Predictive and prognostic value of total tumor load in sentinel lymph nodes in breast cancer patients after neoadjuvant treatment using one-step nucleic acid amplification: the NEOVATTL study.

OBJECTIVE: To evaluate the predictive and prognostic value of total tumor load (TTL) in sentinel lymph nodes (SLNs) in patients with infiltrating breast cancer after neoadjuvant systemic therapy (NST). METHODS: This retrospective multicenter study used data from a Spanish Sentinel Lymph Node database. Patients underwent intraoperative SLN biopsy after NST. TTL was determined from whole nodes using a one-step nucleic acid amplification (OSNA) assay and defined as the total sum of CK19 mRNA copies in all positive SLNs. Cox-regression models identified independent predictive variables, which were incorporated into a nomogram to predict axillary non-SLN metastasis, and identified prognostic variables for incorporation into a disease-free survival (DFS) prognostic score. RESULTS: A total of 314 patients were included; most had no lymph node involvement prior to NST (cN0; 75.0% of patients). Most received chemotherapy with or without biologic therapy (91.7%), and 81 patients had a pathologic complete response. TTL was predictive of non-SLN involvement (area under the concentration curve = 0.87), and at a cut-off of 15,000 copies/µL had a negative predictive value of 90.5%. Nomogram parameters included log (TTL + 1), maximum tumor diameter and study-defined NST response. TTL was prognostic of disease recurrence and DFS at a cut-off of 25,000 copies/µL. After a 5-year follow-up, DFS was higher in patients with ≤ 25,000 copies/µL than those with > 25,000 (89.9% vs. 70.0%; p = 0.0017). CONCLUSIONS: TTL > 15,000 mRNA copies/µL was predictive of non-SLN involvement and TTL > 25,000 mRNA copies/µL was associated with a higher risk of disease recurrence in breast cancer patients who had received NST.

Intestinal toxicity induced by 5-fluorouracil in pigs: a new preclinical model.

BACKGROUND: The goal of this study was to develop an animal model of intestinal injury induced by 5-fluorouracil (5-FU) in pigs. METHODS: Six domestic pigs were used as control (healthy group) and another 6 malnourished pigs orally received 5-FU (treated group). After 4 weeks of treatment, pigs were sacrificed and jejunum, ileum and colon were isolated for histological, immunological and biochemical analyses. RESULTS: 5-FU caused a decrease in the intestinal mass. Disaccharidase, and phosphate alkaline activities, and glutathione redox cycle were disrupted by 5-FU. Histopathological alterations in the crypts and villous were greater in the small intestine than in the colon. 5-FU decreased the number of peripheral and intestinal leukocytes, promoting an increase in T-cytotoxic cells and a decrease in T-helper and B cells. CONCLUSION: This pig model of intestinal dysfunction closely mimics the common side effects of cancer chemotherapy in humans, and provides a useful tool for evaluating novel antimucotoxic agents.

Predictive and prognostic value of total tumor load in sentinel lymph nodes in breast cancer patients after neoadjuvant treatment using one-step nucleic acid amplification: the NEOVATTL study

Objective To evaluate the predictive and prognostic value of total tumor load (TTL) in sentinel lymph nodes (SLNs) in patients with infiltrating breast cancer after neoadjuvant systemic therapy (NST). Methods This retrospective multicenter study used data from a Spanish Sentinel Lymph Node database. Patients underwent intraoperative SLN biopsy after NST. TTL was determined from whole nodes using a one-step nucleic acid amplification (OSNA) assay and defined as the total sum of CK19 mRNA copies in all positive SLNs. Cox-regression models identified independent predictive variables, which were incorporated into a nomogram to predict axillary non-SLN metastasis, and identified prognostic variables for incorporation into a disease-free survival (DFS) prognostic score. Results A total of 314 patients were included; most had no lymph node involvement prior to NST (cN0; 75.0% of patients). Most received chemotherapy with or without biologic therapy (91.7%), and 81 patients had a pathologic complete response. TTL was predictive of non-SLN involvement (area under the concentration curve = 0.87), and at a cut-off of 15,000 copies/µL had a negative predictive value of 90.5%. Nomogram parameters included log (TTL + 1), maximum tumor diameter and study-defined NST response. TTL was prognostic of disease recurrence and DFS at a cut-off of 25,000 copies/µL. After a 5-year follow-up, DFS was higher in patients with ≤ 25,000 copies/µL than those with > 25,000 (89.9% vs. 70.0%; p = 0.0017). Conclusions TTL > 15,000 mRNA copies/µL was predictive of non-SLN involvement and TTL > 25,000 mRNA copies/µL was associated with a higher risk of disease recurrence in breast cancer patients who had received NST (AU)

Sunflower, virgin-olive and fish oils differentially affect the progression of aortic lesions in rabbits with experimental atherosclerosis.

