Prognostic factors in gastric cancer patients: a 10-year mono-institutional experience.

Introduction: Gastric cancer (GC) is one of the main causes of death from cancer globally. Long-term survival, especially in Western countries, remains dismal, with no significant improvements in recent years. Therefore, precise identification of clinical and pathological risk factors is crucial for prognosis, as it allows a better selection of patients suitable for oncologically radical treatments and contributes to longer survivals. Methods: We devised a retrospective observational longitudinal study over 10 years of experience with GC patients operated with curative intent. Results: Several factors were thoroughly investigated in a multivariate analysis to look for significance as independent risk factors for disease-free survival. Our results showed that only BMI, pTNM, and lymph node ratio expressed hazard ratios with implications for survival in our series of patients. Discussion: Although limited by the retrospective nature of the study, this is one of the few cancer reports from Northern Italy showing results over 10 years, which may in our view, have an impact on decision-making processes for multidisciplinary teams dedicated to the care of gastric cancer patients.

Six-month humoral and cellular immune response to the third dose of BNT162b2 anti-SARS-CoV-2 vaccine in patients with solid tumors: a longitudinal cohort study with a focus on the variants of concern.

BACKGROUND: The role and the durability of the immunogenicity of the third dose of vaccine against COVID-19 variants of concern in cancer patients have to be elucidated. PATIENTS AND METHODS: We have prospectively evaluated the immunogenicity of the third dose of the SARS-CoV-2 BNT162b2 messenger RNA vaccine in triggering both humoral and cell-mediated immune response in patients with solid tumors undergoing active treatment 6 months after the booster. Neutralizing antibody (NT Ab) titers and total anti-spike immunoglobulin G concentrations were measured in serum. Heparinized whole blood samples were used for the SARS-CoV-2 interferon-γ release assay (IGRA). RESULTS: Six months after the third dose only two patients (2.4%) showed negative spike-specific immunoglobulin G antibody levels (<33.8 BAU/ml). The median level of SARS-CoV-2 NT Abs decreased and only 39/83 (47%) subjects showed maximum levels of NT Abs. T-cellular positive response was observed in 38/61 (62.3%) patients; the highest median level of response was observed 21 days after the third dose (354 mIU/ml, interquartile range 83.3-846.3 mIU/ml). The lowest median level of NT Ab response was observed against the Omicron variant (1 : 10, interquartile range 1 : 10-1 : 40) with a significant reduced rate of responder subjects with respect to the wild-type strain (77.5% versus 95%; P = 0.0022) and Delta variant (77.5% versus 93.7%; P = 0.0053). During the follow-up period, seven patients (8%) had a confirmed post-vaccination infection, but none of them required hospitalization or oxygen therapy. CONCLUSIONS: Our work highlights a significant humoral and cellular immune response among patients with solid tumors 6 months after the third BNT162b2 vaccine dose, although a reduction in neutralizing activity against Omicron was observed.

Strong impact of sarcopenia as a risk factor of survival in resected gastric cancer patients: first Italian report of a Bicentric study.

Gastric cancer (GC) accounts for 4% of all cancers in Europe. Sarcopenia is a complex syndrome characterized by a loss of muscle mass and function associated with age, often present in neoplastic patients. Recently, several studies have shown a significant association between sarcopenia and poor prognosis in various pathological conditions. The current observational retrospective study investigates the association between sarcopenia and overall survival (OS) and recurrence-free survival (RFS) in patients with GC undergoing up-front surgery with curative intent. Resected GC patients' clinical records and CT images were retrospectively assessed. The preoperative CT calculation of the skeletal muscle index (SMI) at L3 level allowed us to categorize patients as sarcopenic or not. Kaplan-Meyer and univariate and multivariate Cox regression analyses were performed to determine the difference in survival and presence of independent prognostic factors. Fifty-five patients, 28 male and 27 female, out of 298 studied for gastric cancer were enrolled in the current study from two cancer referral centers in Italy. The preoperative CT calculation of the SMI at L3 level allowed us to identify 39 patients with and 16 without sarcopenia. A statistically significant difference between the sarcopenic and non-sarcopenic groups was observed in both OS and RFS (p < 0.023; p < 0.006). Moreover, sarcopenia was strongly correlated to a higher risk of recurrence in univariate and multivariate analysis (p < 0.02). Sarcopenia can be considered a critical risk factor for survival in patients with resectable GC treated with up-front surgery. Identifying sarcopenic patients at the time of diagnosis would direct selection of patients who could benefit from early nutritional and/or physical treatments able to increase their muscle mass and possibly improve the prognosis. More extensive multicenter studies are needed to address this issue.

