Dietary fat sources affect feed intake, digestibility, rumen microbial populations, energy partition and methane emissions in different beef cattle genotypes.

The mitigation of enteric methane emission in beef cattle production is important for reducing feed energy loss and increasing environmental sustainability. The main objective of this study was to evaluate the effect of different oilseeds included in fermented total mixed rations (whole soyabean seed (SBS, control), whole kapok seed (KPS) and cracked oil palm fruit (OPF)) on feed intake, digestibility, rumen microbial populations, energy partition and methane emissions in different cattle genotypes (Charolais crossbred v. Japanese Black crossbred). Three Charolais crossbred and three Japanese Black crossbred bulls were studied in a replicated 3×3 Latin square experimental design; genotypes were analysed in separate squares including three periods of 21 days each and three dietary oilseed treatments fed ad libitum. The cattle were placed in a metabolic cage equipped with a ventilated head box respiration system for evaluating digestibility and energy balance. As compared with Charolais crossbred individuals, Japanese Black crossbred bulls showed consistently lower dry matter intake (15.5%, P0.05) or diet (P>0.05) under the experimental conditions and ranged from 5.8% to 6.0% of gross energy intake. This value is lower than that reported by the Intergovernmental Panel on Climate Change (6.5%) for cattle fed with low-quality crop residues or by-products. Thus, our results imply that the Japanese Black crossbred cattle consume less feed and emits less enteric methane than the Charolais crossbred does, mainly owing to its lower ME requirement for maintenance. The OPF diet could be used to replace SBS for high beef production, although further studies are required to evaluate their application across a wide range of beef production systems.

Effect of media composition, including gelling agents, on isolation of previously uncultured rumen bacteria.

The aim of this study was to develop novel anaerobic media using gellan gum for the isolation of previously uncultured rumen bacteria. Four anaerobic media, a basal liquid medium (BM) with agar (A-BM), a modified BM (MBM) with agar (A-MBM), an MBM with phytagel (P-MBM) and an MBM with gelrite (G-MBM) were used for the isolation of rumen bacteria and evaluated for the growth of previously uncultured rumen bacteria. Of the 214 isolates composed of 144 OTUs, 103 isolates (83 OTUs) were previously uncultured rumen bacteria. Most of the previously uncultured strains were obtained from A-MBM, G-MBM and P-MBM, but the predominant cultural members, isolated from each medium, differed. A-MBM and G-MBM showed significantly higher numbers of different OTUs derived from isolates than A-BM (P < 0·05). The Shannon index indicated that the isolates of A-MBM showed the highest diversity (H' = 3·89) compared with those of G-MBM, P-MBM and A-BM (H' = 3·59, 3·23 and 3·39, respectively). Although previously uncultured rumen bacteria were isolated from all media used, the ratio of previously uncultured bacteria to total isolates was increased in A-MBM, P-MBM and G-MBM.

Mitigation of methane production from cattle by feeding cashew nut shell liquid.

The effects of cashew nut shell liquid (CNSL) feeding on methane production and rumen fermentation were investigated by repeatedly using 3 Holstein nonlactating cows with rumen fistulas. The cows were fed a concentrate and hay diet (6:4 ratio) for 4 wk (control period) followed by the same diet with a CNSL-containing pellet for the next 3 wk (CNSL period). Two trials were conducted using CNSL pellets blended with only silica (trial 1) or with several other ingredients (trial 2). Each pellet type was fed to cows to allow CNSL intake at 4 g/100 kg of body weight per day. Methane production was measured in a respiration chamber system, and energy balance, nutrient digestibility, and rumen microbial changes were monitored. Methane production per unit of dry matter intake decreased by 38.3 and 19.3% in CNSL feeding trials 1 and 2, respectively. Energy loss as methane emission decreased from 9.7 to 6.1% (trial 1) and from 8.4 to 7.0% (trial 2) with CNSL feeding, whereas the loss to feces (trial 1) and heat production (trial 2) increased. Retained energy did not differ between the control and CNSL periods. Digestibility of dry matter and gross energy decreased with CNSL feeding in trial 1, but did not differ in trial 2. Feeding CNSL caused a decrease in acetate and total short-chain fatty acid levels and an increase in propionate proportion in both trials. Relative copy number of methyl coenzyme-M reductase subunit A gene and its expression decreased with CNSL feeding. The relative abundance of fibrolytic or formate-producing species such as Ruminococcus flavefaciens, Butyrivibrio fibrisolvens, and Treponema bryantii decreased, but species related to propionate production, including Prevotella ruminicolla, Selenomonas ruminantium, Anaerovibrio lipolytica, and Succinivibrio dextrinosolvens, increased. If used in a suitable formulation, CNSL acts as a potent methane-inhibiting and propionate-enhancing agent through the alteration of rumen microbiota without adversely affecting feed digestibility.

