Neurochemical mechanisms for cancer anorexia

Under normal conditions, the homeostasis of energy intake is maintained in the hypothalamus by 1) transducing metabolic and sensorial inputs arising from the periphery into neuronal response, 2) integrating the information originating from different tissues, and 3) triggering the appropriate feeding responses. If cancer anorexia is considered a disruption of the physiologic mechanisms controlling energy intake, it is conceivable that its pathogenesis may lie in an abnormal input of information to the hypothalamus, its defective transduction and integration, or the induction of exaggerated and inappropriate feeding responses. Currently available data suggest that the pathogenesis of cancer anorexia is multifactorial and involves most of the neuronal signaling pathways modulating energy intake. Thus, a number of factors has been proposed as putative mediators of cancer anorexia, including hormones (e.g., leptin), neuropeptides (e.g., neuropeptide Y), cytokines (e.g., interleukin-1, interleukin-6, tumor necrosis factor), and neurotransmitters (e.g., serotonin and dopamine). However, it is unlikely that they represent separate and distinct pathogenic mechanisms; rather, it appears that close interrelationships may exist among them. In line with this reasoning, consistent experimental and human data suggest that hypothalamic monoaminergic neurotransmission and serotonergic activity in particular may represent a major target on which different anorexia-related factors converge. Thus, interfering pharmacologically with hypothalamic serotonin synthesis and activity has been tested as a therapeutic strategy in anorectic cancer patients with encouraging results. However, more clinical options will be available by revealing the complex interactions between the many factors participating in controlling energy intake under normal and pathologic conditions. Further, modulation of hypothalamic activity also might result in reduced catabolic signals to skeletal muscles, thus improving the cachexia associated with cancer.     

Whole brain apparent diffusion coefficient histogram: a new tool for evaluation of leukoaraiosis

PURPOSE: To test whole brain apparent diffusion coefficient histogram analysis as an alternative approach to visual score for the assessment of leukoaraiosis (LA). MATERIALS and METHODS: T2 and diffusion weighted images were obtained in 15 elderly patients. LA extension was assessed on T2 weighted images by two observers using a semiquantitative visual score. Apparent diffusion coefficient (ADC) maps of the entire brain were generated and, after exclusion of the skull with manual tracing and of the cerebrospinal fluid (CSF) by application of a threshold value, whole brain (WB)-ADC histogram was obtained. Moreover, a brain volume index (BVI) was calculated on ADC maps as (intracranial volume - CSF volume) /intracranial volume. RESULTS: The kappa inter-observer agreement for LA scoring was 0.69. Manual segmentation of the skull showed a mean inter-operator coefficient of variation below 3%. The median value of whole brain ADC histogram directly correlated with LA extension (P = 0.013). Moreover a significant inverse correlation (P = 0.002) was found between WB-ADC median value and BVI. CONCLUSION: WB-ADC histogram is a reproducible alternative tool for assessing LA extension and severity.     

Multicenter phase II study of brequinar sodium in patients with advanced lung cancer

Summary A total of 53 patients with advanced lung cancer [non-small-cell (NSC), 21; small-cell (SC), 32] were treated with brequinar sodium. All of the NSC patients were chemotherapy-naive, but 31/32 (97%) SC patients had failed a multiagent chemotherapy program prior to study entry. Brequinar was given intravenously at a median weekly dose of 1200 mg/m². The toxicity was moderate, with 19 patients (36%) experiencing grade 3 or 4 toxicity. Objective responses were observed in one NSC and two SC patients. We conclude that at this dose and on this schedule, brequinar does not have sufficient activity in patients with NSC or in patients with previously treated SC to warrant further evaluation. However, since responses were observed in previously treated SC lung-cancer patients, further evaluation in chemotherapy-naive patients may be warranted.This study was supported by The DuPont Pharmaceutical Co., Wilmington, Delaware     

Concurrent adjuvant chemotherapy and immediate breast reconstruction with skin expanders after mastectomy for breast cancer