Role of poorly differentiated cluster in gastric cancer: is it a new prognosis factor?

BACKGROUND: Poorly differentiated Clusters (PDCs) of tumor cells composed of more than five elements have been recently described in gastrointestinal cancers and correlate with a worse prognosis. Our study aims to investigate PDC occurrence in a series of patients with gastric cancer and correlate it with lymph node status and clinical outcome. MATERIAL AND METHODS: 50 patients were included in the study; PDCs count was graduated as G1, G2, and G3 according to Ueno classification (PDCs count at 20× <5, 5-9 and ≥10 respectively). We collected several clinicopathologic variables such as tumor location, pTNM stage, vascular or perineural invasion, and lymph-node ratio for each case. RESULTS: The presence of PDCs was related to vascular invasion (p < .013) and recurrence event (p < .027). When the population was categorized according to the number of PDCs, a significant correlation was found with the presence of lymph node metastasis (p < .000), the Lymph Node Ratio (p < .002), WHO stage at the diagnosis (p < .000) and vascular invasion (p < .001). At the univariate and multivariate analysis, PDCs were found as an independent risk factor for recurrence (HR 1.94; CI 95% 1.209-3.121; p < .006 and HR 0.401; CI 95% 0.187-0.862; p < .017 respectively). The Kaplan-Meier curves for OS and DFS showed a significant association between PDCs and shorter time to recurrence or survival. CONCLUSION: PDC is a strong prognostic factor in gastric cancer, easily detectable, and feasible. As far as we know, this is the first report in Literature of a strong correlation between PDC and survival in patients with operated gastric cancer.

Treatment Following Progression in Metastatic Melanoma: the State of the Art from Scientific Literature to Clinical Need.

INTRODUCTION: In the last few years, the advent of targeted therapy and immunotherapy has improved the management and the prognosis of metastatic melanoma, but the spread of resistance mechanisms can lead to disease progression. The clinical management in this setting can be challenging because the oncologist has to decide what is the best treatment strategy among therapy beyond progression (TBP), therapy change, and the rechallenge approach. This review of the relevant scientific literature is intended to clarify which patients with progressing metastatic melanoma will benefit from continuation of ongoing therapy and which ones will not. The data are based on a total of about 4300 patients coming from the main retrospective studies in the chosen field. The article body is divided into four sections which analyze respectively the targeted therapy beyond progression, the immunotherapy beyond progression, the possible treatment sequences, and finally the rechallenge strategy. RECENT FINDINGS: Despite the possible approaches of TBP or rechallenge, the patient may not have an optimal response and may need new therapy, which is currently missing. To broaden the pharmacological offer in the fight against melanoma, cancer research is studying new disease targets, like the NRAS, PI3K, and cKIT pathways or combination treatment of targeted therapy plus immunotherapy. Despite the limitations of this work, mainly due to the limited number of studies, their retrospective nature and the lack of comparative studies, the analysis performed allows us to draw some important conclusions: therapy beyond progression, both targeted therapy and immunotherapy, represents a valid treatment option with positive effects on disease control and survival outcomes for patients with low clinical risk, expressed as low disease burden, normal LDH levels, and good performance status; moreover, the prognosis and quality of life of these patients improve when TBP is associated with locoregional treatments. In patients with progressive metastatic melanoma and high clinical risk (high disease burden, high LDH levels, and poor performance status), it is recommended to change therapy, without ever forgetting the possibility of enrolling the patient in a clinical trial. Finally, an efficacious treatment alternative is the rechallenge strategy; this approach consists in a re-treatment with the same drug after a variable interval of discontinuation. Preliminary studies seem to have demonstrated that patients retreated with targeted therapy achieved a greater benefit if they had a low clinical risk and if the drug doublet (BRAF + MEK inhibitors) was used. On the side of immunotherapy, the rechallenge strategy produced a major benefit in patients who prior experienced a severe toxic episode.

