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Proliferative activity of microvascular cells in glioblastomas does not correlate with time to recurrence.

The time to recurrence operation (TR) is a good growth parameter, in particular for glioblastomas. Recently, we have shown that Ki-67 labeling index (LI) of tumor cells has a high inverse correlation with this time interval. In the current study, the LI of microvascular cells (MVC) was examined in the same glioblastoma cases. The LI of MVC of primary and recurrent tumors had no relationship and did not show any correlation to TR. The growth fraction of MVC was significantly lower than that of tumor cells. The MVC in glioblastomas seems to have chaotical proliferation properties without any link to the tumor growth potential. This observation may have implications for anti-angiogenic therapy.

Adult↗

Early treatment of endometriosis with GnRH-agonists: impact on time to recurrence.

In a study, 52 patients with histologically confirmed endometriosis underwent a "three-step" therapy. The follow-up period was up to 60 months (median 33.5 months). If r-AFS-score was posttherapeutically 0, recurrence occurred latest after 36 months (median 18 months), if stage III was found posttherapeutically, recurrence occurred already latest after 18 months (median 8 months), (log-rank test P=0.0072). In our study we could confirm a clear relationship of recurrence of symptomatic endometriosis to the post-therapeutically achieved r-AFS-score.

Endometriosis↗

Breast cancer local recurrence: risk factors and prognostic relevance of early time to recurrence.

BACKGROUND: Local recurrence occurs in 10%-20% of patients treated with breast-conserving surgery for stage I-II breast cancer. The aim of the present study was to investigate breast cancer local recurrence, potential risk factors, and prognostic impact. METHODS: A total of 503 patients treated with breast-conserving surgery were included in the study. All patients underwent axillary dissection and postoperative radiotherapy, and all patients had negative margins at pathological examination. Median follow-up was 82 months. Local recurrence was classified as early when it occurred within 2 years from surgery. The risk factors for local recurrence and overall survival were estimated by univariate and multivariate analyses. RESULTS: Forty-six cases (9.1%) of local recurrence were observed, 11 of which occurred within 24 months of surgery; the other 35, sometime later. Statistically significant risk factors for local recurrence were premenopausal status, peritumoral vascular invasion, multifocality, and absence of estrogen receptors. Independent negative prognostic factors for overall survival at 5 and 10 years were N stage, absence of estrogen receptors, and early time to recurrence. Overall survival at 10 years was 10.0% for patients with early recurrence, 87.5% for patients with late recurrence, and 87.9% for patients without recurrence. CONCLUSIONS: None of the studied clinicopathological characteristics alone is a determinant for the choice of surgical treatment. Younger patients treated with breast-conserving surgery should receive aggressive postsurgical treatment and should be followed with an intensive follow-up program when metastatic axillary lymph nodes, negative estrogen receptors, or peritumoral vascular invasion are present.

Adult↗

[Timing of surgery in infective endocarditis: impact on the outcome and recurrence].

Timing of surgery in infective endocarditis remains a challenge in the face of potential drug toxicity on one hand and recurrence of endocarditis on the other. The aim of the study was analysis of risk factors for hospital mortality and recurrent endocarditis. A total of 131 patients with infective endocarditis have been observed during 1999-2001. Eighty seven of them were male and 44 female with mean age of 50+/-16 years. Sixty three (48.1%) patients underwent surgery, remaining 68 (51.9%) were treated conservatively. Hospital mortality was 25.2%. Postoperative perivalvular leak was associated with culture negative endocarditis (p=0.09) as well as with positive valve culture (p=0.04). Recurrence was related to positive valve culture (p=0.08) and embolism (p=0.02). Increased risk of death was associated with neurologic, embolic, renal complications, myocardial abscess, NYHA IV f.cl. and extracardial surgery. According to the data obtained, optimal surgery time in the group appeared to be between 17 and 45 days after the diagnosis of infective endocarditis has been made (p=0.049).

Adult↗

Renal cell carcinoma recurrence after nephrectomy for localized disease: predicting survival from time of recurrence.

