Prediction of Occult Uterine Sarcoma before Hysterectomy for Women with Leiomyoma or Abnormal Bleeding.

STUDY OBJECTIVE: To develop a risk prediction model for occult uterine sarcoma using preoperative clinical characteristics in women undergoing hysterectomy for presumed uterine leiomyomata. DESIGN: Cases of uterine sarcoma were identified from the electronic medical records. Age/race-matched controls were selected at a 2:1 ratio (controls:cases) from a cohort of 45 188 women who underwent hysterectomy for uterine leiomyomata or abnormal bleeding during the same time interval. Unadjusted conditional logistic regression was performed to identify risk factors for occult uterine sarcomas, defined as no preoperative suspicion for malignancy. A risk prediction model was developed using a weighted logistic regression model, and the performance of the model was assessed using the receiver operator characteristic curve and corresponding area under the curve. SETTING: A large integrated health care system in California PATIENTS: Women 18 years of age and older who underwent a hysterectomy and were diagnosed with a uterine sarcoma and matched controls from 2006 to 2013. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: There were 117 cases of occult uterine sarcomas that met inclusion criteria during the study period. The final risk prediction model included age, race/ethnicity, number of myomas, uterine weight, uterine size increase, degree of pelvic pain, and recent history of blood transfusion. The risk prediction model showed high accuracy based on the receiver operating characteristic curve method (area under the curve = 0.83; 95% confidence interval, 0.77-0.90); however, the positive predictive values were low (0.048 or less) at all risk thresholds. CONCLUSION: Multiple clinical features are associated with the presence of a uterine sarcoma, but when incorporated into a prediction model, they fail to provide significantly more information about women who may have an unrecognized sarcoma and only marginally improve the certainty about women who are not likely to have sarcoma.

A Mobile-Based Mindfulness and Social Support Program for Adolescents and Young Adults With Sarcoma: Development and Pilot Testing.

BACKGROUND: Approximately 70,000 adolescents and young adults (AYA) are diagnosed with cancer each year in the United States. Sarcomas carry a particularly high symptom burden and are some of the most common cancers among AYA. Recent work has documented significant levels of unmet needs among AYA with cancer, particularly the need for psychosocial support. Mobile technology may be a cost-effective and efficient way to deliver a psychosocial intervention to AYA with cancer and cancer survivors. OBJECTIVE: The two aims of this study were to (1) develop a pilot version of a mobile-based mindfulness and social support program and (2) evaluate program usage and acceptability. An exploratory aim was to examine change in psychosocial outcomes. METHODS: Thirty-seven AYA with sarcoma or sarcoma survivors, parents, and health care providers participated in the study. Semistructured interviews were conducted with 10 AYA, parents of five of the adolescents, and six health care providers. Themes from the interviews helped to inform the development of a mobile-based mindfulness pilot program and a companion Facebook-based social support group. Twenty AYA consented to participate in a single-arm pre-post evaluation of the program; 17 downloaded the app and joined the Facebook group. Seven of these participants had participated in the semistructured interviews. Six additional health care providers consented to participate in the evaluation stage. RESULTS: On average, participants completed 16.9 of the 28 unique sessions and used the mindfulness app for a mean 10.2 (SD 8.2) days during the 28-day evaluation period. The majority of participants (16/17) engaged in the social group and posted at least one reply to the moderator's prompts. The mean number of responses per person to the moderator of the social group was 15.2 of 31 (49%, range 0%-97%). Both AYA and health care providers responded positively to the Mindfulness for Resilience in Illness program and offered useful recommendations for improvements. Exploratory psychosocial analyses indicated there were no significant differences from pretest to posttest on measures of perceived social support, mindfulness, body image, or psychological functioning. CONCLUSIONS: This study offers preliminary support for the feasibility and acceptability of a mobile-based mindfulness and Facebook-based social support program for AYA with sarcoma. The feedback from AYA and health care providers will assist in creating a fully developed intervention. TRIAL REGISTRATION: ClinicalTrials.gov NCT03130751; https://clinicaltrials.gov/ct2/show/NCT03130751.

