Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Locale”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 1,063 records · Page 59Linked to original sources
PubMedDate not supplied

[Functionally sparing surgery in locally spread malignant maxillary tumors and the use of local chemotherapy].

53 patients underwent functionally sparing operations which imply electrosurgical maxillectomy with alveolar process and hard palate left intact as well as eyeball preserving resections. At termination of the surgical intervention cyanoacrylate glue compounds incorporating cytostatics bleomycin or carminomycin were applied to the walls of the postoperative cavity. Maxillary alveolar process and hard palate were preserved when the tumor arose from maxillary posterior superior segments, ethmoidal labyrinth and upper nasal cavity. In orbital direction of the tumor spread the eyeball was spared when the lesion was confined to orbital wall and if intraorbital fat was uninvolved. 3-year survival after the above operations made up 60.4%. The method is believed oncologically effective and functionally, cosmetically sparing.

Antibiotics, Antineoplastic↗
PubMed1977

Immune responses to influenza virus in rabbits after local immunization. i.--Local and systemic humoral response.

IgA was found to be the predominant immunoglobulin in the bronchoalveolar secretions of rabbits. Significant quantities of IgG antibodies were also present in these secretions after intratracheal immunization with live influenza virus, but IgA/IgG ratios in the secretions were always higher than in corresponding sera, whether the rabbits were immunized or not. The relative excretion coefficients of IgA in these secretions were also found to be higher. In vitro culture of broncho-alveolar wash cells showed active synthesis of all the three major immunoglobulins with IgG as the predominant one. Immunization with live influenza virus induced a higher and more persistant antibody response in the respiratory secretions than the inactivated virus. A rapid and more intense production of IgA and IgG antibodies in these secretions after intratracheal booster antigen strongly suggests the presence of immunological memory in the secretory immune system of the respiratory tract. The role of secretory antiviral antibodies in protection against respiratory infections is also discussed.

Animals↗
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↗
PubMed1995

Local recurrences and distant metastases after conservative breast cancer treatments: partly independent events.

BACKGROUND: Local disease recurrences are a concern in conservative breast cancer surgery, and many studies have attempted to identify risk factors for these events. It is important to distinguish local recurrences linked to increased risk of distant spread from those due to inadequate local treatment. PURPOSE: We evaluated the incidence of local and distant recurrences according to demographic, biological, and pathologic variables in a large series of women who were conservatively and uniformly treated for breast cancer, with the aim of identifying women in whom local failure is predictive for distant metastases and who are therefore candidates for aggressive systemic treatment. METHODS: Medical records of 2233 women who had been hospitalized at the Milan Cancer Institute from 1970 to 1987 were analyzed. All women received quadrantectomy and axillary lymph node dissection followed by radiotherapy for the breast. Quadrantectomy is breast-conserving removal of most of the affected quadrant by a radial incision that includes part of the skin. The end points considered were local failures (including local recurrences and new ipsilateral carcinomas) and distant metastases. Statistical analysis employed the competing risks and multiple failures approaches. RESULTS: There were 119 local recurrences, 32 new ipsilateral carcinomas, and 414 distant metastases as first events. The timing of local failures and distant metastases differed: The yearly probability for local failures was approximately 1% up to the 10th year and for distant metastases was 5% in the 2nd year and decreased progressively until the 8th year. Young age was an important risk factor, with peritumoral lymphatic invasion also predictive for local and distant recurrences. Tumor size and axillary lymph node involvement were not related to local recurrence but were important predictors of distant metastases. Extensive intraductal component was only a risk factor for local recurrence. Early (< 2 years) local failure predicted for distant metastases compared with later failure. In local failure patients, the 5-year survival rate was 69% from failure. CONCLUSIONS: Local recurrences and distant metastases are partially independent events that occur at different times; several predicting factors also differ. However, women with local recurrences have increased risk of distant metastases. In particular, women 35 years old or younger at first diagnosis who had initial peritumoral lymphatic invasion and local recurrence within 2 years are at high risk for distant spread. For recurrence in cases with an extensive intraductal component or where initial local surgery was possibly inadequate, women are at lower risk.

