Comment on “Outcomes of curative liver resection for hepatocellular carcinoma in patients with cirrhosis”

The present letter to the editor is in response to the research “Outcomes of curative liver resection for hepatocellular carcinoma in patients with cirrhosis” by Elshaarawy et al in World J Gastroenterol 2021; 13(5): 424–439. The preoperative assessment of the liver reserve function in hepatocellular carcinoma (HCC) patients with cirrhosis is crucial, and there is no universal consensus on how to assess it. Based on a retrospective study, Elshaarawy et al investigated the impact of various classical clinical indicators on liver failure and the prognosis after hepatectomy in HCC patients with cirrhosis. We recommend that we should strive to explore new appraisal indicators, such as the indocyanine green retention rate at 15 min.     

Relation Between Tumor Size and Lymph Node Metastasis According to Subtypes of Breast Cancer

PurposeTumor size and lymph node metastasis are important factors that contribute to the progression of breast cancer. We aimed to analyze the relationship between tumor size and lymph node metastasis molecular subtype and examine the effects of nodal metastasis on overall survival (OS).MethodsWe retrospectively reviewed the data of 16,552 patients who underwent breast surgery in Samsung Medical Center between 2000 and 2015. Information on tumor size (largest diameter of the invasive component), number of positive lymph nodes, and molecular subtype were obtained. We constructed a linear regression model to evaluate the relationship between tumor size and lymph node metastasis. To determine the effect of nodal metastasis on OS, we performed a Cox proportional regression analysis with Np/T (number of metastatic lymph nodes [n]/tumor size [cm]).ResultsThis study included 12,007 patients with a median follow-up of 62 months. The linear regression coefficients were 1.043 for luminal A, 1.024 for luminal B, 0.656 for HER2, and 0.435 for triple-negative breast cancer (TNBC) subtypes. No significant difference was observed in the coefficients between the luminal A and B subtypes (p = 0.797), while all other coefficients showed significant difference. After adjusting for other risk factors, the hazard ratio (HR) of Np/T for each subtype was significant for OS: luminal A (HR, 1.134; 95% confidence interval [CI], 1.097–1.171; p < 0.001), luminal B (HR, 1.049; 95% CI, 1.013–1.086; p = 0.007), HER2 (HR, 1.069; 95% CI, 1.014–1.126; p = 0.013), and TNBC (HR, 1.038; 95% CI, 1.01–1.067; p = 0.008).ConclusionThe incidence of lymph node metastasis differed according to molecular subtype. Luminal types have higher incidence of nodal metastasis than HER2 and TNBC. The HR of Np/T was highest in luminal A subtypes and lowest in TNBC subtypes.     

Association Between Serum C-Reactive Protein Concentration and Nutritional Status of Malignant Tumor Patients

Background: The level of the systemic inflammatory marker C-reactive protein (CRP) is elevated in many patients with malignant disease and may be related to nutritional status.

Objective: To analyze the association between serum CRP levels in patients with malignant tumors and their nutritional status.

Method: A total of 3,692 cases were analyzed and the serum CRP levels were determined using an immunometric assay. Nutritional status was assessed by using patient-generated subjective global assessment (PG-SGA). The biochemical evaluation of prealbumin (PA), albumin (ALB), cholesterol (CHOL), and triglycerides (TG) were assayed within 48?h admission to the hospital. The association between serum CRP concentration and the nutritional status, the stage of the tumor and other factors was analyzed by univariate and multivariate logistic regression analysis.

Result: Elevated serum CRP was observed in 47.6% (1,548/3,269) of patients compared with the reference value, and the median CRP concentration was 18.29?mg/l. Patient serum CRP concentrations in the malnourished group (PG-SGA B?+?C) were higher than in the well-nourished (PG-SGA A) patients (P?<?0.05). The serum CRP level was related to the patients' age, gender, tumor stage, and was affected by hepatitis, liver cirrhosis, diabetes, but it has no effect on hypertension. The CRP high patients had lower PA and ALB levels, lower Karnofsky performance status scores, and higher PG-SGA scores (P?<?0.05), and there was no relationship with CHOL and TG levels. Weight loss in the previous 1?mo was seen with CRP positive patients (P?<?0.05).

Conclusion: Almost 50% of malignant tumor patients had elevated serum CRP levels indicating a systemic inflammatory state. The nutritional status was worse in cancer patients with higher concentrations of serum CRP. The level of CRP was associated with the tumor stage, and, as stage is a prognostic factor, so can CRP be used as a prognostic maker in malignant tumors patients.     

Factors determining phage stability/activity: challenges in practical phage application

Introduction: Phages consist of nucleic acids and proteins that may lose their activity under different physico-chemical conditions. The production process of phage formulations may decrease phage infectivity. Ingredients present in the preparation may influence phage particles, although preparation and storage conditions may also cause variations in phage titer. Significant factors are the manner of phage application, the patient’s immune system status, the type of medication being taken, and diet.