Phylogenetic diversity of gene sequences isolated from the rumen as analysed using a self-organizing map (SOM).

AIMS: To determine the origins of DNA sequences isolated from the rumen microbial ecosystem using a self-organizing map (SOM). METHODS AND RESULTS: DNA sequences other than 16S small subunit ribosomal RNA (SSU rRNA) gene sequences that were detected from the rumen were analysed by the SOM method reported by Abe et al. [2000, Self-Organizing Map (SOM) unveils and visualizes hidden sequence characteristics of a wide range of eukaryote genomes. Gene 365, 27-34]. Because query sequences positioned by SOM were scattered on the master drawing of SOM, it was suggested that many DNA sequences isolated from the rumen were collected from a broad range of micro-organisms. Although the results obtained by SOM were similar to those obtained by the neighbour-joining (NJ) method, SOM was able to presume the phylotypes of the query sequences without information about the 16S SSU rRNA gene sequences and homology searches, and to reveal existence of novel micro-organisms deduced to be cellulolytic bacteria, archaea and methanotrophic bacterium. CONCLUSIONS: As the SOM method defined phylotypes of unreported rumen micro-organisms, it is presumed that these phylotypes would be involved in rumen fermentation in cooperation with known rumen micro-organisms. Moreover, it is demonstrated that SOM is a useful tool for affiliating DNA sequences, which have no matches in databases. SIGNIFICANCE AND IMPACT OF STUDY: Through SOM analysis, a better means of identifying rumen micro-organisms and estimating their roles in rumen function was provided.

The detection of possible sensor histidine kinases regulating citrate/malate metabolism from the bovine rumen microbial ecosystem.

AIMS: To detect sensor histidine protein kinases (HPKs) similar to accessory gene regulator C (AgrC) from the rumen microbial ecosystem. METHODS AND THE RESULTS: Genes related to sensor HPKs were amplified by PCR using two pairs of agrC-specfic primers from DNA extracted from bovine rumen contents. The PCR products were cloned, sequenced and phylogenetically analysed. It appeared that two sequences were HPKs. CONCLUSIONS: Although amino acid sequences deduced from the nucleotide sequences obtained in this study showed high similarities with sensor HPKs responding to citrate or C(4)-dicarboxylates, they did not show high similarities with AgrC. SIGNIFICANCE AND IMPACT OF THE STUDY: This study revealed the presence in the rumen of sensor HPKs responding to citrate or C(4)-dicarboxylates, which could stimulate rumen fermentation. Therefore, it has been shown that citrate or C(4)-dicarboxylate metabolism is partially regulated by a two-component regulatory system in some rumen bacteria.

Health-related quality-of-life after external beam radiation therapy for localized prostate cancer: intensity-modulated radiation therapy versus conformal radiation therapy.

We compared health-related quality-of-life (HRQL) after intensity-modulated radiotherapy (IMRT) with statuses obtained after old and new protocols of three-dimensional conformal radiation therapy (3DCRT) for localized prostate cancer. We measured the general and disease specific HRQL using the MOS 36-Item Health Survey (SF-36), and the University of California, Los Angeles Prostate Cancer Index (UCLA PCI), respectively. IMRT resulted in similar profiles of general and disease-specific HRQL to two other methods within the first year after treatment. Moreover, IMRT gave rise to comparable urinary, intestinal and sexual side effects despite the high dose of radiation applied.