Adult↗
PubMed2001

Local recurrence of soft tissue sarcoma. A Scandinavian Sarcoma Group Project.

The aim of this project was to investigate the diagnosis, treatment and consequences of local recurrence of soft tissue sarcoma (STS). It is based on patients reported to the Karolinska Hospital Sarcoma Register and the Scandinavian Sarcoma Group Register. Demographic and treatment data, based on 1613 adult patients reported to the Scandinavian Sarcoma Group Register by sarcoma centers in Norway, Sweden and Finland are presented. They all had STS of the extremities or trunk wall, and were diagnosed between 1986 and 1995. One third of the tumors were subcutaneous and two thirds deep-seated. The median size was 7 (1-35) cm and 75% were high grade. Metastases at presentation were diagnosed in 8% of the patients. Two thirds of the patients were referred to a sarcoma center before surgery. The preoperative morphologic diagnosis was made by fine-needle aspiration cytology in 72%. Among patients with final treatment for primary tumor at a sarcoma center (n = 1331), the surgical margins were wide or better in 76% of subcutaneous lesions, and in 58% of deep-seated lesions. Adjuvant radiotherapy has not generally been considered indicated after wide or compartmental excisions in Scandinavia. Overall, 23% of patients managed by surgery had adjuvant radiotherapy. Among patients with an intralesional or marginal excision, 44% had postoperative radiotherapy. Patients treated outside of sarcoma centers were seldom referred for radiotherapy. The crude local recurrence rate was 225/1331 (17%) among the patients with final treatment for primary tumor at a sarcoma center. The local recurrence rate after local surgery for high-malignant deep-seated STS was 103/391 (26%). The rate was 25/64 (39%) after an intralesional/marginal margin without postoperative radiotherapy versus 28/119 (24%) when radiotherapy was given. Fine-needle aspiration cytology (FNAC) was used to diagnose suspected local recurrences. 95 FNAC were performed in 86 patients from Karolinska Hospital. There were 47 local recurrences, of which 44 were diagnosed correctly by FNAC; one biopsy was inconclusive, and two lesions were incorrectly assessed as benign. 39 patients proved to have benign lesions in the scar examined cytologically on 50 occasions. None of the specimens was regarded as malignant, but in 4 cases FNAC was inconclusive. The inconclusive or false cytological diagnoses had no serious clinical consequences. Among 205 patients with local recurrence identified in the SSG Register 1987-1995, 169 patients were surgically treated. An intralesional or marginal margin was achieved in 110 of these patients, 59 of whom were also given radiotherapy. 54 of the 169 patients had a second local recurrence. The second local recurrence rate was 0.50 if the first local recurrence was treated using surgery with a marginal margin alone, compared to 0.28 if treated using either surgery with a marginal margin and radiotherapy, or a wide margin (p = 0.0008). In extremity STS, the amputation rate for local recurrences was 0.22, compared to 0.09 for primary tumors. The overall 5-year MFS was 0.72 (95% CI 0.68-0.76). High histopathological malignancy grade (Relative Risk 3.0; 95% CI 1.5-6.3) and an inadequate surgical margin (2.9; 95% CI 1.8-4.6) were independent risk factors for local recurrence. High histopathological malignancy grade and large tumor size (> 7 cm) were the most important risk factors for metastasis. Local recurrence was associated with an increased risk of metastasis (4.4; 95% CI 2.9-6.8), but an inadequate surgical margin was not a risk factor for metastasis (1.1; 95% CI 0.8-1.7). In conclusion, it is unlikely that local recurrence of STS is a major source of metastases. It nevertheless represents a costly, complicated and emotionally difficult problem. More radical surgical margins would improve the local recurrence rate, but this can hardly be achieved for center-operated patients without increasing the amputation rate. Instead, local control will improve by giving radiotherapy to all patients after marginal surgery, and to selected patients with wide margins. Radiotherapy is indicated especially after a previous open biopsy or when a local recurrence might lead to an amputation. Furthermore, radiotherapy seems indicated after local recurrence, regardless of margin or grade. The most effective way of reducing costs and detriment associated with local recurrence is to increase referral to sarcoma centers before biopsy or surgery as primary surgical margins would then improve.

