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PubMed1998

Comprehensive multimodality blood conservation: 100 consecutive CABG operations without transfusion.

BACKGROUND: Despite the recent introduction of a number of technical and pharmacologic blood conservation measures, bleeding and allogeneic transfusion remain persistent problems in open heart surgical procedures. We hypothesized that a comprehensive multimodality blood conservation program applied algorithmically on the basis of bleeding and transfusion risk would provide a maximum, cost-effective, and safe reduction in postoperative bleeding and allogeneic blood transfusion. METHODS: One hundred consecutive patients undergoing coronary artery bypass grafting were prospectively enrolled in a risk factor-based multimodality blood conservation program (MMD group). To evaluate the relative efficacy and safety of this comprehensive approach, comparison was made with a similar group of 90 patients undergoing coronary artery bypass grafting to whom the multimodality blood conservation program was not applied but in whom an identical set of transfusion guidelines was enforced (control group). To evaluate the cost effectiveness of the multimodality program, comparison was also made between patients in the MMD group and a consecutive series of contemporaneous, diagnostic-related group-matched patients. RESULTS: One hundred consecutive patients in the MMD group underwent coronary artery bypass grafting without allogeneic transfusion. This compared favorably with the control population in whom a mean of 2.2 +/- 6.7 units of allogeneic blood was transfused per patient (34 patients [38%] received transfusion). In addition, the volume of postoperative blood loss at 12 hours in the control group was almost double that of the MMD group (660 +/- 270 mL versus 370 +/- 180 mL [p < 0.001]). Total costs for the MMD group in each of the three major diagnostic-related groups were equivalent to or significantly less than those in the consecutive series of diagnostic-related group-matched patients. CONCLUSIONS: Comprehensive risk factor-based application of multiple blood conservation measures in an optimized, integrated, and algorithmic manner can significantly decrease bleeding and need of allogeneic transfusion in coronary artery bypass grafting in a safe and cost-effective manner.

Algorithms↗

PubMed2002

The FxRxHrS motif: a conserved region essential for DNA binding of the VirR response regulator from Clostridium perfringens.

The VirSR two-component signal transduction pathway regulates virulence and toxin production in Clostridium perfringens, the causative agent of gas gangrene. The response regulator, VirR, binds to repeat sequences located upstream of the promoter and is directly responsible for the transcriptional activation of pfoA, the structural gene for the cholesterol-dependent cytolysin, perfringolysin O. Comparative sequence analysis of the 236 amino acid residue VirR protein revealed a two-domain structure: a typical N-terminal response regulator domain and an uncharacterised C-terminal domain. Database searching revealed that over 40 other proteins, many of which appeared to be response regulators or transcriptional activators, had homology with the VirR C-terminal domain (VirRc). Multiple sequence alignment of this VirRc family revealed a highly conserved region that was designated the FxRxHrS motif. By deletion analysis this motif was shown to be essential for the functional integrity of the VirR protein. Alanine scanning mutagenesis and subsequent phenotypic analysis indicated that conserved residues located within the motif were required for activity. These residues extended from L179 to N194. More detailed site-directed mutagenesis showed that amino acid residues R186, H188 and S190 were essential for activity since even conservative substitutions in these positions resulted in non-functional proteins. Three of the mutant proteins, R186K, S190A and S190C, were purified and shown by in vitro gel shift analysis to be unable to bind to the specific target DNA with the same efficiency as the wild-type protein. These data reveal for the first time that VirRc functions as a DNA binding domain in which the highly conserved FxRxHrS motif has a functional role. These studies have important implications for this new family of transcriptional factors since they imply that the conserved FxRxHrS motif may be involved in DNA binding in all of these proteins, irrespective of their biological role.

Amino Acid Motifs↗

PubMed1985

Comparative efficacy of "specific" potassium citrate therapy versus conservative management in nephrolithiasis of mild to moderate severity.

