Dissecting the biological heterogeneity of HER2-positive breast cancer

HER2-positive (HER2+) breast cancer (BC) is a heterogenous and multifaceted disease, with interesting therapeutic implications. First, all intrinsic molecular subtypes can be identified in HER2+ tumors, with the HER2-enriched being the most frequent. Such subtypes do not differ much from their counterparts in HER2-negative disease, apart for the high expression of genes in/near the HER2 amplicon on chromosome 17. Intrinsic subtyping, along with the quantification of ERBB2 mRNA levels, is associated with higher rates of pathologic complete response across neoadjuvant trials of dual HER2 blockade and might help select patients for de-escalation and escalation treatment strategies. Secondly, HER2+ tumors have a broad range of DNA alterations. ERBB2 mutations and alterations in the PI3K/Akt/mTOR pathway are among the most frequent and might predict benefit from potent pan-HER, PI3K and mTOR inhibitors. Moreover, HER2+ tumors are usually infiltrated by lymphocytes. These tumor infiltrating-lymphocytes (TILs) predict response to neoadjuvant anti-HER2-based treatment and exert a prognostic role. PD-L1, detected in ∼42 % of HER2+ BC, might also be useful to define patients responding to novel anti-PD1/PD-L1 immunotherapies. New multiparametric clinicopathologic and genomic tools accounting for this complexity, such as HER2DX, are under development to define more tailored treatment approaches. Finally, HER2-targeted antibody-drug conjugates (ADC) such as trastuzumab deruxtecan might be active in tumors with low expression of HER2. Overall, there is a need to molecularly characterize and develop novel targeted therapies for HER2+ disease.     

Clinical observation on the effect of Chinese medicine-“TCM formula” intervention on recurrence and metastasis of triple negative breast cancer

ObjectiveThis study used a prospective cohort study to observe the effect of triple-negative breast cancer on the 2-year disease-free survival rate with or without “TCM formula”.MethodsFrom November 1 st, 2016, the first patient was enrolled in the cohort study. A total of 356 patients were enrolled on January 30, 2019. Among them, 154 cases were followed up for 2 years. During the follow-up, there were 6 cases of shedding, so 6 cases were affected. A total of 148 cases were included in the analysis, including 73 in the exposed group and 75 in the non-exposed group. The exposed group was given “TCM formula” on the basis of standardized treatment, and the non-exposed group was treated with simple triple-negative breast cancer. The two groups visited each of the three months. The interview included safety examination (hematology and imaging). The endpoint was the difference in 2-year invasive disease-free survival between the exposed and non-exposed groups and the safety of the “TCM formula”.ResultsThere were 6 cases of shedding during the experiment and the shedding rate was 3.9 %. The 2-year rate of invasive disease-free survival in the exposed team was 88.7 % and the non-exposed group was 82.5 %. Logistic multivariate regression analysis predicted that “TCM formula” could reduce the disease-related recurrence and metastasis rate by 11 % (OR = 0.89, 95 % CI 0.37−0.956, P＜0.05). Through K–M survival analysis, TNBC patients with age ≤35 years and regional lymph node stage N1 may be the benefit group of “TCM formula”(P＜0.05). During the study, the incidence of total adverse events was 8.2 % in the exposed group, mainly manifested as stomach discomfort, diarrhea, and hepatocyte damage.Conclusion1. In the exposed group, the two-year rate of invasive disease-free survival increased by 6.2 % compared with the non-exposed group(P＞0.05). 2. According to K–M survival analysis, TNBC patients with age ≤35 years and regional lymph node metastasis to N1 may be potential beneficiaries of “TCM formula”. 3. “TCM Formula” is safe and tolerable to most patients.     

3-磷酸甘油酸脱氢酶促进丝氨酸合成在肿瘤进展中的机制

丝氨酸生物合成途径活性的上调是许多癌症明显的共同特征。该途径的第一种限速酶3-磷酸甘油酸脱氢酶(PHGDH)在黑色素瘤、乳腺癌和肾癌等癌组织中高表达，对肿瘤细胞增殖、转移、侵袭有着重要作用。糖酵解中间产物3-磷酸甘油酸在PHGDH作用下，氧化为磷酸羟基丙酮酸并最终合成丝氨酸。丝氨酸转化为甘氨酸，然后在核苷酸、s-腺苷甲硫氨酸(SAM)和还原型谷胱甘肽(GSH)的合成中起着重要的作用。PHGDH 有望成为肿瘤治疗的新靶点。     

Chemotherapy and novel therapeutics before radical prostatectomy for high-risk clinically localized prostate cancer

Although both surgery and radiation are potential curative options for men with clinically localized prostate cancer, a significant proportion of men with high-risk and locally advanced disease will demonstrate biochemical and potentially clinical progression of their disease. Neoadjuvant systemic therapy before radical prostatectomy (RP) is a logical strategy to improve treatment outcomes for men with clinically localized high-risk prostate cancer. Furthermore, delivery of chemotherapy and other systemic agents before RP affords an opportunity to explore the efficacy of these agents with pathologic end points.Neoadjuvant chemotherapy, primarily with docetaxel (with or without androgen deprivation therapy), has demonstrated feasibility and safety in men undergoing RP, but no study to date has established the efficacy of neoadjuvant chemotherapy or neoadjuvant chemohormonal therapies. Other novel agents, such as those targeting the vascular endothelial growth factor receptor, epidermal growth factor receptor, platelet-derived growth factor receptor, clusterin, and immunomodulatory therapeutics, are currently under investigation.     