Adolescent↗
PubMed2002

Long-term results of local excision for rectal cancer.

OBJECTIVE: To review the authors' experience with local excision of early rectal cancers to assess the effectiveness of initial treatment and of salvage surgery. SUMMARY BACKGROUND DATA: Local excision for rectal cancer is appealing for its low morbidity and excellent functional results. However, its use is limited by inability to assess regional lymph nodes and uncertainty of oncologic outcome. METHODS: Patients with T1 and T2 adenocarcinomas of the rectum treated by local excision as definitive surgery between 1969 to 1996 at the authors' institution were reviewed. Pathology slides were reviewed. Among 125 assessable patients, 74 were T1 and 51 were T2. Thirty-one patients (25%) were selected to receive adjuvant radiation therapy. Fifteen of these 31 patients received adjuvant radiation in combination with 5-fluorouracil chemotherapy. Median follow-up was 6.7 years. One hundred fifteen patients (92%) were followed until death or for greater than 5 years, and 69 patients (55%) were followed until death or for greater than 10 years. Recurrence was recorded as local, distant, and overall. Survival was disease-specific. RESULTS: Ten-year local recurrence and survival rates were 17% and 74% for T1 rectal cancers and 26% and 72% for T2 cancers. Median time to relapse was 1.4 years (range 0.4-7.0) for local recurrence and 2.5 years (0.8-7.5) for distant recurrence. In patients receiving radiotherapy, local recurrence was delayed (median 2.1 years vs. 1.1 years), but overall rates of local and overall recurrence and survival rates were similar to patients not receiving radiotherapy. Among 26 cancer deaths, 8 (28%) occurred more than 5 years after local excision. On multivariate analysis, no clinical or pathologic features were predictive of local recurrence. Intratumoral vascular invasion was the only significant predictor of survival. Among 34 patients who developed tumor recurrence, the pattern of first clinical recurrence was predominantly local: 50% local only, 18% local and distant, and 32% distant only. Among the 17 patients with isolated local recurrence, 14 underwent salvage resection. Actuarial survival among these surgically salvaged patients was 30% at 6 years after salvage. CONCLUSIONS The long-term risk of recurrence after local excision of T1 and T2 rectal cancers is substantial. Two thirds of patients with tumor recurrence have local failure, implicating inadequate resection in treatment failure. In this study, neither adjuvant radiotherapy nor salvage surgery was reliable in preventing or controlling local recurrence. The postoperative interval to cancer death is as long as 10 years, raising concern that cancer mortality may be higher than is generally appreciated. Additional treatment strategies are needed to improve the outcome of local excision.

Adenocarcinoma↗
PubMed1992

Analysis of local electrogram characteristics correlated with successful radiofrequency catheter ablation of accessory atrioventricular pathways.