Short communication: Amino acids antagonistic to the amino acids inhibitory for growth rate of mixed ruminal bacteria.

Antagonism of some amino acids (AA) to the inhibitory effects of other AA (Ile, Phe, and Thr) on the growth rate of mixed ruminal bacteria was investigated. In vitro growth rate of the mixed ruminal bacteria was inhibited when the 3 inhibitory AA (1 mM each) were each added to individual control treatments in which an ammonium salt was included as a sole N source. The inhibitory effect caused by Ile was relieved by addition of Leu or Val (equimolar to Ile), and no significant inhibition was shown when both Leu and Val were added together with Ile. The growth inhibition caused by Phe was also alleviated by supplementing with Trp, and was completely negated by adding Tyr. The inhibitory effect of Thr, on the other hand, was not affected by addition of Lys or Met (which are synthesized using a common pathway with Thr), but was mitigated by supplementation with Glu, Ser, Val, Ala, or Gln. Among the antagonistic AA, Leu, Val, Trp, Tyr, and Glu were indispensable for the maximum growth rate of the ruminal bacteria under the experimental condition of supplementation of amino-N, the removal of which from a mixture of 20 protein AA caused the growth rate to decline. Removals of Ile along with Leu or Val or both, of Phe along with Trp or Tyr, and of Thr along with Glu recovered the promotion of bacterial growth rate. It was concluded that inhibitions of the bacterial growth rate caused by Ile, Phe, or Thr could be antagonized by some other AA (Leu, Val, Tyr, Trp, or Glu), and the role of these latter AA as relievers of the inhibitory effects could explain why they are indispensable for maximum growth rate of ruminal bacteria.

Phylogenetic analysis of methyl coenzyme-M reductase detected from the bovine rumen.

AIMS: The object of the present study is isolation of methyl coenzyme-M reductase (MCR) genes (mcrA) from the bovine rumen fluid and determination of phylogenetical placements of the genes to investigate mechanisms of methanogenesis in the rumen from a point of view of mcrA genes. METHODS: Genes for methanogen-specific MCR were isolated from the bovine rumen by PCR amplification. The deduced amino acid sequences were fitted to the alignments of mcrA gene products from the referred sequences. SIGNIFICANCE AND IMPACT OF THE STUDY: Although the deduced amino acid sequences of mcrA genes, isolated from the bovine rumen in the present study, were close to that of Methanobrevibacter ruminantium, these amino acid sequences did not fall into known clusters of MCR. The findings suggest that methanogenesis in the rumen would be partially carried out by unknown methanogens.

Stimulatory and inhibitory effects of protein amino acids on growth rate and efficiency of mixed ruminal bacteria.

Mixed ruminal bacteria were incubated in vitro with glucose, xylose, cellobiose, and various protein amino acids replaced isonitrogenously with 25% (i.e., 25 mg of N/L) of ammonia-N, to determine the growth rate and the amount of sugar consumed in the exponential growth phase. The growth rate and efficiency (grams of bacteria per gram of sugars) increased by 46 and 15%, respectively, when a mixture of 20 amino acids was added. On the other hand, neither growth rate nor efficiency increased when any one of these amino acids was added singly, except for Glu and Gln, each of which produced significant but small improvements. The stimulatory effect of the combined amino acids on bacterial growth declined when each of Leu, Trp, Tyr, Glu, Met, Phe, and Val was removed from the original group of 20. When a mixture of only these seven amino acids was used as a supplement, their stimulatory effects on growth rate and efficiency were only 21 and 25%, respectively, of the effects that the mixture of 20 amino acids showed. The effects increased to 76 and 72% on growth rate and efficiency, respectively, when Gly, Cys, and His were supplied in addition to the seven amino acids. The growth rate and efficiency of the ruminal bacteria were inhibited by an addition of each of Ile, Thr, Cys, Phe, Leu, Lys, or Val to ammonia-N, and the effects of the first five of these amino acids were highly significant. Isoleucine, threonine, and phenylalanine were each inhibitory even at a low concentration (1 mg of NL), while cysteine and leucine showed inhibitory effects at higher concentrations (more than 10 mg of N/L). A higher growth rate of the ruminal bacteria when supplemented with amino acid mixtures was accompanied with a higher growth efficiency, which was attributable to a relatively smaller proportion of energy expended on maintenance according to the Pirt derivation.

