ABSTRACT
A novel coccidian species was discovered in the prostate of an Antechinus flavipes (yellow-footed antechinus) in South Australia during the period of postmating male antechinus immunosuppression and mortality. This novel coccidian is unusual because it develops extraintestinally and sporulates endogenously within the prostate gland of its mammalian host. Histological examination of prostatic tissue revealed dense aggregations of spherical and thin-walled tetrasporocystic, dizoic, sporulated coccidian oocysts within tubular lumina, with unsporulated oocysts and gamogonic stages within the cytoplasm of glandular epithelial cells. This coccidian was observed occurring concurrently with dasyurid gammaherpesvirus 1 infection of the antechinus' prostate. Eimeria-specific 18S small-subunit ribosomal (r)DNA polymerase chain reaction amplification was used to obtain a partial 18S rDNA nucleotide sequence from the antechinus coccidian. Bayesian phylogenetic analysis based on 18S rDNA gene sequences revealed that the novel coccidian clusters with reptile-host coccidians, forming an ancestral basal lineage of the eimeriid clade. The species has been named Eimeria taggarti n. sp. on the basis of both sporulated oocyst morphology and molecular characterization. It is suspected that E. taggarti is sexually transmitted via excretion of sporulated oocysts or free sporocysts with prostatic secretions in semen.
Subject(s)
Coccidiosis/veterinary , Eimeria/isolation & purification , Marsupialia/parasitology , Prostate/parasitology , Prostatic Diseases/veterinary , Animals , Base Sequence , Coccidiosis/parasitology , DNA, Protozoan/chemistry , DNA, Protozoan/isolation & purification , DNA, Ribosomal/chemistry , DNA, Ribosomal/isolation & purification , Eimeria/classification , Eimeria/genetics , Eimeria/ultrastructure , Immune Tolerance , Male , Marsupialia/immunology , Microscopy, Electron, Transmission/veterinary , Oocysts/growth & development , Oocysts/ultrastructure , Phylogeny , Prostatic Diseases/parasitology , RNA, Protozoan/genetics , RNA, Ribosomal, 18S/genetics , Sequence Alignment/veterinary , South AustraliaABSTRACT
OBJECTIVE: To determine the effect of a single intravenous (IV) fluid bolus on the hydration of an avian patient, using packed cell volume (PCV) and plasma total solids (TS) to estimate hydration. PROCEDURE: Ten birds were allocated randomly to one of three groups, and administered 30 mL/kg or 50 mL/kg intravenous fluid, or were part of a control group and did not receive IV fluid. Blood was collected before the IV fluid bolus was administered, and at 1 minute, 3 hours and 6 hours after administration of the fluid. Samples were used to determine PCV and TS and results were compared between groups and between the different time points. RESULTS: Administration of 30 mL/kg or 50 mL/kg compound sodium lactate solution caused a statistically significant decrease in PCV. Within 3 hours, the PCV was not significantly different to the initial value or to the PCV of control birds. Administration of 30 mL/kg compound sodium lactate solution did not result in a significant decrease in TS. However, administration of 50 mL/kg produced a significant decrease in TS, which was still significantly less than controls 6 hours after the fluid was administered. CONCLUSION: These findings suggest that an intravenous bolus of fluid may be safely administered to an anaemic bird, since PCV is significantly decreased for less than 3 hours. Up to 50 mL/kg of fluid may be administered as an intravenous bolus to a bird, to produce significant haemodilution that persists for up to 6 hours.
Subject(s)
Bird Diseases/therapy , Dehydration/veterinary , Fluid Therapy/veterinary , Hematocrit/veterinary , Parrots , Anemia/therapy , Anemia/veterinary , Animals , Bird Diseases/blood , Dehydration/therapy , Dose-Response Relationship, Drug , Fluid Therapy/methods , Injections, Intravenous/veterinary , Parrots/blood , Random Allocation , Treatment OutcomeABSTRACT
PURPOSE: The outcome for women with a local failure after breast conservation treatment is not well described in the literature. Because local recurrence is a potentially salvageable event, this study was performed to evaluate the outcome of patients with local recurrence after breast conservation surgery and definitive radiation treatment. METHODS AND MATERIALS: The study population consisted of 112 patients with ipsilateral breast tumor recurrence. There were 100 isolated local recurrences and 12 local-plus-regional recurrences. There were 93 invasive local recurrences and 19 DCIS (ductal carcinoma in situ) local recurrences. Local recurrences were detected by physical examination alone in 42 patients, mammography alone in 47 patients, and both modalities in 23 patients. All patients were initially treated with breast conservation treatment with or without systemic therapy and subsequently treated at the time of local recurrence with salvage mastectomy with or without systemic therapy. The mean and median follow-up times after local recurrence were 49 and 44 months, respectively. RESULTS: For the entire group of 112 patients, the overall survival at 10 years after local recurrence was 69%, the cause-specific survival was 71%, and the freedom from distant metastases was 47%. For the 93 patients with an invasive local recurrence, the overall survival at 10 years was 64%, cause-specific survival was 67%, and freedom from distant metastases was 44%. For the 93 patients with an invasive local recurrence, interval from diagnosis to local recurrence (< or =2 years vs. 2.1-5 years vs. >5 years) predicted for overall survival at 5 years (65% vs. 84% vs. 89%; p = 0.03). Method of detection of local recurrence (physical examination