It generally is believed that conservative measures of high fluid intake and dietary modification in the setting of a stone clinic could favorably influence the course of renal stone disease. To establish the effect of specific medical treatment from the stone clinic effect, we compared the results of potassium citrate therapy to those of 11 reported conservative or placebo trials. The 54 patients receiving potassium citrate chosen for this comparison had mild to moderately severe stone disease (less than 1 stone per patient per year), similar to that encountered in conservative placebo trials (mean 0.54 stones per patient per year). New stone formation was virtually eliminated by potassium citrate therapy (a decrease from 0.52 to 0.02 stones per patient per year, a remission rate of 96 per cent, p less than 0.001), whereas it continued in 39 per cent of the patients during conservative or placebo trials. However, in patients participating in conservative or placebo trials new stone formation decreased by only 54 per cent (from 0.54 to 0.25 stones per patient per year). The superior response to potassium citrate suggested that this specific medical treatment exerted an additional favorable effect on the course of stone disease above the stone clinic effect.

Citrates↗

PubMed1994

Breast conservation therapy for invasive breast cancer: a review of prior trials and the Mayo Clinic experience.

OBJECTIVE: To assess the role of breast conservation therapy in the management of early-stage invasive breast cancer. DESIGN: We reviewed the results of previously published trials and summarized 165 cases of breast conservation surgical procedures and irradiation at the Mayo Clinic between January 1979 and September 1989. MATERIAL AND METHODS: From the prior clinical trials, the criteria for selection of patients, the surgical and radiation techniques used, the complications of treatment, the cosmetic results, and the follow-up assessment and survival were analyzed. The 165 Mayo patients were also characterized, and their results were described. RESULTS: Breast conservation therapy consists of excision of the primary tumor followed by irradiation. A coordinated multidisciplinary approach should be used for selection of patients. Several large-scale clinical trials have demonstrated that breast conservation therapy is an appropriate option for most women with early-stage breast cancer and provides tumor control and survival rates equivalent to mastectomy. With a collaborative treatment program and judicious application of contemporary standards of practice, a good-to-excellent cosmetic outcome can be achieved in most patients, and the risk of treatment-related sequelae is minimal. The Mayo Clinic experience with breast conservation therapy is consistent with these observations and compares favorably with other institutional and clinical trial results. CONCLUSION: Patients should be fully educated about the options for primary management of early-stage breast cancer because the selection of therapy may profoundly influence psychologic adjustment and acceptance of the treatment program.

Breast Neoplasms↗

PubMed1993

Conservative surgery and radiation for early-stage breast cancer.

In selected patients with early-stage breast cancer, conservative surgery and radiation represent an alternative equal to mastectomy in terms of local recurrence, distant metastasis, survival, and long-term complications. Patients with early-stage breast cancer who are candidates for conservative surgery and radiation include those whose primary tumor is less than 4 to 5 cm in size without evidence of gross multicentricity or diffuse microcalcifications. Patients with an extensive intraductal component may be appropriate candidates provided that margins of resection are negative. Young age is not a contraindication to the conservative treatment. A preexisting history of collagen vascular disease or prior mantle irradiation for Hodgkin's or non-Hodgkin's lymphoma represents a contraindication to conservative surgery and radiation because of the potential for severe complications. An additional contraindication is the pregnant woman in whom delivery cannot be accomplished before the initiation of radiation. Mammography is essential in the pretreatment evaluation and posttreatment follow-up of the conservatively treated patient. The goal of the pretreatment mammogram is to assess the extent of disease in the ipsilateral breast as well as to evaluate the contralateral breast. In patients who present with microcalcifications, a postbiopsy mammogram before radiation is essential to document complete removal of all malignant-appearing microcalcifications. Mammography is an essential part of the follow-up program in order to detect a recurrence in the treated breast as well as a cancer in the contralateral breast cancer. The optimal interval for follow-up mammography has not been determined, although programs employing mammography on a yearly basis after treatment have been associated with the detection of early recurrences and excellent survival after salvage mastectomy for these recurrences.

