Effective Strategy of the Combination of High-Intensity Focused Ultrasound and Transarterial Chemoembolization for Improving Outcome of Unresectable and Metastatic Hepatoblastoma: a Retrospective Cohort Study

The combination of high-intensity focused ultrasound (HIFU) and transarterial chemoembolization (TACE) has been experimentally performed in a variety of malignant tumors, and its validity has not yet been evaluated for hepatoblastoma (HB). We evaluated the disease-response rate, resection rate, and toxicity in children with unresectable or metastatic HB (stage III and stage IV HB) after sequential treatment with TACE plus HIFU in a controlled clinical trial. The 35 patients with unresectable or metastatic HB were nonrandomly assigned to HIFU ablation (n = 12) or C5V chemotherapy (n = 23). The rates of complete resection, tumor response, and treatment toxicity were evaluated for both regimens. Nine patients who received C5V and 10 patients who received TACE plus HIFU became operable (P = .02). The 3-year event-free survival and overall survival rates were 43.03% and 56.68% in the C5V group and 38.57% and 57.86% in the TACE plus HIFU group, respectively. Acute grade 3 or 4 adverse events, including neutropenia, thrombocytopenia, and anemia, were more frequent in patients treated with C5V therapy than in patients receiving TACE plus HIFU. HIFU ablation achieved a higher rate of complete resection and a lower rate of severe complications compared with C5V treatment in children with advanced HB (Chinese Clinical Trials Registry No. ChiCTR-PRCH-08000182).     

Release of endogenous danger signals from HIFU-treated tumor cells and their stimulatory effects on APCs

The effects of high-intensity focused ultrasound (HIFU) on the release of endogenous danger signals from tumor cells and subsequent activation of antigen-presenting cells (APCs) were evaluated in vitro. MC-38 mouse tumor cells were treated using a 1.1 MHz HIFU transducer under two different protocols (P-=6.7 MPa, 30% duty cycle, 5 s vs. P-=10.7 MPa, 3% duty cycle, 30 s) to produce either thermal necrosis or mechanical lysis of the tumor cells. Here, we report that HIFU treatment can cause the release of endogenous danger signals (ATP and hsp60) and exposure of dendritic cells (DCs) and macrophages to the supernatants of HIFU-treated tumor cells leads to an increased expression of co-stimulatory molecules (CD80 and CD86) with enhanced secretion of IL-12 by the DCs and elevated secretion of TNF-alpha by the macrophages. The potency in APC activation produced by mechanical lysis is much stronger than thermal necrosis of the tumor cells. These findings suggest that optimization of treatment strategy may help to enhance HIFU-elicited anti-tumor immunity.     

Traitement par ultrasons focalisés du cancer localisé de la prostate: Résultats carcinologiques et pronostic sexuel

Introduction

Since 1999, a therapeutic device using High Intensity Focused Ultrasound (HIFU) technology has been marketed in Europe for the treatment of localized prostate cancer. Clinical and technical development was designed to provide a minimally invasive alternative for these patients. The purpose of this study was to evaluate the efficacy of HIFU therapy for localized prostate cancer and its impact on sexual function.

Material and Methods

HIFU technology is based on a convergent beam of high intensity ultrasound that creates a sudden and sharp increase in temperature (85°C to 100°C) in the tissues at the focal point. This leads to a precise lesion in the tissue, adjustable from 19 to 24 mm in height and 2 mm in diameter. Successive displacements of the focal point are computer-driven, allowing treatment of a defined volume. All patients were treated with the ABLATHERM® device (EDAP SA, France); they were treated using the device prototypes between 1993 to 1999 and then with the marketed machine. The treatment procedure was improved from 2000 onwards with the combination of transurethral resection of the prostate (TURP) in order to reduce post-treatment catheter time. A nerve-sparing procedure was also tested in 2002. The selected population included 120 patients considered to be potentially curable with clinical stage T1–T2 prostate cancer and an initial PSA < 10 ng/ml (group 1). A larger group of 167 patients with an initial PSA < 30 ng/ml was also considered (group 2). All patients were not candidates for surgery due to their age or comorbidities. In the two groups, clinical failure was defined by the need for administration of an adjuvant prostate cancer treatment (hormone deprivation or external radiation). Disease progression, or biochemical failure, was strictly defined as any evidence of residual cancer on follow-up biopsies (regardless of the PSA level), or 3 successive increases of the PSA level (with negative follow-up biopsies), with a velocity > 0.75 ng/ml/year. Disease-free survival rates were calculated using the Kaplan-Meier method. Survival rates were compared using the log-rank test. The impact of HIFU treatment on sexual function was assessed by a questionnaire in 70 patients who underwent standard HIFU treatment and in 28 patients in whom a nerve-sparing procedure was performed.