Therapeutic management of peritoneal ascitic sarcomatosis by Ruta graveolens: A study in experimental mice.

RELEVANCE: Malignant peritoneal sarcomatosis related ascitic formation often leads to grave consequences but the therapeutic management of the fatal pathophysiological condition remains a rarely discussed issue. The present study investigates the anti-neoplastic activity of the plant alkaloid from Ruta graveolens on ascitic Sarcoma-180 bearing mice as a model of human malignant peritoneal ascites. MATERIALS AND METHODS: The efficacy of the loco-regional administration of Ruta graveolens on tumour cells was explored with cytopathological and cytotoxicological studies, along with the expressional modulation vital regulatory molecules viz. Chk2, c-Myc, CD95 and Aurora kinase. RESULTS: The study revealed a series of anti-neoplastic events exerted by Ruta graveolens that included the boosting of anti-tumour immunity, generation of tumour cell cytotoxicity and disruption of cellular energetics which lead to the induction of apoptosis and simultaneous impairment of cell division in tumour cells. Expressional decline of c-Myc oncoproteins and mitosis promoter Aurora kinase A together with up regulation of vital tumour suppressor Chk-2 and apoptosis inducer CD 95 in ascitic tumour cells was also found to be associated with Ruta administration. CONCLUSION: Our observations revealed that loco-regional Ruta administration resulted in the anti-neoplastic effect on peritoneal sarcoma related ascites and the alteration of vital regulatory molecules which depicted the therapeutic utility of Ruta in the management of peritoneal malignant ascites.

Fufang Kushen injection inhibits sarcoma growth and tumor-induced hyperalgesia via TRPV1 signaling pathways.

Cancer pain is a deleterious consequence of tumor growth and related inflammation. Opioids and anti-inflammatory drugs provide first line treatment for cancer pain, but both are limited by side effects. Fufang Kushen injection (FKI) is GMP produced, traditional Chinese medicine used alone or with chemotherapy to reduce cancer-associated pain. FKI limited mouse sarcoma growth both in vivo and in vitro, in part, by reducing the phosphorylation of ERK and AKT kinases and BAD. FKI inhibited TRPV1 mediated capsaicin-induced ERK phosphorylation and reduced tumor-induced proinflammatory cytokine production. Thus, FKI limited cancer pain both directly by blocking TRPV1 signaling and indirectly by reducing tumor growth.

A massagem na criança com câncer: eficácia de um protocolo / Massage in children with cancer: effectiveness of a protocol

OBJETIVOS: a massagem é uma intervenção que pode contribuir para o alívio da dor, embora as evidências empíricas sejam escassas e contraditórias. O objetivo deste trabalho foi avaliar a eficácia de um protocolo de massagem no alívio da dor na criança internada, com patologia oncológica. MÉTODOS: através de um estudo randomizado e controlado com cegamento simples, foram estudadas 52 crianças, com idades compreendidas entre os 10 e os 18 anos, internadas num serviço de oncologia pediátrica. A intervenção consistiu na aplicação de um protocolo de massagem de três sessões com duração entre 20 a 30 minutos em dias alternados durante uma semana. A eficácia do protocolo foi medida através da avaliação da dor com a aplicação do Inventário Resumido de Dor e a eficácia de cada sessão de massagem pela Escala Visual Analógica (EVA). RESULTADOS: o protocolo de massagem apenas se revelou eficaz na diminuição da interferência da dor no andar (p < 0,05), apesar de ter contribuído para o alívio da dor e sua interferência nas atividades da criança. Após cada sessão de massagem a intensidade da dor sentida pela criança diminuiu (p < 0,001). CONCLUSÕES: apesar da reduzida dimensão da amostra, a massagem parece ser uma intervenção útil no alívio da dor da criança que sofre de patologia oncológica, embora permaneçam dúvidas quanto à eficácia deste protocolo de massagem. Todavia, os autores recomendam a sua utilização pela sua contribuição na promoção do bem-estar e qualidade de vida da criança.