vs. mammography vs. both methods) also predicted for 5-year overall survival (73% vs. 91% vs. 93%, respectively; p = 0.04). On multivariable analysis, interval from diagnosis to local recurrence was an independent predictor of overall survival (p = 0.03). Method of detection of local recurrence (physical examination vs. mammography vs. both methods) was borderline in predicting for 5-year cause-specific survival (73% vs. 91% vs. 93%, respectively; p = 0.06). Similarly, interval from diagnosis to local recurrence (< or =2 years vs. 2.1-5 years vs. >5 years) was a borderline predictor of 5-year cause-specific survival (65% vs. 84% vs. 89%; p = 0.08). No factors that predicted for freedom from distant metastases were identified. There were three second locoregional failures on the chest wall. Two of the 19 patients with a DCIS local recurrence have died of metastatic breast cancer. Death was probably not related to their local recurrence, but rather a result of persistent risk from an invasive primary cancer. CONCLUSIONS: This analysis provides long-term data after salvage treatment for patients who experience local recurrence after breast conservation treatment. The variables of method of detection and interval from diagnosis to local recurrence are identified as having prognostic significance for overall and cause-specific survival. In view of the potential for long-term survival, aggressive attempt at salvage treatment is warranted for the patient with local recurrence after breast conservation treatment. Second local recurrence after salvage mastectomy is an uncommon event. Although DCIS local recurrences may not in themselves cause an increase in the risk of mortality, the risk from the primary invasive cancer persists.
Subject(s)
Breast Neoplasms/mortality , Carcinoma, Ductal, Breast/mortality , Neoplasm Recurrence, Local/mortality , Neoplasms, Second Primary/mortality , Adult , Analysis of Variance , Breast Neoplasms/pathology , Breast Neoplasms/radiotherapy , Carcinoma, Ductal, Breast/pathology , Carcinoma, Ductal, Breast/radiotherapy , Female , Follow-Up Studies , Humans , Neoplasm Recurrence, Local/radiotherapy , Neoplasms, Second Primary/pathology , Neoplasms, Second Primary/radiotherapy , Salvage Therapy , Survival Analysis , Treatment OutcomeABSTRACT
The authors present findings from their study of 167 child welfare parents referred for substance abuse assessments. Relationships between gender, prior treatment, court-ordered intervention, significant others' support, and treatment and placement outcomes are examined. Findings indicate significant others' support positively influences all outcomes while court-ordered intervention is not predictive. Prior treatment is associated with continued substance abuse. Gender differences exist for assessment completion and several client characteristics. Implications for practice are drawn.
Subject(s)
Child Welfare/legislation & jurisprudence , Outcome Assessment, Health Care , Parents/psychology , Substance-Related Disorders/rehabilitation , Adult , Child Custody/legislation & jurisprudence , Child, Preschool , Female , Humans , Male , Pennsylvania , Referral and Consultation , Sex FactorsABSTRACT
PURPOSE: This study was performed to determine the long-term outcome for women with mammographically detected ductal carcinoma in situ (DCIS; intraductal carcinoma) of the breast treated with breast-conserving surgery followed by definitive breast irradiation. METHODS AND MATERIALS: An analysis was performed of 422 mammographically detected intraductal breast carcinomas in 418 women from 11 institutions in North America and Europe. All patients were treated with breast-conserving surgery followed by definitive breast irradiation. The median follow-up time was 9.4 years (mean, 9.4 years; range, 0.1-19.8 years). RESULTS: The 15-year overall survival rate was 92%, and the 15-year cause-specific survival rate was 98%. The 15-year rate of freedom from distant metastases was 94%. There were 48 local failures in the treated breast, and the 15-year rate of any local failure was 16%. The median time to local failure was 5.0 years (mean, 5.7 years; range, 1.0-15.2 years). Patient age at the time of treatment and final pathology margin status from the primary tumor excision were both significantly associated with local failure. The 10-year rate of local failure was 31% for patient age < or = 39 years, 13% for age 40-49 years, 8% for age 50-59 years, and 6% for age > or = 60 years (p = 0.0001). The 10-year rate of local failure was 24% when the margins of resection were positive, 9% when the margins of resection were negative, 7% when the margins of resection were close, and 12% when the margins of resection were unknown (p = 0.030). Patient age < or = 39 years and positive margins of resection were both independently associated with an increased risk of local failure (p = 0.0006 and p = 0.023, respectively) in the multivariable Cox regression model. CONCLUSIONS: The 15-year results from the present study demonstrated high rates of overall survival, cause-specific survival, and freedom from distant metastases following the treatment of mammographically detected ductal carcinoma in situ of the breast using breast-conserving surgery and definitive breast irradiation. Younger age and positive margins of resection were both independently associated with an increased risk of local failure. The 15-year results in the present study serve as an important benchmark for comparison with other treatment modalities. These results support the use of breast-conserving surgery and definitive breast irradiation for the treatment of appropriately selected patients with mammographically detected ductal carcinoma in situ of the breast.