Results

Patient baseline characteristics (± SD) were, in group 1 and group 2 respectively: mean age: 71.2 (± 5.34) years and 71.8 (± 5.11) years; clinical stage: T1 for 61 patients and T2 for 59 patients in group 1, and T1 for 77 patients, T2 for 85 patients and T3 for 5 patients in group 2; mean initial PSA level: 5.67 (± 2.47) ng/ml and 9.30 (± 6.01) ng/ml; Gleason score: 2–6 for 77 patients and 7–10 for 43 patients in group 1, and 2–6 for 98 patients, 7 for 44 patients, and 8–10 for 25 patients in group 2; mean prostate volume: 33.6 (± 16.5) ml and 34.4 (± 16.7) ml, respectively. Mean follow-up was 27 months (range: 3–96 months) in group 1, and 23 months (range: 3–90 months) in group 2. In group 1, a residual cancer was diagnosed in 17 patients, but only 6 patients needed adjuvant treatment due to a significant rise of the PSA level (hormone deprivation: n=2, external radiation: n=4), leading to a clinical success rate of 95%. Similarly, in group 2, 36 patients presented with positive follow-up biopsies, and 21 of them required adjuvant treatment (hormone deprivation: n=10, external radiation: n=11), leading to a clinical success rate of 87.5%. The disease-free survival rates (previously defined on the combined biopsy and PSA criteria) were 76.9% and 66% in group 1 and 2, respectively. In addition, the disease-free survival rate in group 2 was stratified according to the initial prognosis risk level: 85% in low-risk patients (i.e. patients with clinical stage T1–T2a and PSA < 10 ng/ml and Gleason score < 7), 67.5% in intermediate-risk patients (i.e. clinical stage T2b or PSA 10–20 ng/ml or Gleason score = 7), and 42% in high-risk patients (i.e. clinical stage T2c or PSA > 20 ng/ml or Gleason score > 7). In the overall population, 70 patients had normal sexual function prior to HIFU treatment; 25 patients (36%) still had erections allowing sexual intercourse with penetration after treatment. A nerve-sparing procedure was also performed in 28 potent patients: 43% of these patients had persistent erections allowing sexual intercourse with penetration after treatment, indicating that this nerve-sparing procedure still needs to be improved.

Conclusion

The efficacy results observed after HIFU treatment are similar to those observed after other non-surgical treatments for prostate cancer. After complete HIFU treatment of the gland, more than 1/3 of patients still reported erections allowing sexual intercourse with penetration; these results must be interpreted for an elderly population (mean age: 72 years). A nerve-sparing procedure is currently being perfected and tested.     

The Value of Proton Magnetic Resonance Spectroscopy in High-Intensity Focused Ultrasound Treatment of Experimental Liver Cancer

