Correction to: Tumor location-based classification of surgery-related language impairments in patients with glioma

Journal of Neuro-Oncology -     

Conditional animal models: a strategy to define when oncogenes will be effective targets to treat cancer

The ability to model cancer in the mouse has provided a robust methodology to dissect the molecular etiology of cancer. These models serve as potentially powerful platforms to preclinically evaluate novel therapeutics. In particular, the recent development of strategies to conditionally induce the or knockout the function of genes in a tissue specific manner has enabled investigators to engineer mice to demonstrate that the targeted inactivation of specific oncogenes can be effective in inducing sustained regression of tumors. Thus, these animal models will be useful to define the specific genes that will be therapeutically useful to target for the treatment of particular human cancers.     

Intracellular patterns of sialophorin expression define a new molecular classification of breast cancer and represent new targets for therapy

Background:

Sialophorin is a transmembrane sialoglycoprotein. Normally, the molecule is only produced by white blood cells where it regulates functions such as intercellular adhesion, intracellular signalling, apoptosis, migration and proliferation.

Methods:

Normal breast tissue and primary breast tumours were analysed by immunohistochemistry for sialophorin expression. The sialophorin-positive breast cancer cell line MCF7 was engineered to stably express either non-targeted or sialophorin-targeted small interfering RNA (siRNA). Assays were then performed in vitro to assess apoptosis, intracellular adhesion, transendothelial migration and cytotoxicity. An orthotopic mouse model assayed ability to produce tumours in vivo.

Results:

Normal breast epithelial cells exhibit expression of the N-terminal domain of sialophorin in the cytoplasm but not the nucleus. The majority of these normal cells are also negative for expression of the C-terminal domain. In contrast, malignant breast epithelial cells exhibit N-terminal expression both in the cytoplasm and nucleus and the majority express the C-terminus in the nucleus. Using differential patterns of intracellular expression of the N and C termini of sialophorin, we define six subtypes of breast cancer that are independent of histological and receptor status classification. Targeting sialophorin with siRNA resulted in the MCF7 breast cancer cell line exhibiting increased homotypic adhesion, decreased transendothelial migration, increased susceptibility to apoptosis, increased vulnerability to lysis by natural killer cells and decreased ability to produce tumours in mice.

Conclusion:

Our results indicate that intracellular patterns of sialophorin expression define a new molecular classification of breast cancer and that sialophorin represents a novel therapeutic target.     

Tumor location-based classification of surgery-related language impairments in patients with glioma

Journal of Neuro-Oncology - Many patients with glioma experience surgery-related language impairment. This study developed a classification system to predict postoperative language prognosis....     

Clinical interventions to break the obesity and cancer link: a narrative review

Cancer and Metastasis Reviews - Excess body weight is a significant risk factor for the development and recurrence of many types of cancer. Patients with a history or current diagnosis of cancer...     

Radioimmunoguided-intraoperative radiation therapy in colorectal carcinoma: a new technique to precisely define the clinical target volume

PURPOSE: The clinical target volume (CTV) to be irradiated by intraoperative radiation therapy (IORT) after resection is generally based on the surgeon's estimation of close margins. We have developed a new technique, radioimmunoguided-intraoperative radiation therapy (RIG-IORT), that uses an intraoperative hand-held gamma-detecting probe to define areas of residual microscopic disease containing radiolabeled monoclonal antibodies to tumor associated antigen, to more precisely delineate the CTV for IORT. METHODS AND MATERIALS: Patients were injected i.v. with 2 mCi 125I- radiolabeled CC49 antibody approximately 3 weeks before surgery. They then underwent radioimmunoguided surgery (RIGS) with maximal resection of tumor. A hand-held gamma-detecting probe (Neoprobe 1000) was used intraoperatively to detect and resect areas of high radioactivity, representing tumor. Areas with persistently high probe counts after resection were the areas of occult residual disease, and represented the CTV to be irradiated. The IORT was given with either 6-9 MeV electron beam from a dedicated linear accelerator, or with high-dose-rate brachytherapy from a remote afterloader. If all RIGS-positive tissue had been resected, or if widely disseminated disease remained, the patient was not considered for IORT. RESULT: This technique was used in 31 patients with colorectal adenocarcinoma recurrent into the pelvis (n = 23) or paraortic nodes (n = 8). The CTV for IORT was delineated by increased RIGS count in 13 of 19 patients (68%) with microscopic residual, and in 11 of 12 patients (92%) with gross residual. In the other 7 patients, the tumor area did not accumulate the radiolabeled antibody; therefore, these tumor beds were irradiated based on the surgeon's estimation of close margins. Hence, overall, the RIG-IORT technique was used to define the tumor bed for IORT in 24 of 31 patients (77%). This technical report focuses on the development of the RIG-IORT technique and does not address the outcome results of the treated patients. CONCLUSION: A new technique, RIG-IORT, which uses radiolabeled monoclonal antibodies to precisely determine the CTV for IORT, is described. Whether the use of this technique will lead to improved tumor control will only be known upon the outcome analysis of RIG-IORT-treated patients compared with those obtained using traditional IORT techniques.     