Subject(s)
Breast Neoplasms/radiotherapy , Breast Neoplasms/surgery , Carcinoma in Situ/radiotherapy , Carcinoma in Situ/surgery , Carcinoma, Ductal, Breast/radiotherapy , Carcinoma, Ductal, Breast/surgery , Adult , Age Factors , Aged , Breast Neoplasms/diagnostic imaging , Breast Neoplasms/mortality , Carcinoma in Situ/diagnostic imaging , Carcinoma in Situ/mortality , Carcinoma, Ductal, Breast/diagnostic imaging , Carcinoma, Ductal, Breast/mortality , Databases, Factual , Follow-Up Studies , Humans , Male , Mammography , Middle Aged , Neoplasm Recurrence, Local , Neoplasm, Residual , Prognosis , Proportional Hazards Models , Survival Rate , Treatment OutcomeABSTRACT
BACKGROUND: The purpose of the current study is to evaluate the outcome of salvage treatment for local recurrence after breast-conserving surgery and radiation as initial treatment for mammographically detected ductal carcinoma in situ (DCIS; intraductal carcinoma) of the breast. METHODS: An analysis was performed of 42 patients with local only first failure (n = 41) or local-regional only first failure (n = 1) after breast-conserving surgery and radiation treatment had been given for DCIS of the breast. Surgical treatment at the time of local recurrence included mastectomy (n = 37; 88%) or excision (n = 5; 12%). Adjuvant systemic therapy at the time of local recurrence was chemotherapy (n = 3; 7%), tamoxifen (n = 8; 19%), both (n = 1; 2%), none (n = 29; 69%), or unknown (n = 1; 2%). The median interval from the time of initial treatment to local recurrence was 4.8 years (range = 1.0-15.2 yrs). The median follow-up after salvage treatment was 4.5 years (range = 0.2-12.8 yrs). RESULTS: At the time of the local recurrence, 22 patients (52%) had invasive ductal carcinoma, 18 patients (43%) had DCIS, 1 patient (2%) had invasive lobular carcinoma, and 1 patient (2%) had angiosarcoma. After salvage treatment, the rate of overall survival and the rate of cause specific survival for all 42 patients were 92% at both 5- and 8-years after treatment. The rate of freedom from distant metastases was 89% at 5 and 8 years. Favorable prognostic factors after salvage treatment were DCIS as the histology of the local recurrence and mammography only as the method of detection of the local recurrence. CONCLUSIONS: The results of salvage treatment in the current study demonstrated that local recurrences were salvaged with high rates of survival and freedom from distant metastases. These results support the use of breast-conserving surgery and radiation for initial management of DCIS of the breast.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Breast Neoplasms/drug therapy , Breast Neoplasms/surgery , Carcinoma, Intraductal, Noninfiltrating/drug therapy , Carcinoma, Intraductal, Noninfiltrating/surgery , Mastectomy, Segmental , Neoplasm Recurrence, Local/drug therapy , Neoplasm Recurrence, Local/surgery , Adult , Aged , Antineoplastic Agents, Hormonal/administration & dosage , Breast Neoplasms/pathology , Carcinoma, Intraductal, Noninfiltrating/pathology , Databases, Factual , Female , Humans , Mammography , Mastectomy , Middle Aged , Retrospective Studies , Salvage Therapy , Survival Analysis , Tamoxifen/administration & dosage , Treatment OutcomeABSTRACT
PURPOSE: The success of adjuvant chemotherapy has prolonged the interval between surgery and postmastectomy radiation therapy for high-risk breast cancer patients. The purpose of this study is to determine whether a delay in radiation therapy after mastectomy results in an increased risk of local-regional recurrence of breast cancer. MATERIALS AND METHODS: A retrospective review was performed of the University of Pennsylvania database of 221 patients with high-risk breast cancer treated with postmastectomy radiation therapy between 1977 and 1992. The surgery to postmastectomy radiation therapy time interval was 2 months or less in 82 patients (37%), 2.1 to 6 months in 50 patients (23%), and greater than 6 months in 89 patients (40%). Adjuvant chemotherapy was utilized in 151 patients (68%). The median follow-up was 4.3 years after postmastectomy radiation therapy. RESULTS: Because the three groups showed significant differences for a number of prognostic factors, outcomes are reported in terms of local-regional recurrence only and not survival. The actuarial rate of local-regional recurrence at 8 years was 13% for patients with a surgery to radiation therapy interval of 2 months or less, 4% for those with an interval of 2.1 to 6 months, and 12% for those with an interval of greater than 6 months. A similar analysis performed for 4 months or less versus greater than 4 months between surgery and postmastectomy radiation therapy showed no difference in local-regional recurrence (11% versus 10%, respectively). CONCLUSIONS: A delay in the institution of postmastectomy radiation therapy in favor of the prolongation of chemotherapy for high-risk breast cancer patients does not adversely affect outcome for local-regional recurrence at 8 years.
