Protective Effects of Omega-3 Fatty Acids in Cancer-Related Complications.

Omega-3 polyunsaturated fatty acids (PUFAs) are considered immunonutrients and are commonly used in the nutritional therapy of cancer patients due to their ample biological effects. Omega-3 PUFAs play essential roles in cell signaling and in the cell structure and fluidity of membranes. They participate in the resolution of inflammation and have anti-inflammatory and antinociceptive effects. Additionally, they can act as agonists of G protein-coupled receptors, namely, GPR40/FFA1 and GPR120/FFA4. Cancer patients undergo complications, such as anorexia-cachexia syndrome, pain, depression, and paraneoplastic syndromes. Interestingly, the 2017 European Society for Clinical Nutrition and Metabolism (ESPEN) guidelines for cancer patients only discuss the use of omega-3 PUFAs for cancer-cachexia treatment, leaving aside other cancer-related complications that could potentially be managed by omega-3 PUFA supplementation. This critical review aimed to discuss the effects and the possible underlying mechanisms of omega-3 PUFA supplementation in cancer-related complications. Data compilation in this critical review indicates that further investigation is still required to assess the factual benefits of omega-3 PUFA supplementation in cancer-associated illnesses. Nevertheless, preclinical evidence reveals that omega-3 PUFAs and their metabolites might modulate pivotal pathways underlying complications secondary to cancer, indicating that this is a promising field of knowledge to be explored.

Cancer Cachexia: More Than Skeletal Muscle Wasting.

Cancer cachexia is a multifactorial condition characterized by body weight loss that negatively affects quality of life and survival of patients with cancer. Despite the clinical relevance, there is currently no defined standard of care to effectively counteract cancer-associated progressive tissue wasting. Skeletal muscle atrophy represents the main manifestation of cancer cachexia. However, cancer cachexia is increasingly seen as a systemic phenomenon affecting and/or influenced by various organs. Here, we describe recent developments elucidating the roles of different tissues as well as tissue crosstalk in this wasting syndrome, including potential links to other cancer-associated morbidities. A more comprehensive understanding of cancer cachexia etiology and heterogeneity may enable the development of intervention strategies to prevent or reverse this devastating condition.

Consumption of low-fat dairy products and energy and protein intake in cancer patients at risk of malnutrition.

Current nutritional guidelines encourage the reduction of fat intake from animal sources like dairy products. The aim was to determine whether the consumption of low-fat dairy is related to poorer dietary intake and nutritional status in cancer patients at risk of malnutrition. This cross-sectional included patients with solid or hematological malignancies at risk of malnutrition. Nutritional status was studied using Subjective Global Assessment, anthropometry, and grip strength. Dietary intake was evaluated with a 24-h recall and dairy consumption with a structured questionnaire. Seventy-four patients were recruited; 71.6% males of 64.8 yr, most with gastrointestinal malignancies. Only 37.8% consumed whole milk, and 61.4% consumed whole yogurt. Reasons for consumption of low-fat dairies were healthy diet (58.0%), hypercholesterolemia (20.0%), and digestive intolerance (10.0%). There were similar rates of malnutrition according the type of dairy (whole 60.9% vs. low-fat 66.7%, P = 0.640). Low-fat dairies were related to a reduction in energy (whole 1980.1 kcal vs. low-fat 1480.9, P = 0.007) and protein intake (whole 86.0 g vs. low-fat 63.0 g, P = 0.030).

The consumption of omega-3 polyunsaturated fatty acids improves clinical outcomes and prognosis in pancreatic cancer patients: a systematic evaluation.

