不可手术结直肠癌肝转移瘤二程放疗疗效和安全性分析

目的 分析不可手术结直肠癌肝转移瘤接受二程放疗的疗效和安全性。方法 回顾性收集2017—2023年于北京大学肿瘤医院接受二程放疗的28例不可手术结直肠癌肝转移患者的资料,分析二程放疗的可行性。结果 28例患者二程放疗后中位随访时间为20.2个月。二程放疗距首程放疗的中位时间为11.1个月。首程放疗和二程放疗的中位生物有效剂量(BED)分别为100和96 Gy,分别有25例(89.3%)和24例(85.7%)患者接受了体部立体定向放射治疗。首程放疗和二程放疗的正常肝脏平均受量的2 Gy分次的等效剂量(EQD2)分别为10.1和 7.9 Gy。二程放疗后的完全缓解率和部分缓解率分别为54.5%和18.2%,客观反应率为72.7%。二程放疗后基于患者的2年的累积局部失败率为17.0%,基于病灶的2年的累积局部失败率为15.1%,1年无进展生存(PFS)为27.4%,3年总生存(OS)为46.7%。二程放疗后患者的耐受性良好,大部分患者(75.0%)出现1~2级急性不良反应,只有1例(3.6%)患者出现3级急性不良反应。结论 对于不可手术结直肠癌肝转移患者,二程放疗安全有效。     

超声联合微泡在肿瘤化疗增敏的基础研究与临床应用进展

恶性肿瘤是一类死亡率很高的疾病,化疗是其重要的治疗方法之一。应用微泡的声孔效应提高细胞对化疗药物的摄取以增加肿瘤组织局部药物浓度达到增敏化疗的目的,是目前肿瘤治疗研究的新方向之一。超声联合微泡可增加肿瘤组织局部药物浓度、增强细胞毒作用,促进肿瘤细胞凋亡,缩小肿瘤体积,改善肿瘤对化疗药物的耐药性,具有良好的临床应用价值及前景。本文拟从超声联合微泡增敏肿瘤化疗的基础研究及临床运用方面进行综述。     

Exosomes play roles in sequential processes of tumor metastasis

Overwhelming evidence demonstrates that exosomes, a series of biologically functional small vesicles of endocytic origin carrying a variety of active constituents, especially tumor-derived exosomes, contribute to tumor progression and metastasis. This review focuses on the specific multifaceted roles of exosomes in affecting sequenced four crucial processes of metastasis, through which cancer cells spread from primary to secondary organs and finally form macroscopic metastatic lesions. First, exosomes modulate the primary tumor sites to assist cancer growth and dissemination. In this part, five main biological events are reviewed, including the transfer of oncogenic constituents, the recruitment and activation of fibroblasts, the induction of angiogenesis, immunosuppression and epithelial-mesenchymal transition (EMT) promotion. In Step 2, we list two recently disclosed mechanisms during the organ-specific homing process: the exosomal integrin model and exosomal epidermal growth factor receptor (EGFR)/miR-26/hepatocyte growth factor (HGF) model. Subsequently, Step 3 focuses on the interactions between exosomes and pre-metastatic niche, in which we highlight the specific functions of exosomes in angiogenesis, lymphangiogenesis, immune modulation and metabolic, epigenetic and stromal reprogramming of pre-metastatic niche. Finally, we summarize the mechanisms of exosomes in helping the metastatic circulating tumor cells escape from immunologic surveillance, survive in the blood circulation and proliferate in host organs.     

