Current management of cancer-associated anorexia and weight loss

Loss of appetite and weight predict a poor prognosis for cancer patients. Although caloric supplementation might benefit subgroups of patients--specifically, perioperative, severely malnourished cancer patients, stem cell and bone marrow transplant patients and head and neck cancer patients--its use remains controversial and is not recommended for the majority of patients with cancer-associated weight loss. Most patients with advanced cancer, anorexia, and/or weight loss do not appear to benefit from nutritional supplementation. Instead, discussions with patients and families about realistic eating goals ans, at time armacologic interventions with progestational agents or corticosteroids--both of which are aimed at palliating anorexia--provide clinical benefit. Other phamalogic interventions such as eicosapentaenoic acid, thalidomide (Thalomid), adenosine triphosphate and nonsteriodal anti-inflammatory agents focus on the fact that cancer-assciated weight loss is an enitty dintinct for simple starvation These interventions promise to replenish lean tissue but require further investigation before they can be recommndedas standard clinical practice.     

Appetite and cancer-associated anorexia: a review.

Appetite is governed by peripheral hormones and central neurotransmitters that act on the arcuate nucleus of the hypothalamus and nucleus tactus solitarius of the brainstem. Cancer anorexia appears to be the result of an imbalance between neuropeptide-Y and pro-opiomelanocortin signals favoring pro-opiomelanocortin. Many of the appetite stimulants redress this imbalance. Most of our understanding of appetite neurophysiology and tumor-associated anorexia is derived from animals and has not been verified in humans. There have been few clinical trials and very little translational research on anorexia despite its prevalence in cancer.     

Megestrol acetate in cancer anorexia and weight loss.

High-dose megestrol acetate has been associated with increased appetite and weight. To examine the effects of high-dose megestrol acetate in the treatment of anorexia and weight loss in patients with advanced hormone-insensitive malignant lesions, a randomized double-blind placebo-controlled trial was conducted. Patients receiving megestrol acetate for 1 month reported a significant improvement in appetite and adequacy of food intake compared with those receiving placebo. A three-item scale measuring appetite, adequacy of food intake, and concern about weight revealed a higher improvement with megestrol acetate than with placebo. Patients who worsened while receiving placebo had similar favorable changes after the cross over to megestrol acetate. These data indicate that megestrol acetate may improve appetite and food intake in patients with advanced cancer.     

The cancer anorexia/weight loss syndrome: Therapeutic challenges

The cancer anorexia/weight loss syndrome is characterized by loss of weight, loss of appetite, overall decline in quality of life, and shortened survival in patients with advanced incurable cancer. It is highly prevalent. To date, treatment options that have been firmly established with good scientific evidence are limited to progestational agents and corticosteroids, both of which have been demonstrated to improve appetite but have otherwise failed to have a favorable impact on some of the other aspects of this syndrome. As the mechanisms behind this syndrome are further elucidated, more effective therapeutic strategies will likely emerge.     

Rosiglitazone delayed weight loss and anorexia while attenuating adipose depletion in mice with cancer cachexia

Cachexia is characterized by severe weight loss, including adipose and muscle wasting, and occurs in a large percentage of cancer patients. Insulin resistance contributes to dysregulated metabolism in cachexia and occurs prior to weight loss in mice with colon-26 tumor-induced cachexia. Therefore, we hypothesized that the insulin sensitizer, rosiglitazone, would attenuate the loss of adipose and muscle to result in improved outcomes for mice with late-stage cachexia. Male CD2F1 mice were inoculated with colon-26 adenocarcinoma cells or vehicle. Treatments included vehicle, rosiglitazone (10 mg/kg body weight/day) or rosiglitazone plus pair-feeding to food intake of vehicle-treated mice with tumors. Rosiglitazone delayed weight loss onset by 2 d over the 16 d duration of this aggressive tumor model. This finding was associated, in part, with increased food intake. In addition, adipose mass, adipocyte cross-sectional area and inflammation were improved with rosiglitazone. However, at the time of necropsy 16 d after tumor inoculation rosiglitazone had no effect on retention of muscle mass, strength or proteolysis in late-stage cachexia. We did not measure stamina or endurance in this study. In early-stage cachexia, rosiglitazone normalized PDK4 and PPAR-delta mRNA in quadriceps muscle and rescued the decrease in insulin-stimulated glucose disappearance in mice with tumors. Rosiglitazone may delay weight loss onset by decreasing tumor-induced markers of metabolic change in early-stage cachexia. These changes predict for modest improvement in adipose, but no improvement in muscle strength in late-stage cachexia.     