Negative pressure wound therapy (NPWT) after cytoreductive surgery (CRS) and intraperitoneal chemotherapy (HIPEC) for peritoneal surface malignancies: preliminary report.

AIM: Surgical site (SSI) infection is a common complication that occurs in the post-operative period because it still has a decisive impact on the morbidity and mortality of patients and the costs associated with therapy and prolongation of hospitalization. In recent years, therefore, several authors have published their experience in the use of negative pressure prevention systems (NPWT) for the management of surgical wounds. Few authors in the literature have discussed the use of NPWT in patients undergoing cytoreductive surgery (CRS) for peritoneal surface malignancies associated with hyperthermic intraperitoneal chemotherapy (HIPEC). PATIENTS AND METHODS: Nineteen patients undergoing open surgery, of which 15 underwent CRS+HIPEC operations; in 2 cases the dressing was applied to patients undergoing colon surgery, 1 case after emergency laparotomy for intestinal occlusion in a patient with a BMI of 29 and 1 case after gastric surgery for a tumour. At the and of the surgery, NPWT was placed on the surgical site; the therapy includes a closed and sealed system which maintains a negative pressure between at -125 mmHg on the surgical wound and which remains in place for five days. RESULTS: The rationale for using an NPWT is to determine a barrier between the wound and external contamination, reducing wound tension and reducing the formation of seroma and hematoma. Moreover, during the HIPEC, several litres of water are used to wash the patient's abdominal cavity and then the patient is sutured again without the peritoneum, losing the function of protection from external microorganism and also of reabsorbing the intra-abdominal serum. A recent Cochrane collaboration about the application of NPWT demonstrates that it may reduce the rate of SSI compared with SSD, even if there is no sure evidence about the reduction of complications like seromas or dehiscence. CONCLUSION: After the analysis of the preliminary data, we confirm the possibility to start with a randomised clinical trial, as suggested by the literature.

Cushing's syndrome due to ectopic ACTH production by a nasal paraganglioma.

UNLABELLED: Ectopic secretion of ACTH is an infrequent cause of Cushing's syndrome. We report a case of ectopic ACTH syndrome caused by a nasal paraganglioma, a 68-year-old female with clinical features of Cushing's syndrome, serious hypokalaemia and a right paranasal sinus' lesion. Cranial magnetic resonance image showed a 46-mm mass on the right paranasal sinuses. Endocrinological investigation confirmed the diagnosis of ectopic ACTH production. Resection of the tumour normalised ACTH and cortisol secretion. The tumour was found to be a paraganglioma through microscopic analysis. On follow-up 3 months later, the patient showed nearly complete clinical recovery. Ectopic ACTH syndrome due to nasal paraganglioma is extremely uncommon, as only two other cases have been discussed in the literature. LEARNING POINTS: Ectopic Cushing's syndrome accounts for 10% of Cushing's syndrome etiologies.Most paraganglioma of the head and neck are not hormonally active.Nasal paraganglioma, especially ACTH producing, is a very rare tumour.

Corneal hemangiosarcoma in a cat.

A 10 year-old castrated male Domestic Short-hair cat with a history of chronic bilateral keratitis was referred for assessment of a red, elevated mass involving the left cornea. The rapid growth of the mass, over a month period in combination with pronounced vascularization and invasion of the corneal surface suggested an aggressive inflammatory or neoplastic process. Following keratectomy, the lesion was diagnosed histopathologically as a hemangiosarcoma. The tumor recurred locally within 3 weeks and enucleation was performed. Histopathologic examination of the globe confirmed the diagnosis and did not reveal infiltration of the limbus and conjunctiva. No signs of local recurrence or metastatic disease have been observed 18 months following enucleation. To the authors' knowledge this is the first case of primary corneal hemangiosarcoma described in the feline species.