Subject(s)
Breast Neoplasms/radiotherapy , Breast Neoplasms/surgery , Treatment Outcome , Female , Humans , Mastectomy , Menopause , Neoplasm Recurrence, Local , Retrospective Studies , Time FactorsABSTRACT
PURPOSE: The purpose of this study was to evaluate the relationship between a family history of breast or ovarian cancer and outcome after breast-conserving surgery and radiation in women presenting with an initial diagnosis of ductal carcinoma in situ (DCIS) of the breast. METHODS AND MATERIALS: A total of 146 consecutive women with a pathologic diagnosis of ductal carcinoma in situ as their first diagnosis of any breast cancer were identified; 28 (19%) had a positive family history of breast or ovarian cancer in a first-degree relative, 27 (19%) had a positive family history in a second-degree relative, and 91 (62%) had no family history. Pathologic, clinical, and treatment factors, and clinical outcomes for each family history group were compared. Cosmesis and complications were recorded at each follow-up. Patients were treated between 1978 and 1995, and the median follow-up was 7.1 years. RESULTS: Patients with a positive family history in a first- or second-degree relative each had an 8% incidence of local failure at 10 years, while the negative family history group demonstrated a 16% local failure rate (p = 0.33). Overall survival at 10 years for patients with a positive family history in a first- or second-degree relative was 100% and for those with a negative family history was 91% (p = 0.08). The negative family history group had a higher median age that may account for the difference in overall survival. Cause-specific survival (CSS) was 97%, 100%, and 99%, respectively, at 10 years (p = 0.25). There were no differences in the cosmetic results or complication rates between women with a positive or negative family history. CONCLUSION: We have shown that a family history of breast and/or ovarian cancer is not associated with an adverse outcome for women treated with breast conservation therapy for DCIS. Local recurrence, cause-specific survival, overall survival, cosmesis, and complication rates were comparable to that of similarly treated women with negative family histories. Therefore, a positive family history is not a contraindication for breast conservation therapy in women with DCIS.
Subject(s)
Breast Neoplasms/genetics , Carcinoma in Situ/genetics , Carcinoma, Ductal, Breast/genetics , Adult , Age Factors , Aged , Breast Neoplasms/diagnosis , Breast Neoplasms/therapy , Carcinoma in Situ/diagnosis , Carcinoma in Situ/therapy , Carcinoma, Ductal, Breast/diagnosis , Carcinoma, Ductal, Breast/therapy , Esthetics , Family , Female , Follow-Up Studies , Genetic Predisposition to Disease/genetics , Humans , Mastectomy, Segmental , Middle Aged , Neoplasm Recurrence, Local , Ovarian Neoplasms/genetics , Survival Analysis , Treatment Failure , Treatment OutcomeABSTRACT
Acyl-acyl carrier protein (ACP) desaturases function to position a single double bond into an acyl-ACP substrate and are best represented by the ubiquitous Delta9 18:0-ACP desaturase. Several variant acyl-ACP desaturases have also been identified from species that produce unusual monoenoic fatty acids. All known acyl-ACP desaturase enzymes use ferredoxin as the electron-donating cofactor, and in almost all previous studies the photosynthetic form of ferredoxin rather than the non-photosynthetic form has been used to assess activity. We have examined the influence of different forms of ferredoxin on acyl-ACP desaturases. Using combinations of in vitro acyl-ACP desaturase assays and [(14)C]malonyl-coenzyme A labeling studies, we have determined that heterotrophic ferredoxin isoforms support up to 20-fold higher unusual acyl-ACP desaturase activity in coriander (Coriandrum sativum), Thunbergia alata, and garden geranium (Pelargonium x hortorum) when compared with photosynthetic ferredoxin isoforms. Heterotrophic ferredoxin also increases activity of the ubiquitous Delta9 18:0-ACP desaturase 1.5- to 3.0-fold in both seed and leaf extracts. These results suggest that ferredoxin isoforms may specifically interact with acyl-ACP desaturases to achieve optimal enzyme activity and that heterotrophic isoforms of ferredoxin may be the in vivo electron donor for this reaction.
