Long-term outcome after neoadjuvant radiochemotherapy in locally advanced noninflammatory breast cancer and predictive factors for a pathologic complete remission : results of a multivariate analysis.

BACKGROUND: An earlier published series of neoadjuvant radiochemotherapy (NRT-CHX) in locally advanced noninflammatory breast cancer (LABC) has now been updated with a follow-up of more than 15 years. Long-term outcome data and predictive factors for pathologic complete response (pCR) were analyzed. PATIENTS AND METHODS: During 1991-1998, 315 LABC patients (cT1-cT4/cN0-N1) were treated with NRT-CHX. Preoperative radiotherapy (RT) consisted of external beam radiation therapy (EBRT) of 50 Gy (5 × 2 Gy/week) to the breast and the supra-/infraclavicular lymph nodes combined with an electron boost in 214 cases afterwards or-in case of breast conservation-a 10-Gy interstitial boost with (192)Ir afterloading before EBRT. Chemotherapy was administered prior to RT in 192 patients, and concomitantly in 113; 10 patients received no chemotherapy. The update of all follow-up ended in November 2011. Age, tumor grade, nodal status, hormone receptor status, simultaneous vs. sequential CHX, and the time interval between end of RT and surgery were examined in multivariate terms with pCR and overall survival as end point. RESULTS: The total pCR rate after neoadjuvant RT-CHX reached 29.2%, with LABC breast conservation becoming possible in 50.8% of cases. In initially node-positive cases (cN+), a complete nodal response (pN0) after NRT-CHX was observed in 56% (89/159). The multivariate analysis revealed that a longer time interval to surgery increased the probability for a pCR (HR 1.17 [95% CI 1.05-1.31], p < 0.01). However, in large tumors (T3-T4) a significantly reduced pCR rate (HR 0.89 [95% CI 0.80-0.99], p = 0.03) was obtained. Importantly, pCR was the strongest prognostic factor for long-term survival (HR 0.28 [95% CI 0.19-0.56], p < 0.001). CONCLUSION: pCR identifies patients with a significantly better prognosis for long-term survival. However, a long time interval to surgery (> 2 months) increases the probability of pCR after NRT-CHX.

Nitrogen requirement of pregnant gilts.

Eleven Yorkshire x Landrace gravid gilts were used in two Latin square trials to determine the N requirement for pregnancy. Semipurified diets were formulated to be adequate in indispensable amino acids (IAA) and other nutrients. Diets were fed once daily (1.82 kg); L-glutamic acid, corn sugar, powdered cellulose, and soybean oil percentages differed to maintain isocaloric diets. In Trial 1, six gilts were fed diets containing 6.6 to 17.2% CP equivalent (19.2 to 50.1 g of N/d) during six 10-d periods beginning on d 40 postcoitum. In Trial 2, five gilts were fed diets containing 4.3 to 12.6% CP equivalent (12.5 to 36.8 g of N/d) during five 10-d periods beginning on d 50 postcoitum. Nitrogen balance trials were conducted during the last 5 d of each period. Blood samples were taken both before and 3 h after the last feeding of each period. Results from Trial 1 suggested that adequate N retention (10 g/d) could be attained by pregnant gilts fed less than 28 g of N/d intake when the diet contained indispensible amino acids at levels suggested by Nutrient Requirements of Swine (NRC, 1988). An intake of 20.6 g of N/d (7.1% CP equivalent) yielded near maximum N retention among pregnant gilts fed the semipurified diets in Trial 2. Other criteria measured (urine urea nitrogen and plasma urea nitrogen) had limited value in the evaluation of the N status of the pregnant gilts in these trials.

Estimation of the isoleucine and aromatic amino acid requirements of pregnant swine.

The requirements of the pregnant gilt for isoleucine (Ile), total aromatic amino acids (TAAA), phenylalanine (Phe) and the replacement of Phe with tyrosine (Tyr) were investigated in these studies. Five balanced 6 x 6 latin-square arrangements of treatments and time periods were conducted with six pregnant gilts in each trial. Each diet treatment was fed (1.8 kg once daily) for 10 d beginning on d 40 of pregnancy. Nitrogen balance trials were conducted from the 6th to 10th d during each period. Blood samples were obtained from each gilt before and 2 h after the last feeding in each period. Based on the titration trials, the L-Ile requirement was satisfied at .23% of the diet. Assuming that crystalline L-Ile was 100% available, the L-Ile requirement for pregnant gilts fed a corn-soybean meal diet is estimated at .25%. A dietary requirement of no more than .43% satisfied all the criteria measured in the L-TAAA trial. Adjustment for availability of crystalline L-Phe used in the diets would increase the requirement to about .48% dietary L-TAAA. About 42% of the L-TAAA requirement for pregnancy should be supplied by L-Phe.