This study was aimed to systematically evaluate results of trials examining the effects of omega-3 polyunsaturated fatty acid (n-3 PUFA) consumption on body weight, lean body mass, resting energy expenditure, and overall survival in pancreatic cancer patients. We searched Medline, Pubmed, Embase, and Cochrane databases. We selected randomized controlled trials of n-3 PUFA vs. conventional nutrition in unresectable pancreatic cancer patients. We analyzed our data using the Cochrane statistical package RevMan 5.1. Eleven trials met our inclusion criteria. There was a significant increase in body weight [weighted mean difference (WMD) = 0.62; 95% confidence interval (CI), 0.54-0.69, P < 0.00001) and lean body mass (WMD = 0.96; 95% CI, 0.86-1.06, P < 0.00001), a significant decrease in resting energy expenditure (WMD = -29.74; 95% CI, -55.89-3.59, P = 0.03), and an increase in overall survival (130-259 days vs. 63-130 days) in unresectable pancreatic cancer patients who consumed an oral nutrition supplement enriched with n-3 PUFAs compared to those who consumed conventional nutrition. This preliminary study suggests that n-3 PUFAs are safe and have a positive effect on clinical outcomes and survival in pancreatic cancer patients.

Humoral hypercalcemia caused by uterine corpus carcinosarcoma consisting of squamous cell carcinoma in its epithelial component.

Humoral hypercalcemia of malignancy (HHM) is a paraneoplastic syndrome primarily caused by a tumor-producing parathyroid hormone-related protein (PTH-rP). We describe the first reported case of a uterine carcinosarcoma causing HHM. A 70-year-old patient was transferred to our hospital for a uterine tumor accompanied by impaired consciousness. The laboratory tests indicated anemia, malnutrition, elevated serum calcium and elevated PTH-rP. Emergency surgery, including abdominal hysterectomy and bilateral salpingo-oophorectomy, was performed due to uncontrollable uterine bleeding. The pathological diagnosis was carcinosarcoma consisting of pure squamous cell carcinoma in its epithelial component. Postoperatively, chemotherapy with paclitaxel and carboplatin was performed. The patient had recurrent tumors at the para-aortic lymph nodes 11 months after the initial surgery and underwent a pelvic and para-aortic lymphadenectomy, which removed all of the recurrent tumors.

Clinical significance of zoledronic acid and strontium-89 in patients with asymptomatic bone metastases from non-small-cell lung cancer.

BACKGROUND: The purpose of this study was to clarify the treatment value of zoledronic acid (ZA) and/or strontium-89 (Sr-89) in patients with non-small-cell lung cancer (NSCLC) with asymptomatic bone metastases (BMs). PATIENTS AND METHODS: Eligible patients were those with resectable NSCLC and asymptomatic BMs. These candidates were randomized into 4 groups: group A was treated with ZA and Sr-89 simultaneously, group B was treated with ZA, group C was treated with Sr-89, and group D was untreated. Patients were monitored and analyzed for the first skeletal-related event (SRE), overall survival (OS), and annual incidence of SREs. RESULTS: One hundred eighty patients were enrolled. Time to first SRE in group A was 15 months (95% confidence interval [CI], 14.0-16.0 months), in group B it was 12 months (95% CI, 11.1-13.0 months), in group C it was 9 months (95% CI, 8.5-9.5 months), and in group D it was 8 months (95% CI, 7.1-8.9 months) (P = .000). The overall survival (OS) in group A was 17 months (95% CI, 16.0-18.1 months); in group B, it was 16 months (95% CI, 14.2-17.8 months); in group C, it was 12 months (95% CI, 11.1-12.9 months); and in group D, it was 12 months (95% CI, 10.8-13.2 months). The annual incidence of SREs in group A was 24.4%; in group B, it was 55.6%; in group C, it was 75.6%; in group D, it was 91.1% (P = .000). CONCLUSIONS: Treatment with ZA and/or Sr-89 significantly extended the time to first SRE as well as survival time and reduced the annual incidence of SREs. Treatment with the combined use of ZA and Sr-89 was safe and well tolerated and achieved the best effect on asymptomatic BMs of NSCLC.

[Skin diseases in geriatric patients. Epidemiologic data]. / Hauterkrankungen beim geriatrischen Patienten. Epidemiologische Daten.