Detection of Proteobacteria from the rumen by PCR using methanotroph-specific primers.

AIMS: To detect Proteobacteria, including methanotrophs, from the rumen fluid and the bacteria inhabiting the rumen epithelium. METHODS AND RESULTS: Proteobacteria inhabiting the rumen were detected by PCR using methanotroph-specific primers. The detected Proteobacteria were divided into clusters A, B, and C in addition to one clone, which was distinct from the clusters and closely related to Nitrosomonas sp. The clusters A, B, and C were close to Succinivibrio dextrinosolvens, Enterobacter cloacae, and Actinobacillus minor, respectively. The clones obtained from the rumen fluid each belonged to cluster A or B. The clones obtained from the rumen epithelium belonged to cluster B or C or to Nitrosomonas sp. CONCLUSIONS: It has been assumed that the rumen fluid and the rumen epithelium host different populations of Proteobacteria. Moreover, detection of Nitrosomonas from the rumen epithelium would indicate the possibility that the bacterium oxidizes ammonia and methane on the rumen surface. SIGNIFICANCE AND IMPACT OF THE STUDY: These findings suggest that the rumen fluid and the epithelium support different microbial populations, which would play specific roles in rumen function. Future study should focus on the relationship between these communities and physiological functions in the rumen.

Impact of boost irradiation with surgically placed radiopaque clips on local control in breast-conserving therapy.

BACKGROUND: The purpose of this study was to determine whether boost irradiation relying on radiopaque clips placed surgically around the resected margin of breast cancer contributes to increasing the local control rate in patients with close or positive margins in breast-conserving therapy (BCT). METHODS: Among 837 patients with breast cancer who underwent BCT between November 1987 and December 1998, 181 patients with close or positive surgical margins received boost irradiation following conventional tangential whole breast irradiation. Since 1994, four radiopaque clips were surgically placed around the resected margin of the breast cancer in 155 patients treated with wide excision. The four clips were clearly and accurately identified with a CT-simulator (CT-S). The boost irradiation field was automatically determined with a safety margin of 3 cm according to one-to-one correspondence of radiopaque clips to pathologically close or positive surgical margins. In the remaining 26 patients treated before 1994, the boost irradiation field was determined according to the skin tattoo of the primary tumor. RESULTS: The median follow-up period of the 155 patients receiving the radiopaque clips was 42 months (range: 19 to 78), and that of the 26 patients without the clips was 87 months. Local recurrence was observed in two of the 155 patients who underwent boost irradiation using the radiopaque clips 39 and 54 months after the surgery, while 4 of the 26 patients developed local recurrence 14, 23, 51, and 76 months after BCT. In three of the four patients without the clips developing local recurrences, local recurrences were observed at the margin of the boost irradiation field. The 5-year local recurrence-free survival rate of patients who received boost irradiation with the radiopaque clips was 97%, and that of patients without the clips was 88%. The difference of local recurrence-free survival rates between the patients with and without the clips was significant (p<0.05). CONCLUSION: Surgically placed radiopaque clips appear to be useful for determining adequate boost field in the BCT using the CT-S and help increase the local control rate.

Results of breast-conserving therapy for ductal carcinoma in situ: the Kyoto University experiences.

BACKGROUND: The purpose of this study was to evaluate the results of breast-conserving therapy (BCT), defined as the combination of breast-conserving surgery with axillary dissection and definitive radiation therapy for ductal carcinoma in situ (DCIS). METHODS: Between November 1987 and March 1998, 33 patients with DCIS undergoing BCT at our hospital were examined. The mean age was 48. All patients underwent quadrantectomy or wide excision as well as axillary dissection. Radiation therapy consisted of 50 Gy to the ipsilateral whole breast. Boost irradiation of 10 Gy was given to 15 patients with close or positive margins. Nearly all patients received adjuvant chemotherapy with 5-fluorouracil or its derivatives and adjuvant endocrine therapy with tamoxifen for 2 years. RESULTS: The minimum and median follow-up periods were 32 and 80 months, respectively. All patients but one were followed. Only one patient had a non-invasive local recurrence, 23 months after her operation. This patient was salvaged with simple mastectomy. Her prognostic index score was 8. The five-year local control rate was 97%. No serious acute or late complications were noted. CONCLUSION: The results of this retrospective study substantiate favorable data and appear to confirm the efficacy and reasonable local recurrence rate of BCT for the treatment of DCIS.