Pharmacologic therapy for the cancer anorexia/weight loss syndrome: A data-driven, practical approach

The cancer anorexia/weight loss syndrome occurs in over 80% of patients with incurable cancer and is associated with a poor prognosis and negative effects on quality of life. Educating patients and families plays an important role in its management, and caregivers sometimes forget that in select patients who are candidates for it, antineoplastic therapy can occasionally reverse some aspects of this syndrome. Patients may also benefit from appetite stimulants such as corticosteroids and progestational agents,and this review summarizes the benefits of using these agents as well as their contraindications.     

Systematic review of cancer treatment programmes in remote and rural areas.

In an attempt to ensure high quality cancer treatment for all patients in the UK, care is being centralized in specialist centres and units. For patients in outlying areas, however, access problems may adversely affect treatment. In an attempt to assess alternative methods of delivering cancer care, this paper reviews published evidence about programmes that have set out to provide oncology services in remote and rural areas in order to identify evidence of effectiveness and problems. Keyword and textword searches of on-line databases (MEDLINE, EMBASE, HEALTHSTAR and CINAHL) from 1978 to 1997 and manual searches of references were conducted. Fifteen papers reported evaluations of oncology outreach programmes, tele-oncology programmes and rural hospital initiatives. All studies were small and only two were controlled, so evidence was suggestive rather than conclusive. There were some indications that shared outreach care was safe and could make specialist care more accessible to outlying patients. Tele-oncology, by which some consultations are conducted using televideo, may be an acceptable adjunct. Larger and more methodologically robust studies are justified and should be conducted.     

Dose-response study of ibandronate in the treatment of cancer-associated hypercalcaemia.

Hypercalcaemia is an important cause of morbidity in malignant disease. We studied the efficacy and safety of intravenous ibandronate (a new, potent bisphosphonate) in a multicentre study of 147 patients with severe cancer-associated hypercalcaemia which had been resistant to treatment with rehydration alone. Of 131 randomized patients who were eligible for evaluation, 45 were allocated to receive 2 mg ibandronate, 44 patients to receive 4 mg and 42 patients to receive 6 mg. Serum calcium values fell progressively in each group from day 2, reaching a nadir at day 5, and in some patients normocalcaemia was maintained for up to 36 days after treatment. The 2-mg dose was significantly less effective than the 4-mg or 6-mg dose in correcting hypercalcaemia, as the number of patients who achieved serum calcium values below 2.7 mM after treatment was 50% in the 2-mg group compared with 75.6% in the 4-mg group and 77.4% in the 6-mg group (P < 0.05; 2 mg vs others). In a logistic regression analysis, three factors were found to predict response; ibandronate dose (higher doses were more effective), severity of presenting hypercalcaemia (severe hypercalcaemia was associated with less complete response) and tumour type (patients with breast carcinoma and haematological tumours responded better than those with other tumours). Ibandronate was generally well tolerated and no serious drug-related adverse events were observed. We conclude that ibandronate is a safe, well tolerated and effective treatment for cancer-associated hypercalcaemia, which should prove a useful addition to the current range of therapies available to treat this condition.     

Importance of nutritional screening in treatment of cancer-related weight loss

Weight loss is common in patients with cancer. Many factors, such as physiological abnormalities, response to the tumour, and treatment, contribute to this weight loss. Cancer-related weight loss affects a patient's response to treatment, as well as survival and quality of life. Several nutritional screening and assessment tools have been developed for patients with cancer. This review describes the weight loss seen in patients with cancer as well as the methods of screening for nutritional deterioration and weight loss early in a cancer diagnosis. Nutritional approaches to the supportive care of patients with cancer are also discussed.     