UNLABELLED: Due to the limited myocardial lesions produced by radiofrequency current, the ablation of accessory pathways (AP) requires precise localization of such connections. The purpose of this study was to ascertain which characteristic(s) of the local bipolar electrogram, recorded from the ablation and adjacent electrode immediately prior to the application of radiofrequency current, correlated with precision in localization adequate to permit AP ablation. Signal analysis was performed for 326 sets of electrograms preceding the attempted ablation of 107 APs in 100 consecutive patients. For 80 antegrade APs, the following variables were evaluated: (1) the presence or absence of an AP potential; (2) the local atrial-AP interval; (3) the local atrioventricular (AV) interval; and (4) the relationship between the onset of local ventricular depolarization and onset of delta wave of the surface electrocardiogram. For the 27 concealed APs, the following characteristics were evaluated: (1) the presence or absence of an AP potential; and (2) the local VA interval during reciprocating tachycardia or ventricular pacing. RESULTS: Antegrade APs: By statistical analysis, the best correlate of successful ablation of an antegrade AP was a local AV interval less than or equal to 40 msec (positive predictive value = 94%; 95% confidence intervals [CI] = 81%-100%). Local AV intervals less than or equal to 50 msec preceded 88% of successful AP ablations, compared to only 8% of failed radiofrequency current applications. The positive predictive value of the other variables were: presence of an AP potential: 35% (95% CI = 27%-40%); local atrial-AP intervals less than or equal to 40 msec: 54% (95% CI = 43%-66%); and local ventricular depolarization preceding onset of the delta wave 43% (95% CI = 34%-52%). For concealed APs, the positive predictive value of a VA interval less than 60 msec was 71% (95% CI = 48%-88%); the positive predictive value for the presence of an AP potential was 58% (95% CI = 32%-81%). CONCLUSIONS: No single electrogram characteristic had a positive predictive value and a sensitivity greater than 90% for AP localization adequate for radiofrequency current ablation. For antegrade APs, the best correlate of adequate localization was a local AV interval less than or equal to 40 msec; as a corollary, radiofrequency current applications at sites where the local AV was greater than 60 msec, were unlikely to be effective. Objective criteria for the localization of concealed APs were less certain. Electrogram analysis, as a guide to AP localization and ablation, requires careful analysis of multiple variables, with analysis of the local AV interval a salient objective factor.

Adult↗
PubMed1995

Potential benefit of improved local tumor control in patients with prostate carcinoma.

BACKGROUND: In the case of prostate carcinoma, radiation therapy is a locally applied treatment modality in a malignancy known for systemic dissemination. Because significant efforts and resources currently are being consumed to improve local tumor control, failure patterns and potential curative gain deserve appropriate assessment. METHODS: From 1975-1989, 647 patients with clinically localized prostate carcinoma were definitively irradiated for biopsy-proven adenocarcinoma of the prostate. Failure patterns were examined, and survival advantage based on improvement in either local or distant disease control was calculated. Distant metastatic rate and cause-specific survival analyses were used as parameters by which to compare the outcome for patients in whom local tumor control was achieved with patients who experienced local failure, thereby assessing further the importance of the effectiveness of locally applied therapy. RESULTS: Three hundred ninety-two (61%) patients at the time of this writing were clinically disease free. Sixty-two (10%) patients failed locally only, 133 (20%) distantly only, and 60 (9%) developed local and distant recurrent disease. Both local and distant failure rates were higher in patients with more advanced stage lesions at presentation, and distant failure rates significantly increased in patients with less differentiated tumors. Pretreatment prostate-specific antigen was found to be useful in predicting recurrence patterns. Overall, there appeared to be more potential for improvement in survival secondary to reducing distant metastasis. The distant survival advantage (DSA) of reducing distant metastases, compared with the local survival advantage (LSA) of improving local tumor control, was 26 versus 14%. Although DSA was greater than LSA within each stage category, the potential to improve survival was most significant in the Stage C group, where DSA was 35% and LSA 16%. Although LSA varied little according to tumor grade, DSA was dependent on tumor grade and varied from 13% for well differentiated lesions to 38% for poorly differentiated lesions. Distant failure free survival at 10 years was 63% for patients with local control and 45% for those with local failure (P = 0.01). Similarly, 10-year cause-specific survival was 75% in locally controlled patients compared with 48% for those with local recurrence (P < 0.001). CONCLUSIONS: Although better local tumor control should translate into at least modest survival gain for patients with prostate carcinoma, additional advantage may be seen with improved systemic therapy or perhaps earlier diagnosis to reduce further the distant metastasis rate.

Adenocarcinoma↗
PubMed2001

Local excision of rectal cancer: what is the evidence?