OBJECTIVES: massage can help relieve pain, although empirical evidence is scarce and contradictory. This study aims to assess the effectiveness of a massage protocol in relieving pain in children hospitalized with cancer. METHODS: a randomized, controlled, and single-blind trial was performed in a sample of 52 children aged between 10 and 18 years who were hospitalized in a pediatric cancer ward. The intervention consisted of the implementation of a massage protocol with three sessions of 20 to 30 minutes on alternate days over a one-week period. The effectiveness of the protocol was evaluated by assessing pain using the Brief Pain Inventory (BPI), while the effectiveness of each massage session was measured using the Visual Analogue Scale (VAS). RESULTS: the massage protocol was only effective in reducing the interference of pain in walking (p < 0.05), although it also contributed to relieve pain and its impact on the children's activities. After each massage session, the intensity of the pain experienced by the child decreased (p < 0.001). CONCLUSIONS: despite the small sample size, massage therapy appears to be a useful intervention in reducing pain in children with cancer. However, there are still questions regarding the effectiveness of this massage protocol. The authors recommend its use due to its contribution to the promotion of the child's well-being and quality of life.

Massage in children with cancer: effectiveness of a protocol.

OBJECTIVES: massage can help relieve pain, although empirical evidence is scarce and contradictory. This study aims to assess the effectiveness of a massage protocol in relieving pain in children hospitalized with cancer. METHODS: a randomized, controlled, and single-blind trial was performed in a sample of 52 children aged between 10 and 18 years who were hospitalized in a pediatric cancer ward. The intervention consisted of the implementation of a massage protocol with three sessions of 20 to 30minutes on alternate days over a one-week period. The effectiveness of the protocol was evaluated by assessing pain using the Brief Pain Inventory (BPI), while the effectiveness of each massage session was measured using the Visual Analogue Scale (VAS). RESULTS: the massage protocol was only effective in reducing the interference of pain in walking (p<0.05), although it also contributed to relieve pain and its impact on the children's activities. After each massage session, the intensity of the pain experienced by the child decreased (p<0.001). CONCLUSIONS: despite the small sample size, massage therapy appears to be a useful intervention in reducing pain in children with cancer. However, there are still questions regarding the effectiveness of this massage protocol. The authors recommend its use due to its contribution to the promotion of the child's well-being and quality of life.

Timing of antioxidant supplementation is critical in improving anorexia in an experimental model of cancer.

Increased oxidative stress may contribute to cancer anorexia, which could be ameliorated by antioxidant supplementation. methylcholanthrene (MCA) sarcoma-bearing Fisher rats were studied. After tumour inoculation, rats were randomly assigned to standard diet (CTR group, n = 6), or to an antioxidant-enriched diet (AOX group, n = 8). Eight more rats (STD-AOX group) switched from standard to antioxidant diet when anorexia developed. At the end of the study, food intake (FI, g/d), body weight and tumour weight (g) were recorded, and plasma samples were obtained. On day 16, anorexia has appeared only in CTR and STD-AOX animals. At the end of the study, FI in AOX animals was still higher than in the other groups (p = 0.08). No differences in body and tumour weights were observed among groups. However, hydrogen peroxide and interleukin-1ß levels were significantly reduced only in AOX rats. Data obtained suggest that early antioxidant supplementation improves cancer anorexia, ameliorates oxidative stress and reduces inflammation.

Sarcomas mandibulares: experiencia quirúrgica en los últimos 10 años / Mandibular sarcomas: surgical experience over the past 10 years

Introducción: Los sarcomas mandibulares representan una entidad de difícil estudio por su escasa incidencia e histopatología. Pacientes y métodos: Presentamos la experiencia del servicio de Cirugía Oral y Maxilofacial del Hospital Vall d’Hebron de Barcelona en los últimos 10 años (2001-2010) en el manejo de los sarcomas mandibulares, realizando una revisión retrospectiva de 12 casos de pacientes afectos por este tipo de tumor. Resultados: La técnica más utilizada para la reconstrucción fue el colgajo microvascularizado (hueso peroné: 8/12), recibiendo tratamiento adyuvante (quimioterapia y/o radioterapia) el 82% de los pacientes. Cinco pacientes fallecieron (42%), 2 se encuentran con progresión de la enfermedad (16%) y 5 sobreviven libres de enfermedad (42%) hasta la finalización del seguimiento. Conclusiones: Los casos descritos representan una serie singular debido a la localización mandibular, no antes publicadas en la literatura. Aún así, los resultados obtenidos en términos de supervivencia y factores pronóstico son similares a los descritos para los sarcomas de cabeza y cuello. La consecución de márgenes libres con la cirugía es la clave del tratamiento, siendo necesario el tratamiento complementario para mejorar el pronóstico(AU)