Preoperative intra-arterial chemotherapy with docetaxel,cisplatin, and peplomycin combined with intravenous chemotherapy using 5-fluorouracil for oral squamous cell carcinoma

The objectives of this study were to evaluate survival in 141 patients with stage II–IV oral squamous cell carcinoma (OSCC) treated with preoperative intra-arterial chemotherapy with docetaxel, cisplatin, and peplomycin combined with intravenous chemotherapy using 5-fluorouracil (IADCPIVF) via the superficial temporal artery, and to clarify the prognostic factors. The study population included 59 patients with stage II OSCC, 34 with stage III, and 48 with stage IV. After IADCPIVF, 139 patients underwent surgery; minimally invasive surgeries (MIS) including excisional biopsy were performed on 96 patients with a remarkably good response to IADCPIVF. The primary tumour response rate was 99.3% (complete response rate 56.7%, good partial response rate 17.0%, fair partial response rate 25.5%). Additionally, there were no serious adverse events associated with IADCPIVF. The 5-year overall survival rate was 74.6% (stage II 83.6%, stage III 72.7%, stage IV 64.8%). In the multivariate analysis of survival, T classification and clinical tumour response were significant prognostic factors. Eight (8.3%) of the patients who received MIS had primary recurrence and six were salvaged. In conclusion, IADCPIVF is safe and efficacious for treating OSCC, and MIS could reduce the extent of primary tumour resection in the case of a remarkably good response.     

Breast Elastography: How to Perform and Integrate Into a “Best-Practice” Patient Treatment Algorithm

Breast elastography has been available for more than 15 years but is not widely incorporated into clinical practice. Many publications report extremely high accuracy for various breast elastographic techniques. However, results in the literature are extremely variable. This variability is most likely due to variations in technique, a relatively steep learning curve, and variability in methods between vendors. This article describes our protocol for performing breast elastography using both strain elastography and shear wave elastography, which produces high sensitivity and specificity. Additionally, we will describe the most commonly known false-positive and false-negative lesions as well as how to detect them.     

全麻复合硬膜外在高龄患者腹腔镜直肠癌根治术中的应用

目的:研究全麻复合硬膜外在高龄患者腹腔镜直肠癌根治术中的应用效果。方法:选择60岁以上择期行腹腔镜直肠癌根治术患者60例,随机分为G组和GA组,每组各30例。G组患者为单纯全麻组,GA组患者为硬膜外复合全麻组。GA组患者在诱导前取L1~2硬膜外穿刺置管,予0.5%罗哌卡因5 ml,术中每小时追加5~7 ml。两组患者诱导方法相同:即,咪哒唑仑0.04 mg/kg、舒芬太尼0.3~0.4μg/kg、顺阿曲库铵0.15~0.20 mg/kg、依托咪酯0.2~0.3 mg/kg。监测并记录患者血压(BP),心率(HR),心电图(ECG),术中全麻药用量及术后患者苏醒情况。结果:GA组患者气腹后、拔管前BP、HR明显低于G组(P<0.05),且全麻药用量明显低于G组(P<0.05)。结论:全麻复合硬膜外应用于老年腹腔镜直肠癌手术较单纯全麻用药量减少,术中循环更加稳定,是腹腔镜直肠癌根治术比较安全可行的麻醉方法。     

Hormone exposure and its suppressive effect on risk of high-grade gliomas among patients with breast cancer

BackgroundPrior reports demonstrate the expression of estrogen and progesterone receptors in high-grade gliomas (HGGs), but the relationship between hormone receptor-positive disease and risk of HHGs in patients with breast cancer (BC) remains uncharacterized.MethodsUsing the SEER 18 registries (2000–2017), we examined the temporal trend of the incidence of HGGs and BC. The standardized incidence ratio was calculated to assess the risk of subsequent HGG in BC patients.ResultsDuring the study period, the incidence of BC and HGGs remained comparable for men and women. Among 976,134 patients with BC, we found a decreased incidence of HGGs in females, but not in males. Female BC patients with hormone receptor-positive disease were at a lower risk of developing glioblastoma and anaplastic astrocytoma.ConclusionOur study findings allude to the protective role of hormone exposure in the development of HGGs, which may lead to the development of therapies targeting hormonal pathways.     

Islanded facial artery osteomyomucosal/osseous flap in head and neck reconstruction

A local pedicled vascularized bone flap can prevent the morbidity and cost of free bone flap surgery in small segmental bone defects or long cartilaginous defects of the head and neck. Such flaps can also be useful in patients who are high risk for surgery. The periosteal vascularity of the mandible can be used to design islanded facial artery-based bone flaps, which can be utilized to that extent. Two patients with a small segmental mandibulectomy defect and one patient with a long cricotracheal resection defect underwent reconstruction using three different designs of islanded facial artery osteomyomucosal/osseous flap (iFOMM). The patients had a minimum follow-up period of 18 months. All flaps were successful, with satisfactory healing and without any functional deficit or disease at last follow-up.     

Postoperative development of sarcopenia is a strong predictor of a poor prognosis in patients with adenocarcinoma of the esophagogastric junction and upper gastric cancer

Background

There were few studies assessed the postoperative sarcopenia in patients with cancers. The objective of present study was to assess whether postoperative development of sarcopenia could predict a poor prognosis in patients with adenocarcinoma of esophagogastric junction, (AEG) and upper gastric cancer (UGC).