Partitioning nitrogen and amino acids for pregnancy and lactation in swine: a review.

Nitrogen and amino acid requirements for maintenance, maternal growth, mammary growth and products of conception were partitioned on the basis of data from numerous sources. These data were compared with N retention values obtained from balance trials conducted during pregnancy. Carefully conducted N balance trials will yield N retention data that are reasonably comparable with N deposition data determined from tissue analyses. Based on indispensable amino acid (IAA) requirements for maintenance and pregnancy, the IAA were partitioned among maintenance, maternal growth, and products of conception including mammary growth. The nonspecific N requirement also was estimated in these calculations. Results indicate that the pregnancy requirements for total N and nonspecific N could be reduced considerably from present recommendations (NRC, 1988). Nitrogen and IAA requirements for lactation were partitioned between maintenance and milk production. Estimates of total N and nonspecific N that were derived factorially also were substantially less than present recommendations (NRC, 1988).

Phenylalanine requirement of the lactating sow.

Six mature Yorkshire X Landrace sows were randomly assigned to a 6 X 6 Latin-square experiment on d 3 of lactation to determine the phenylalanine (Phe) requirement in the presence of excess tyrosine (Tyr). A control diet of corn sugar, cornstarch, whey, L-glutamic acid, solka floc, soybean oil, amino acids, minerals and vitamins was supplemented with L-Phe to provide .175, .250, .325, .400, .475 and .550% Phe and .47% Tyr. Each diet was fed to a maximum of 5.5 kg/d within each of six 7-d periods. Sow milk yield and average pig weight gain decreased (cubic, P less than .01) with increasing time period. Feed intake and average pig weight gain were depressed (quadratic, P less than .05) on the lowest Phe diet, but milk yield was not significantly affected. Daily nitrogen (N) intake was depressed (quadratic, P less than .01) when sows consumed the .175% Phe diet, but percent fecal N was not affected. Percent urine N decreased (quadratic, P less than .001) and percent N retained (without milk) increased with increasing Phe to .288 and .296%, respectively. Daily secretion of milk N as a percentage of N intake was not affected by diet. Percent overall N balance (with milk) increased with increasing Phe to .307%. Urea N decreased with increasing dietary Phe in both plasma (linear, P less than .01) and urine (quadratic, P less than .001) to a breakpoint at .285% Phe. A sharp rise (quadratic, P less than .01) in plasma Phe occurred at .299% dietary Phe. Plasma Tyr increased (quadratic, P less than .05) as dietary Phe increased, but no clear inflection point was obtained.(ABSTRACT TRUNCATED AT 250 WORDS)

Aromatic amino acid requirement of the lactating sow.

Six mature Yorkshire X Landrace sows were randomly assigned to a 6 X 6 Latin-square experiment on d 5 of lactation to determine the total phenylalanine (Phe) and tyrosine (Tyr) requirement. A control diet of corn sugar, cornstarch, whey, L-glutamic acid, solka floc, soybean oil, amino acids, minerals and vitamins was supplemented with L-Phe to provide .30 (basal), .45, .60, .75, .90 and 1.05% total aromatic amino acids (TAAA). Each diet was fed to a maximum of 5.5 kg/d within each of six 10-d periods. Feed intake, average pig weight gain and sow milk yield decreased linearly (P less than .01) with increasing period. Sow milk yield was maximized at .75% TAAA (quadratic, P less than .10), but average pig weight gain did not reflect the higher yield. Urea nitrogen decreased quadratically with increasing dietary Phe in both plasma (P less than .05) and urine (P less than .01) to a breakpoint at .56% TAAA. Plasma Phe increased (quadratic, P less than .01) as dietary TAAA increased, but no clear inflection point was obtained. A sharp rise (quadratic, P less than .001) in plasma Tyr occurred at .73% dietary TAAA. Plasma lysine decreased (linear, P less than .001) to a low level at .76% TAAA, but plasma methionine was unaffected by treatment. Urine allantoin/urea X protein intake was maximized at .61% TAAA (quadratic, P less than .01). Nitrogen (N) intake varied among diets (quadratic, P less than .05), but fecal N was not altered by TAAA level.(ABSTRACT TRUNCATED AT 250 WORDS)

Efficacy of nosiheptide as a growth promotant for growing-finishing swine--a cooperative study.