PURPOSE: Although local excision of rectal cancers is a less morbid alternative to radical resection, its role as a curative procedure is unclear. The role of adjuvant therapy after local excision is also controversial. This review aims to examine current evidence on local excision of rectal cancers and how it fits into the management algorithm for rectal cancer. METHODS: A literature review was undertaken through the MEDLINE database and by cross-referencing previous publications, thus identifying 41 studies on curative local excision of rectal cancer published in English. Details of preoperative staging, surgical procedures, adjuvant therapy, follow-up, and outcome measures, including complications, survival data, recurrences, and salvage were examined. RESULTS: Preoperative staging of rectal cancers is variable. Digital rectal examination and computerized tomography are used in most studies. Endorectal ultrasound is used in some patients in 9 of 41 studies. Local excision preserves anorectal function, and seems to have limited morbidity (0-22 percent). Local excision alone is associated with local recurrences in 9.7 (range, 0-24) percent of T1, 25 (range, 0-67) percent of T2 and 38 (range, 0-100) percent of T3 cancers. The addition of adjuvant chemoradiotherapy after local excision yields local recurrence rates of 9.5 (range, 0-50) percent for T1, 13.6 (range, 0-24) percent for T2, and 13.8 (range, 0-50) percent for T3 cancers. Data on local excision after preoperative chemoradiotherapy for tumor down staging are limited. Factors other than T-stage that lead to higher local recurrence rates after local excision include poor histologic grade, the presence of lymphovascular invasion, and positive margins. Local recurrences after local excision can be surgically salvaged (84 of 114 patients in 15 studies), with a disease-free survival rates between 40 and 100 percent at a follow-up of 0.1 to 13.5 years. CONCLUSIONS: Local excision for rectal cancers is associated with a low morbidity and provides satisfactory local control and disease-free survival rates for T1 rectal cancers. There is, however, a need for a randomized, controlled trial for T2 cancers, comparing local excision with adjuvant chemoradiotherapy to radical resection.

Algorithms↗
PubMedDate not supplied

Understanding allergic reactions to local anesthetics.

OBJECTIVE: To review the pharmacology and mechanisms by which local anesthetics cause allergic reactions. Recommendations concerning appropriate use of local anesthetics and alternative therapies in patients with documented local anesthetic allergies are given. DATA SOURCE: A MEDLINE search of English-language literature identified pertinent clinical studies, case reports, and reviews. The periods of review were Med1, 1990-present, and Med2, 1985-1989, using the MeSH terms drug hypersensitivity and anesthetics. References from the selected studies, case reports, and reviews were reviewed. STUDY SELECTION: Controlled and uncontrolled prospective studies and case reports pertaining to local anaesthetic allergies were reviewed. The selection focused on information pertaining to the etiology and diagnosis of allergic reactions to local anesthetics and alternative therapies for patients with local anesthetic allergies. DATA SYNTHESIS: Local anesthetics are classified as either ester or amide compounds. Esters are associated with a higher incidence of allergic reactions, due to a p-aminobenzoic acid (PABA) metabolite. Amide agents do not undergo such metabolism. However, preservative compounds (methylparaben) used in the preparation of amide-type agents are metabolized to PABA. Patients who are allergic to ester local anesthetics should be treated with a preservative-free amide local anesthetic. If the patient is not allergic to ester local anesthetics, these agents may be used in amide-sensitive patients. In the rare instance that hypersensitivity to both ester and amide local anesthetics occurs, or if skin testing cannot be performed, than alternative therapies including diphenhydramine, opioids, general analgesia, or hypnosis can be used. CONCLUSIONS: A true immunologic reaction to a local anesthetic is rare. Intradermal skin testing of local anesthetic compounds, methylparaben, and metabisulfite should be performed in patients when a thorough history does not rule out a possible allergic reaction to local anesthetics and future local anesthesia is necessary. Skin testing enables the clinician to identify autonomic responses to minor surgical procedures and toxic reactions to anesthetics so that patients are not incorrectly labeled as "caine" allergic. Diphenhydramine can be used as an alternative to ester and amide local anesthetics in minor procedures of short duration.

Anesthesia, Local↗
PubMed1993

Wide local excision of recurrent breast cancer in the thoracic wall.