Meningeal carcinomatosis in patients with breast cancer: report of 8 patients.

BACKGROUND: Meningeal carcinomatosis (MC) is an uncommon but aggressive complication of advanced breast cancer with a recently increasing incidence. Although the prognosis is extremely poor for MC patients, early diagnosis and appropriate treatment are important. SUBJECTS AND METHODS: We reviewed 8 cases of MC from breast cancer at Kyoto University Hospital from 1990 to 1999. The median age was 51.5 years. All patients had widespread systemic metastases when diagnosed with MC. clinical symptoms were categorized into 3 groups: cranial nerve symptoms, spinal nerve symptoms, and other symptoms. Imaging studies were positive for MC in only 4 patients. Initial CSF cytology studies were positive in 4 patients, and repeated CSF cytology yielded positive results in the remaining 4 patients. Thus the median interval between the onset of any clinical symptom of MC and the initiation of treatment was 22.5 days (range 7 to 120 days ). All patients received whole brain radiotherapy (WBRT). Four patients were given intrathecal chemotherapy and/or intrathecal immunotherapy in addition to WBRT. RESULTS: Improvement of cranial nerve symptoms, spinal nerve symptoms, and other symptoms were observed in 3/5, 1/3, and 5/7 patients, respectively. Patients with cranial nerve symptoms who started WBRT within 29 days of the onset of the symptoms showed at least partial recovery whereas patients who started WBRT later showed no recovery. The median survival was 123 days (53 to 310 days). MC was the direct cause of death in 1 of 8 patients. CONCLUSION: When MC is clinically suspected, neither a negative imaging study nor a single negative CSF cytology can rule out MC. Prompt initiation of WBRT with or without intrathecal chemotherapy may be important for recovery from cranial nerve symptoms.

A case of allergic reaction to surgical metal clips inserted for postoperative boost irradiation in a patient undergoing breast-conserving therapy.

We report a case of a 28-year-old woman with right-sided breast cancer. The patient had been treated for atopic dermatitis since her infancy. She underwent breast-conserving surgery (BCS) in July 1998, and three titanium clips were placed at the margin of the excision cavity at the time of surgery. Two months after surgery, the patient exhibited a rapid exacerbation of atopic dermatitis. Various drugs were suspected to be the cause of the allergic reaction, but the results of a bi-digital O-ring test (BDORT) suggested an allergic reaction to titanium clips. In August 1999, the patient underwent a second operation to remove the titanium clips under local anesthesia. Allergy to surgical titanium clips is a rare complication, but in patients with a history of severe allergic diseases, a preoperative immunologic examination should be performed and the patient's history of metal allergy should be investigated.

Evaluation of glass microspheres for intra-arterial radiotherapy in animal kidneys.

PURPOSE: To evaluate the histologic distribution of nonradioactive microspheres when intra-arterially infused into normal kidneys, and to evaluate the histologic changes after the infusion. MATERIALS AND METHODS: The glass microspheres were SiO2 microspheres with a smooth spherical shape measuring 20-30 micrometers in diameter with a specific gravity of 2.2 g/cm3. After the microspheres were mixed with contrast medium, they were infused into the renal artery. Twelve rabbits were sacrificed at 1 day, 3 days, 1 week, and 8 weeks after the treatment, respectively. The specimen was fixed with 10% buffered formalin, specially embedded in methyl methacrylate (MMA) resin and was stained by hematoxylin-eosin. The distribution of the microspheres in the kidney was analyzed microscopically, and histologic changes were also evaluated. RESULTS: The microspheres were found in arterioles whose diameters were about 20-30 micrometers, within normal kidneys. All vessels containing microspheres were confined to arterioles or arteries. No migration of microspheres was detected in the normal lung or the contralateral kidney. Severe ischemic changes were observed in kidneys, developing within 8 weeks of the infusion. CONCLUSION: Glass microspheres seemed to be a useful embolic material for intra-arterial radiation therapy.