The incidence of skin diseases more common in older patients, e.g. inflammatory and autoimmune diseases, benign and malignant tumors and paraneoplastic syndromes, is increasing worldwide rapidly mainly due to early or lifelong UV-overexposure and to an aging population. In order to transform this demographic change into a chance a better understanding of the pathomechanisms of these diseases, an early diagnosis and therapy are essential steps. In addition, a joint effort to raise public awareness, patient education, preventive measures and consistent monitoring of high-risk groups is of great importance. In this article, the relationship between aging and associated skin diseases will be presented with a particular focus on the epidemiology and risk factors.

Inhibition of tumor progression and paraneoplastic syndrome development in a murine lung adenocarcinoma by medroxyprogesterone acetate and indomethacin.

Mice bearing LP07 lung adenocarcinoma present some characteristics similar to those shown in patients with several malignant diseases. LP07 tumor bearers develop paraneoplastic syndromes such as cachexia, leukocytosis, and hypercalcemia, partly due to a systemic inflammatory response. We analyzed some of the mechanisms involved in the effectiveness of the association of the appetite-stimulant medroxiprogesterone acetate (MPA) and the nonselective cyclooxigenase (COX) inhibitor indomethacin (INDO) in LP07 tumor bearing mice. INDO and INDO plus MPA treatments significantly inhibited tumor growth, which was not inhibited by MPA. The number of lung metastatic nodules was decreased with all treatments, being most effective INDO alone and INDO plus MPA. A significant decrease of plasmatic levels of the matrix metalloproteinases MMP-9 and MMP-2 correlated with these results. Paraneoplastic syndromes, leukocytosis, and cachexia were abolished by all treatments. We determined effects of the treatments on circulating cytokines shown to regulate cachexia and inflammation. Both treatments alone, and INDO plus MPA, reduced circulating IL-6 throughout tumor evolution. A pronounced increase in serum IL-1ss levels was detected in untreated tumor bearers. These levels decreased and were closer to normal serum values when LP07 mice were treated with INDO plus MPA. The combination of a nonsteroidal antiinflammatory drug as INDO and MPA showed to be effective in inhibiting tumor and metastatic growth and diminishing paraneoplastic symptoms and SIR. A variety of specific molecules are implicated as playing a role in cancer-induced cachexia and hematological alterations.

Effect of selenium-enriched malt on hepatocarcinogenesis, paraneoplastic syndrome and the hormones regulating blood glucose in rats treated by diethylnitrosamine.

233 SD rats weighing 100 approximately 120 g were divided randomly into 6 groups. The animals in group I and group II received 0.1 mg/kg selenium in the form of sodium selenite only and served as the negative control and positive control, respectively. Animals in groups III, IV and V were fed with selenium as Se-enriched malt supplemented diets (0.3, 1 and 3 mg/kg), and group VI with selenium by using sodium selenite supplemented diets (3 mg/kg). Animals of groups II approximately VI were induced hepatoma by diethylnitrosamine (100 mg/l) for 16 weeks, then drunk with sterilized water for 2 more weeks. Subsequently, the effects of Se-enriched malt and sodium selenite on hepatoma nodules, relative liver weight, the liver function indices including alanine aminotransferase (ALT), alkaline phosphatase (ALP), albumin (ALB), total bilirubin (TBIL), and the tumor markers, named as gamma-glutamyltranspeptidase (GGT), alpha-fetoprotein (AFP), insulin-like growth factor-II (IGF-II) were recorded. The calcium concentration, glucose content in plasma and values of the hormones regulating blood glucose, such as insulin, glucagons and thyroid hormones (3,5,3'-tetraiodothyronine, T(3); 3,5,3'5'-tetraiodothyronine, T(4)) were observed as well. At the same time, the correlations between the concentration of plasma glucose and related hormones were also analyzed. The results indicated that Se-enriched malt showed a better chemopreventive efficiency in decreasing the number of hepatoma nodules, relative liver weight and the contents of AFP, GGT, IGF-II, ALT, ALP and TBIL in the plasma, and delaying the descent of hormones in the serum, names as insulin, glucagons, T(3) and T(4) than those feeding with sodium selenite. Effect of Se-enriched malt excelled sodium selenite in the aspects of deadening the descent of glucose concentration in the plasma and the rise of calcium concentration in the serum of the rats with hepatoma induced by diethylnitrosamine. The values of glucose and calcium were significantly related to those items fore-named. In conclusion, the function of Se-enriched malt in deadening the lesion and delaying the development of hepatoma of rats induced by diethylnitrosamine was better than that of sodium selenite. Hypoglycemia and hypercalcemia were significantly correlated with the multifactors mentioned above.