A cooperative study involving 296 pigs was conducted at two experiment stations and at a commercial research farm to evaluate the efficacy of nosiheptide as a growth promotant for growing-finishing swine. At each station, five or six replicate pens of four or five pigs/pen were fed a fortified, corn-soybean meal basal diet with 0, 5.5, 11 or 22 ppm nosiheptide. Initial and final weights averaged 11 and 92 kg, respectively. Daily gain increased quadratically (623, 664, 669, 678 g/d; P less than .03) and feed/gain decreased quadratically (3.35, 3.24, 3.24, 3.28; P less than .02) with increasing level of nosiheptide. Breakpoint analysis indicated that gain plateaued at 6.8 ppm and feed/gain at 5.5 ppm of nosiheptide. Averaged across all levels of nosiheptide, gain and feed/gain during the growing phase (11 to 52 kg body weight) were improved by 13.1 and 7.6%, respectively, by feeding the antibiotic. For the entire growing-finishing period, gain was improved by 5.3% and feed/gain by 2.9% in pigs fed nosiheptide. Although there were large differences in gain and feed/gain, the responses to dietary treatments were similar among the three stations. The results indicate that nosiheptide is an effective growth-promoting agent for growing-finishing swine.

Estimating milk yield of sows.

Hourly milk yields were obtained for nine consecutive hours at d 14 of lactation from 92 crossbred (four breed) sows during their first and second lactations. Additionally, milk yields were obtained at d 14 and 20 of lactation from 175 mature Yorkshire X Landrace sows for nine consecutive hours. Each measurement (4,806 observations) was obtained by weighing the pigs before and after each hourly nursing. These data were examined with the objective of understanding the consequences of reducing the number of measurements obtained from each sow. Four data sets were formed from the measurements, namely, first parity crossbred sows, second parity crossbred sows, d 14 and d 20 milk yields from the Yorkshire X Landrace sows. Differences (P less than .01) among the hourly milk yield estimates found in all four data sets were largely accounted for by the low yield for h 1 and moderate reduction for h 2 compared with the means of nine measurements. There were no significant differences among the hourly yields for h 3 through 5 compared with h 3 through 9 in three of the four data sets. Mean hourly milk yield for first parity crossbred sows, however, increased as additional hourly measurements were taken. Using the mean hourly milk yield estimate of h 3 through 5 would give an unbiased estimate of h 3 through 9, except for first parity sows, and a standard error only 13% greater than the standard error for nine hourly measurements. The shorter procedure would save considerable time and labor.

Valine requirement for reproduction in swine.

Five levels of L-valine [3.3 (basal), 5.5, 7.8, 10.1 and 12.4 g/d] were fed to gilts from one estrus before mating through two pregnancies and for 30 d of a third pregnancy. Five litter-mate outcome groups of five animals each were allocated randomly to the diet treatments. Animals were individually fed 1.82 kg/d premating and during pregnancy. A common diet was fed to all animals during lactation at levels of 4.0 and 4.75 kg/d for first and second farrowings, respectively. Animals fed 3.3 g/d L-valine retained less N (P less than .10) at d 45 and 90 for two pregnancies than did animals fed higher valine levels. Plasma valine concentrations determined after a 24-h fast and 2 h postfeeding increased sharply (P less than .01) among animals fed more than 5.5 g/d L-valine. There was a treatment X bleeding time interaction (P less than .01) for plasma valine, explained by a postfeeding depression compared with a higher fasting concentration for animals fed 3.3 g/d L-valine. At all other levels of valine, the fasting and postfeeding plasma valine concentrations were equal or increased after feeding. Sow weight gain during the experiment increased (linear, P less than .05) as dietary L-valine increased. Estimated milk yield was greatest for animals fed 5.5 g/d, but average pig gain was maximized at 7.8 g/d L-valine. We conclude that 5.5 g/d L-valine met the requirement for pregnancy in this experiment.(ABSTRACT TRUNCATED AT 250 WORDS)

Protein-amino nutrition of nonruminant animals with emphasis on the pig: past, present and future.