Background. Immediate breast reconstruction (IBR) by means of skin expander is currently one of the most widely used methods of breast reconstruction in mastectomized patients. However, given that many breast cancer patients usually receive adjuvant chemotherapy, the adoption of IBR raises new questions concerning possible cumulative toxicity. The present study reports our experience in the use of concurrent adjuvant chemotherapy and immediate breast reconstruction with skin expander after mastectomy for breast cancer and the acute cumulative toxicity of the treatments. Methods. We evaluated a consecutive series of 52 breast cancer patients who have received IBR by skin expander after radical mastectomy and adjuvant chemotherapy concurrently during skin expansion between 1995 and 1998 (IBR/CT group). We identified two series of control patients treated during the same period: 51 consecutive patients undergoing radical mastectomy and IBR without adjuvant chemotherapy (IBR group) and 63 consecutive patients undergoing radical mastectomy and adjuvant chemotherapy without IBR (CT group). For each patient, we evaluated the incidence of surgical complications and chemotherapy's side effects and dose intensity. Results. The interval between surgery and the start of expander inflation was similar in IBR/CT (range 0–19, median 5 days) and IBR groups (range 0–40, median 5 days) and the timing of inflation was not influenced by chemotherapy. The overall incidence of surgical complications in patients undergoing IBR was low: seroma in eight cases, infection in one, skin necrosis in one, expander rupture in two and erythema in three. There were no statistically significant differences in the distribution of complications between the IBR/CT and IBR groups. The dose intensity of chemotherapy was similar between IBR/CT and CT groups, with a median dose intensity of 96% and 95% of the projected dose, respectively. The only statistically significant difference in terms of chemotherapy side effects (p=0.03) was that stomatitis was more frequent and intense in the CT than in the IBR/CT group. Conclusions. Concurrent treatment with IBR and adjuvant chemotherapy appears feasible and safe, it does not increase acute surgical complications or chemotherapy side effects, and does not require any changes in dose intensity or the timing of inflation.     

Effect of physical exercise on secretion of growth hormone, glucagon, and cortisol in obese and diabetic children.

The effect of muscular exertion of moderate intensity on blood sugar (BS), plasma levels of growth hormone (GH), glucagon, and cortisol (F) has been studied in endocrinologically normal children with short stature and compared with children with clinical diabetes mellitus and obese children with normal and diminished carbohydrate tolerance. In diabetic children, physical exertion induces a rise in plasma GH levels comparable to that in controls; in obese children with normal or with diminished glucose tolerance, the rise is considerably smaller. Physical exertion caused no change in F levels in the groups tested, although basal level in the obese children was significantly higher than in the controls. Basal glucagon levels were similar in all groups and showed no change on physical exertion. The behavior of GH and glucagon in diabetic children was comparable to that in the controls even where blood sugar level was high.     

Interviewee matching of interviewer temporal speech behaviors as related to perceived empathy, warmth, and genuineness.

The present study used an experimental analogue of the initial interview to examine the relationship of therapist durational speech characteristics to therapist empathy, warmth, genuineness and the state of the "therapeutic relationship" as rated by the interviewee. Cross-validated results revealed a modest direct relationship between interviewee speech modelling (DOU) and all process variables examined, with the exception of genuineness. Efficacy of the automated standardized interview as a research tool also was demonstrated. The results implicate the future examination of the relationship between therapist-client speech and silence measures and process variables.     

"Radical but conservative" is the main goal for ultrasonography-guided liver resection: prospective validation of this approach

BACKGROUND: Despite higher blood loss, morbidity, and mortality, rate of major resection is still high in most surgical institutions because of fear of incomplete tumor removal. To verify whether intraoperative ultrasonography (IOUS) minimizes the rate of major hepatectomies while maintaining treatment radicality, we have prospectively validated our policy, based on extensive use of IOUS resection guidance. STUDY DESIGN: Ninety-three consecutive patients with liver tumors were prospectively enrolled. There were 61 men and 32 women with a mean age of 65.6 years. Fifty-nine patients had hepatocellular carcinoma and 34 had colorectal cancer liver metastases. Surgical strategy was based on the relationship between the tumor and intrahepatic vascular structures at IOUS. Rates of major and minor resection, mortality, morbidity, and rate of local recurrences were evaluated. RESULTS: There was no hospital mortality; major morbidity occurred in 2.2% of patients and minor complications in 17%. Six (6.5%) patients required blood transfusion. Major resections (two or more segments) were accomplished in 14 patients (15%), and 5 (5.4%) patients had more than three segments removed. Major vascular invasion was present in 16 patients (17%), and contact without infiltration with major vessels was present in another 16; part of the wall of the inferior vena cava was resected in 1 patient. Surgical clearance was achieved in all patients without local recurrence at a mean followup of 18 months (median 13, range 6 to 52 months). CONCLUSIONS: This study shows that liver operations performed under IOUS guidance are safe and radical and reduce need for major hepatectomies.