Subject(s)
Acyl Carrier Protein/metabolism , Ferredoxins/metabolism , Mixed Function Oxygenases/metabolism , Plants/metabolism , Ferredoxins/genetics , Ferredoxins/pharmacology , Phylogeny , Plants/drug effects , Plants/genetics , Protein Isoforms/genetics , Protein Isoforms/metabolism , Protein Isoforms/pharmacologyABSTRACT
OBJECTIVES: To evaluate whether the calculated volume of prostate cancer (cVca) in patients with clinical Stage T1c prostate cancer who were treated surgically was a good predictor of biochemical disease-free prostate-specific antigen (PSA) recurrence. METHODS: Between 1990 and 1996, patients with prostate cancer who were surgically treated for clinical Stage T1c at Brigham and Women's Hospital were retrospectively evaluated, and 188 patients (median PSA 6.9 ng/mL) were included in this study. cVca (determined by cancer-specific PSA, prostate volume, and Gleason grade), pathologic stage, and time to PSA failure were assessed. RESULTS: cVca correlated strongly with the preoperative PSA level (P <0.00001, chi-square test), Gleason grade (P <0.00001), and pathologic stage (P <0.00001). Kaplan-Meier curves for PSA disease-free survival were constructed for patients with cVca less than 0.5 cm(3) (group 1), cVca of 0.5 to 4.0 cm(3) (group 2), and cVca greater than 4.0 cm(3) (group 3). The 2-year PSA disease-free survival rate was 100%, 81%, and 36% for groups 1, 2, and 3, respectively (P <0.0001). Cox multiple regression analysis demonstrated that cVca was superior to PSA and Gleason score for determination of serologic PSA failure after surgery. CONCLUSIONS: Our results demonstrated that cVca is a good predictor of biochemical recurrence in patients with clinical Stage T1c prostate cancer. Perhaps, after validation by others, cVca can serve as a tool in choosing various treatment options for prostate cancer.
Subject(s)
Prostate-Specific Antigen/blood , Prostate/pathology , Prostatectomy , Prostatic Neoplasms/pathology , Prostatic Neoplasms/surgery , Chi-Square Distribution , Disease-Free Survival , Humans , Male , Neoplasm Recurrence, Local/diagnosis , Neoplasm Staging/statistics & numerical data , Patient Selection , Postoperative Complications/diagnosis , Prognosis , Prostatic Neoplasms/diagnosis , Recurrence , Retrospective Studies , Treatment OutcomeABSTRACT
Local anaesthesia is increasingly being used for vitreoretinal surgery, but the optimal technique for sedation remains unclear. Anaesthetist-administered midazolam, which is often used, was compared in this study to patient-controlled sedation with propofol in 43 patients undergoing 50 vitreoretinal procedures. A variety of patient, anaesthetist and surgical endpoints were measured. There were no significant outcome differences between the two agents except that midazolam produced more amnesia for the local anaesthetic eye block. However, several outcomes and the observations in patients who experienced both agents showed a trend in favour of propofol for intraoperative sedation. We conclude that both approaches are safe and that patient-controlled sedation with propofol is at least as satisfactory as anaesthetist-administered midazolam.
Subject(s)
Conscious Sedation , Hypnotics and Sedatives , Midazolam , Propofol , Retina/surgery , Vitreous Body/surgery , Cross-Over Studies , Humans , Hypnotics and Sedatives/administration & dosage , Midazolam/administration & dosage , Middle Aged , Ophthalmologic Surgical Procedures , Patient Satisfaction , Propofol/administration & dosage , Treatment OutcomeABSTRACT
PURPOSE: We compared pathological findings in ectopic and undescended testis to determine whether the pathological evidence supports the hypothesis that the 2 conditions are variants of the same congenital anomaly. MATERIALS AND METHODS: We identified 24 boys with ectopic testis not in the superficial inguinal pouch of Denis Browne. Seven boys were excluded from study due to unavailable clinical records for 3, contralateral undescended testis in 2 and inadequate biopsy specimens in 2. Pathological findings of ectopic testis in the remaining 17 patients were compared with those of age matched patients with unilateral undescended testis. Total germ cell count, testicular volume, patency of the processus vaginalis and epididymal abnormalities were compared. Data were analyzed using the Wilcoxon matched pairs signed rank and Fisher's exact tests. RESULTS: No difference was noted in total germ cell count (p = 0.33), testicular volume (p = 0.1475), processus vaginalis patency (p = 0.0854) or epididymal abnormalities (p = 1.00) in the 2 groups. Of the 24 boys (8%) with ectopic testis 2 also had a contralateral undescended testis. CONCLUSIONS: Similar pathological findings in ectopic and undescended testes as well as the association of ectopic testis with a contralateral undescended testis suggest that ectopic and undescended testes are variants of the same congenital anomaly. Thus, boys with ectopic testis may have an increased incidence of subfertility and testicular malignancy. This spectrum of abnormal testicular position, and its range of pathological conditions and complications may appropriately be called the undescended testis sequence.