High-intensity focused ultrasound (HIFU) is a rapidly developing, non-invasive technique for local treatment of solid tumors that produce coagulative tumor necrosis. This study is aimed to investigate the feasibility of proton magnetic resonance spectroscopy (MRS) on early assessing treatment of HIFU ablation in rabbit with VX2 liver tumor. HIFU ablation was performed on normal liver and VX2 tumor in rabbit, and MRS was performed on normal liver and VX2 tumor before and 2 days after 100% HIFU ablation or 80% ablation in tumor volume. Choline (Cho) and choline/lipid (Cho/Lip) ratios between complete and partial HIFU ablation of tumor were compared. Tissues were harvested and sequentially sliced to confirm the necrosis. In normal liver, the Cho value liver was not obviously changed after HIFU (P > .05), but the Cho/Lip ratio was decreased (P < .05). Cho in liver VX2 tumor was much higher than that in normal liver (P < .001). Cho and Cho/Lip ratio were significantly decreased in tumor after complete HIFU ablation and partial HIFU ablation, and the Cho value in complete HIFU tumor ablation did not show any difference from that in normal liver after HIFU (P > .05); however, the Cho value in partial ablation was still higher than that in normal liver before or in tumor after complete HIFU treatment due to the residual part of tumors, and Cho/Lip ratio is lower than that in complete HIFU treatment (P < .001). The changes in MRS parameters were consistent with histopathologic changes of the tumor tissues after treatment. MRS could differentiate the complete tumor necrosis from residual tumor tissue, when combined with magnetic resonance imaging. We conclude that MRS may be applied as an important, non-invasive biomarker for monitoring the thoroughness of HIFU ablation.     

Chronic effects of total or partial digit denervation on raccoon somatosensory cortex.

Electrophysiological recordings were made in the primary somatosensory cortex of anesthetized raccoons 14 to 169 days following digit amputation or 60 to 129 days after transection of the two nerves innervating the ventral surface of the fourth digit. The incidence of inhibitory responses decreased from 50% of the penetrations immediately after amputation to 35% over the first 3 weeks and to almost zero after 2 months. The number of sites with low-threshold excitatory responses increased from 4% to 14% to 50% during these same intervals. Initially, the excitatory fields were small and located over the nerve stumps, and were therefore probably due to direct stimulation of the damaged nerves. At 2 months after amputation, the excitatory receptive fields were large and diffuse. Although the size of receptive fields decreased during the later period (when the thresholds were also decreasing), there was no recovery of any precise somatotopic organization in the deafferented cortex. The reorganization process in the raccoon thus consists of at least two stages: The early stage is dominated by inhibitory connections, whereas the second involves a recovery and restructuring of excitatory inputs. From 2 to 4 months after partial digit denervation, there were only minor changes in response properties or somatotopic organization in the deafferented cortex as compared to immediately after nerve transection. Thus, few of the characteristics of reorganization induced by digit amputation were elicited by this treatment, which leaves some of the digit innervation intact. There was, however, an unexpected increase in the portion of the ventral digit that was able to activate the cortex, suggesting complexities in the peripheral innervation of the digit that need to be resolved.     

Survival after intratumoral interleukin-2 treatment of 72 melanoma patients and response upon the first chemotherapy during follow-up

Systemic high-dose interleukin-2 (IL-2) treatment achieves long-term survival in a subset of advanced patients with melanoma. As we reported previously, intratumoral IL-2 induced complete local responses in more than 60% of melanoma patients. This study aimed to analyze the long-term outcome of 72 patients treated in two prior trials. Melanoma patients (49 stage III, 23 stage IV) with injectable metastases received intratumoral IL-2 injections thrice weekly at individually escalated doses (median duration, 6.5 weeks; median total IL-2 dose, 72 MIU; median number of injected metastases, 10). The observed 2-year overall survival rates were 95.5% for stage III patients with cutaneous metastases only (stage IIIB), 72% for those with combined cutaneous and lymph node involvement (stage IIIC), 66.7% for stage IV patients with disease limited to distant soft-tissue metastases (stage IV M1a), and 9.1% for those with visceral metastases (stage IV M1b and stage IV M1c). Thirty patients who reported recurrence of unresectable distant metastases subsequently received chemotherapy in the further course of disease and showed an overall response rate of 36.7% (16.7% complete responses, 20% partial responses). A high total dose of IL-2 and a dacarbazine/temozolomide-based chemotherapy regimen were variables correlated with a clinical response. In conclusion, patients with cutaneous metastasis without lymph node involvement in stage III and with soft-tissue metastasis without visceral involvement in stage IV showed unexpected favorable survival rates after intratumoral treatment with IL-2. Furthermore, the intratumoral IL-2 treatment seemed to be associated with increased complete and partial responses in subsequent chemotherapies.     