Inter-laboratory comparison of elemental analysis and gas chromatography combustion isotope ratio mass spectrometry (GC-C-IRMS). Part I: delta13C measurements of selected compounds for the development of an isotopic Grob-test.

This study was directed towards investigating suitable compounds to be used as stable isotope reference materials for gas chromatography combustion isotope ratio mass spectrometry (GC-C-IRMS) calibration. Several compounds were selected from those used in the 'Grob-test' mixture. Oxygen- and nitrogen-containing substances were added to these compounds to allow the mixture to be used as a possible multi-isotopic calibration tool for 2H/1H, 13C/12C, 15N/14N and 18O/16O ratio determinations. In this paper we present the results of delta13C measurements performed by the consortium of the five laboratories taking part in this inter-calibration exercise. All the compounds were individually assessed for homogeneity, short-term stability and long-term stability by means of EA-IRMS, as required by the bureau communitaire de reference (BCR) Guide for Production of Certified Reference Materials. The results were compared then with the GC-C-IRMS measurements using both polar and non-polar columns, and the final mixture of selected compounds underwent a further certification exercise assessing limits of accuracy and reproducibility under specified GC-C-IRMS conditions.

[Randomised clinical trial of an intensive intervention into life-styles of patients with hyperfibrinogenaemia in primary prevention of cardiovascular pathology in primary health care]. / Ensayo clínico aleatorizado de una intervención intensiva sobre los estilos de vida de pacientes con hiperfibrinogenemia en prevención primaria de las enfermedades cardiovasculares en el ámbito de la atención primaria de salud.

OBJECTIVES: To study the effect of an intensive programme to modify life-style on levels of plasma fibrinogen in patients without cardiovascular pathology, with high fibrinogen and normal cholesterol levels. To analyse whether the effect on fibrinogen is independent, or otherwise, of the effect on lipids. DESIGN: Randomised clinical trial with a control. SETTING: 11 health districts in L'Hospitalet de Llobregat and Barcelona. PARTICIPANTS: 436 patients will be included, 218 individuals between 35 and 75 years old in each group, and without cardiovascular pathology (ischaemic cardiopathy, cerebral vascular accident or peripheral arteriopathy), with hyperfibrinogenaemia (fibrinogen > 300 mg/dL) and with plasma control < 250 mg/dL. INTERVENTIONS: One group of patients will receive an intensive intervention (in frequency and intensity of counselling and treatment) for life-style changes, i.e. stopping smoking, low-calorie diet in case of overweight or obesity, and physical exercise. The follow-up of the intervention group will be every 2 months. The control group will follow customary treatments. MEASUREMENTS: Levels of plasma fibrinogen. In addition, other relevant events will be recorded over a 2-year monitoring period: modification of risk factors, changes in quality of life, cardiovascular events or death. DISCUSSION: The introduction of an intensive primary prevention intervention (life-style changes) in patients with hyperfibrinogenaemia could be a more effective measure than the habitual intervention for reducing plasma fibrinogen figures. In addition, these measures could be translated into a reduction of cardiovascular risk and an improvement in the patient s quality of life.

17beta-O-Aminoalkyloximes of 5beta-androstane-3beta,14beta-diol with digitalis-like activity: synthesis, cardiotonic activity, structure-activity relationships, and molecular modeling of the Na(+),K(+)-ATPase receptor.