Subject(s)
Choristoma/diagnosis , Cryptorchidism/diagnosis , Testis , Abdomen , Child , Child, Preschool , Diagnosis, Differential , Humans , Infant , MaleABSTRACT
Magnetic resonance imaging (MRI) may be more sensitive than mammography for detecting breast cancer and may have an adjunctive role in assessing patients with early-stage disease for breast conservation treatment. This study was performed to analyze the impact of breast MRI on the clinical management of 83 patients being considered for breast conservation treatment. Eighty-three consecutive cases of patients undergoing breast MRI during standard workup and evaluation for breast conservation treatment from 1993 to 1996 were retrospectively reviewed. Records were reviewed for patient and tumor characteristics, mammographic findings, MRI findings, timing of MRI study, findings from MRI-guided surgery (when done), and whether the patient underwent breast conservation treatment. MRI definitely altered management in 15 patients (18%), may have affected management in 4 patients (5%), and did not change management in 64 patients (77%). Thirteen patients underwent additional surgery because of MRI findings; the positive predictive value for MRI-guided surgery was 38% (5 of 13). Ultimately, 82% of the patients received breast conservation treatment. No predictive factor was identified to characterize the patients most likely to have management affected by MRI findings. These findings suggest that breast MRI may be useful in the evaluation of patients with early-stage breast cancer for breast conservation treatment. A larger study population and outcome data will be required to confirm these findings and to define those patients most likely to benefit from breast MRI.
Subject(s)
Breast Neoplasms/diagnosis , Breast Neoplasms/surgery , Magnetic Resonance Imaging , Mastectomy, Segmental , Adult , Aged , Female , Humans , Middle Aged , Retrospective StudiesABSTRACT
Seeds of coriandrum sativum (coriander) and Thunbergia alata (black-eyed Susan vine) produce unusual monoenoic fatty acids which constitute over 80% of the total fatty acids of the seed oil. The initial step in the formation of these fatty acids is the desaturation of palmitoyl-ACP (acyl carrier protein) at the delta(4) or delta(6) positions to produce delta(4)-hexadecenoic acid (16:1(delta(4)) or delta(6)-hexadecenoic acid (16:1(delta(6)), respectively. The involvement of specific forms of ACP in the production of these novel monoenoic fatty acids was studied. ACPs were partially purified from endosperm of coriander and T. alata and used to generate 3H- and 14C-labelled palmitoyl-ACP substrates. In competition assays with labelled palmitoyl-ACP prepared from spinach (Spinacia oleracea), delta(4)-acyl-ACP desaturase activity was two- to threefold higher with coriander ACP than with spinach ACP. Similarly, the T. alata delta(6) desaturase favoured T. alata ACP over spinach ACP. A cDNA clone, Cs-ACP-1, encoding ACP was isolated from a coriander endosperm cDNA library. Cs-ACP-1 mRNA was predominantly expressed in endosperm rather than leaves. The Cs-ACP-1 mature protein was expressed in E. coli and comigrated on SDS-PAGE with the most abundant ACP expressed in endosperm tissues. In in vitro delta(4)-palmitoyl-ACP desaturase assays, the Cs-ACP-1 expressed from E. coli was four- and 10-fold more active than spinach ACP or E. coli ACP, respectively, in the synthesis of delta(4)-hexadecenoic acid from palmitoyl-ACP. In contrast, delta(9)-stearoyl-ACP desaturase activity from coriander endosperm did not discriminate strongly between different ACP species. These results indicate that individual ACP isoforms are specifically involved in the biosynthesis of unusual seed fatty acids and further suggest that expression of multiple ACP isoforms may participate in determining the products of fatty acid biosynthesis.
Subject(s)
Acyl Carrier Protein/metabolism , Fatty Acids/biosynthesis , Plant Proteins/metabolism , Seeds/metabolism , Acyl Carrier Protein/genetics , Amino Acid Sequence , Apiaceae/genetics , Apiaceae/metabolism , Base Sequence , DNA, Complementary/genetics , DNA, Plant/genetics , Gene Expression , Magnoliopsida/genetics , Magnoliopsida/metabolism , Mixed Function Oxygenases/metabolism , Molecular Sequence Data , Plant Proteins/genetics , Protein Isoforms/genetics , Protein Isoforms/metabolism , Sequence Homology, Amino Acid , Species Specificity , Thiolester Hydrolases/metabolismABSTRACT
PURPOSE: Postmastectomy radiation therapy is often recommended for patients at high risk for local-regional recurrence after mastectomy. However, long-term outcomes after radiation therapy are not well described. PATIENTS AND METHODS: Between 1977 and 1992, 221 patients at high risk for local-regional recurrence of breast cancer after mastectomy were treated with radiation therapy, with or without adjuvant systemic therapy. Patients were classified as high risk because of T3 or T4 tumors (14%), positive lymph nodes (29%), close or positive margins of resection (15%), or multiple risk factors (39%); 4% did not meet current criteria for radiation therapy. The median age of patients was 51 years. Radiation therapy consisted of 45 to 50.4 Gy to the chest wall in 1.8 to 2.0 Gy fractions. The regional lymph nodes were treated in 187 patients (85%). There were 151 patients (68%) who received adjuvant chemotherapy. Patients who received chemotherapy were younger (median age, 48 years vs 64 years) and had more positive lymph nodes (median, 5 vs 1) than patients not receiving chemotherapy. Adjuvant hormonal therapy was utilized in 116 patients (53%). The median follow-up was 4.3 years. RESULTS: The actuarial 10-year local-regional failure rate was 11% (95% CI: 6.5% to 16.7%). The site of first failure was distant metastases in 75 patients (34%), local-regional recurrence in 11 patients (5%), and both sites in three patients (1%); 60% had no evidence of disease at last follow-up. Of the patients who presented with local-regional recurrence as first failure, nine patients (82%) subsequently developed metastatic disease. The median time to local-regional first failure was 1.3 years. The median time to distant metastases after local-regional first failure was 0.3 years. DISCUSSION: Postmastectomy radiation therapy is associated with an 89% rate of local-regional control in this high-risk population. Patients who experience a local-regional recurrence after radiation therapy are at a very high risk for metastatic disease. Radiation therapy after mastectomy is recommended to optimize local-regional control for high-risk breast cancer patients.