Systematic review of pleurectomy in the treatment of malignant pleural mesothelioma

Introduction

Pleurectomy/decortication (P/D) in the treatment of malignant pleural mesothelioma includes a number of procedures with different clinical indications and therapeutic intents. To unify the nomenclature, IMIG and IASLC recently defined P/D-related procedures according to surgical technique, including ‘extended P/D’, ‘P/D’ and ‘partial pleurectomy’. The present systematic review aimed to assess the safety and efficacy of these techniques.

Methods

A systematic review of relevant studies was performed by electronic search of five online databases from 1985 to 2012 by two independent reviewers according to predefined selection criteria.

Results

Thirty-four studies involving 1916 patients who underwent pleurectomy were included for quantitative analysis. These included 12 studies on ‘extended P/D’, 8 studies on ‘P/D’ and 14 studies on ‘partial pleurectomy’. Perioperative mortality ranged from 0% to 11% and perioperative morbidity ranged from 13% to 43%. Median overall survival ranged from 7.1 to 31.7 months and disease-free survival ranged from 6 to 16 months. One study reported on quality-of-life outcomes using a standardized questionnaire suggesting superior outcomes for ‘extended P/D’ compared to extrapleural pneumonectomy.

Conclusions

Results of the present systematic review suggested similar perioperative mortality outcomes between different P/D techniques but a trend towards higher morbidity and length of hospitalization for patients who underwent ‘extended P/D’. However, overall and disease-free survival appeared to favour ‘extended P/D’ compared to less aggressive techniques. Future studies on P/D should adhere to recent definitions to enable accurate analysis of similar procedures. Direct comparisons of pleurectomy to extrapleural pneumonectomy remain challenging, and should be restricted to ‘extended P/D’ procedures only.     

Interleukin-1 genetic polymorphisms and their relationship to the cancer anorexia/weight loss syndrome in metastatic gastric and gastroesophageal junction adenocarcinoma

Interleukin-1 (IL-1) beta is a putative mediator of the cancer anorexia/weight loss syndrome, and certain polymorphisms of its gene are thought to be associated with a greater risk of gastric cancer. Do these IL-1 beta genetic polymorphisms predispose patients with gastric and gastroesophageal cancer to the anorexia/weight loss syndrome? This study focused on 44 patients with metastatic gastric and gastroesophageal cancer. All underwent genotyping, completed serial quality-of-life questionnaires germane to appetite, and underwent meticulous serial follow-up. Patients with the IL-1 beta-31 C/T and T/T genotypes were more likely to describe a worse appetite at baseline than were those with the C/C genotype. In addition, patients with the IL-1 beta+3954 C/T and T/T genotypes showed greater improvements in their weight (P = 0.02) and in survival (hazard ratio, 0.3; P = 0.04) over time than did patients with the C/C genotype. These associations occurred independently of tumor response. These preliminary data suggest that certain interleukin-1 beta genetic polymorphisms may modulate the cancer anorexia/weight loss syndrome in patients with metastatic gastric and esophageal cancer. Confirmatory studies are warranted.     

食管小细胞癌治疗与预后的系统评价

目的：分析以往文献数据,探讨食管小细胞癌的主要临床特征,并对其治疗方法与预后关系作系统评价。方法：检索 PubMed、Embase、Ovid 数据库1990年-2012年10月发表的所有相关文献,按照严格的纳入排除标准纳入相关研究,提取文献数据,采用 SPSS 13.0统计软件进行数据分析。结果：共获得食管小细胞癌病例441例。男性304例,女性78例。首发症状以进食哽咽/咽下困难（81.12%）最为常见。病变位于颈段、胸上段、胸中段、胸下段及多段者分别占0.97%、8.71%、47.74%、40.65%和1.94%。36%的患者首诊时为广泛期。局限期和广泛期 SCEC 患者中位生存时间分别为16个月和10个月,1、2、3、5年生存率分别为62.75%/43.37%（P =0.004）、32.03%/9.64%（P ﹤0.001）、18.30%/4.82%（P =0.004）、10.46%/2.41%（P =0.014）。局限期食管小细胞癌的治疗：综合治疗较单纯局部治疗6个月及1年生存率分别为94.39%/59.38%（P ﹤0.001）和73.83%/40.63%（P =0.001）。综合治疗较单纯化疗6个月、1年、2年、3年生存率分别为94.39%/35.71%（P ﹤0.001）、73.83%/28.57%（P =0.001）、38.32%/7.14%（P =0.021）、23.36%/0.00%（P =0.042）。手术＋化疗、放疗＋化疗及手术＋放疗＋化疗三种治疗方法总体生存率无明显差异。广泛期患者综合治疗组与化疗组的6个月生存率分别为91.43%/61.11%（P =0.011）。结论：原发性 SCEC发病率低,恶性度高,采取局部治疗＋化疗的治疗方法有助于延长患者的生存期,但手术的应用对于改善局限期 SCEC 患者的预后无明显意义。广泛期 SCEC 患者的治疗仍以局部治疗＋化疗的综合治疗为首选方案。     

