Isolated limb infusion: Efficacy,toxicity and an evolution in the management of in-transit melanoma

BACKGROUND:Isolated limb infusion (ILI) delivers low-flow chemotherapy via percutaneous catheters to treat melanoma in-transit metastases.OBJECTIVE:To describe the experience of two regional referral centres with ILI.METHODS:A retrospective review of patients who underwent ILI between 2002 and 2012 was performed. Outcomes were measured using the WHO criteria for response, the Wieberdink toxicity score and long-term limb function using the Toronto Extremity Salvage Score (TESS).RESULTS:Fifty-two patients (mean age 66 years [range 27 to 90 years], female sex 65%, and lower [treated] limb in 86%) with 54 ILIs were reviewed. Wieberdink toxicity score was ≥3 in 21 (39%) procedures. Median follow-up was 18 months (range one to 117 months). Initial complete response (CR) was 29%, partial response 27%, stable disease 18% and progressive disease 27%. Predictors of better initial response were low disease burden and previous treatment. One or more treatments after ILI were common (65%). At 12 months, 19% of ILI patients had died from melanoma but 44% of surviving patients experienced limb CR. At 24 months, 57% of surviving patients experienced limb CR. The quality of life in the surviving, contactable patients according to the Toronto Extremity Salvage Score was 89%.CONCLUSION:Even if ILI does not result in CR for melanoma intransit metastases. it may slow disease progression as a single therapy, but more frequently in combination with other modalities.     

NDRG2 Expression Decreases Tumor-Induced Osteoclast Differentiation by Down-regulating ICAM1 in Breast Cancer Cells

Bone matrix is properly maintained by osteoclasts and osteoblasts. In the tumor microenvironment, osteoclasts are increasingly differentiated by the various ligands and cytokines secreted from the metastasized cancer cells at the bone metastasis niche. The activated osteoclasts generate osteolytic lesions. For this reason, studies focusing on the differentiation of osteoclasts are important to reduce bone destruction by tumor metastasis. The N-myc downstream-regulated gene 2 (NDRG2) has been known to contribute to the suppression of tumor growth and metastasis, but the precise role of NDRG2 in osteoclast differentiation induced by cancer cells has not been elucidated. In this study, we demonstrate that NDRG2 expression in breast cancer cells has an inhibitory effect on osteoclast differentiation. RAW 264.7 cells, which are monocytic preosteoclast cells, treated with the conditioned media (CM) of murine breast cancer cells (4T1) expressing NDRG2 are less differentiated into the multinucleated osteoclast-like cells than those treated with the CM of 4T1-WT or 4T1-mock cells. Interestingly, 4T1 cells stably expressing NDRG2 showed a decreased mRNA and protein level of intercellular adhesion molecule 1 (ICAM1), which is known to enhance osteoclast maturation. Osteoclast differentiation was also reduced by ICAM1 knockdown in 4T1 cells. In addition, blocking the interaction between soluble ICAM1 and ICAM1 receptors significantly decreased osteoclastogenesis of RAW 264.7 cells in the tumor environment. Collectively, these results suggest that the reduction of ICAM1 expression by NDRG2 in breast cancer cells decreases osteoclast differentiation, and demonstrate that excessive bone resorption could be inhibited via ICAM1 down-regulation by NDRG2 expression.     

The prognostic role of tumour‐infiltrating lymphocytes in oral squamous cell carcinoma: A meta‐analysis

It has been suggested that tumour‐infiltrating lymphocytes (TILs) are associated with the progression of oral squamous cell carcinoma (OSCC). However, the prognostic value of TILs is inconclusive due to the heterogeneity of immune cells within the tumour microenvironment. In this meta‐analysis, we aimed to assess the prognostic value of TILs in OSCC. The PubMed, Cochrane, Embase, Scopus and Web of Science databases were searched up to April 20, 2019, and 33 studies were ultimately included in this meta‐analysis. Our pooled meta‐analysis showed that high infiltration of CD8⁺ TILs, CD45RO⁺ TILs and CD57⁺ TILs favoured better overall survival (OS). However, high infiltration of CD68⁺ macrophages and CD163⁺ macrophages was associated with poor prognosis in OSCC. These findings suggest that CD8⁺ TILs, CD45RO⁺ TILs, CD57⁺ TILs, CD68⁺ macrophages and CD163⁺ macrophages might serve as novel prognostic factors and therapeutic targets in OSCC.     