Areas covered: We discuss factors determining phage activity and stability, which is relevant for the preparation and application of phage formulations with the highest therapeutic efficacy. Our article should be helpful for more insightful implementation of clinical trials, which could pave the way for successful phage therapy.

Expert opinion: The number of naturally occurring phages is practically unlimited and phages vary in their susceptibility to external factors. Modern methods offer engineering techniques which should lead to enhanced precision in phage delivery and anti-bacterial activity. Recent data suggesting that phages may also be used in treating nonbacterial infections as well as anti-inflammatory and immunomodulatory agents add further weight to such studies. It may be anticipated that different phage activities could have varying susceptibility to factors determining their actions.     

Clinical Practice Guidance: Surveillance for phaeochromocytoma and paraganglioma in paediatric succinate dehydrogenase gene mutation carriers

The succinate dehydrogenase (SDH) enzyme complex functions as a key enzyme coupling the oxidation of succinate to fumarate in the citric acid cycle. Inactivation of this enzyme complex results in the cellular accumulation of the oncometabolite succinate, which is postulated to be a key driver in tumorigenesis. Succinate accumulation inhibits 2‐oxoglutarate‐dependent dioxygenases, including DNA and histone demethylase enzymes and hypoxic gene response regulators. Biallelic inactivation (typically resulting from one inherited and one somatic event) at one of the four genes encoding the SDH complex (SDHA/B/C/D) is the most common cause for SDH deficient (dSDH) tumours. Germline mutations in the SDHx genes predispose to a spectrum of tumours including phaeochromocytoma and paraganglioma (PPGL), wild type gastrointestinal stromal tumours (wtGIST) and, less commonly, renal cell carcinoma and pituitary tumours. Furthermore, mutations in the SDHx genes, particularly SDHB, predispose to a higher risk of malignant PPGL, which is associated with a 5‐year mortality of 50%. There is general agreement that biochemical and imaging surveillance should be offered to asymptomatic carriers of SDHx gene mutations in the expectation that this will reduce the morbidity and mortality associated with dSDH tumours. However, there is no consensus on when and how surveillance should be performed in children and young adults. Here, we address the question: “What age should clinical, biochemical and radiological surveillance for PPGL be initiated in paediatric SDHx mutation carriers?”.     

Protective role of histone deacetylase 4 from ultraviolet radiation-induced DNA lesions

Ultraviolet B (UVB) exposure is a core factor that leads to skin disease or carcinogenesis through the insufficient repair of DNA lesions. UVB-induced DNA lesions are mainly removed by the nucleotide excision repair (NER) mechanism. The expression of histone deacetylase 4 (HDAC4) is altered in the skin upon UVB exposure, indicating its possible implication in UVB-induced DNA lesions repair. Here, we investigated the role of HDAC4 in the NER removal of the main classes of UVB-induced DNA lesions consisting of cyclobutane pyrimidine dimers and pyrimidine (6-4) pyrimidone photoproducts (6-4PPs). We found that UVB irradiation increased HDAC4 expression at both the mRNA and protein levels. HDAC4 interacted with NER factor XPC, which played an important role in effectively removing the UVB-induced DNA lesions. This study provides an understanding of the HDAC4 function in DNA repair, which will allow the development of efficient strategies to protect the skin from UVR-induced diseases.     

加味黄连解毒汤灌肠辅助治疗重症肺炎合并胃肠功能障碍临床研究

目的:观察加味黄连解毒汤灌肠辅助治疗重症肺炎痰热壅肺证合并胃肠功能障碍的临床疗效。方法:选取64例重症肺炎痰热壅肺证合并胃肠功能障碍患者,依据不同的治疗方法分为治疗组和对照组,每组32例。对照组给予抗菌药、胃肠功能保护药、机械通气等对症治疗,治疗组在对照组基础上联合加味黄连解毒汤灌肠治疗。比较2组临床疗效、治疗前后中医证候积分及血清降钙素原(PCT)水平,记录不良反应发生情况。结果:治疗组总有效率93.75%,高于对照组的71.88%,差异有统计学意义(P<0.05)。治疗后,2组中医证候积分均较治疗前降低,治疗组中医证候积分比对照组下降更明显,差异均有统计学意义(P<0.05)。治疗3天与治疗7天,治疗组PCT水平均低于对照组,差异均有统计学意义(P<0.05)。治疗期间,治疗组发生不良反应5例,对照组发生不良反应4例,未经处理均自行缓解。结论:加味黄连解毒汤灌肠辅助治疗重症肺炎痰热壅肺证合并胃肠功能障碍,可以有效减轻患者的临床症状,改善胃肠功能,抑制炎症反应。