Meningeal lymphatics regulate radiotherapy efficacy through modulating anti-tumor immunity

As a first-line treatment, radiotherapy (RT) is known to modulate the immune microenvironment of glioma, but it is unknown whether the meningeal lymphatic vessel (MLV)-cervical lymph node (CLN) network regulates the process or influences RT efficacy. Here, we show that the MLV-CLN network contributes to RT efficacy in brain tumors and mediates the RT-modulated anti-tumor immunity that is enhanced by vascular endothelial growth factor C (VEGF-C). Meningeal lymphatic dysfunction impaired tumor-derived dendritic cell (DC) trafficking and CD8⁺ T cell activation after RT, whereas tumors overexpressing VEGF-C with meningeal lymphatic expansion were highly sensitive to RT. Mechanistically, VEGF-C-driven modulation of RT-triggered anti-tumor immunity was attributed to C-C Motif Chemokine Ligand 21 (CCL21)-dependent DC trafficking and CD8⁺ T cell activation. Notably, delivery of VEGF-C mRNA significantly enhanced RT efficacy and anti-tumor immunity in brain tumors. These findings suggest an essential role of the MLV-CLN network in RT-triggered anti-tumor immunity, and highlight the potential of VEGF-C mRNA for brain tumor therapy.Subject terms: Tumour immunology, Radiotherapy     

High-Intensity Focused Ultrasound (HIFU) for Dissolution of Clots in a Rabbit Model of Embolic Stroke

It is estimated that only 2-6% of patients receive thrombolytic therapy for acute ischemic stroke suggesting that alternative therapies are necessary. In this study, we investigate the potential for high intensity focused ultrasound (HIFU) to initiate thrombolysis in an embolic model of stroke. Iron-loaded blood clots were injected into the middle cerebral artery (MCA) of New Zealand White rabbits, through the internal carotid artery and blockages were confirmed by angiography. MRI was used to localize the iron-loaded clot and target the HIFU beam for treatment. HIFU pulses (1.5 MHz, 1 ms bursts, 1 Hz pulse repetition frequency, 20 s duration) were applied to initiate thrombolysis. Repeat angiograms and histology were used to assess reperfusion and vessel damage. Using 275 W of acoustic power, there was no evidence of reperfusion in post-treatment angiograms of 3 rabbits tested. In a separate group of animals, 415 W of acoustic power was applied and reperfusion was observed in 2 of the 4 (50%) animals treated. In the last group of animals, acoustic power was further increased to 550 W, which led to the reperfusion in 5 of 7 (～70%) animals tested. Histological analysis confirmed thatthe sonicated vessels remained intact after HIFU treatment. Hemorrhage was detected outside of the sonication site, likely due to the proximity of the target vessel with the base of the rabbit skull. These results demonstrate the feasibility of using HIFU, as a stand-alone method, to cause effective thrombolysis without immediate damage to the targeted vessels. HIFU, combined with imaging modalities used to identify and assess stroke patients, could dramatically reduce the time to achieve flow restoration in patients thereby significantly increasing the number of patients which benefit from thrombolysis treatments.     

The Cardioprotective Protein Apolipoprotein A1 Promotes Potent Anti-tumorigenic Effects

Here, we show that apolipoprotein A1 (apoA1), the major protein component of high density lipoprotein (HDL), through both innate and adaptive immune processes, potently suppresses tumor growth and metastasis in multiple animal tumor models, including the aggressive B16F10L murine malignant melanoma model. Mice expressing the human apoA1 transgene (A1Tg) exhibited increased infiltration of CD11b⁺ F4/80⁺ macrophages with M1, anti-tumor phenotype, reduced tumor burden and metastasis, and enhanced survival. In contrast, apoA1-deficient (A1KO) mice showed markedly heightened tumor growth and reduced survival. Injection of human apoA1 into A1KO mice inoculated with tumor cells remarkably reduced both tumor growth and metastasis, enhanced survival, and promoted regression of both tumor and metastasis burden when administered following palpable tumor formation and metastasis development. Studies with apolipoprotein A2 revealed the anti-cancer therapeutic effect was specific to apoA1. In vitro studies ruled out substantial direct suppressive effects by apoA1 or HDL on tumor cells. Animal models defective in different aspects of immunity revealed both innate and adaptive arms of immunity contribute to complete apoA1 anti-tumor activity. This study reveals a potent immunomodulatory role for apoA1 in the tumor microenvironment, altering tumor-associated macrophages from a pro-tumor M2 to an anti-tumor M1 phenotype. Use of apoA1 to redirect in vivo elicited tumor-infiltrating macrophages toward tumor rejection may hold benefit as a potential cancer therapeutic.     