Prophylaxis of oral mucositis in irradiated head-and-neck cancer patients: a proposed classification scheme of interventions and meta-analysis of randomized controlled trials

PURPOSE: To identify, classify, and evaluate agents used in the prophylaxis of oral mucositis in irradiated head and neck cancer patients. METHODS: Data sources included multiple databases and manual citation review of relevant literature. Based on the eligibility criteria, 59 studies were independently reviewed by two reviewers. Forty-two studies were included in the classification scheme, of which 15 met the criteria for inclusion in the meta-analysis. Data were extracted by duplicate independent review, with disagreement resolved by consensus. RESULTS: Overall, the interventions reduced the odds of developing severe oral mucositis, when assessed by clinicians, by 36% (OR: 0.64; 95% CI: 0.46, 0.88). Subgroup analysis suggested that only the narrow-spectrum antibacterial lozenges were effective (OR: 0.45; 95% CI: 0.23, 0.86); however, the power of the aggregated data in the other classes may have been insufficient to detect differences. When the outcome was assessed by patients, no significant difference was seen in the outcome between the treatment and the control groups (OR: 0.79; 95% CI: 0.56-1.12). CONCLUSIONS: Overall, interventions chosen on a sound biologic basis to prevent severe oral mucositis are effective. In particular, when oral mucositis is assessed by clinicians, narrow-spectrum antibiotic lozenges appear to be beneficial. Methodologic limitations were evident in many of the studies. Further research using validated measurement tools in larger, methodologically sound trials is warranted.     

Using cost-effectiveness analysis to define a breast cancer benefits package for the uninsured

Objectives. In 1999, California was considering legislation to fund breast cancer treatment for its uninsured. We sought to define the most cost-effective breast cancer benefits package in order to inform this debate. Methods. We use cost-effectiveness analysis to calculate the additional costs and benefits of various adjuvant therapy strategies, radiation after breast conserving surgery, and reconstruction compared to those of surgery alone in order to define the most cost-effective breast cancer benefits package for uninsured women. Results. Using cost-effectiveness analysis, we define a Minimum Breast Cancer Benefits Package that includes only the most cost-effective life-saving breast cancer treatments. To provide these benefits for an estimated 550 breast cancer patients will cost $10,200,000. We present two options that each cost an additional $1,700,000 – to expand the benefits to these patients to include post-mastectomy radiation and breast reconstruction; or to provide the Minimum Package to an additional 93 uninsured women. Conclusions. California legislators must decide whether to offer comprehensive benefits to a limited number of breast cancer patients or to provide only the most life-saving treatments to a greater number of women.     

The CIRAS study: a case control study to define the clinical, immunologic, and radiographic features of aromatase inhibitor-induced musculoskeletal symptoms

Aromatase inhibitors (AIs) are widely prescribed for post-menopausal hormone receptor-positive breast cancer; however, musculoskeletal symptoms limit their tolerability. The purpose of this study was to determine whether joint pain in women receiving AIs is associated with inflammatory arthritis as measured by the disease activity score-28 (DAS-28), and to evaluate association with tenosynovitis on ultrasound. A total of 48 postmenopausal women with stage I–III breast cancer and hand pain were recruited from the Lombardi Comprehensive Cancer Center. Those receiving AIs were cases (n = 25), and those not receiving AIs were controls (n = 23). During a single study visit, subjects underwent blinded rheumatologic evaluation, DAS-28, health assessment questionnaires, autoantibodies, inflammatory markers, hand X-ray, and hand Duplex ultrasound. There were no significant differences between cases and controls in DAS-28, or inflammatory markers. A positive ANA (titer > 1:160) was found in ten patients, four of whom met criteria for autoimmune disease (two with rheumatoid arthritis and two with Sjogren’s syndrome, equally distributed among cases and controls). This highlights the importance of considering underlying autoimmune disease in subjects with musculoskeletal complaints. Morning stiffness was more prolonged in women receiving AIs, but this did not reach statistical significance (P = 0.07). Ultrasound evidence of flexor tenosynovitis was common in both groups. Although tenosynovitis was not correlated with AI use (P = 0.26), there was a trend toward an association between tenosynovitis and morning stiffness (P = 0.089). While aromatase inhibitor-induced musculoskeletal symptoms (AIMSS) were more common in subjects receiving AIs, they were not unique to AI users. There was no association between presence of AIMSS features and other chemotherapy or medication exposures. Although the majority of subjects had been using AIs for more than 6 months, this study did not find evidence for inflammatory arthritis in women with hand pain receiving AIs. Further studies are needed to develop a case definition of AIMSS, and to confirm whether these symptoms are attributable to AI use.     