ELAM-1在鼻咽癌裸鼠移植瘤中的表达及其与转移的关系

目的 建立裸鼠鼻咽癌转移模型并探讨 E-选择素（ELAM-1）与鼻咽癌转移的相关性。方法 将鼻咽癌5-8F细胞悬液注射于裸鼠左后肢爪垫，观察裸鼠状态、成瘤情况并测量裸鼠体重及移植瘤长短径；采用连续病理切片苏木精-伊红染色观察移植瘤及转移情况，将16只人鼻咽癌荷瘤裸鼠分为转移组和非转移组；采用免疫组织化学法检测两组移植瘤组织中ELAM-1的表达。 结果 16只裸鼠均成瘤，成瘤率为100.0%，其中10只裸鼠出现转移瘤，转移率为62.5%。建模前，两组裸鼠体重差异无统计学意义［（13.83±0.56）g vs （14.62±0.30） g，t=1.026，P=0.071］。建模后4~7周，裸鼠瘤体体积呈指数增长，且转移组移植瘤增长速度较非转移组快，非转移组裸鼠瘤体体积小于转移组［（198.91 ± 163.29） mm³ vs （268.76 ±174.31） mm³，t=4.376，P=0.005］。ELAM-1在鼻咽癌裸鼠移植瘤、淋巴结转移灶及远处转移灶中的表达均为阳性，主要表达于细胞膜。转移组移植瘤光密度值高于非转移组（0.4497±0.0705 vs 0.0435±0.0082，t=4.388，P＝0.001）。结论 本研究成功构建稳定性好、转移率高的鼻咽癌裸鼠移植瘤转移模型，且ELAM-1在裸鼠移植瘤中高表达，可促进鼻咽癌裸鼠移植瘤生长和转移。     

肿瘤标志物和肺门淋巴结与肺腺癌全身骨显像骨转移的关系

 目的 探讨肺腺癌肿瘤标志物与骨转移之间的关系。方法 回顾性分析278例肺腺癌患者的全身骨显像，采用单因素Pearson卡方分析和Logistic二分类回归法对肺腺癌骨转移的相关因素进行分析。结果 （1）单因素卡方分析结果: CA125（P=0.000）、CYFRA21-1（P=0.000）、NSE（P=0.000）、SCC（P=0.036）、CEA（P=0.000）、ALP（P=0.000）、肺门淋巴节（P=0.000）均是骨转移的危险因素（均P<0.05）；（2）二分类分析结果：CA125（P=0.009, OR=1.007）、NSE（P=0.012, OR=1.097）、ALP（P=0.001, OR=1.022）、CEA（P=0.013, OR=1.004）、肺门淋巴节（P=0.029, OR=2.136）是骨转移的危险因素（均P<0.05, 均OR>1），具有统计学意义; SCC（P=0.169, OR=1.194)、ProGRP（P=0.703, OR=1.004）是骨转移的危险因素（均OR>1），但不具统计学意义（均P>0.05）。结论 CA125、NSE、ALP、CEA、肺门淋巴节与骨转移有关；SCC、ProGRP是骨转移的危险因素，但不具统计学意义；CYFRA21-1与骨转移无关。     

晚期肺癌肝转移的综合治疗进展

肝脏是肺癌血液转移常见的部位。存在肝转移患者病情迅速发展，多在7个月内死亡。因此，采取积极有效的治疗措施，对进一步改善晚期肺癌患者的预后有极其重要的意义。目前，针对肺癌肝转移的治疗还没有达成统一的治疗计划，常见的治疗方法有手术治疗、全身化疗、介入治疗、射频消融治疗、立体定向放疗、靶向治疗、免疫治疗等。对此，我们就近年来肺癌肝转移的综合治疗进展作一综述。