Determination of optimal radiation energy for different breast sizes using CT-simulator [correction of simulatior] in tangential breast irradiation.

BACKGROUND: The purpose of this study is to determine and recommend the optimal radiation source according to breast size for tangential irradiation in breast conserving therapy. METHODS: Twenty-eight patients treated at our department from January 1994 to January 1996 were studied. The dose distribution within the irradiated breast was calculated using a (60)Co-gamma ray and 6 MV-X ray. Then we compared 3-D dose distributions of the (60)Co-gamma ray and 6 MV-X ray in different-sized breasts. Three parameters (breast volume, chest wall separation, and breast height) were adopted as representative of breast size. We also examined correlations among the three parameters. RESULTS: When the breast size was large (breast volume >400 cm(3), chest wall separation > 19.5 cm, or breast height > 6.5 cm), the average volume of normal tissue which received more than 110% of the isocenter dose ("hot spot") was significantly greater with the (60)Co-gamma ray than with the 6 MV-X ray (p < 0.05). A similar result was obtained with regard to hot spots in the clinical target volume. The cold area that received less than 95% of the isocenter dose was greater using a 6 MV-X ray when the breast size was small (breast volume <200 cm(3), chest wall separation <17.5 cm, or breast height <5.0 cm). However, the difference was not significant. There was a significant correlation between breast volume and chest wall separation (r =0.849, p <0.001). Breast volume and breast height were also significantly correlated (r =0.813, p <0.001). CONCLUSIONS: Since breast volume and shape are different in each patient, the optimal energy should be selected for each case to obtain uniform dose distribution in breast-conserving therapy. Chest wall separation or breast height, which are measurable without a 3-D planning system, can substitute for breast volume as parameters for breast size. We recommend that the (60)Co-gamma ray not be used for treating large breasts, those with chest wall separation > or =19.5 cm or breast height > or =6.5 cm.

Results of breast-conserving therapy for early stage breast cancer: Kyoto University experiences.

This study evaluated the results of breast-conserving therapy (BCT). Nine hundred six patients who underwent BCT at our hospital between November 1987 and February 1998 were analyzed. The mean age was 48 years. According to the Union Internationale Contre le Cancer 1997 classification system, stages 0, I, IIA, IIB, IIIA, and IIIB were 37, 400, 344, 117, 7, and 1, respectively. Radiation therapy consisted of 50 Gy to the ipsilateral whole breast. Boost irradiation of 10 Gy was administered to 186 of 231 patients with close or positive margins. Nearly all patients received adjuvant chemohormonal therapy with tamoxifen and 5-fluorouracil or its derivatives for 2 years. The minimum and median follow-up periods were 18 and 52 months, respectively. The 5-year overall survival, cause-specific survival, local recurrence-free survival, and disease-free survival rates were 97.3%, 98.4%, 98.1%, and 91.5%, respectively. Local recurrence in preserved breast occurred in 20 patients 7 to 86 months after surgery. Multivariate analysis revealed that the most predictive factor for disease-free survival rates and distant failures was the number of pathologically positive lymph nodes (p < 0.0001), and that the factor for local failure was marginal status (p = 0.005). This study demonstrated that BCT was suitable for the treatment of early-stage breast cancer with its reasonable survival rates and acceptable toxicity.

Cosmetic results and complications after breast conserving therapy for early breast cancer.

