidence of RCC in the United States since the mid-1990s. Public health interventions focused on reducing overweight and obesity could help substantially in curbing this trend.     

Clinical characteristics and surgical outcomes of resectable acinar cell carcinoma of the pancreas-propensity score matching analysis with pancreatic ductal adenocarcinoma

BackgroundSurgical resection is recommended for patients with resectable acinar cell carcinoma (ACC). The aim of this study was to investigate the clinical characteristics and surgical outcomes of resectable ACC in comparison to pancreatic ductal adenocarcinoma (PDAC).MethodA retrospective analysis was performed on all patients who consecutively underwent radical resection with pathologically confirmed ACC and PDAC from December 2011 to December 2018. Clinicopathologic characteristics and follow-up information were analyzed. A 1:3 propensity score matching (PSM) method was used to minimize the bias between ACC and PDAC.ResultsA total of 26 patients with ACC and 1351 with PDAC were included. Compared to PDAC, ACC tended to be larger (4.5 vs. 3.0 cm; p < 0.001) and more frequently located in the pancreatic body/tail (61.5% vs. 36.6%, p = 0.009), with lower total bilirubin levels, lower neutrophil lymphocyte ratio (NLR) levels and lower carbohydrate antigen 19-9 (CA19-9) levels and carcinoembryonic antigen (CEA) levels. There was no difference in postoperative morbidities in patients with ACC and PDAC. The median OS and RFS were longer in ACC when compared to PDAC (OS: 43.5 mo vs. 19.0 mo, p = 0.004; RFS: 24.5 mo vs. 11.6 mo, p = 0.023). After the 1:3 PSM, ACC remained to be a better histological type for OS (p = 0.024), but had comparable RFS with PDAC (p = 0.164).ConclusionPatients with ACC after radical resection had better OS than that with PDAC. However, ACC is also an aggressive tumor with a similar trend of RFS with PDAC after the matching, necessitating the multidisciplinary treatment for resectable ACC disease.     

Proteases and their inhibitors as prognostic factors for high-grade serous ovarian cancer

Ovarian carcinoma is one of the most lethal malignancies, but only very few prognostic biomarkers are known. The degradome, comprising proteases, protease non-proteolytic homologues and inhibitors, have been involved in the prognosis of many cancer types, including ovarian carcinoma. The prognostic significance of the whole degradome family has not been specifically studied in high-grade serous ovarian cancer. A targeted DNA microarray known as the CLIP-CHIP microarray was used to identify potential prognostic factors in ten high-grade serous ovarian cancer women who had early recurrence (<1.6 years) or late/no recurrence after first line surgery and chemotherapy. In women with early recurrence, we identified seven upregulated genes (TMPRSS4, MASP1/3, SPC18, PSMB1, IGFBP2, CFI – encoding Complement Factor I – and MMP9) and one down-regulated gene (ADAM-10). Using immunohistochemistry, we evaluated the prognostic effect of these 8 candidate genes in an independent cohort of 112 high-grade serous ovarian cancer women. Outcomes were progression, defined according to CA-125 criteria, and death. Multivariate Cox proportional hazard regression models were done to estimate the associations between each protein and each outcome. High ADAM-10 expression (intensity of 2–3) was associated with a lower risk of progression (adjusted hazard ratio (HR): 0.51; 95% confidence interval (CI): 0.29-0.87). High complement factor I expression (intensity 2–3) was associated with a higher risk of progression (adjusted HR: 2.30, 95% CI: 1.17–4.53) and death (adjusted HR: 3.42; 95% CI: 1.72–6.79). Overall, we identified the prognostic value of two proteases, ADAM-10 and complement factor I, for high-grade serous ovarian cancer which could have clinical significance.     

皮肤鳞状细胞癌的中医药治疗进展

皮肤鳞状细胞癌是具有发病率高、发展快、可转移、易误诊等特点的一种恶性肿瘤，对人类的健康造成威胁。随着中医的发展和现代医学实验研究技术的进步，中医药在皮肤鳞状细胞癌的现代研究方面也取得一定成果。目前临床上治疗鳞状细胞癌多采取手术及药物化疗等，因不良反应的存在，患者接受度低。中药具有多靶点、安全性高、不良反应少等优势，在治疗皮肤鳞状细胞癌中中医具有一定优势，本文将围绕中药单体、中药复方，以及针灸在治疗皮肤鳞状细胞癌的研究进展展开论述和思考。     

Efficacy of percutaneous and transcutaneous tibial nerve stimulation in women with idiopathic overactive bladder: A prospective randomised controlled trial