Subject(s)
Breast Neoplasms/radiotherapy , Breast Neoplasms/surgery , Neoplasm Recurrence, Local/radiotherapy , Actuarial Analysis , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Breast Neoplasms/drug therapy , Chemotherapy, Adjuvant , Cisplatin/administration & dosage , Combined Modality Therapy , Cyclophosphamide/administration & dosage , Doxorubicin/administration & dosage , Female , Fluorouracil/administration & dosage , Follow-Up Studies , Humans , Methotrexate/administration & dosage , Middle Aged , Neoplasm Recurrence, Local/prevention & control , Risk Factors , Treatment OutcomeABSTRACT
PURPOSE: To evaluate the significance of final microscopic resection margin status on treatment outcomes in women with early breast cancer who are treated with breast-conserving surgery and definitive breast irradiation. METHODS AND MATERIALS: An analysis was performed of 1021 consecutive women with clinical Stage I or II invasive carcinoma of the breast treated with breast-conserving surgery and definitive breast irradiation. Complete gross excision of tumor was performed in all cases, and an axillary staging procedure was performed to determine pathologic axillary lymph node status. The 1021 patients were divided into four groups based on the final microscopic margin from the tumor excision or from the re-excision if performed. These four groups were: (a) 518 patients with negative margins; (b) 124 patients with focally positive margins; (c) 96 patients with focally close margins (< or = 2 mm); and (d) 283 patients with unknown margins. RESULTS: Local failure was not significantly different in patients with negative, focally positive, focally close or unknown final pathologic margins of resection at 8 years (8% vs. 10% vs. 17% vs. 16%, respectively, p = 0.21). The 8-year outcome also was not different among the four groups for overall survival (86% vs. 83% vs. 88% vs. 81%, respectively, p = 0.13), cause-specific survival (89% vs. 86% vs. 88% vs. 83%, respectively, p = 0.14), no evidence of disease survival (81% vs. 73% vs. 86% vs. 77%, respectively, p = 0.09), and freedom from distant metastases (85% vs. 75% vs. 86% vs. 79%, respectively, p = 0.08). CONCLUSION: These results demonstrate that selected patients with focally positive or focally close microscopic resection margins can be treated with breast-conserving surgery and definitive breast irradiation with 8-year local control rates and survival rates that are similar to those seen in breast-conservation patients with negative or unknown final resection margins.
Subject(s)
Breast Neoplasms/radiotherapy , Breast Neoplasms/surgery , Adult , Aged , Aged, 80 and over , Breast Neoplasms/pathology , Combined Modality Therapy , Disease-Free Survival , Female , Humans , Middle Aged , Neoplasm Staging , Neoplasm, Residual , Radiotherapy Dosage , Treatment OutcomeABSTRACT
The patterns of treatment for newly diagnosed breast carcinomas in older women aged 65 years or more have not been well studied, particularly in relation to screening mammography performed for the early detection of breast cancer. Therefore, the present study was performed to determine the patterns of treatment for newly diagnosed breast carcinomas in older women aged 65 years or more and to determine the impact of screening mammography on these patterns of treatment. The study population consisted of 130 women aged 65 years or more with newly diagnosed breast carcinoma from 1993 through 1994 enrolled in a large health maintenance organization. The medical records of these 130 patients were reviewed. The breast cancers detected in women who had undergone mammographic screening were more often eligible for breast-conservation treatment than the breast cancers detected in women who had not undergone mammographic screening (79% vs. 48%, respectively; p = 0.0044). For the breast cancers that were eligible for breast-conservation treatment, breast-conservation treatment was used more often for the women who had undergone mammographic screening than for the women who had not undergone mammographic screening (70% vs. 27%, respectively; p = 0.0077). Definitive radiation therapy was delivered after breast-conservation surgery in 89% (55/62) of the patients. Medical oncology consultation was obtained more commonly for more advanced staged breast cancers. Clinical management was altered in 9% (12/130) of the patients because of older patient age, comorbid medical conditions, or both. These findings have documented the patterns of treatment for older women aged 65 years or more with newly diagnosed breast cancer. Screening mammography had a significant impact on the patterns of breast cancer management, as demonstrated by the association of screening mammography with an increased eligibility for breast-conservation treatment and an increased use of breast-conservation treatment for eligible patients.