Breast Neoplasms↗

PubMed1999

Automatic detection of conserved base pairing patterns in RNA virus genomes.

Almost all RNA molecules--and consequently also almost all subsequences of a large RNA molecule-form secondary structures. The presence of secondary structure in itself therefore does not indicate any functional significance. In fact, we cannot expect a conserved secondary structure for all parts of a viral genome or a mRNA, even if there is a significant level of sequence conservation. We present a novel method for detecting conserved RNA secondary structures in a family of related RNA sequences. The method is based on combining the prediction of base pair probability matrices and comparative sequence analysis. It can be applied to small sets of long sequences and does not require a prior knowledge of conserved sequence or structure motifs. As such it can be used to scan large amounts of sequence data for regions that warrant further experimental investigation. Applications to complete genomic RNAs of some viruses show that in all cases the known secondary structure features are identified. In addition, we predict a substantial number of conserved structural elements which have not been described so far.

Algorithms↗

PubMed2002

Interventional versus conservative treatment for patients with unstable angina or non-ST-elevation myocardial infarction: the British Heart Foundation RITA 3 randomised trial. Randomized Intervention Trial of unstable Angina.

BACKGROUND: Current guidelines suggest that, for patients at moderate risk of death from unstable coronary-artery disease, either an interventional strategy (angiography followed by revascularisation) or a conservative strategy (ischaemia-driven or symptom-driven angiography) is appropriate. We aimed to test the hypothesis that an interventional strategy is better than a conservative strategy in such patients. METHODS: We did a randomised multicentre trial of 1810 patients with non-ST-elevation acute coronary syndromes (mean age 62 years, 38% women). Patients were assigned an early intervention or conservative strategy. The antithrombin agent in both groups was enoxaparin. The co-primary endpoints were a combined rate of death, non-fatal myocardial infarction, or refractory angina at 4 months; and a combined rate of death or non-fatal myocardial infarction at 1 year. Analysis was by intention to treat. FINDINGS: At 4 months, 86 (9.6%) of 895 patients in the intervention group had died or had a myocardial infarction or refractory angina, compared with 133 (14.5%) of 915 patients in the conservative group (risk ratio 0.66, 95% CI 0.51-0.85, p=0.001). This difference was mainly due to a halving of refractory angina in the intervention group. Death or myocardial infarction was similar in both treatment groups at 1 year (68 [7.6%] vs 76 [8.3%], respectively; risk ratio 0.91, 95% CI 0.67-1.25, p=0.58). Symptoms of angina were improved and use of antianginal medications significantly reduced with the interventional strategy (p<0.0001). INTERPRETATION: In patients presenting with unstable coronary-artery disease, an interventional strategy is preferable to a conservative strategy, mainly because of the halving of refractory or severe angina, and with no increased risk of death or myocardial infarction.

Angina Pectoris↗

PubMedDate not supplied

Routine invasive strategy within 24 hours of thrombolysis versus ischaemia-guided conservative approach for acute myocardial infarction with ST-segment elevation (GRACIA-1): a randomised controlled trial.