Systematic review of irreversible electroporation in the treatment of advanced pancreatic cancer

BackgroundIrreversible electroporation (IRE) is a novel procedure to combat pancreatic cancer, whereby high voltage pulses are delivered, resulting in cell death. This represents an ideal alternative to other thermal treatment modalities, as there is no overriding heat effect, therefore reducing the risk of injury to vessels and ducts.MethodsMultiple databases were searched to January 2014. Primary outcome measures were survival and associated morbidity. 41 articles were initially identified; of these 4 studies met the inclusion criteria, yielding 74 patients in total.Results94.5% of patients had locally advanced tumours, the remainder had metastatic disease. Treated tumour size ranged from 1 to 7 cm. IRE approach included open (70.3%), laparoscopic (2.7%) and percutaneous (27%; ultrasound-guided 30%, CT-guided 70%) Morbidity ranged from 0 to 33%; due to the high number of simultaneous procedures performed (resection/bypass) it was difficult to ascertain IRE-related complications. However no significant bleeding occurred when IRE-alone was performed. Survival statistics suggest a prognostic benefit. Reported survival included: 6 month survival of 40% (n = 5) and 70% (n = 14); PFS and OS 14 and 20 months respectively (n = 54). Results of most interest showed a significant survival benefit in matched IRE vs non-IRE groups (PFS 14 vs 6 mths; p = 0.01, OS 20 vs 11 mths; p = 0.03).ConclusionInitial evidence suggests IRE incurs a prognostic benefit with minimal morbidity. More high quality research is required to determine the role IRE may play in the multi-modal management of pancreatic cancers.     

Successful treatment of cancer-associated retinopathy with alemtuzumab

We herein report a patient with cancer-associated retinopathy who experienced multiple bouts of paraneoplastic retinopathy and optic neuropathy but responded to treatments with alemtuzumab and was able to maintain useful vision over the course of 8 years of follow-up.     

Systematic review of high-dose and standard-dose chemotherapies in the treatment of primary well-differentiated osteosarcoma

The objective of this study is to evaluate whether high-dose chemotherapy is more efficacious than standard-dose chemotherapy in the treatment of primary well-differentiated osteosarcoma. The Cochrane systematic evaluation method was adopted. A database search was conducted in MEDLINE, Embase, OVID, the Cochrane Central Register of Controlled Trials database and the Chinese Biomedical Literature CD-ROM Database. The quality of the included studies was jointly evaluated by two reviewers, and homogeneous studies were included for meta-analysis. A total of five studies were included in this meta-analysis, with 1,415 subjects with primary, nonmetastatic, well-differentiated osteosarcoma in the limbs. No statistically significant differences were found between the high-dose chemotherapy group and the low-dose group in 5-year event-free survival [RR 1.04, 95 %CI (0.95, 1.13)], 5-year overall survival [RR 1.02, 95 %CI (0.95, 1.10)], local recurrence rate [RR 0.90, 95 %CI (0.59, 1.39)], proportion of subjects with good histological response [RR 0.93, 95 %CI (0.81, 1.07)], or limb salvage rate [RR 0.97, 95 %CI (0.92, 1.02)]. A statistically significant difference was observed in the 5-year event-free survival between the subjects with good histological response to preoperative chemotherapy and the subjects with poor histological response [RR 1.55, 95 %CI (1.19, 2.00), P?相似文献   