Individual prediction of lateral neck metastasis risk in patients with unifocal papillary thyroid carcinoma

IntroductionMuch controversy exists over whether to perform lateral neck dissection (LND) on patients with papillary thyroid carcinoma (PTC). This study aimed to build predictive nomograms that could individually estimate lateral neck metastasis (LNM) risk and help determine follow up intensity.Patients and methodsUnifocal PTC patients who underwent LND between April 2012 and August 2014 were identified. Clinical and pathological variables were retrospectively evaluated using univariate and stepwise multivariate logistic regression analysis. Variables that had statistical significance in final multivariate logistic models were chosen to build nomograms, which were further corrected using the bootstrap resampling method.ResultsIn all, 505 PTC patients were eligible for analysis. Among these, 178 patients (35.2%) had lateral neck metastasis. Two nomograms were generated: nomogram (c) and nomogram (c + p). Nomogram (c) incorporated four clinical variables: age, tumor size, tumor site, and extrathyroidal extension (ETE). It had a good discriminative ability, with a C-index of 0.79 (bootstrap-corrected, 0.78). Nomogram (c + p) incorporated two clinical variables and two pathological variables: tumor size, tumor site, extranodal extension (ENE), and number of positive nodes in the central compartment. Nomogram (c + p) showed an excellent discriminative ability, with a C-index of 0.86 (bootstrap-corrected, 0.85).ConclusionTwo predictive nomograms were generated. Nomogram (c) is a clinical model, whereas nomogram (c + p) is a clinicopathological model. Each nomogram incorporates only four variables and can give an accurate estimate of LNM risk in unifocal PTC patients, which may assist clinicians in patient counseling and decision making regarding LND.     

Systemic inflammatory response after hyperthermic intraperitoneal chemotherapy (HIPEC): The perfusion protocol matters!

BackgroundCRS/HIPEC gained acceptance as a treatment for selected patients with peritoneal metastasis. However, the pathophysiology behind HIPEC is poorly understood, and a variety of regimens are currently in use. In this study, we describe for the first-time changes in the postoperative systemic inflammatory reaction, highly different among HIPEC treatment protocols.MethodsHIPEC was performed with three protocols, different with regard to perfusion times and drugs: (mitomycinC/doxorubicin, 90min), (cisplatin, 90min) (oxaliplatin, 30min). Serial blood samples were assessed for C-reactive protein (CRP), white blood cells (WBC), pancreatic stone protein (PSP) and bacterial component (16s rDNA). The study was approved by the local ethics committee and registered at clinicaltirals.gov (NCT02741167).ResultsOverall, 140 patients from two European centers were included. In patients without postoperative complications, a secondary peak of inflammatory parameters, CRP (p = 0.015) and PSP (p = 0.004) was observed after HIPEC for 90 min with mitomycinC/doxorubicin or cisplatin but not after 30 min oxaliplatin. In patients after 90 min HIPEC, postoperative serum bacterial 16srDNA level were 2.1 times higher (95% CI 0.646–3.032, p = 0.015) compared to 30 min oxaliplatin.DiscussionIn conclusion, we identified a secondary inflammatory reaction after 90 min HIPEC, either with mitomycinC/doxorubicin or cisplatin, not observed after short course HIPEC with oxaliplatin. This protocol dependent physiology of acute phase proteins should be known in the clinical management of patients after HIPEC.     

Lymphatic spread of T2 gallbladder carcinoma: Regional lymphadenectomy is required independent of tumor location

BackgroundThis study aimed to investigate the incidence and distribution of regional lymph node metastasis according to tumor location, and to clarify whether tumor location could determine the extent of regional lymphadenectomy in patients with pathological T2 (pT2) gallbladder carcinoma.MethodsIn total, 81 patients with pT2 gallbladder carcinoma (25 with pT2a tumors and 56 with pT2b tumors) who underwent radical resection were enrolled. Tumor location was determined histologically in each gallbladder specimen.ResultsSurvival after resection was significantly worse in patients with pT2b tumors than those with pT2a tumors (5-year survival, 72% vs. 96%; p = 0.027). Tumor location was an independent prognostic factor on multivariate analysis (hazard ratio, 14.162; p = 0.018). The incidence of regional lymph node metastasis was significantly higher in patients with pT2b tumors than in those with pT2a tumors (46% vs. 20%; p = 0.028). However, the number of positive nodes was similar between the two groups (median, 2 vs. 2; p = 0.910). For node-positive patients with pT2b tumors, metastasis was found in every regional node group (12%–63%), whereas even for node-positive patients with pT2a tumors, metastasis was observed in regional node groups outside the hepatoduodenal ligament.ConclusionsTumor location in patients with pT2 gallbladder carcinoma can predict the presence or absence of regional lymph node metastasis but not the number and anatomical distribution of positive regional lymph nodes. The extent of regional lymphadenectomy should not be changed even in patients with pT2a tumors, provided that they are fit enough for surgery.     