PURPOSE: Prognostic factors for patients with metastatic renal cell carcinoma (RCC) are well established. However, the risk profile is unknown for patients with recurrent RCC after a nephrectomy for localized disease. PATIENTS AND METHODS: From January 1989 to July 2005, we identified patients with localized RCC treated by nephrectomy who subsequently developed recurrent disease. We applied a validated prognostic scoring system previously developed for patients with metastatic RCC. Each patient was given a total risk score of 0 to 5, with one point for each of five prognostic variables (recurrence < 12 months after nephrectomy, serum calcium > 10 mg/dL, hemoglobin < lower limit of normal, lactate dehydrogenase > 1.5x upper limit of normal, and Karnofsky performance status < 80%). Patients were categorized into low- (score = 0), intermediate- (score = 1 to 2), and high-risk subgroups (score = 3 to 5). RESULTS: Our final cohort included 118 patients, with a median survival time of 21 months from the time of recurrence. Median follow-up time for survivors was 27 months. Overall survival was strongly associated with risk group category (P < .0001). Low-risk, intermediate-risk, and high-risk criteria were fulfilled in 34%, 50%, and 16% of patients, respectively. Median survival time for low-risk, intermediate-risk, and high-risk patients was 76, 25, and 6 months, respectively. Two-year overall survival rates for low-risk, intermediate-risk, and high-risk patients were 88% (95% CI, 77% to 99%), 51% (95% CI, 37% to 65%), and 11% (95% CI, 0% to 24%), respectively. CONCLUSION: At disease recurrence after nephrectomy for localized disease, a scoring system based on objective clinical and laboratory data provides meaningful risk stratification for both patient counseling and clinical trial entry.

Aged↗

A comparison of segmental vs subtotal/total colectomy for colonic Crohn's disease: a meta-analysis.

OBJECTIVE: Using meta-analytical techniques the present study evaluated differences in short-term and long-term outcomes of adult patients with colonic Crohn's disease who underwent either colectomy with ileorectal anastomosis (IRA) or segmental colectomy (SC). METHODS: Comparative studies published between 1988 and 2002, of subtotal/total colectomy and ileorectal anastomosis vs segmental colectomy, were used. The study end points included were surgical and overall recurrence, time to recurrence, postoperative morbidity and incidence of permanent stoma. Random and fixed-effect meta-analytical models were used to evaluate the study outcomes. Sensitivity analysis, funnel plot and meta-regressive techniques were carried out to explain the heterogeneity and selection bias between the studies. RESULTS: Six studies, consisting of a total of 488 patients (223 IRA and 265 SC) were included. Analysis of the data suggested that there was no significant difference between IRA and SC in recurrence of Crohn's disease. Time to recurrence was longer in the IRA group by 4.4 years (95% CI: 3.1-5.8), P < 0.001. There was no difference between the incidence of postoperative complications (OR = 1.4., 95% CI 0.16-12.74) or the need for a permanent stoma between the two groups (OR = 2.75, 95% CI 0.78-9.71). Patients with two or more colonic segments involved were associated with lower re-operation rate in the IRA group, a difference which did not reach statistical significance (P = 0.177). CONCLUSIONS: Both procedures were equally effective as treatment options for colonic Crohn's disease however, patients in the SC group exhibited recurrence earlier than those in the IRA group. The choice of operation is dependent on the extent of colonic disease, with a trend towards better outcomes with IRA for two or more colonic segments involved. Since no prospective randomised study has been undertaken, a clear view about which approach is more suitable for localised colonic Crohn's disease cannot be obtained.

Colectomy↗

Bacillus Calmette-Guérin therapy in stage Ta/T1 bladder cancer: prognostic factors for time to recurrence and progression.