脂肪“变色”与减重

目前,肥胖已成为较严重的影响社会健康的问题, 其主要形成原因是长期能量摄入和消耗失衡。人体脂肪组织 一般分为三种：白色脂肪用于储存脂肪,保持体温并参与脂肪代谢;棕色脂肪在外界条件刺激下可燃烧生热,其在成人体 内含量极少,在新生儿及冬眠动物中较多,有助于帮助其抵抗寒冷;在寒冷刺激下或者 β 肾上腺素能受体激动剂处理后, 小鼠皮下白色脂肪中会出现散在的棕色样脂肪细胞,称米色脂肪。白色脂肪“棕色化”被认为可增加机体能量消耗。运动 对机体健康有多重益处,近期有研究证实了运动可引起脂肪组织表型改变 , 即从储存能量的白色脂肪转变成能够产热的棕 色脂肪,从而成为治疗肥胖及相关代谢性疾病的潜在方法。目前研究较多的可调控白色脂肪“棕色化”的因子主要有：鸢 尾素、成纤维细胞生长因子 21 和白细胞介素 -6,并且在临床应用中,间歇性禁食已被证实可通过调节肠道菌群影响白色脂 肪“棕色化”。本文综述几种调控因子在机体运动时促进白色脂肪“棕色化”过程的机制,为临床减重提供新的思路。     

Antimicrobial treatment of Stenotrophomonas maltophilia invasive infections: Systematic review

Stenotrophomonas maltophilia can cause serious infections in immunocompromised patients. The aim of this systematic review was to establish what invasive infections in humans are caused by S. maltophilia and to evaluate the optimal choice of antibiotics for their treatment. MEDLINE, EBSCO, SCOPUS, SCINDEKS and GOOGLE SCHOLAR were systematically searched for clinical trials, observational studies, case reports or case series describing invasive infections with S. maltophilia in patients of any age. S. maltophilia may cause invasive infections of various tissues in hospitalized patients. In the great majority of cases it was susceptible to co-trimoxazole, levofloxacin and ceftazidime. In about three fourths of the cases, the treatment was successful, while less than 20% of the patients died. S. maltophilia is increasingly associated with serious invasive infections in hospitalized patients and due to growing trend of resistance to almost all antibiotics requires a careful approach to patients who is harboring this bacterium.     

Dronabinol versus megestrol acetate versus combination therapy for cancer-associated anorexia: a North Central Cancer Treatment Group study.

PURPOSE: To determine whether dronabinol administered alone or with megestrol acetate was more, less, or equal in efficacy to single-agent megestrol acetate for palliating cancer-associated anorexia. PATIENTS AND METHODS: Four hundred sixty-nine assessable advanced cancer patients were randomized to (1) oral megestrol acetate 800 mg/d liquid suspension plus placebo, (2) oral dronabinol 2.5 mg twice a day plus placebo, or (3) both agents. Eligible patients acknowledged that loss of appetite or weight was a problem and reported the loss of 5 pounds or more during 2 months and/or a daily intake of less than 20 calories/kg of body weight. RESULTS: Groups were comparable at baseline in age, sex, tumor type, weight loss, and performance status. A greater percentage of megestrol acetate-treated patients reported appetite improvement and weight gain compared with dronabinol-treated patients: 75% versus 49% (P =.0001) for appetite and 11% versus 3% (P =.02) for > or = 10% baseline weight gain. Combination treatment resulted in no significant differences in appetite or weight compared with megestrol acetate alone. The Functional Assessment of Anorexia/Cachexia Therapy questionnaire, which emphasizes anorexia-related questions, demonstrated an improvement in quality of life (QOL) among megestrol acetate-treated and combination-treated patients. The single-item Uniscale, a global QOL instrument, found comparable scores. Toxicity was also comparable, with the exception of an increased incidence of impotence among men who received megestrol acetate. CONCLUSION: In the doses and schedules we studied, megestrol acetate provided superior anorexia palliation among advanced cancer patients compared with dronabinol alone. Combination therapy did not appear to confer additional benefit.