A series of digitalis-like compounds with a 17-aminoalkoxyiminoalkyl or -alkenyl substituent was synthesized and evaluated for inhibition of Na(+),K(+)-ATPase and for inotropic activity. The highest inhibition was found with compounds having the substituent in configuration 17beta and the amino group at a distance of 6 or 7 bonds from C(17) of the digitoxigenin skeleton. The presence of the oxime function strengthens the interaction with the receptor, more if alpha,beta-unsaturated, thus mimicking the electronic situation of the unsaturated lactone in natural digitalis compounds. The most active compounds showed Na(+),K(+)-ATPase inhibitory potencies (IC(50)) 17-25 times higher than the standards digitoxigenin and digoxin and 3-11 times higher inotropic potencies (EC(50)) in isolated guinea pig left atria. These features are supported by a molecular model suggesting the possible interactions of the groups described above with particular amino acid residues in the H1-H2 domains of Na(+),K(+)-ATPase. Some interactions are the classical ones already described in the literature; a new, very strong interaction of the basic group with the Cys138 was found and adds new possibilities to design compounds interacting with this region of the receptor. The most interesting compounds were also studied in vivo in the anesthetized guinea pig for evaluating their inotropic effect versus the lethal dose. Compounds 9 and 12 showed a slightly higher safety ratio than digoxin and deserve further evaluation.

Autologous graft-versus-host disease after CD34+-purified autologous peripheral blood progenitor cell transplantation.

Autologous graft-versus-host disease (GVHD) has been frequently reported after cyclosporine A (CsA) administration in the autologous setting. This complication is related to the disruption of self-tolerance mechanisms induced by CsA and may exert an antitumor effect. We report the spontaneous occurrence of autologous GVHD after CD34+-purified peripheral blood progenitor cell transplantation (PBPCT) in 5 out of 24 consecutive patients (20.8%). The syndrome was characterized by skin rash (5/5), pruritus (5/5), eosinophilia (5/5), and fever (2/5) occurring at a median of 37 days (range 22-60) after transplantation. Diagnosis was confirmed by skin biopsy in all patients. The syndrome was self-limiting, lasted a median of 25 days, and did not require treatment. The rate of autologous GVHD was high after CD34+-purified autologous PBPCT. In fact, no autologous GVHD was documented in an historical control of 100 consecutive patients submitted to unmanipulated PBPCT at the same institution. The manipulation of the graft by the purging procedure causes a profound T lymphocyte depletion, thus possibly perturbing the equilibrium between autoregulatory cells and autocytotoxic T cells. These observations add new interest to the antitumor efficacy of autologous GVHD and suggest new questions regarding the role of transplantation for autoimmune diseases.

Quercetin inhibits p21-RAS expression in human colon cancer cell lines and in primary colorectal tumors.

Immunocytochemical studies have revealed that 10 microM quercetin reduced the steady state levels of p21-ras proteins in both colon cancer cell lines and primary colorectal tumors. These findings were confirmed by Western blot and flow cytometric analysis showing that the inhibition of p21-ras expression by quercetin was time- and concentration-dependent. Twenty-four-hour treatment with 10 microM quercetin reduced p21-ras levels to about 50% of control values. Quercetin was similarly effective in inhibiting the expression of K-, H-, and N-ras proteins. Moreover, the effect of quercetin on ras oncogene expression was not dependent on the cell cycle position of colon cancer cells and appeared to be specific and not merely a consequence of overall inhibition of protein synthesis. Northern blot analysis revealed that quercetin produced in colon cancer cells an early (30 min) reduction of the steady state levels of K-, H-, and N-ras mRNAs. This reduction was also present after 6 hr of flavonoid treatment. These effects of quercetin suggest a possible chemopreventive role for this compound in colorectal carcinogenesis.

Morphometric prognostic index in breast cancer.