During the period of 1958 to 1983, the fortified corn-soybean meal diet became standard for swine production systems. Dietary formulation changed from a protein to an amino acid basis. Amino acid requirements were established for all classes of swine. For growing swine, some of these studies led to refinements of earlier estimated requirement values, but for brood sows, both gestating and lactating, requirements for virtually all of the indispensable amino acids were established for the first time. With requirement values available, attention turned to factors affecting requirements, e.g., protein level, energy level, amino acid balance, sex and criterion of response. In addition, initial attempts were made to obtain amino acid bioavailability values for swine feedstuffs. Other nonruminant species were also represented in the dramatic changes that occurred in protein-amino acid nutrition. Improved and highly palatable purified crystalline amino acid diets were developed for rats, chicks, dogs, cats, rabbits and fish. Nitrogen nutrition and metabolism of nonruminant herbivores (e.g., rabbits and horses) likewise became better understood during the last 25 yr.

Threonine requirement for reproduction in swine.

An experiment was conducted to estimate the threonine requirement of pregnant swine. L-threonine was added to a fortified corn-gelatin diet and fed at a rate to provide five threonine levels of 3.59, 4.95, 6.31, 7.67 and 9.03 g/d. Twenty-five crossbred gilts were randomly assigned to these five dietary treatments. Increasing threonine resulted in a difference (P less than .01) in nitrogen (N) retention, with maximum retention at 4.95 g/d threonine intake. Blood samples were drawn before and after feeding. Although plasma urea N did not change significantly, the lowest level occurred at an intake of 4.95 g/d threonine. As threonine intake increased, plasma threonine increased quadratically (P less than .05). This increase was accompanied by a quadratic (P less than .005) decrease in plasma lysine. Sow weight gains increased quadratically (P less than .01) with increasing threonine levels. Litter weight, number of pigs born, baby pig gains, daily milk yield and milk protein were not influenced by threonine levels. The lysine-alpha-ketoglutarate reductase activity of the sow liver samples increased linearly (P less than .05) as dietary threonine levels increased. Based upon metabolic criteria 4.95 g/d L-threonine met the requirement for animals in this experiment. If 75% of threonine in a corn-soybean meal diet is available, the threonine requirement for reproduction would be no higher than 5.4 g/d or .30% dietary threonine when daily feed intake is 1.82 kg.

Valine requirement of the lactating sow.

An experiment was conducted using production and metabolic criteria to estimate the valine requirement of the lactating sow. Ground corn, gelatin, corn sugar, vitamins, minerals and indispensable amino acids were used to formulate a diet containing all the essential nutrients except valine. L-valine was added to provide .23 (basal), .38, .53, .68 and .83% valine. Twenty-five mature Landrace x Yorkshire sows were randomly assigned to the five dietary treatments. Milk production and average pig weight gain increased quadratically (P less than .01) and were maximized at .68% dietary valine. Total solids production (p less than .05) and protein production (P less than .01) increased with increasing level of valine, and both were maximized at .68% dietary valine. Protein content also was maximized (P less than .01) at .68% dietary valine. Fecal (P less than .05) and urinary (P less than .01) nitrogen decreased with increasing valine, yielding greatest (P less than .01) nitrogen retention (excluding milk nitrogen) at .53% dietary valine. Because daily milk nitrogen production also increased (P less than .01) with increasing valine, there were no treatment differences (P greater than .05) in nitrogen balance (including milk nitrogen). Plasma valine concentration increased (P less than .01) gradually until .53% valine was fed, after which there was a rapid increase in concentration. Plasma isoleucine and leucine decreased (P less than .01) with increasing dietary valine. Plasma urea concentration was minimal (P less than .05) with .38% dietary valine. When all the criteria measured are considered, the lactating sow's requirement of valine is between .53 and .68%. The metabolic data support .53% dietary valine for the requirement, although the maximum response in production parameters at .68% dietary valine suggests that the requirement is above .53% dietary valine.