Introduction: Sarcomas located in the mandible are difficult to study due to their relatively rare appearance and histology. Patients and Methods: We present the experience of the Oral and Maxillofacial Surgery Department of the Vall d’Hebron Hospital in Barcelona over the last 10 years (2001-2010) in the management of jaw sarcomas, performing a retrospective review of 12 cases of patients affected by this type of tumour. Results: The technique mostly used for the reconstruction was the microvascularised bone graft (fibula: 8/12), with 82% of the patients receiving adjuvant therapy (chemotherapy and radiotherapy). Five of the patients died (42%), twowere found with disease progression (16%), and 5 survived free of disease (42%) until the end of follow-up. Conclusions: The cases described are a unique series due to the mandibular location. Prognostic factors and survival rates are similar to those described for head and neck sarcomas. Free margin during surgery must be the goal of treatment, additional chemotherapy or radiotherapy or both being required to improve the survival rates(AU)

Encephalopathy after high-dose Ifosfamide: a retrospective cohort study and review of the literature.

BACKGROUND: Encephalopathy occurs in 10-40% of patients treated with high-dose ifosfamide. Proposed risk factors for encephalopathy include hepatic or renal dysfunction, brain metastases, electrolyte imbalances and drug-drug interactions. OBJECTIVE: The purpose of this retrospective cohort study and literature review was to estimate the prevalence of encephalopathy, identify characteristics associated with encephalopathy and evaluate the effectiveness of methylthioninium chloride (methylene blue) in its prevention. STUDY DESIGN AND METHODS: A total of 19 patients received high-dose ifosfamide for soft tissue sarcoma during a 4-year period at our medical centre. Eight patients developed encephalopathy based on adverse drug event (ADE) reports submitted by a clinical pharmacist. These reports incorporate the Naranjo probability scale, which is used to assess the likelihood that a change in clinical status is the result of an ADE rather than the result of other factors, such as progression of disease. The demographics, concurrent medication therapy, co-existing illnesses and laboratory parameters were documented from the medical records. We also conducted a review of the literature by searching MEDLINE (1996-October 2007). MAIN OUTCOME AND RESULTS: A total of 19 patients received high-dose ifosfamide; eight patients experienced encephalopathy (group I, 42%) and 11 patients did not experience encephalopathy (group II, 58%). More women than men developed encephalopathy (group I, 87.5% vs group II, 27.3%). Serum albumin (group I, 3.1 +/- 0.3 vs group II, 3.6 +/- 0.3 g/dL), haemoglobin (10.5 +/- 1.5 vs 12.4 +/- 1.7 g/dL) and total bilirubin (0.5 +/- 0.2 vs 0.8 +/- 0.3 mg/dL) levels were substantially lower in patients with encephalopathy, whereas the ratio of actual bodyweight to the ideal bodyweight (1.4 +/- 0.3 vs 1.1 +/- 0.2) was substantially higher in these patients. Five (62.5%) patients received a subsequent cycle of high-dose ifosfamide; all of these patients received methylthioninium chloride to minimize the risk of encephalopathy. All of these patients developed encephalopathy. Other reports have found that hypoalbuminaemia is associated with encephalopathy and that methylthioninium chloride does not prevent ifosfamide-induced encephalopathy. CONCLUSIONS: In summary, female sex, low total bilirubin, albumin and haemoglobin levels, and obesity appear to be associated with ifosfamide-induced encephalopathy. Methylthioninium chloride did not appear to prevent encephalopathy with subsequent doses of high-dose ifosfamide.

Effects of omega-3 fatty acid supplementation on tumor-bearing rats.