Risk factors of postoperative recurrences in patients with clinical stage I NSCLC

Background

Despite advances in radiation therapy, chemotherapy, and newly developed molecular targeting therapies, long-term survival after resection for patients with NSCLC remains less than 50%. We investigated factors predicting postoperative locoregional recurrences and distant metastases in patients with clinical stage I non-small-cell lung cancer (NSCLC) after surgical resection.

Methods

All patients with clinical stage I NSCLC, who underwent surgical resection between January 2002 and June 2006, were reviewed retrospectively. Multiple logistic regression analyses were used to identify independent risk factors for patients with locoregional recurrences and distant metastases.

Results

A total of 261 patients were eligible. Overall survival was significant related to locoregional recurrences (P?=?0.03) and distant metastases (P <0.001). There were significant differences of locoregional recurrence in tumor differentiation (P?=?0.032) and advanced pathological stage (P?=?0.002). In the group of distant metastases, there were significant differences in tumor differentiation (P?=?0.035), lymphovascular space invasion (P?=?0.031). Among the relationship between pattern of distant metastasis and clinicopathologic variables in patients with clinical stage I NSCLC, SUVmax (P?=?0.02) and tumor size (P?=?0.001) had significant differences. According to multiple logistic regression analysis, tumor differentiation is the only risk factor of postoperative outcome for locoregional recurrence and serum CEA (>3.5 ng/mL) is the predictor of distant metastasis.

Conclusions

Tumor differentiation and serum CEA were predictors of postoperative relapse for clinical stage I NSCLC after surgical resection. Risk factors of postoperative recurrence in patients with clinical stage I NSCLC may enable us to optimize the patient selection for postoperative adjuvant therapies or neoadjuvant treatment before surgery.     

The “A, B and C” of Her-2 DNA vaccine development

INTRODUCTION: The development of Her-2 DNA vaccine has progressed through three phases that can be categorized as phase "A": the pursuit of Her-2 as a tumor-associated "antigen", phase "B": tilting the "balance" between tumor immunity and autoimmunity and phase "C": the on-going "clinical trials". MATERIALS AND METHODS: In phase "A", a panel of human ErbB-2 or Her-2 plasmids were constructed to encode non-transforming Her-2 derivatives. The immunogenicity and anti-tumor activity of Her-2 DNA vaccines were tested in human Her-2 transgenic mice with or without the depletion of regulatory T cells (Tregs). However, Treg depletion or other immune modulating regimens may increase the risk of autoimmunity. In phase "B", the balance between tumor immunity and autoimmunity was assessed by monitoring the development of experimental autoimmune thyroiditis (EAT). To test the efficacy of Her-2 DNA vaccines in cancer patients, clinical trials have been initiated in phase "C". RESULTS AND CONCLUSIONS: Significant anti-Her-2 and anti-tumor activity was observed when Her-2 transgenic mice were electro-vaccinated after Treg depletion. Susceptibility to EAT was also enhanced by Treg depletion and there was mutual amplification between Her-2 immunity and EAT development. Although Tregs regulate both EAT and Her-2 immunity, their effector mechanisms may differ. It may be possible to amplify tumor immunity with improved strategies that can by-pass undue autoimmunity. Critical information will be revealed in the next decade to expedite the development of cancer vaccines.     