BACKGROUND: In patients with ST-segment elevated myocardial infarction (STEMI), early post-thrombolysis routine angioplasty has been discouraged because of its association with high incidence of events. The GRACIA-1 trial was designed to reassess the benefits of an early post-thrombolysis interventional approach in the era of stents and new antiplatelet agents. METHODS: 500 patients with thrombolysed STEMI (with recombinant tissue plasminogen activator) were randomly assigned to angiography and intervention if indicated within 24 h of thrombolysis, or to an ischaemia-guided conservative approach. The primary endpoint was the combined rate of death, reinfarction, or revascularisation at 12 months. Analysis was by intention to treat. FINDINGS: Invasive treatment included stenting of the culprit artery in 80% (199 of 248) patients, bypass surgery in six (2%), non-culprit artery stenting in three, and no intervention in 40 (16%). Predischarge revascularisation was needed in 51 of 252 patients in the conservative group. By comparison with patients receiving conservative treatment, by 1 year, patients in the invasive group had lower frequency of primary endpoint (23 [9%] vs 51 [21%], risk ratio 0.44 [95% CI 0.28-0.70], p=0.0008), and they tended to have reduced rate of death or reinfarction (7% vs 12%, 0.59 [0.33-1.05], p=0.07). Index time in hospital was shorter in the invasive group, with no differences in major bleeding or vascular complications. At 30 days both groups had a similar incidence of cardiac events. In-hospital incidence of revascularisation induced by spontaneous recurrence of ischaemia was higher in patients in the conservative group than in those in the invasive group. INTERPRETATION: In patients with STEMI, early post-thrombolysis catheterisation and appropriate intervention is safe and might be preferable to a conservative strategy since it reduces the need for unplanned in-hospital revascularisation, and improves 1-year clinical outcome.

Angioplasty, Balloon, Coronary↗

PubMedDate not supplied

Early surgery versus initial conservative treatment in patients with spontaneous supratentorial intracerebral haematomas in the International Surgical Trial in Intracerebral Haemorrhage (STICH): a randomised trial.

BACKGROUND: Spontaneous supratentorial intracerebral haemorrhage accounts for 20% of all stroke-related sudden neurological deficits, has the highest morbidity and mortality of all stroke, and the role of surgery remains controversial. We undertook a prospective randomised trial to compare early surgery with initial conservative treatment for patients with intracerebral haemorrhage. METHODS: A parallel-group trial design was used. Early surgery combined haematoma evacuation (within 24 h of randomisation) with medical treatment. Initial conservative treatment used medical treatment, although later evacuation was allowed if necessary. We used the eight-point Glasgow outcome scale obtained by postal questionnaires sent directly to patients at 6 months follow-up as the primary outcome measure. We divided the patients into good and poor prognosis groups on the basis of their clinical status at randomisation. For the good prognosis group, a favourable outcome was defined as good recovery or moderate disability on the Glasgow outcome scale. For the poor prognosis group, a favourable outcome also included the upper level of severe disability. Analysis was by intention to treat. FINDINGS: 1033 patients from 83 centres in 27 countries were randomised to early surgery (503) or initial conservative treatment (530). At 6 months, 51 patients were lost to follow-up, and 17 were alive with unknown status. Of 468 patients randomised to early surgery, 122 (26%) had a favourable outcome compared with 118 (24%) of 496 randomised to initial conservative treatment (odds ratio 0.89 [95% CI 0.66-1.19], p=0.414); absolute benefit 2.3% (-3.2 to 7.7), relative benefit 10% (-13 to 33). INTERPRETATION: Patients with spontaneous supratentorial intracerebral haemorrhage in neurosurgical units show no overall benefit from early surgery when compared with initial conservative treatment.

Aged↗

PubMed2003

Babesia bovis merozoite surface protein-2c (MSA-2c) contains highly immunogenic, conserved B-cell epitopes that elicit neutralization-sensitive antibodies in cattle.