BACKGROUND: Dietary fish oil (rich in omega-3 fatty acids: eicosapentaenoic acid and docosahexaenoic acid) suppresses synthesis and activity of proinflammatory cytokines that induce anorexia. We hypothesized that dietary fish oil reverses the feeding pattern of tumor anorexia, increasing food intake and retarding tumor growth. STUDY DESIGN: Thirty-two Fischer rats were placed in Automated Eater Meter cages and randomly divided into four groups: tumor bearing (TB) rats eating normal chow diet (TB-Chow); TB rats eating chow diet supplemented with omega-3 fatty acids (TB-omega-3FA); Controls, non-tumor bearing (NTB) rats eating normal chow (NTB-Chow); and NTB rats with omega-3 fatty acid supplementation (NTB-omega-3FA). Doses of 10(6) methylcholanthrene (MCA) sarcoma cells were subcutaneously injected in TB rats. Daily food intake, meal size (MZ), meal number (MN), body weight, and tumor volume were measured, and rats were euthanized at onset of anorexia. Data were statistically analyzed using analyses of variance (ANOVA) and t-tests. Data are reported as mean +/- SE. RESULTS: Tumor appeared significantly earlier in TB-Chow than in TB-omega-3FA rats (7.5 +/- 0.3 days versus 11.6 +/- 0.8 days, p < 0.05). Daily food intake declined significantly in TB-Chow versus TB-omega-3FA rats 18 days after tumor inoculation and, at onset of anorexia, was 9.41 +/- 1.77 g/day versus 13.32 +/- 0.81 g/day, p < 0.05. Food intake decreased initially by decrease in meal number (at day 15) followed by a decrease in meal size (at day 18). At onset of anorexia, meal size and meal number were significantly decreased in TB-Chow versus TB-omega-3FA rats (0.75 +/- 0.067 g/meal versus 1.05 +/- 0.08 g/meal, p < 0.05) and (9.5 +/- 1.32 versus 12.79 +/- 0.93 meals/day, p < 0.05), respectively. Tumor volume was significantly smaller in TB-omega-3FA versus TB-Chow rats (7.6 +/- 0.6 cm(3) versus 16.5 +/- 1.0 cm(3), p < 0.05), as was tumor weight (7.5 +/- 2.2 g versus 18.1 +/- 1.6 g, p < 0.05). CONCLUSIONS: In TB rats, omega-3FA improved food intake; restored normal eating pattern, delayed onset of anorexia, tumor appearance, and growth; and prevented body weight loss. Supplementation of omega-3 fatty acids has therapeutic potential in cancer anorexia.

Analgesic effects of a soy-containing diet in three murine bone cancer pain models.

UNLABELLED: Bone is a common metastatic site for prostate and breast cancer, and bone cancer is usually associated with severe pain. Traditional treatments for cancer pain can sometimes be ineffective or associated with side effects. Thus an increasing number of patients seek alternative therapies. In this study we investigated the analgesic effects of a soy diet on 3 experimental models of bone cancer pain. Mice were fed a diet in which the protein source was either soy or casein. After 1 week on the diet, sarcoma cells (NCTC 2472) were injected into the medullary cavity of the humeri, femur, or calcaneus. Experimenters blinded to diet of the animal assessed the pain behavior in these animals, forelimb grip force in the humerus model and paw withdrawal frequency to mechanical stimuli in the calcaneus and femur models. The effect of morphine on cancer-induced pain behavior was investigated in calcaneus and femur models. In addition, in the femur model, the effects of soy on tumor size and bone destruction were studied. The soy diet reduced secondary mechanical hyperalgesia in the femur model but had no effect on primary mechanical hyperalgesia in the calcaneus model or on movement-related hyperalgesia in the humerus model. No dietary impact was discerned in measurements of tumor size, bone destruction, and body weight in the femur model, suggesting that the soy diet had no effect on cancer growth. Morphine dose-dependently reduced hyperalgesia with no diet-based difference. These results suggest that a soy diet might provide analgesia in certain forms of hyperalgesia associated with bone cancer. PERSPECTIVE: The study raises the possibility of dietary supplements influencing aspects of cancer pain. Further research will help determine if use of nutritional supplements, such as soy proteins, can reduce opioid analgesic use in chronic pain states and help minimize the side effects associated with long term use of opioids.