BACKGROUND: Local recurrence is one of the major problems in treatment of breast cancer. Approximately 20% of patients who have radical or modified radical mastectomy have a local recurrence. METHODS: The records of 98 women with locally recurrent breast cancer treated with wide local excision, in the years 1983-1987, were reviewed. The median age at excision was 62 years (range, 32-84 years). All patients were observed until death or December 31, 1989. The median follow-up period was 36 months (range, 2-79 months). RESULTS: At follow-up, 44 of 98 patients (45%) had had a new local relapse and 47 of 98 (48%) were dead. The median duration of local control for all patients was 21 months (range, 1-79 months). The diameter of the local recurrence seemed to influence the duration of local disease control but not total survival. Patients admitted directly for surgery had a longer period of local control compared with patients admitted after unsuccessful oncologic treatment of the local recurrence. The 5-year local control rates were 50% and 24%, respectively (P > 0.92). No statistically significant difference in local control could be shown whether or not the patient received additional oncologic therapy in continuity with the wide local excision. The 5-year local control rate in patients treated only by surgery was 33% compared with 42% in patients also receiving additional oncologic treatment (P > 0.63). CONCLUSIONS: Wide local excision of recurrent breast cancer seems to provide as good or even better local control than other treatment modalities. Surgery should not be postponed in cases of ineffective medical treatment or radiation therapy.

Adult↗
PubMed1991

The effect of local control on metastatic dissemination in carcinoma of the prostate: long-term results in patients treated with 125I implantation.

The study evaluates the effect of the locally recurring tumor on the incidence of metastatic disease in early stage carcinoma of the prostate. The probability of distant metastases was studied in 679 patients with Stage B-C/N0 carcinoma of the prostate treated at MSKCC between 1970 and 1985 (median follow-up of 97 months). Patients were staged with pelvic lymph node dissection and treated with retropubic 125I implantation. The actuarial distant metastases free survival (DMFS) for patients at risk at 15 years after initial therapy was 37%. Cox proportional hazard regression analysis of covariates affecting the metastatic outcome showed that local failure, used in the model as a time dependent variable, was the most significant covariate, although stage, grade, and implant volume were also found to be independent variables. The relative risk of metastatic spread subsequent to local failure was 4-fold increased compared to the risk without evidence of local relapse. The 15-year actuarial DMFS in 351 patients with local control was 77% compared to 24% in 328 patients who developed local relapses (p less than 0.00001). The relation of distant spread to the local outcome was observed regardless of stage, grade, or implant dose. Even stage B1/N0-Grade I patient with local control showed a 15-year actuarial DMFS of 82%, compared to 22% in patients with local relapse; p less than 0.00001). The median local relapse-free survival (LRFS) in the 268 patients with local recurrences who did not receive hormonal therapy before distant metastases were detected was 51 months, compared to a median of 71 months for DMFS in the same patients (p less than 0.001), consistent with the possibility that distant dissemination may develop secondary to local failure. Furthermore, distant metastases in patients with local control, apparently already existing as micrometastases before treatment, were detected earlier (median DMFS of 37 months) than in patients with local relapse (median DMFS of 54 months; p = 0.009). These data suggest that the existence and re-growth of local residual disease in localized prostatic carcinoma promotes an enhanced spread of metastatic disease, and that early and complete eradication of the primary tumor is required if a long term cure is to be achieved, although the clinical expression of secondary metastases may not become apparent for 6.5 years or more in one-half of the patients.

Adenocarcinoma↗
PubMed2005

Effects of radiotherapy and of differences in the extent of surgery for early breast cancer on local recurrence and 15-year survival: an overview of the randomised trials.