The search for vaccine candidates against bovine babesiosis caused by Babesia bovis is greatly focused on the identification of merozoite surface-exposed antigens that are widely conserved, functionally relevant and immunodominant in cattle protected against B. bovis infections. We have recently identified msa-2c, a member of the B. bovis variable merozoite surface antigen (VMSA) gene family, which in contrast to other members, appears to be highly conserved among geographically distant B. bovis strains. In this study, we further investigated the potential of the msa-2c gene product as diagnostic and vaccine candidate for bovine babesiosis. RT-PCR studies demonstrated that MSA-2c is transcribed in merozoites of the Argentine R1A strain. In addition, antibodies against R1A recombinant MSA-2c reacted in immunoblots with a single protein of approximately 30kDa in B. bovis merozoite extracts from both R1A and Australian "S" strains, demonstrating translation of this protein in these two strains and conservation of B-cell epitopes between them. These antibodies reacted with the cell surface of R1A merozoites in fixed immunofluorescence assays, indicating the surface localization of MSA-2c. This localization was confirmed by live immunofluorescence studies in two different strains, R1A and S2P. These results also demonstrate the conservation of MSA-2c surface-exposed B-cell epitopes between these two strains. Sera from cattle either naturally or experimentally infected with Argentine strains of B. bovis specifically recognized rMSA-2c in immunoblots, reinforcing the idea that B-cell epitopes in rMSA-2c are widely conserved among field strains of B. bovis. Furthermore, our results show that these B-cell epitopes are highly immunogenic, suggesting that MSA-2c may be a useful diagnostic tool for the detection of bovine babesiosis by B. bovis. Experimental vaccination of five bovines with rMSA-2c resulted in elicitation of high specific anti-rMSA-2c IgG titers, with similar amounts of IgG(1) and IgG(2) produced. Importantly, bovine anti-rMSA-2c antibodies were able to neutralize in vitro bovine erythrocyte invasion by R1A merozoites suggesting a significant functional role for MSA-2c. Taken together these results postulate MSA-2c as a candidate for the development of novel tools for improved control of bovine babesiosis.

Animals↗

PubMedDate not supplied

Conservative management of T1-T2N0 supraglottic cancer: a retrospective study.

PURPOSE: Evaluate the results of conservative management of early-stage supraglottic cancer. PATIENTS AND METHODS: A retrospective analysis of 166 consecutive T1-T2N0 cases of squamous cell carcinoma of the supraglottic larynx, treated conservatively between 1983 and 1992, was performed. Sixty-six patients received conservative surgery (CS), whereas 100 patients received definitive radiation therapy (RT). Surgical procedures included horizontal supraglottic laryngectomy in 38 patients, extended supraglottic laryngectomy in 16 patients, and reconstructive laryngectomy with cricohyoidopexy in 12 patients. Elective bilateral neck dissection was always performed. Radiotherapy was delivered with 60Co or 6 MV photons to the primary laryngeal tumor and the upper and mid neck nodes (level II and III), whereas supraclavicular nodes (level IV) were electively irradiated only in 54 patients with T2N0 tumors. Fifty-two patients received conventional fractionation, whereas 31 patients were irradiated according to a twice-a-day fractionation regimen. The median total tumor dose was 67 Gy (range, 64 to 72 Gy). RESULTS: The 5-year overall survival of the whole series was 72.7% +/- 4.5. In patients treated with CS, the 5-year disease-free survival was 88.4% +/- 4.5 versus 76.4% +/- 6.1 for patients who received RT. Salvage surgery was effective in rescuing 2 of 3 CS failures and 12 of 25 RT failures. The overall incidence of secondary tumors (11%) and distant metastases (5%) was relatively low, although together they account for 15% of all deaths. Complications of CS were significantly correlated to the extent of surgical procedure. A multivariate analysis performed in the RT group showed that performance status, tumor grade, and fractionation regimen significantly influenced disease-free survival. CONCLUSION: Conservative management of T1-T2N0 supraglottic cancer, either by CS or RT, can achieve good cure rates with larynx preservation for the majority of the patients (82% overall; 95% in the CS group and 72% in the RT group). The decision between different conservative treatment modalities may be influenced by the patient's conditions, tumor characteristics, treatment modalities, and also economic costs.

Adult↗

PubMed2001

Long-term results of local recurrence after breast conservation treatment for invasive breast cancer.

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.

Adult↗

PubMed1997

Conservative treatment by irradiation of epidermoid cancers of the anal canal: prognostic factors of tumoral control and complications.