Vaccine-induced ErbB (EGFR/HER2)-specific immunity in spontaneous canine cancer

Epidermal Growth Factor Receptor (EGFR) is overexpressed on a number of human cancers, and often is indicative of a poor outcome. Treatment of EGFR/HER2 overexpressing cancers includes monoclonal antibody therapy (cetuximab/trastuzumab) either alone or in conjunction with other standard cancer therapies. While monoclonal antibody therapy has been proven to be efficacious in the treatment of EGFR/HER2 overexpressing tumors, drawbacks include the lack of long-lasting immunity and acquired resistance to monoclonal therapy. An alternative approach is to induce a polyclonal anti-EGFR/HER2 tumor antigen response by vaccine therapy. In this phase I/II open-label study, we examined anti-tumor immunity in companion dogs with spontaneous EGFR expressing tumors. Canine cancers represent an outbred population in which the initiation, progression of disease, mutations and growth factors closely resemble that of human cancers. Dogs with EGFR expressing tumors were immunized with a short peptide of the EGFR extracellular domain with sequence homology to HER2. Serial serum analyses demonstrated high titers of EGFR/HER2 binding antibodies with biological activity similar to that of cetuximab and trastuzumab. Canine antibodies bound both canine and human EGFR on tumor cell lines and tumor tissue. CD8 T cells and IgG deposition were evident in tumors from immunized dogs. The antibodies inhibited EGFR intracellular signaling and inhibited tumor growth in vitro. Additionally, we illustrate objective responses in reducing tumors at metastatic sites in host animals. The data support the approach of amplifying anti-tumor immunity that may be relevant in combination with other immune modifying therapies such as checkpoint inhibitors.     

磁感应热疗联合放疗治疗颈部淋巴结复发的临床观察

目的：探索磁感应热疗技术联合放疗治疗不宜手术的颈部淋巴结复发的疗效和安全性。方法：2012年2月至2012年7月选取27例不宜手术的颈部淋巴结复发病例,给予2次磁热籽植入和4—8次不等的加热治疗,计划治疗目标温度为48—50℃、维持30min,磁感应治疗后一周内行放射治疗,治疗结束后1—3个月时复查CT,治疗后6月内不予化疗。结果：治疗结束后3个月时,27例患者中CR55．6％,PR37％,NC3．7％,PD3．7％,治疗总有效率为92．6％;25例疼痛缓解,疼痛缓解有效率92．6％。治疗结束后6个月未发现远处转移病例,未发生大出血、放射性食管炎、放射性骨坏死、骨髓抑制、粒子移位脱落等并发症。结论：磁感应热疗联合放疗治疗不宜手术的复发颈部淋巴结安全、有效。     

Synergistic effects of glycated chitosan with high-intensity focused ultrasound on suppression of metastases in a syngeneic breast tumor model

Stimulation of the host immune system is crucial in cancer treatment. In particular, nonspecific immunotherapies, when combined with other traditional therapies such as radiation and chemotherapy, may induce immunity against primary and metastatic tumors. In this study, we demonstrate that a novel, non-toxic immunoadjuvant, glycated chitosan (GC), decreases the motility and invasion of mammalian breast cancer cells in vitro and in vivo. Lung metastatic ratios were reduced in 4T1 tumor-bearing mice when intratumoral GC injection was combined with local high-intensity focused ultrasound (HIFU) treatment. We postulate that this treatment modality stimulates the host immune system to combat cancer cells, as macrophage accumulation in tumor lesions was detected after GC-HIFU treatment. In addition, plasma collected from GC-HIFU-treated tumor-bearing mice exhibited tumor-specific cytotoxicity. We also investigated the effect of GC on epithelial–mesenchymal transition-related markers. Our results showed that GC decreased the expression of Twist-1 and Slug, proto-oncogenes commonly implicated in metastasis. Epithelial-cadherin, which is regulated by these genes, was also upregulated. Taken together, our current data suggest that GC alone can reduce cancer cell motility and invasion, whereas GC-HIFU treatment can induce immune responses to suppress tumor metastasis in vivo.     