OBJECTIVE: To assess the ability of the morphometric prognostic index (MPI) in predicting clinical outcome in a group of breast cancer patients with short-term follow-up and to assess the relationship between MPI and other prognosticators. STUDY DESIGN: The study group consisted of 63 cases of breast cancer. Follow-up data were available for 48 patients. MPI values were calculated, and degree of nuclear and tubular differentiation was investigated in each tumor. S-phase fraction (SPF), estrogen and progesterone receptors were also studied. RESULTS: The group of patients with MPI values < 0.60 had percent values of disease-free survival significantly higher than did those with MPI values > or = 0.60. Furthermore, significant direct correlations were found between MPI and degree of nuclear atypia and between MPI and SPF. Significant inverse relationships were found between MPI and tumor progesterone receptor levels and between MPI and degree of histologic tubular differentiation. CONCLUSION: The validity of MPI as a prognosticator in breast cancer was confirmed, even in a limited number of patients observed in short-term follow-up. MPI seems to be a reliable and economical prognosticator in selecting breast cancer patients for adjuvant chemotherapy.

Scintigraphic assessment of swallowing after horizontal supraglottic laryngectomy.

OBJECTIVE: Oral-pharyngo-esophageal scintigraphy (OPES) proved to be able to demonstrate the pharyngeal residue of the radioactive bolus after deglutition and the presence and amount of tracheobronchial aspiration, and to calculate exactly the transit time of the various swallowing phases. The aim of this study was to evaluate the real objective effectiveness of OPES in order to assess the degree of swallowing recovery after horizontal supraglottic laryngectomy (HSL). METHODS: Nineteen patients entered the study, and 17 healthy subjects were included as control group (group 1). Nineteen patients in whom HSL had been performed at least 1 year before underwent OPES. They were divided into two groups: 13 patients (group 2) in whom the tracheal cannula had been removed and swallowing, phonatory, and respiratory functions were satisfactory and 6 patients (group 3) in whom the tracheostomy tube was still in situ for aspiration of liquids and scarring of the laryngeal vestibule. RESULTS: Our results showed that in the patients who underwent HSL, all scintigraphic semiquantitative parameters and particularly aspiration percentage values and Pharyngeal Ritention Index (PRI) at 10 and 60 seconds were able to pinpoint some residual "subclinical" alteration and/or minimal surgical sequelae frequently observed after this kind of functional surgery, even though a substantially satisfactory recovery was achieved clinically (group 2 versus group 1). In addition, aspiration amounts in group 3 were markedly higher than those in group 2 (p < .0002), and mean PRI values at 10 and 60 seconds were significantly different (p < .0001) from normal mean control values (group 1). CONCLUSION: Oral-pharyngo-esophageal scintigraphy may be regarded as a noninvasive, well-tolerated technique, with a radiation body burden within satisfactory limits of radioprotection. It appeared to be also sensitive in assessing the swallowing recovery after HSL.

[Intestinal infarct caused by giant cell arteritis]. / Infarto intestinal causado por arteritis de células gigantes.

Arteritis of giant cells compromising extracranial and particularly intestinal tissues is not frequent. Therefore, it is common practice to make the diagnosis retrospectively after analyzing the surgical sample. A case is presented of an 83 year old woman admitted to the Clinical Department with a clinical course of 3 days of evolution characterized by fever and pain in the left hemiabdomen. Her personal medical history included multiple diverticulosis of colon, collecistectomy and appendicectomy. Laboratory tests showed that uremia was 0.75 g/L (N.L to 0.45 g/L), V.E.S. 90 mm at the first hour, and the rest of the determinations were normal. The chest and abdomen rays as well as the abdomen and pelvis ecographies were normal. A diagnosis was reached as acute diverticulitis and the patient was treated with 400 mgr of ciprofloxacina and 2,000 mgr a day of metronidazol. She continued in a feverish state and with abdominal pain, so that an anexial tomography of abdomen was taken. It showed a widening of peritoneal fascias with scarce liquid in the left parietocolic dripping and Douglas septum. After 96 hours, surgery exploration was done and injuries in the left colon revealed compatibility with an infarct of the colon which had to be extirpated. Pathological examination revealed an infarct of colon due to a secondary arterial thrombosis characteristic of giant cell arteritis. After the diagnosis, immunological studies and biopsy of the left temporal artery were performed and reported as normal. The patient was treated with 40 mgr of prednisone a day improving rapidly.

Involvement of the retinoblastoma protein in brown and white adipocyte cell differentiation: functional and physical association with the adipogenic transcription factor C/EBPalpha.