BACKGROUND: In early breast cancer, variations in local treatment that substantially affect the risk of locoregional recurrence could also affect long-term breast cancer mortality. To examine this relationship, collaborative meta-analyses were undertaken, based on individual patient data, of the relevant randomised trials that began by 1995. METHODS: Information was available on 42,000 women in 78 randomised treatment comparisons (radiotherapy vs no radiotherapy, 23,500; more vs less surgery, 9300; more surgery vs radiotherapy, 9300). 24 types of local treatment comparison were identified. To help relate the effect on local (ie, locoregional) recurrence to that on breast cancer mortality, these were grouped according to whether or not the 5-year local recurrence risk exceeded 10% (<10%, 17,000 women; >10%, 25,000 women). FINDINGS: About three-quarters of the eventual local recurrence risk occurred during the first 5 years. In the comparisons that involved little (<10%) difference in 5-year local recurrence risk there was little difference in 15-year breast cancer mortality. Among the 25,000 women in the comparisons that involved substantial (>10%) differences, however, 5-year local recurrence risks were 7% active versus 26% control (absolute reduction 19%), and 15-year breast cancer mortality risks were 44.6% versus 49.5% (absolute reduction 5.0%, SE 0.8, 2p<0.00001). These 25,000 women included 7300 with breast-conserving surgery (BCS) in trials of radiotherapy (generally just to the conserved breast), with 5-year local recurrence risks (mainly in the conserved breast, as most had axillary clearance and node-negative disease) 7% versus 26% (reduction 19%), and 15-year breast cancer mortality risks 30.5% versus 35.9% (reduction 5.4%, SE 1.7, 2p=0.0002; overall mortality reduction 5.3%, SE 1.8, 2p=0.005). They also included 8500 with mastectomy, axillary clearance, and node-positive disease in trials of radiotherapy (generally to the chest wall and regional lymph nodes), with similar absolute gains from radiotherapy; 5-year local recurrence risks (mainly at these sites) 6% versus 23% (reduction 17%), and 15-year breast cancer mortality risks 54.7% versus 60.1% (reduction 5.4%, SE 1.3, 2p=0.0002; overall mortality reduction 4.4%, SE 1.2, 2p=0.0009). Radiotherapy produced similar proportional reductions in local recurrence in all women (irrespective of age or tumour characteristics) and in all major trials of radiotherapy versus not (recent or older; with or without systemic therapy), so large absolute reductions in local recurrence were seen only if the control risk was large. To help assess the life-threatening side-effects of radiotherapy, the trials of radiotherapy versus not were combined with those of radiotherapy versus more surgery. There was, at least with some of the older radiotherapy regimens, a significant excess incidence of contralateral breast cancer (rate ratio 1.18, SE 0.06, 2p=0.002) and a significant excess of non-breast-cancer mortality in irradiated women (rate ratio 1.12, SE 0.04, 2p=0.001). Both were slight during the first 5 years, but continued after year 15. The excess mortality was mainly from heart disease (rate ratio 1.27, SE 0.07, 2p=0.0001) and lung cancer (rate ratio 1.78, SE 0.22, 2p=0.0004). INTERPRETATION: In these trials, avoidance of a local recurrence in the conserved breast after BCS and avoidance of a local recurrence elsewhere (eg, the chest wall or regional nodes) after mastectomy were of comparable relevance to 15-year breast cancer mortality. Differences in local treatment that substantially affect local recurrence rates would, in the hypothetical absence of any other causes of death, avoid about one breast cancer death over the next 15 years for every four local recurrences avoided, and should reduce 15-year overall mortality.

Aged↗
PubMed2002

Benefit and risks of local anesthetics in infants and children.