UNLABELLED: We analyzed in a retrospective series of patients treated by conservative irradiation for an epidermoid cancer of the anal canal (ECAC) the prognostic factors of locoregional control (LRC), survival, late severe complications (LSC), and sphincter conservation (SC). METHODS AND MATERIALS: From 1976 until 1994, 118 patients presenting with an ECAC were conservatively treated (mean age, 65 years). According to the 1987 International Union Against Cancer (TNM) classification, they were: 19 T1, 70 T2, 22 T3, 7 T4, 94 N0, and 24 N1-3. The treatment started with external beam irradiation (EBI) (36 Gy in 3 weeks or 45 Gy in 5 weeks). Concomitant chemotherapy (5-fluorouracil and mitomycin C) was delivered to 31 patients. Two months later, a boost of 20 Gy was delivered by interstitial 192Ir brachytherapy to 101 patients and EBI in 5. Twelve other patients had an abdominoperineal resection (APR). The mean follow-up was 6 years. RESULTS: At 5 years the overall survival was 60%, and specific survival (SS) was 75%; it was 94% for T1, 79% for T2, 53% for T3, and 19% for T4. In multivariate analysis, tumor size (> or = 4 cm), node involvement, and no response to the EBI were factors of poor prognosis for SS. Thirty-two locoregional recurrences occurred of which 21 were local recurrences in the 106 patients treated by a conservative schedule. Only tumor size and response to the EBI were prognostic factors on multivariate analysis for local and LRC. A total of 17 patients presented with LSC (Grade 3, 16 patients; and Grade 4, 1 patient), which was treated by APR in 4 patients and colostomy in 11 (of which 7 were definitive). The only significant prognostic factor for LSC in the multivariate analysis was the total extrapolated response dose of irradiation. The definitive rate of SC after conservative treatment in cured patients was 100% for T1, 82% for T2, 58% for T3, and 100% for T4. Since 1989, improvements of the technique have allowed reduction of the LSC in maintaining the same local control. CONCLUSION: The results of this series are similar to those of the literature. The confirmation of pretherapeutic prognostic factors related to response to the treatment should allow us to adapt the therapeutic intensity for each case to obtain better tumor control, with as few sequelae as possible, to yield a better rate of SC.

Adult↗

PubMed1997

Early-stage bilateral breast cancer treated with breast-conserving surgery and definitive irradiation: the University of Pennsylvania experience.

PURPOSE: To determine whether patients with early-stage bilateral breast cancer can be treated with definitive irradiation following breast-conserving surgery with acceptable survival, local control, complications, and cosmesis. METHODS AND MATERIALS: During the period 1977-1992, 55 women with Stage 0, I, or II concurrent (n = 12) or sequential (n = 43) bilateral breast cancer were treated with definitive irradiation following breast-conserving surgery. The records of these 55 patients with 110 treated breasts were reviewed for tumor size, histology, pathologic axillary lymph node status, first and overall site(s) of failure, and adjuvant chemotherapy or hormonal therapy. Curves for survival, local control, and regional control were determined. Cosmetic outcome, complication rates, and matching technique were analyzed. The median total radiation dose delivered was 64 Gy (range 42-72) using tangential whole-breast irradiation followed by an electron or iridium implant boost. The tangential fields were matched with no overlap in 40 patients (73%); there was overlap on skin of up to 4 cm in 14 patients (25%); and the matching technique was unknown in 1 patient (2%). The median follow-up for the 12 women with concurrent bilateral breast cancer was 4.0 years. The median follow-up for the other 43 women with sequential cancer was 9.3 and 4.9 years, respectively, after the first and second cancers. RESULTS: For the overall group of 55 patients, the 5- and 10-year overall survival rates were 96% and 94%, respectively, after treatment of the first cancer, and 96% and 92%, respectively, after treatment of the second cancer. The 5- and 10-year actuarial relapse-free survival rates were 90% and 75%, respectively, after treatment of the first cancer, and 83% and 72%, respectively, after treatment of the second cancer. For the 110 treated breast cancers, the 5- and 10-year actuarial local failure rates were 5% and 15%, respectively. Complication rates were: 28% breast edema, 8% arm edema, 4% pneumonitis, 3% cellulitis, 1% rib fracture, and 1% brachial plexopathy; no patient developed matchline fibrosis. For patients with a minimum of 3 years of relapse-free follow-up, the rate of excellent or good cosmetic outcome for 104 treated breasts was 85%. CONCLUSION: Definitive irradiation after breast-conserving surgery is technically feasible for selected patients with concurrent or sequential early-stage bilateral breast cancer. Survival, local control, complication rates, and cosmetic outcomes appear comparable to historical reports of breast conservation treatment for unilateral disease. Bilateral definitive breast irradiation after breast-conservation surgery should be considered an acceptable alternative treatment to bilateral mastectomy for selected patients with concurrent or sequential early-stage bilateral breast cancer.