Reduction of tumor progression and paraneoplastic syndrome development in murine lung adenocarcinoma by nonsteroidal antiinflammatory drugs.

Mice bearing LP07 lung adenocarcinoma show some characteristics that are similar to those present in patients with NSCLC. LP07 tumor-bearing mice develop the paraneoplastic syndromes of cachexia, leukocytosis and hypercalcemia. These symptoms may be partly due to a systemic inflammatory response. Our aim was to determine if treatment with NSAIDs would lower tumor and metastasis growth and their accompanying syndromes. The nonselective COX inhibitor indomethacin and the selective COX-2 inhibitor celecoxib reduced tumor growth and metastasis outcome in s.c. LP07 tumor-bearing mice. Both drugs also inhibited the development of leukocytosis and the weight loss associated with LP07 progression. Serum levels of the inflammatory cytokines IL-1beta and IL-6, mediators of cachexia, were modulated by NSAIDs. Inhibition of in vitro migration and invasion and reduction in angiogenesis were attained when cells were treated with either indomethacin or celecoxib. MMP-9 activity was also reduced in conditioned media from LP07 cells treated with celecoxib. These data suggest that several processes implicated in tumor progression can be modulated with NSAID treatment. Improvement in performance status through modulation of cachexia may offer a possibility for combining anti-inflammatory treatments with more aggressive therapies.

Neuromuscular disorders in systemic malignancy.

Paraneoplastic neuronopathies are presumed to be the result of an autoimmune attack directed at neuronal proteins, and both humoral and cell-mediated mechanisms have been postulated. The lower motor neuron syndrome after irradiation to the spinal column is caused by a proximal motor polyradiculopathy. Prevention of brachial plexopathy after radiotherapy for breast cancer may be accomplished by lower doses and surgical management of the axilla. Polymerase chain reaction casts doubt on the distinction between neoplastic and paraneoplastic mechanisms of neuromuscular manifestations of lymphoproliferative diseases. Shared antigenic components may underlie the association between inflammatory neuropathy and malignant melanoma. Advances in chemotherapy strategies against responsive tumors are hindered by the toxic effects of agents on peripheral nerves.

Problems of anticoagulation within a palliative care setting: an audit of hospice patients taking warfarin.

Patients with cancer have an increased risk of venous thromboembolism (VTE) compared with a healthy population. The risk increases as cancer progresses and this is reflected in the number of hospice inpatients with VTE. These patients also have an increased risk of bleeding due to tumour site, complications of treatment, progressive liver involvement and concurrent medication such as nonsteroidal anti-inflammatory agents. Therefore anticoagulation of cancer patients with VTE is fraught with difficulty. This audit of hospice inpatients taking warfarin showed a high incidence of bleeding which was possibly improved with very stringent international normalized ratio (INR) monitoring: 15 episodes in 17 patients improved to 11 episodes in 18 patients. Patient numbers were small and the two groups heterogeneous, thus formal statistical analysis could not be applied. One patient in each group continued to thrombose despite over anticoagulation with warfarin. Monitoring of INR increased from an average of once every six days to once every 2.4 days. Such frequent monitoring is likely to be highly impractical in many hospice and general practice settings. Control of warfarin as measured by average percentage of INRs in, above or below the therapeutic range if anything appeared to be worse in the second group. Any bleeding in these patients was distressing. As a result of this audit, practice in Huntershill Marie Curie Centre has changed. Low molecular weight heparins are proven to be efficacious in the treatment of VTE, are renally excreted and therefore do not interact with many commonly used concurrent medications. They can be administered once daily and do not need monitoring of anticoagulant effect. Thus they will be used in patients for whom anticoagulation is indicated during a six-month period, after which practice will be again reviewed.