原发性腹膜后副神经节瘤临床诊疗分析

目的:探讨原发性腹膜后副神经节瘤的手术治疗效果,复发及死亡的影响因素。方法:回顾性分析1985年1月至2015年1月30年间于我院治疗的91例原发性腹膜后副神经节瘤的手术患者的临床资料,统计学方法分析腹原发性腹膜后副神经节瘤手术的治疗效果,预后及复发和死亡的相关因素。结果:77例原发性腹膜后良性副神经节瘤患者,l、3、5年总生存率均为98.5%,复发率分别为2%,4.5%,16%。手术根治度与复发相关(X~2=10.368,P=0.01),手术未完整切除复发率高。性别、年龄、肿瘤部位、肿瘤直径与复发无关(P0.05)。14例原发性腹膜后恶性副神经节瘤患者,1、3、5年总生存率分别为78.5%、50%,41.5%。14例恶性副神经节瘤复发率分别为71%,85%,100%。肿瘤级别与腹膜后恶性副神经节瘤预后(X~2=5.536,P=0.019)和复发相关(X~2=5.734,P=0.017),肿瘤级别低,死亡率高,复发率高;远处转移与复发相关(X~2=4.067,P=0.044),远处转移患者复发率高;性别、年龄、肿瘤部位、肿瘤直径、手术根治度与预后及复发无关(P0.05)。结论:良性腹膜后副神经节瘤患者预后较好,手术根治度与复发相关,根治性手术是其主要治疗方式;恶性副神经节瘤预后差,肿瘤分级与其复发及死亡相关,肿瘤分级低复发及死亡率高,远处转移与复发相关,远处转移患者复发率高。     

622例肺癌患者远处转移临床特征的回顾性分析

目的:探讨不同病理类型IV期原发性支气管肺癌的远处转移特点。方法:回顾性分析我科收治的622例诊断明确、资料完整的IV期肺癌患者,比较不同病理类型肺癌患者各器官远处转移发生率,并进行统计学分析。结果:622例IV期肺癌患者中,鳞状细胞癌188例(30.2%),腺癌275例(44.2%),小细胞癌130例(20.9%),大细胞癌5例(0.8%),腺鳞癌14例(2.3%)。平均年龄55.4岁,男女比例为2.60:1,高发年龄为40~60岁。各器官远处转移发生率从高到低依次为:骨267例(42.9%),胸膜212例(34.1%),双肺162例(26.0%),脑148例(23.8%),肝132例(21.2%),肾上腺53例(8.5%),心包50例(8.0%),皮下转移6例(1.0%),肌肉3例(0.5%),眼球和脊髓各1例(0.2%)。单器官转移共283例(45.5%),多器官转移共339例(54.5%),最多为6个器官远处转移。结论:不同病理类型肺癌有各自不同的远处转移特点及临床特征,应选择相应的检查并制定针对性治疗方案。     

Retrospective Analysis of 234 Nasopharyngeal Carcinoma Patients with Distant Metastasis at Initial Diagnosis: Therapeutic Approaches and Prognostic Factors

Purpose

The purpose of this retrospective study was to identify the independent prognostic factors and optimize the treatment for nasopharyngeal carcinoma (NPC) patients with distant metastasis at initial diagnosis.

Methods

A total of 234 patients referred between January 2001 and December 2010 were retrospectively analyzed. Among the 234 patients, 94 patients received chemotherapy alone (CT), and 140 patients received chemoradiotherapy (CRT). Clinical features, laboratory parameters and treatment modality were examined with univariate and multivariate analyses.

Results

The median overall survival (OS) time was 22 months (range, 2-125 months), and the 1-year, 2-year, 3-year overall survival rates were 82.2%, 51.3% and 34.1%. The overall response and disease control rates of metastatic lesions after chemotherapy were 56.0% and 89.8%. The factors associated with poor response were karnofsky performance score (KPS) <80, liver metastasis, lactate dehydrogenase (LDH)>245 IU/L, and number of chemotherapy cycles <4. The 3-year OS of patients receiving CRT was higher than those receiving CT alone (48.2% vs. 12.4%, p<0.001). Subgroup analysis showed that significantly improved survival was also achieved by radiotherapy of the primary tumor in patients who achieved complete remission (CR)/partial remission (PR) or stable disease (SD) of metastatic lesions after chemotherapy. Significant independent prognostic factors of OS were KPS, liver metastasis, levels of LDH, and multiple metastases. Treatment modality, response to chemotherapy and chemotherapy cycles were also associated with OS.