Late effects surveillance system for sarcoma patients.

BACKGROUND: In 1998, a prospective multicenter pilot study of the 'Late Effects Surveillance System' (LESS) was started to investigate late effects of patients with Ewing, osteo- or soft-tissue sarcoma. PROCEDURE: Two hundred thirty patients were included in this pilot study. The patients were treated between 1/1/1998 and 6/30/1999 according to the sarcoma protocols COSS-96, CWS-96, and EICESS-92, the median cumulative doses of the focussed drugs were for cisplatin: 360 mg/m(2), for doxorubicin: 270 mg/m(2), and for ifosfamide: 24 g/m(2). The patients were investigated using an organ related standardized screening methodology. We report on toxicities in the first year after cessation of therapy-the beginning of the patient follow-up-and the feasibility of LESS. RESULTS: Cardiotoxicity: 16/129 (12%) patients treated with doxorubicin exhibited a reduced systolic heart function (fractional shortening (FS) <29%). Altogether three patients required cardiac drug therapy. Ototoxicity: In 5/73 (7%) patients treated with cisplatin a hearing deficit <4 kHz (>20 dB) was found. One patient needed a hearing aid. Nephrotoxicity: 2 of 214 (1%) patients treated with ifosfamide suffered from a tubulopathy, which required supplementation therapy. 10/50 (20%) showed a reduced fractional phosphate reabsorption. Incidence of hypomagnesemia was significantly increased in patients additionally treated with cisplatin. CONCLUSIONS: Some relevant impairments are noted in the first year after antineoplastic therapy. We expect to detect more major late sequelae in our prospective study during the increasing posttherapeutic interval. Our pilot study shows the feasibility of the methodology.

A report of two cases of Werner's syndrome and review of the literature.

Two cases of Werner's syndrome are reported. The first case is that of a man with grey hair since his 20s, and alopecia since aged about 50 years. At the age of 53 years, Werner's syndrome was diagnosed, along with a malignant soft tissue tumour of the hand. The patient underwent ray amputation for the tumour. The subsequent histopathological diagnosis was synovial cell sarcoma, and the patient died of lung metastasis at 15 weeks postsurgery. The second case is that of a woman diagnosed with diabetes mellitus when aged 34 years. At 39 years, a bilateral cataract was diagnosed and at 40 years, diabetic gangrene of the left calcaneal region and calcaneal osteomyelitis necessitated left below-knee amputation. The incidence of Werner's syndrome in Japan is extremely high (1000 of the around 1300 cases reported worldwide) compared to other countries. Most patients develop malignant tumour or arteriosclerosis, the most important complications of this syndrome. The average life expectancy for patients with Werner's syndrome is 46 years. The incidence of epithelial cancer and mesenchymal sarcoma is 10 times that of the general population. The onset of symptoms of Werner's syndrome generally precedes any later symptoms of associated conditions, such as malignant tumour. Therefore, early recognition of Werner's syndrome is important to assist identification of malignant tumours at an early stage in this patient group.

Erythropoietin restores the anemia-induced reduction in radiosensitivity of experimental human tumors in nude mice.

PURPOSE: The effect of recombinant human erythropoietin (rhEPO) on the radiosensitivity of human tumor xenografts growing in anemic and nonanemic nude mice was studied. METHODS AND MATERIALS: Anemia was induced by total body irradiation ([TBI], 2 x 4 Gy) of mice before tumor implantation into the subcutis of the hind leg. The development of anemia was prevented by rhEPO (750 U/kg s.c.) given 3 times weekly starting 2 weeks before TBI. Fourteen days after fractionated TBI (tumor volume of approx. 40 mm(3)), single-dose irradiation of the tumor with varying doses was performed so that in full dose-response relationship for the probability of tumor cure was obtained. RESULTS: Radiation-induced anemia (hemoglobin concentration [cHb] = 9.9 g/dl) led to a reduced radiosensitivity compared to controls [49.4 vs. 40.1 Gy radiation dose to control 50% of the tumors (TCD50)]. Upon rhEPO treatment for anemia prevention (cHb = 13.3 g/dl), the TCD50 was 39.8 Gy, illustrating restored radiosensitivity compared to anemic mice. CONCLUSION: These data provide further experimental evidence for restored radiosensitivity upon prevention of anemia with rhEPO.