Twelve years experience of vena cava filtration.

Fourteen patients have required vena caval interruption in a period of 12 years at St Thomas' Hospital. Half of these patients had an underlying malignancy. None of these patients have had clinical or lung scan evidence of recurrent emboli. There were no deaths related to filter insertion and no patient died of a pulmonary embolism. Vena caval interruption is a procedure that is rarely necessary but may be valuable in carefully selected patients.

Palliative embolization of fibrosarcoma for control of tumor-induced hypoglycemia.

A 77-year-old woman with prior long-standing insulin-dependent diabetes presented with malignant hypoglycemia secondary to insulin-like substances excreted from a large unresectable fibrosarcoma of the left thigh. Partial embolization of the tumor supply from the deep femoral artery was performed using 150-250 microns polyvinyl alcohol foam particles. After embolization, the patient's serum glucose levels reverted to normal and she could be discharged from the hospital.

Subgroup and cost-benefit analysis of the Finnish multicentre trial of clodronate in multiple myeloma. Finnish Leukaemia Group.

Osteolytic lesions and pathological fractures are the major problems in the clinical management of multiple myeloma. We previously reported the main results of a randomized, controlled multicentre trial in 350 Finnish patients with multiple myeloma. All patients received standard melphalan-prednisolone treatment and were randomized to receive either clodronate 2.4 g daily or a placebo for 24 months. The proportion of patients with progression of osteolytic bone lesions was twice as high in the placebo group as in the clodronate group (24.0% v 12.0%, P = 0.026). The purpose of the present study was to investigate factors associated with the progression of osteolytic lesions and to identify subgroups of patients who would benefit most from clodronate treatment. In univariate logistic regression analysis, including treatment (placebo, clodronate), sex, age, pain index, serum calcium and creatinine, myeloma stage, number of osteolytic lesions at baseline, and number of vertebral fractures at baseline as independent variables and the progression of osteolytic lesions as a dependent variable, only the treatment with a placebo was associated with the progression of osteolytic bone lesions. Separate analyses with respect to the progression of osteolytic bone lesions were carried out in the following subgroups: male v female, < or = 64 v > 64 years, stage I v stage II-III myeloma, no osteolytic lesions at baseline versus osteolytic lesions at baseline, no vertebral fractures at baseline versus vertebral fractures at baseline. and a 50% treatment response to cytotoxic drugs versus no treatment response to cytotoxic drugs. The treatment with clodronate delayed the progression of osteolytic lesions similarly in these subgroups, with the exception of a subgroup of patients who did not have a 50% treatment response to cytotoxic drugs. The treatment with clodronate did not significantly increase treatment costs. We conclude that the treatment effect of clodronate seems to be independent of sex and age of the patients, the stage of myeloma, and the severity of bone lesions at diagnosis, but not of treatment response to cytotoxic drugs.

Extracts of porcine pancreas prevent progression of hypercalcemia and cachexia and prolong survival in nude mice bearing a human squamous carcinoma.

Porcine pancreatic extracts (PXs) have previously been shown to decrease blood ionized calcium in BALB/c mice (T. Yoneda, Y. Takaoka, and G. R. Mundy. FEBS Lett., 278: 171-174, 1991). In the present study, we show that the PX is effective in preventing progression of hypercalcemia and decreasing osteoclastic bone resorption associated with a human squamous carcinoma in nude mice. PX inhibited osteoclast-like cell formation in mouse bone marrow cultures and bone resorption in organ cultures of fetal rat long bones which had been stimulated by serum-free culture supernatants of this cancer. In addition, PX increased food intake, decreased weight loss, and prevented development of cachexia. In parallel with these effects, PX prolonged survival of tumor-bearing animals. PX might have therapeutic potential for management of hypercalcemia and cachexia associated with malignancy.