Anatomic extent of lymph node metastases as an independent prognosticator in node-positive major salivary gland carcinoma: A study of the US SEER database and a Chinese multicenter cohort

BackgroundWe aimed to explore whether the anatomic extent of lymph node metastases (AE-LNM) could independently predict prognosis of node-positive major salivary gland carcinoma (MaSGC).MethodsA total of 376 pathologically node-positive MaSGC patients were identified from the Surveillance, Epidemiology and End Results database and constituted the training cohort. Using the X-Tile program, these patients were divided into three groups based on AE-LNM degrees. Discrimination of overall survival (OS) and disease-specific survival (DSS) was evaluated and compared with the 8th American Joint Committee on Cancer (AJCC) pN classification. The results were externally validated by 220 patients in a Chinese multicenter cohort (Validation cohort).ResultsUsing the training cohort, AE-LNM was divided into Extent 1 (spread to parotid LNs or level I), Extent 2 (spread to level II-IV) and Extent 3 (spread to level V or bilateral LNs or rare LNs). Regarding both OS and DSS, the AE-LNM model revealed clear separation of survival curves, while the pN classification failed to discriminate the prognosis of pN1 and pN2 patients. When we incorporated both the AE-LNM model and AJCC pN classification into the same multivariate Cox analyses, AE-LNM was still an independent prognostic factor, while the AJCC pN classification lost its significance. These results were externally validated by the validation cohort.ConclusionAE-LNM is an independent nodal prognosticator for node-positive MaSGC and may have improved discriminative ability over the current AJCC pN classification. Integration of anatomic extent of LNM into the current AJCC N classification could be considered.     

Colon Cancer Tumor Location Defined by Gene Expression May Disagree With Anatomic Tumor Location

BackgroundCancers of the right colon have been shown to differ from left-side colon cancers in prognosis, response to epithelial growth factor receptor inhibitors, microsatellite instability and BRAF mutation status, and other molecular characteristics. Clinical application of these differences will benefit from a deeper understanding of how tumor location defines and is defined by gene expression.Materials and MethodsThis study was carried out using Affymetrix microarray datasets (Cohort A: training set, n = 352; validation set, n = 519) and samples from The Cancer Genome Atlas Colon Adenocarcinoma database (Cohort B: n = 408), in which tumor location was reported. Gene expression patterns characteristic of tumor side were identified in a manner unbiased by statistical classification method.ResultsIn the Cohort A validation set, the anatomic locations of 75% of tumors agree with the locations predicted by gene expression (so-called genomic location), whereas 8% of tumors had genomic locations discordant with their anatomic locations, and 17% of tumors had ambiguous genomic locations. Genomic location was a better predictor of microsatellite instability, CpG island methylator phenotype status, and BRAF mutation status than anatomic location. Tumors with ambiguous genomic location were significantly (P = 1.3 × 10⁻⁷) more likely to have the mesenchymal consensus molecular subtype (40%) than those with a specific genomic location (18%). A genomic signature to predict genomic location was defined.ConclusionTumor location is increasingly considered in deciding treatment of a colon tumor. We showed that genomic location was superior to anatomic location as a predictor of molecular characteristics, suggesting that it may be a more accurate predictor of response.