Regional anesthesia has become a routine part of the practice of anesthesiology in infants and children. Local anesthetic toxicity is extremely rare in infants and children; however, seizures, dysrhythmias, cardiovascular collapse, and transient neuropathic symptoms have been reported. Infants and children may be at increased risk from local anesthetics compared with adults. Larger volumes of local anesthetics are used for epidural anesthesia in infants and children than in adults. Metabolism and elimination of local anesthetics can be delayed in neonates, who also have decreased plasma concentrations of alpha(1)-acid glycoprotein, leading to increased concentrations of unbound bupivacaine. Most regional anesthetic procedures in infants and children are performed with the patient heavily sedated or anesthetized; because of this, and because a test dose is not a particularly sensitive marker of intravenous injection in the anesthetized patient, detection of intravascular local anesthetic injection is extremely difficult. The same local anesthetics used in adult anesthetic practice are also used in infants and children. Because of its extremely short duration of action, chloroprocaine has been used primarily for continuous epidural techniques in infants and children. The use of tetracaine has generally been limited to spinal and topical anesthesia. Lidocaine (lignocaine) has been used extensively in infants and children for topical, regional, plexus, epidural and spinal anesthesia. The association between prilocaine and methemoglobinemia has generally restricted prilocaine use in infants and children to the eutectic mixture of local anesthetics (EMLA). Because of its greater degree of motor block compared with other long-acting local anesthetics, etidocaine has generally been limited to plexus blocks in infants and children. Mepivacaine has been used for both plexus and epidural anesthesia in infants and children. Because postoperative analgesia is often the primary justification for regional anesthesia in infants and children, bupivacaine, a long-acting local anesthetic, is the most commonly reported local anesthetic for pediatric regional anesthesia. Given the lower toxic threshold of bupivacaine compared with other local anesthetics, the risk-benefit ratio of bupivacaine may be greater than that of other local anesthetics. Two new enantiomerically pure local anesthetics, ropivacaine and levobupivacaine, offer clinical profiles comparable to that of bupivacaine but without its lower toxic threshold. The extreme rarity of major toxicity from local anesthetics suggests that widespread replacement of bupivacaine with ropivacaine or levobupivacaine is probably not necessary. However, there are clinical situations, including prolonged local anesthetic infusions, use in neonates, impaired hepatic metabolic function, and anesthetic techniques requiring a large mass of local anesthetic, where replacement of bupivacaine with ropivacaine, levobupivacaine or (for continuous techniques) chloroprocaine appears prudent.

Anesthesia, Conduction↗
PubMed1990

Sensitive and critical periods for visual calibration of sound localization by barn owls.

This study describes developmental changes in the capacity of owls to adjust sound localization in response to chronic prismatic displacement of the visual field and to recover accurate sound localization following the restoration of normal vision. Matched, binocular displacing prisms were mounted over the eyes of 19 barn owls (Tyto alba) beginning at ages ranging from 10 to 272 d. In nearly all cases, the visual field was shifted 23 degrees to the right. Sound localization was assessed on the basis of head orientations to sound sources, measured in a darkened sound chamber with a search coil system. Chronic exposure to a displaced visual field caused the owls to alter sound localization in the direction of the visual field displacement, thereby inducing a sound-localization error. The size of the sound-localization error that resulted depended on the age of the animal when prism experience began. Maximal errors of about 20 degrees were induced only when prism experience began by 21 d of age. As prism experience began at later ages, the magnitude of induced errors decreased. A bird that wore prisms beginning at 102 d of age, altered sound localization by only 6 degrees. An adult owl, when exposed chronically to a displaced visual field, altered sound localization by about 3 degrees. We refer to the early period in life when displaced vision induces exceptionally large sound-localization errors (relative to those induced in the adult) as a sensitive period. The capacity to recover accurate sound localization following restoration of normal vision was tested in 7 owls that had been raised wearing prisms. Four owls that had prisms removed by 182 d of age recovered accurate localization rapidly (over a period of weeks), whereas 3 owls that were older when the prisms were removed did not recover accurate localization when tested for up to 7 months after prism removal. Adjustment of sound localization slowed greatly or ceased at about 200 days of age, referred to here as the critical period for visual calibration of sound localization. Three owls were subjected repetitively to displacement of the visual field. An owl that adjusted sound localization to the left of normal during the sensitive period retained the capacity to adjust again to the left, but not to the right of normal, later in the critical period. The converse was true for an owl that adjusted sound localization to the right of normal during the sensitive period.(ABSTRACT TRUNCATED AT 400 WORDS)

Adaptation, Physiological↗