Subject(s)
Breast Neoplasms/therapy , Mammography/statistics & numerical data , Mastectomy/statistics & numerical data , Aged , Breast Neoplasms/diagnostic imaging , Combined Modality Therapy , Female , Health Maintenance Organizations , Humans , United StatesABSTRACT
PURPOSE: The present study reports the effects of patient age and family history on outcome after breast-conservation treatment. In addition, the interaction of age and family history is examined to determine outcome for younger patients with a positive family history of breast cancer (i.e., at a higher risk of having the BRCA1 or BRCA2 gene) after breast-conservation treatment. PATIENTS AND METHODS: From 1977 to 1992, 1021 women underwent breast-conservation treatment for American Joint Committee on Cancer stage I and II breast cancer at the Hospital of the University of Pennsylvania. In all patients, breast-conservation treatment included complete gross excision of the primary tumor and axillary lymph node dissection, followed by definitive breast irradiation. When indicated, radiation to the regional lymphatics, adjuvant chemotherapy, and/or adjuvant hormones were given. Patients were divided for analysis into three age groups (< or = 40 years, 41 to 50 years, and > or = 51 years) as well as three family history groups (first-degree relative positive for breast cancer, other family history positive for breast cancer, and negative family history for breast cancer). Median follow-up after treatment was 6.1 years. RESULTS: The 10-year actuarial overall survival rates were 74% for women aged < or = 40 years, 82% for women aged 41 to 50 years, and 82% for women aged > or = 51 years (P = 0.12). For the younger women, aged < or = 40 years, there was a higher 10-year rate of deaths from breast cancer (P = 0.007) but a lower rate of deaths from other causes (P = 0.08) than in the older two age groups. The younger women had a higher rate of local failure at 10 years compared with the two older age groups (22%, 18%, and 12%, respectively), but this difference was not statistically significant (P = 0.10). No significant differences were found between the three family history groups (first-degree relative positive for breast cancer, other family history positive for breast cancer, and negative family history for breast cancer) for survival, freedom from distant metastases, or local failure (all P > or = 0.25). For younger women, aged < or = 40 years, the 5-year outcomes for survival, freedom from distant metastases, and local failure were not different according to family history status (all P > or = 0.18). Similarly, the 5-year outcomes were not different according to family history status for women aged 41 to 50 years (all P > or = 0.46) and for women aged > or = 51 years (all P > or = 0.54). DISCUSSION: The present study has confirmed that breast-conservation treatment is suitable for appropriately selected younger patients or patients with a positive family history of breast cancer. Further, a positive family history of breast cancer in younger women does not represent a contraindication to breast-conservation treatment. In summary, younger age, positive family history of breast cancer, or younger age plus a positive family history of breast cancer should not preclude the use of breast-conservation treatment for appropriately selected patients.
Subject(s)
Breast Neoplasms/radiotherapy , Breast Neoplasms/surgery , Adult , BRCA2 Protein , Breast Neoplasms/genetics , Combined Modality Therapy , Family Health , Female , Genes, BRCA1 , Genetic Predisposition to Disease , Humans , Middle Aged , Neoplasm Proteins/genetics , Survival Analysis , Transcription Factors/genetics , Treatment OutcomeABSTRACT
PURPOSE: Long-term outcome after radiation therapy for local-regional recurrence of breast cancer after mastectomy is generally poor. This study was performed to evaluate the long-term outcome for a potentially favorable subgroup of patients with chest wall recurrence. METHODS AND MATERIALS: Of 71 patients with an isolated local-regional recurrence of breast cancer after mastectomy, 18 were identified who met the following favorable selection criteria: 1) a disease-free interval after mastectomy of 2 years or more, 2) an isolated chest wall recurrence, and 3) tumor size < 3 cm or complete excision of the recurrent disease. All 18 patients were treated with local-regional irradiation between 1967 and 1988. Radiotherapy (RT) was delivered to the chest wall to a median total dose of 60 Gy (range 30-66 Gy). Four patients received adjuvant chemotherapy and six patients received adjuvant hormonal therapy. RESULTS: With a median follow-up of 8.4 years, nine of 18 patients were alive and free of disease. The 10-year actuarial overall and cause-specific survivals were 72% and 77%, respectively. The 10-year actuarial relapse-free survival and local control were 42% and 86%, respectively. CONCLUSION: Treatment for a local-regional recurrence of breast cancer after mastectomy in a favorable subgroup of patients results in a high rate of long-term survival as well as excellent local control. Aggressive treatment is warranted in this favorable subgroup of patients.