Adult↗

PubMed1998

Lobular carcinoma in situ as a component of breast cancer: the long-term outcome in patients treated with breast-conservation therapy.

PURPOSE: The purpose of this study is to assess the long-term outcome of breast cancer patients with a component of lobular carcinoma in situ (LCIS) treated with conservative surgery and radiation therapy. METHODS AND MATERIALS: The pathology reports of all patients treated with conservative surgery and radiation therapy at our institution prior to 1992 were reviewed to identify patients who had LCIS as a histologic component. A total of 51 patients were identified. Primary histology of the 51 patients was as follows: 53% infiltrating lobular, 20% invasive and intraductal, 18% invasive ductal, 10% intraductal. There were no patients treated who had LCIS only. One thousand forty-five patients treated conservatively during the same time interval without LCIS served as a control group. All patient characteristics, staging, treatment and outcome variables were entered into a computer database. RESULTS: As of 3/96, the median follow-up for the LCIS-containing group and control group was 10.6 and 11.4 years, respectively. There were no significant differences in age of presentation, clinical stage, nodal status, estrogen receptor status, or adjuvant therapy received between the two groups. Twenty-two patients (43%) in the LCIS group underwent reexcision. Of those, 69% had residual LCIS in the reexcision specimen. LCIS was characterized as focal in 29%, diffuse in 25%, and not specified in all other cases. The primary histology of the two populations differed significantly with a larger percentage of infiltrating lobular primaries in the LCIS group (53 vs. 5%, p < 0.001). The LCIS group also differed from the control group with respect to the percentage of patients with bilateral disease (17 vs. 8%, p = 0.05), and the percentage of patients with "false negative" mammograms (20 vs. 10%, p = 0.02). There was no statistically significant difference between the LCIS group and control group in the 10-year overall survival (67 vs. 72%), distant disease-free survival (62 vs. 79%), or ipsilateral breast tumor recurrence-free survival (77% LCIS vs. 84% control). CONCLUSION: Patients with LCIS as a histologic component of breast cancer do not carry a worse prognosis than breast cancer patients without an LCIS component. Furthermore, the comparable local control rates between conservatively treated patients with or without LCIS suggests that patients with a histologic component of LCIS are suitable candidates for conservative surgery and radiation therapy.

Adult↗

PubMed1999

Nine breast angiosarcomas after conservative treatment for breast carcinoma: a survey from French comprehensive Cancer Centers.