We investigated the expression of the retinoblastoma protein (pRB) in adipocytes and its possible interaction with the adipogenic transcription factor CCAAT/enhancer-binding protein alpha (C/EBPalpha) in controlling the acquisition of the terminally differentiated adipocyte phenotype. The pRB was expressed (as measured by immunoblotting and/or immunofluorescence) in mice brown and white adipose tissue and in cultured adipocytes that showed lipid accumulation and expressed specific differentiation markers such as aP2 (measured using a specific cDNA probe) and in the case of brown adipocytes UCP-1 (measured using specific antibodies), but was undetectable in proliferative undifferentiated preadipocytes. Transient transfection experiments revealed a functional interaction between pRB and C/EBPalpha affecting transcription from the ucp-1 gene promoter. Thus, in immortalized brown adipocytes, co-transfection of both a C/EBPalpha and a pRB expression vectors maximally enhanced the expression of reporter chloramphenicol acetyltransferase driven by the ucp-1 promoter. Interestingly, C/EBPalpha inhibited reporter gene expression in CHO cells in an effect that was also potentiated in the presence of pRB. A positive effect of pRB on transcription from the ucp-1 promoter could be detected in C/EBPalpha-/-fibroblasts only after forced to overexpress C/EBPalpha, suggesting that the effect of pRB is dependent on its interaction with C/EBPalpha. We also found evidence that pRB and C/EBPalpha can directly bind to each other in vitro. Our results show that the expression of pRB is restricted to differentiated adipocytes, and provide evidence of a physical and functional interaction between pRB and C/EBPalpha that affects the transcriptional activity of the later on a brown adipocyte-specific gene.

Long-lasting complete remission in plasma cell leukemia after aggressive chemotherapy and CD34-selected autologous peripheral blood progenitor cell transplant: molecular follow-up of minimal residual disease.

Plasma cell leukemia is a rare disease associated with very poor survival with standard treatment. We report a patient affected by plasma cell leukemia treated with aggressive chemotherapy and autologous CD34-selected PBPC who achieved a complete remission now lasting more than 2 years. Molecular studies confirmed the presence of minimal residual disease (MRD) despite the absence of disease activity. High-dose chemotherapy with stem cell rescue may be applied to selected patients considering the impact of the treatment on survival. The meaning of molecular MRD in this setting is unclear.

Energy restriction with high-fat diet enriched with coconut oil gives higher UCP1 and lower white fat in rats.

OBJECTIVE: To investigate the effects of overfeeding on a high fat diet, enriched in coconut oil, and the influence of food restriction on the uncoupling protein (UCP1) expression and on body fat content. DESIGN AND SUBJECTS: In experiment I, female Wistar rats were fed ad libitum either a normal-fat diet (control group, C) or a high-fat diet (HF), enriched in coconut oil, for 7 weeks. In experiment II, HF rats after finishing experiment I were fed (for 3 weeks) either the normal-fat diet (group CAHF, Control After High Fat) or food restricted diets which provided 60% of the energy intake of group CAHF: a group fed a low-energy, normal-fat diet (LENF) and another fed a low-energy, high-fat diet (LEHF). MEASUREMENTS: Body and fatty depot weights. Food intake. Protein and UCP1 levels of interscapular brown adipose tissue. RESULTS: High-fat diet feeding promoted an increase in body fat content, body weight and UCP1 levels. Energy restriction induced similar body weight reduction in groups LENF and LEHF. However, some adipose depots were more strongly reduced in the rats fed the high-fat diet enriched in coconut oil (group LEHF) than in the rats fed the normal-fat diet (Group LENF). Specific UCP1 was 2.0 (group LENF) and 3.4 (group LEHF) times higher than in controls (group CAHF). CONCLUSION: The coconut-oil enriched diet is effective in stimulating UCP1 expression during ad libitum feeding and in preventing its down regulation during food restriction, and this goes hand in hand with a decrease of the white fat stores.