In this study we report the effects of sunflower, virgin olive and fish oils on the progression of aortic lesions. A total of 24 male New Zealand rabbits (six per each group) were fed for 50 days on a diet containing 3% lard and 1.3% cholesterol, to induce atherosclerosis. An atherogenic control group (A) was killed after this period and three groups were fed for an additional period of 30 days with a diet composed of (1.75 g of supplemented oil and 98.25 of standard chow): sunflower oil (S), virgin olive oil (O) and fish oil (F). A control group (n=6) was fed with a standard chow diet for 80 days. LDL lipid composition and histological analysis of aortic atherosclerotic lesions were assayed. The atherogenic diet caused a significant increase of cholesterol levels in LDL and aorta tissue. Cholesterol ester content rose significantly in the aortic arch of groups S, O and F. Fatty streaks were found in all aortic sections, although only group S showed a significant progression of the lesion compared with group A. We conclude that the replacement of a high cholesterol-saturated fat diet by another cholesterol free-unsaturated fat diet does not regress atherosclerosis in rabbit. However, sunflower oil provokes a significant progression in lesion development, whereas diet enrichment with extra virgin olive oil and, to a lesser extent, fish oil, stops this progression.

Oral administration of a turmeric extract inhibits LDL oxidation and has hypocholesterolemic effects in rabbits with experimental atherosclerosis.

The oxidation of low-density lipoproteins (LDL) plays an important role in the development of atherosclerosis. Curcumin is a yellow pigment obtained from rhizomes of Curcuma longa and is commonly used as a spice and food colouring. Curcumin and turmeric extracts have several pharmacological effects including antitumour, anti-inflammatory, antioxidant and antiinfectious activities although the precise mechanisms involved remain to be elicited. We evaluated the effect of an ethanol-aqueous extract obtained from rhizomes of C. longa on LDL oxidation susceptibility and plasma lipids in atherosclerotic rabbits. A total of 18 rabbits were fed for 7 weeks on a diet containing 95.7% standard chow, 3% lard and 1. 3% cholesterol, to induce atherosclerosis. The rabbits were divided into groups, two of which were also orally treated with turmeric extract at doses of 1.66 (group A) and 3.2 (group B) mg/kg body weight, respectively. A third group (group C) acted as a control. Plasma and LDL lipid composition, plasma alpha-tocopherol, plasma retinol, LDL TBARS, LDL lipid hydroperoxides and analysis of aortic atherosclerotic lesions were assayed. The low but not the high dosage decreased the susceptibility of LDL to lipid peroxidation. Both doses had lower levels of total plasma cholesterol than the control group. Moreover, the lower dosage had lower levels of cholesterol, phospholipids and triglycerides in LDL than the 3.2-mg dosage. In conclusion, the use of this extract could be useful in the management of cardiovascular disease in which atherosclerosis is important.

[Primary intraoral epithelioid hemangioendothelioma. Case report and review of the literature]. / Hemangioendotelioma epitelioide primario intraoral. Presentación de un caso y revisión de la literatura.

Epithelioid Hemangioendothelioma (EH) is a vascular neoplasm of soft tissue, recently described by Weiss and Enzinger. The biologic al behavior of the tumor has a intermediate malignant potential, in the sense that it has an indolent course, with the potential for recurrence, but rarely metastasizes. This tumor arises from medium- to large-sized vessels, primarily involves the soft tissues of the extremities, as well as the liver, lung, and bone, and rarely occurs in the head and neck region. Only fifteen well--documented cases of Epithelioid Hemangioendothelioma involving the head and neck region have been reported. Nine cases have been recently reported in the oral cavity. This is a report of one additional case in the tongue. Because of the intermediate malignant potential of Epithelioid Hemangioendothelioma, complete tumor resection is recommended for intraoral lesions.