Does a high Mandard score really define a poor response to chemotherapy in oesophageal adenocarcinoma?

Background A high Mandard score implies a non-response to chemotherapy in oesophageal adenocarcinoma. However, some patients exhibit tumour volume reduction and a nodal response despite a high score. This study examines survival and recurrence patterns in these patients.Methods Clinicopathological factors were analysed using multivariable Cox regression assessing time to death and recurrence. Computed tomography-estimated tumour volume change was examined in a subgroup of consecutive patients.Results Five hundred and fifty-five patients were included. Median survival was 55 months (Mandard 1–3) and 21 months (Mandard 4 and 5). In the Mandard 4 and 5 group (332 patients), comparison between complete nodal responders and persistent nodal disease showed improved survival (90 vs 18 months), recurrence rates (locoregional 14.75 vs 28.74%, systemic 24.59 vs 48.42%) and circumferential resection margin positivity (22.95 vs 68.11%). Complete nodal response independently predicted improved survival (hazard ratio 0.34 (0.16–0.74). Post-chemotherapy tumour volume reduction was greater in patients with a complete nodal response (−16.3 vs −7.7 cm³, p = 0.033) with no significant difference between Mandard groups.Conclusion Patients with a complete nodal response to chemotherapy have significantly improved outcomes despite a poor Mandard score. High Mandard score does not correspond with a non-response to chemotherapy in all cases and patients with nodal downstaging may still benefit from adjuvant chemotherapy.Subject terms: Oesophageal cancer, Surgical oncology     

甲状腺乳头状癌患者术后并发症的分析与护理

目的探讨甲状腺乳头状癌患者术后并发症的发生情况与护理方法。方法回顾性选取2018年10月至2019年1月间中国医学科学院肿瘤医院收治的247例甲状腺乳头状癌患者的临床资料,统计术后并发症,分析发生原因及护理要点。结果247例甲状腺乳头状癌手术患者中,术后伤口出血2例,喉返神经损伤2例,甲状旁腺功能减退55例,低钙血症54例,淋巴漏1例,伤口积液1例,颈面部肿胀、颈周麻木疼痛、抬肩困难共12例,压力性损伤1例。术后平均住院时间(2.74±1.37)d,均痊愈出院。结论甲状腺乳头状腺癌术后并发症不能完全避免,术后密切观察、早期发现和及时处理是并发症护理的要点。     

The TNM classification adapted to palliative care]

The staging of tumors according to the "TNM" system was developed by P Denoix between 1943 and 1952. The "TNM" system is based on 3 items of data: the clinical aspect of the tumor "T", the regional lymph nodes "N", and the presence or absence of distant metastases. According to the extent of the local, regional and distant sites the TNM system permits definition of tumor stage. These stages allow comparison of the results from different centers to be made and the establishment of treatment protocols. We have taken the principles of the TNM staging of the UICC and the AJCC staging and applied them to "palliative stages" of cancer patients in an attempt to define the profile of the "palliative care patient", and to exchange the results of treatment between cancer centers.     

The importance of patient monitoring in clinical cytokine trials: use of serum markers to define biologically active doses

Due to their pleiotropic activities, network-like interactions, unknown mode of action and peculiar pharmacokinetics, the in vivo application of cytokines in clinical therapy studies is a difficult task. This paper deals with two therapeutic strategies which imply either maximum tolerated or biological active doses of human recombinant cytokines. Evidence is presented that the serum markers beta-2-microglobulin, which relates to HLA-AB antigen biosynthesis, and neopterin, which relates to macrophage activation, are useful response parameters for the definition of biological activity of IFN-alpha and IFN-gamma. Defined by such means, biological active doses are shown to be considerably less toxic than maximum tolerated doses, but are equally or more effective in the treatment of certain malignant disease states.