Conclusion

A combination of radiotherapy and chemotherapy seems to have survival benefits for selected patients with distant metastases at initial diagnosis. Clinical and laboratory characteristics can help to guide treatment selection. Prospective randomized studies are needed to confirm the result.     

Adverse events of extracorporeal ultrasound-guided high intensity focused ultrasound therapy

Background

High-intensity focused ultrasound (HIFU) is considered to be an alternative to surgery. Extracorporeal ultrasound-guided HIFU (USgFU) has been clinically used to treat solid tumors. Preliminary trials in a small sample of a Western population suggested that this modality was safe. Most trials are performed in China thereby providing comprehensive data for understanding the safety profile. The aim of this study was to evaluate adverse events of USgFU therapy.

Methods and Findings

Clinical data were searched in 2 Chinese databases. Adverse events of USgFU were summarized and compared with those of magnetic resonance-guided HIFU (MRgFU; for uterine, bone or breast tumor) and transrectal ultrasound-guided HIFU (for prostate cancer or benign prostate hyperplasia). USgFU treatment was performed using 7 types of device. Side effects were evaluated in 13262 cases. There were fewer adverse events in benign lesions than in malignant lesions (11.81% vs. 21.65%, p<0.0001). Rates of adverse events greatly varied between the disease types (0–280%, p<0.0001) and between the applied HIFU devices in both malignant (10.58–44.38%, p<0.0001) and benign lesions (1.67–17.57%, p<0.0001). Chronological analysis did not demonstrate a decrease in the rate of adverse events. Based upon evaluable adverse events, incidences in USgFU were consistent with those in MRgFU or transrectal HIFU. Some side effects frequently occurred following transrectal HIFU were not reported in USgFU. Several events including intrahepatic metastasis, intraoperative high fever, and occlusions of the superior mesenteric artery should be of particular concern because they have not been previously noted. The types of adverse events suggested that they were ultrasonic lesions.

Conclusion

The frequency of adverse events depended on the location of the lesion and the type of HIFU device; however, side effects of USgFU were not yet understood. USgFU did not decrease the incidence of adverse events compared with MRgFU.     

Update on cancer related issues of mesenchymal stem cell-based therapies

Mesenchymal stem cells (also known as multipotent stromal cells, MSCs) are considered as promising candidate cells for stem cell-based therapy. However, the applications of MSCs are facing controversial concerns of potential tumorigenic risks. There is also increasing evidence that MSCs may play a modulatory role in the development and progression of tumors. MSCs have the potential to migrate to tumor sites and promote tumor cell proliferation, invasion and metastasis. In addition to these risks, MSCs also have shown to be an attractive target for gene/cell-mediated anti-tumor therapy. These complicated behaviors of MSCs in cancer warrant further study to evaluate the benefits of MSCs treatment and the long-term risk of tumor origin or incidence from MSCs under different pathological conditions.     

Obesity paradox in amputation risk among nonelderly diabetic men

The association between BMI and amputation risk is not currently well known. We used data for a cohort of diabetic patients treated in the US Department of Veterans Affairs Healthcare System in 2003. Men aged <65 years at the end of follow-up were examined for their amputation risk and amputation-free survival during the next 5 years (2004-2008). Compared to overweight individuals (BMI 25-29.9 kg/m(2)), the risks of amputation and treatment failure (amputation or death) were higher for patients with BMI <25 kg/m(2) and were lower for those with BMI ≥30 kg/m(2). Individuals with BMI ≥40 kg/m(2) were only half as likely to experience any (hazard ratios (HR) = 0.49; 95% confidence interval (CI), 0.30-0.80) and major amputations (HR = 0.53; 95% CI, 0.39-0.73) during follow-up as overweight individuals. While the amputation risk continued to decrease for higher BMI, amputation-free survival showed a slight upturn at BMI >40 kg/m(2). The association between obesity and amputation risk in our data shows a pattern consistent with "obesity paradox" observed in many health conditions. More research is needed to better understand pathophysiological mechanisms that may explain the paradoxical association between obesity and lower-extremity amputation (LEA) risk.