BackgroundDifferent studies have reported the efficacy of percutaneous tibial nerve stimulation (PTNS) and transcutaneous tibial nerve stimulation (TTNS) in treating idiopathic overactive bladder (OAB). However, no study has compared the effectiveness of PTNS and TTNS added to bladder training (BT) in idiopathic OAB.ObjectiveTo compare the efficacy of PTNS and TTNS added to BT in women with idiopathic OAB.MethodsWe randomised 60 women with idiopathic OAB into 3 groups. Group 1 (n = 19) received BT, Group 2 (n = 19) received PTNS in addition to BT, and Group 3 (n = 20) received TTNS in addition to BT. PTNS and TTNS were performed 2 days a week, for 30 min a day, for a total of 12 sessions for 6 weeks. Patients were evaluated by incontinence severity (pad test), a 3-day voiding diary (frequency of voiding, incontinence episodes, nocturia and number of pads used), symptom severity, quality of life, treatment success (positive response rate), treatment satisfaction (Likert scale), discomfort level and preparation time for stimulation (sec).ResultsAt the end of treatment; severity of incontinence, frequency of voiding, incontinence episodes, nocturia, number of pads used, symptom severity and quality of life were significantly improved in Groups 2 and 3 versus Group 1 (P < 0.0167). Treatment success and treatment satisfaction were higher in Groups 2 and 3 than Group 1 (P < 0.001 and P < 0.0167, respectively). Level of discomfort was lower, treatment satisfaction was higher and preparation time for stimulation was shorter in Group 3 than Group 2 (P < 0.05).ConclusionBoth the PTNS plus BT and TTNS plus BT were more effective than BT alone in women with idiopathic OAB. These 2 tibial nerve stimulation methods had similar clinical efficacy but with slight differences: TTNS had shorter preparation time, less discomfort level and higher patient satisfaction than PTNS.     

Enhanced antitumour activity of doxorubicin and simvastatin combination loaded nanoemulsion treatment against a Swiss albino mouse model of Ehrlich ascites carcinoma

Doxorubicin (DOX) is the most commonly used anticancer drug; however, it has limited use because prolonged administration may result in severe cardiotoxicity. Simvastatin (SIM), generally prescribed for hypercholesterolaemia, has also shown salubrious results in the monotherapy or combinational drug therapy of different cancers in various models. Nanoparticle drug delivery systems are a novel way of improving therapeutics and also improving the absorption and specificity of drugs towards tumour cells. In this study, we exploited this technology to increase drug specificity and minimize imminent adverse effects. In this study, the antitumour activity of the combination formulas of DOX and SIM, either loaded in water (DOX‐SIM‐Solution) or nanoemulsions (NEs) (DOX‐SIM‐NE), was evaluated in a Swiss albino mouse model of Ehrlich ascites carcinoma. The anticancer effect was assessed by quantifying the change in body weight, mean survival time, and percent increase in lifespan (%ILS), determining haematological and serum biochemical parameters (liver function test, kidney function test and lipid profile parameters) as well as studying the histopathological alterations in liver tissues. We observed a clear increase in %ILS of the DOX‐SIM‐Solution group (265.30) that was double the %ILS of the DOX‐SIM‐NE group (134.70). However, DOX‐SIM‐NE had a non‐toxic effect on the haematological parameters, whereas DOX‐SIM‐Solution increased the levels of haemoglobin and lymphocytes. Furthermore, the encapsulation of SIM and DOX into NEs improved the levels of all serum biochemical parameters compared to the DOX‐SIM‐Solution. A reduction in the side effects of DOX‐SIM‐NE on the liver was also established using light microscopy, which revealed that the morphologies of the hepatocytes of the mice were less affected by administration of the DOX‐SIM‐NE treatment than with the DOX‐SIM‐Solution treatment. The study showed that incorporating SIM into the DOX‐loaded‐NE formulation remarkably improved its efficiency and simultaneously reduced its adverse effects.     

Adjuvant chemotherapy could improve the survival of pulmonary sarcomatoid carcinoma: A systematic review and meta-analysis

BackgroundComplete surgical removal is currently considered to be the best treatment option for pulmonary sarcomatoid carcinoma (PSC) especially in early stage operable disease; however, the reported recurrence-free survival is low. Benefits of adjuvant chemotherapy in PSC patients are still controversial, and there is no obvious agreement on the optimal treatment modalities of this disease. Therefore, we aimed to investigate the prognosis in terms of overall survival (OS) in patients with PSC who received adjuvant chemotherapy.MethodsThe review protocol was registered in PROSPERO (CRD42022306084). Patients with PSC who underwent surgical therapy with or without adjuvant chemotherapy were included into the meta-analysis. Hazard ratios (HR) with 95% confidence intervals (CIs) for OS were pooled and ROBINS-I tool was used to assess risk of bias of the included studies.ResultsWe identified four retrospective cohort studies with 6768 records from MEDLINE, Embase, and CENTRAL databases up to 9th September 2021, and altogether 1835 patients were included to the analysis. The present meta-analysis shows that patients receiving adjuvant chemotherapy had a significantly longer OS than patients who underwent surgical treatment alone (HR = 0.5657, 95%CI: 0.4391–0.7290, p < 0.0001).ConclusionsDespite the limited information on the chemotherapy regimens in the included studies, patients with PSC may benefit from adjuvant chemotherapy. More publications are required to evaluate and compare efficient adjuvant chemotherapy protocols in PSC cases.