OBJECTIVES: To conduct a survey of the angiosarcomas developing after breast conservation for carcinoma in the French Cancer Centers, to study the evolution of these cases in detail, and to review literature in an attempt to propose an optimal treatment scheme. MATERIAL AND METHODS: Eleven of the 20 French Cancer Centers agreed to research and retrospectively analyze all angiosarcomas discovered in patients previously treated by conservative treatment. The majority of the patients were node negative, T1N0M0. The mean age of the patients at the time of primary breast cancer treatment was 62.5 years, and 69 years at the diagnosis of the angiosarcoma. RESULTS: During the last two decades, nearly 20,000 patients have been treated conservatively in these 11 centers, and only 9 cases of angiosarcoma were found. The median latency period between the treatment of the breast carcinoma and the diagnosis of the breast angiosarcoma was approximately 74 months, with a range of 57-108 months. Mastectomy was performed as the main treatment of this angiosarcoma. All recurrences after mastectomy for the angiosarcoma appeared within 16 months after the mastectomy. A median time of recurrence was found to be 7.5 months, regardless of the treatment. The angiosarcomas appeared to be very aggressive, and chemotherapy, radiotherapy, and sometimes hyperthermia could only palliate the condition for a short time. After the diagnosis of angiosarcoma, the median survival was 15.5 months, showing a particularly poor prognosis. Only 1 patient of 9 is alive without progressive disease at 32 months after salvage mastectomy for the recurrence of the angiosarcoma. Precise data obtained from 11 centers show that, of 18115 breast carcinomas treated conservatively, only 9 breast angiosarcomas are reported, which represents a prevalence of 5 cases of angiosarcoma per 10,000, which is the same prevalence for primary breast angiosarcomas occurring in healthy breasts. CONCLUSION: Angiosarcoma developing after breast conserving therapy for carcinoma is a rare event, and induction of it by treatment is controversial. However, early diagnosis is essential and it appears that radical mastectomy gives the highest chance of cure and the best long-term survival.

Age of Onset↗

PubMed2003

An Escherichia coli strain, BJ5183, that shows highly efficient conservative (two-progeny) DNA double-strand break repair of restriction breaks.

We examined the mode of recombination in an Escherichia coli strain, BJ5183, which has been frequently used in recovery and cloning of eukaryotic DNA. One of the important criteria in characterizing a homologous recombination mechanism is whether it produces two recombinant DNA molecules or only one recombinant DNA molecule out of two parental DNA molecules. Our previous work transferring plasmid molecules with a restriction break into Escherichia coli cells distinguished two modes in recombination stimulated by a double-strand break. In a recBC sbcA mutant strain, where recET genes on the Rac prophage are responsible for recombination (RecE pathway), recombination is often conservative, in the sense that it generates two recombinants out of two parental DNAs. In a recBC sbcBC mutant strain, in which recA and recF genes are responsible (RecF pathway), recombination is non-conservative, in the sense that it generates only one recombinant out of two parental DNAs. Unexpectedly, BJ5183, described as recBC sbcBC, showed very efficient conservative (two-progeny) double-strand break repair. Moreover, this recombination was not eliminated by disruption of its recA gene, which is essential to the RecF pathway. Our polymerase chain reaction analysis detected a recET gene homologue in this strain. This region was easily replaced by a RECT::Tn10 through general transduction and the resulting recT-negative derivative was defective in the conservative double-strand break repair. These results led us to conclude that, in strain BJ5183, the action of recET homologue is responsible for the conservative double-strand break repair as in the RecE pathway. BJ5183 carries a mutation in the endA gene, which codes for Endonuclease I. An endA mutation conferred a higher double-strand break-repair activity to a recBC sbcA mutant strain.

Bacterial Proteins↗

PubMed2000

Conservation of sperms: current status and new trends.

Preserving genetic resources for next millennium is of great importance, whereas the major contribution of conserving sperms has the potential in many applications such as agriculture, biotechnology, species conservation and clinical medicine. Two major systems (liquid and frozen) of storage technologies have been developed for sperm conservation until the 20th century. The combinations of storage temperature, the cooling rate, chemical composition of extender, cryoprotectant concentration and the hygienic control are the key factors that affect the life span of spermatozoa. In the past decades, a slow progress have been made in improvement of storage technology, however, the recent advancement in reproduction technology and well understanding of the reproductive physiology have opened the door to a new era in conservation of sperm. This paper focuses on current sperm conservation systems as well as alternative strategies that would be effective for preserving genetic resources in future.

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