BACKGROUND: The cosmetic and functional results of breast conserving therapy for early breast cancer were evaluated. These are important endpoints in the assessment of breast conserving therapy in addition to tumor control and survival. The factors suspected to influence cosmesis were also analyzed. METHODS: In 206 patients with stage I and II breast cancer treated by wide excision and axillary dissection followed by radiation therapy, the cosmetic results and complications were analyzed. The cosmetic outcome was assessed by a scoring method and breast retraction assessment (BRA). As complications, arm edema and restriction of shoulder movement and late skin reactions were analyzed. RESULTS: Of the 206 patients 92% showed an excellent to good cosmetic score before radiation therapy. The score deteriorated, but gradually improved and stabilized after 1 year. Eighty-one percent of the patients had an excellent to good cosmetic score at 3 years. The BRA of the 206 patients was 1.8 cm on average before radiation therapy. It increased to 2.3 cm after termination of radiation therapy, and did not change thereafter. Tumor size over 2 cm (p = 0.005) and tumors in the inner quadrant (p = 0.003) were factors which negatively affected the cosmetic score at 3 years. Tumor size over 2 cm (p = 0.003), tumors in the upper quadrant (p = 0.005), or a nipple-tumor distance of more than 2 cm (p = 0.01) were also negative factors for the BRA at 3 years. Arm edema, restriction of shoulder movement, and late skin reaction were generally mild, and were observed in 12%, 0% and 34% of patients at 3 years, respectively. CONCLUSIONS: The overall cosmetic results of breast conserving therapy are acceptable and the complication rate is low. Tumor characteristics, tumor size, location and nipple-tumor distance are factors that affect cosmesis.

Long-term results of radiation therapy for pituitary adenoma.

PURPOSE: Local control for pituitary adenomas treated with external beam radiation therapy was retrospectively analyzed to evaluate the efficacy of radiation. MATERIALS AND METHODS: Thirty-eight patients treated with radiation therapy between 1979 and 1994 were analyzed. The median age was 46. Nineteen newly diagnosed tumors were treated with surgery and radiation therapy, while the others were recurrent cases. Twenty-two tumors were non-functioning, while 10 produced growth hormone (GH) and three each were prolactin-, and adrenocorticotropic hormone (ACTH)-producing tumors. The median-radiation dose was 50 Gy in 25 fractions. RESULTS: Non-functioning adenomas and prolactin-producing adenomas were completely controlled, judging from the absence of tumor progression on neuroimaging studies and clinical symptoms, and normalization of the serum prolactin level (< 25 ng/ml). On the other hand, local control was obtained in only one of the 3 patients with ACTH-producing adenomas, and the control rate at 10 years was only 46% for GH-producing adenomas. Panhypopituitarism developed in 35% of the patients after radiation therapy. No other serious complications were noted. CONCLUSION: Non-functioning pituitary adenomas and prolactin-producing adenomas were well controlled with external radiation therapy combined with surgery. However, dose escalation might be necessary to control GH-or ACTH-producing tumors. It is important to replace corticosteroid hormone and thyroid hormone in many patients.

Outcome at 8 years after breast-conserving surgery and radiation therapy for invasive breast cancer: influence of margin status and systemic therapy on local recurrence.

PURPOSE: To examine the relationship between pathologic margin status and outcome at 8 years after breast-conserving surgery and radiation therapy. PATIENTS AND METHODS: The study population comprised 533 patients with International Union Against Cancer/American Joint Committee on Cancer clinical stage I or II breast cancer who had assessable margins, who received at least 60 Gy to the primary tumor bed, and who had more than 8 years of potential follow-up. Each margin was scored (according to the presence of invasive or in situ disease that touched the inked surgical margin) as one of the following: negative, close, focally positive, or extensively positive. Outcome at 8 years was calculated using crude rates of first site of failure. A polychotomous logistic regression analysis was performed. Median follow-up time was 127 months. RESULTS: At 8 years, patients with close margins and those with negative margins both had a rate of local recurrence (LR) of 7%. Patients with extensively positive margins had an LR rate of 27%, whereas patients with focally positive margins had an intermediate rate of LR of 14%. In the polychotomous logistic regression model, margin status and the use of systemic therapy were the only two variables that had significant effects on the risk ratio of LR to remaining alive and free of disease. Among the 45 patients with focally positive margins who received systemic therapy, the crude LR rate was 7% at 8 years (95% confidence interval, 1% to 20%). CONCLUSION: Pathologic margin status and the use of adjuvant systemic therapy are the most important factors associated with LR among patients treated with breast-conserving surgery and radiation therapy.