Decreased NPY innervation of the hypothalamic nuclei in rats with cancer anorexia.

Whether the decrease in food intake that occurs at the onset of anorexia in tumor bearing (TB) rats is related to a change in the hypothalamic neuropeptide Y (NPY) system was tested by comparing NPY expression in sham operated Fischer Control and anorectic TB rats. Coronal cryocut sections of their fixed brain were processed by the peroxidase-antiperoxidase method with NPY polyclonal antibodies. NPY-immunoreactive fibers were widely distributed throughout the forebrain, but were most prominent in the hypothalamic paraventricular, suprachiasmatic, arcuate and periventricular nuclei. NPY-immunoreactive neurons were visualized in Control and anorectic TB rats in the preoptic region, the arcuate nucleus, and occasionally in the lateral hypothalamus. Semiquantitative image analysis showed a significant decrease in the NPY immunostaining in some hypothalamic nuclei of the anorectic TB rats, most prominently in the supraoptic nucleus, the parvocellular portion of the paraventricular nucleus, and, to a lesser extent, the suprachiasmatic and arcuate nuclei. No changes in NPY innervation were seen in the ventromedial nucleus and the lateral hypothalamus. The data support the hypothesis of an altered hypothalamic NPY system at the onset of anorexia in TB rats and also reveal the hypothalamic nuclei through which NPY influences food intake.

Is there a role for melatonin in supportive care?

Melatonin (MLT) is the main hormone released from the pineal gland and has proved to have physiological antitumor activity. MLT has been shown to exert anticancer activity through several biological mechanisms: antiproliferative action, stimulation of anticancer immunity, modulation of oncogene expression, and anti-inflammatory, anti-oxidant and anti-angiogenic effects. Several experimental studies have shown that MLT may inhibit cancer cell growth, and preliminary clinical studies seem to confirm its anticancer property in humans. In addition, MLT may have other biological effects, which could be useful in the palliative therapy of cancer, namely anticachectic, anti-asthenic and thrombopoietic activities. On this basis, the present clinical investigation was performed in an attempt at better definition of the therapeutic properties of MLT in human neoplasms. In a first clinical study, we evaluated the effects of MLT in a group of 1,440 patients with untreatable advanced solid tumors, who received supportive care alone or supportive care plus MLT. In a second study, we evaluated the influence of MLT on the efficacy and toxicity of chemotherapy in a group of 200 metastatic patients with chemotherapy-resistant tumor histotype, who were randomized to receive chemotherapy alone or chemotherapy plus MLT. In both studies, MLT was given orally at 20 mg/day during the dark period of the day. The frequency of cachexia, asthenia, thrombocytopenia and lymphocytopenia was significantly lower in patients treated with MLT than in those who received supportive care alone. Moreover, the percentage of patients with disease stabilization and the percentage 1-year survival were both significantly higher in patients concomitantly treated with MLT than in those treated with supportive care alone. The objective tumor response rate was significantly higher in patients treated with chemotherapy plus MLT than in those treated with chemotherapy alone. Moreover, MLT induced a significant decline in the frequency of chemotherapy-induced asthenia, thrombocytopenia, stomatitis, cardiotoxicity and neurotoxicity. These clinical results demonstrate that the pineal hormone MLT may be successfully administered in medical oncology in the supportive care of untreatable advanced cancer patients and for the prevention of chemotherapy-induced toxicity.

Fever and cancer in perspective.

CONTEXT: A relationship between feverish infection and concurrent remission from cancer has been known about for a very long time. However, a systematic investigation of the phenomenon has not yet been made. OBJECTIVE: To bring together the isolated observations about the coincidence of spontaneous remissions with feverish infections and William Coley's seminal work, as a basis for devising an immunological hypothesis about the putative anti-cancer effect of fever. CONCLUSION: Fever induction under medical guidance may be considered as part of a therapy regimen for cancers of mesodermal origin.