OBJECTIVE: To report prognostic factors for time to recurrence and progression after bacillus Calmette-Guérin (BCG) prophylaxis in patients with stage Ta/T1 papillary bladder cancer. PATIENTS AND METHODS: The clinical records were assessed retrospectively for 236 patients with papillary stage Ta/T1 bladder cancer treated with BCG between 1986 and 2000. Patients with known carcinoma in situ were excluded. The median (range) follow-up was 44 (4-155) months. The effect of 13 variables on the time to recurrence and progression was evaluated using multivariate Cox proportional hazard regression and Kaplan-Meier analyses. RESULTS: The recurrence rate was markedly reduced for all grades and stages. Patients with a negative first cystoscopy and maintenance BCG had a significantly longer time to recurrence than those treated with an induction course alone (P < 0.001). Thirty-seven patients (16%) progressed in stage. The result of the first cystoscopy (P < 0.001), tumour grade (P = 0.003) and six or fewer initial instillations (P = 0.002) had prognostic importance for the time to progression. Twenty-eight patients (12%) had a history of an upper tract tumour, which was 3-10 times the expected rate. Age, number of tumours, number of positive cystoscopies, length of tumour history before BCG, BCG strain and treatment year had no influence on time to recurrence and progression. CONCLUSIONS: Maintenance treatment does not seem to be necessary among patients with TaG1-G2 disease after a negative first cystoscopy, as the progression rate was very low. One new finding was that BCG seemed to be equally effective among patients with or with no history of an upper tract tumour. Another new and surprising finding was that patients treated with fewer than six induction instillations, because of very bothersome side-effects, had an increased risk of tumour progression and of local failure.

Adjuvants, Immunologic↗

Under-nutrition affects time to recurrence of gastroenteritis among Aboriginal and non-Aboriginal children.

This study investigated whether under-nutrition affected time to hospitalization for recurrence of gastroenteritis in Australian children. Linked hospitalization records of all infants, born in 1995 and 1996 in Western Australia, who were admitted for gastroenteritis during their first year of life (n=1001), were retrieved. A survival frailty model was used for determining the factors influencing the recurrent times over the subsequent seven years. Aboriginality and under-nutrition were significantly associated with an increased risk of recurrence (hazard ratios of 2.59 and 1.28). Hospitalizations due to gastroenteritis were common among Aboriginal children who had a higher mean re-admission rate and much shorter intervals between re-admissions than other patients. The proportion of patients with recurrence was also significantly higher for Aboriginals (38.5%) than for other patients (14.2%). Gastroenteritis remains a serious problem in Aboriginal children. This presents a complex challenge to be addressed with public-health principles, political determination and commitment, and adequate resources.

Cohort Studies↗

Chromosome 11q13 amplification in head and neck squamous cell carcinoma. Association with poor prognosis.

OBJECTIVE: To determine the clinical and prognostic significance of chromosome 11q13 amplification in squamous cell carcinoma of the head and neck. DESIGN: Retrospective clinical analysis. SETTING: University and private cancer centers. PATIENTS: Fifty-six patients with pathologically confirmed head and neck squamous cell carcinoma whose tumors had been assayed for the presence or absence of chromosome 11q13 amplification. MEASUREMENTS: The degree of DNA amplification in each tumor was determined using chromosome 11q13 probes for the bcl-1 major translocation cluster, PRAD1/cyclin D1 (CCND1), the fibroblast growth factor gene HST1, EMS1, and glutathione-S-transferase-pi-1. The presence or absence of amplification in each patient was correlated with primary site, tumor stage, nodal status, presence or absence of distant metastasis, disease recurrence, time to recurrence, clinical outcome (disease status), and overall survival. RESULTS: Amplification of chromosome 11q13 was identified in 39% (22/56) of patients. Recurrent or persistent disease was identified in 82% (18/22) of cases with amplification and 50% (14/28) of nonamplified cases (P = .04). Mean time to recurrence was shorter in cases with amplification (6.2 months) than those without amplification (10.1 months) (P = .01). Eighteen patients (82%) with amplification and 10 patients (38%) without amplification died of disease or are alive with disease (P = .001). The mean follow-up period was 15.8 months for patients with amplification and 18.6 months for patients without amplification. Overall survival was significantly diminished in patients with amplification (P = .002). Amplification was not related to nodal status, distant metastases, or initial disease stage. CONCLUSIONS: Amplification of chromosome 11q13 loci may be an important biologic marker indicating poor prognosis, independent of clinical stage in head and neck squamous cell carcinoma, and it should be assessed in prospective trials to determine its utility for stratifying treatment and determining prognosis.

Adult↗

Ki-67 labeling is correlated with the time to recurrence in primary glioblastomas.

The Ki-67 labeling index (LI) was shown in many cut-off studies to be significantly correlated to the postoperative survival probability in gliomas in univariate and multivariate analyses. However, a direct relationship of the Ki-67 LI and the growth fraction, respectively, to clinical growth parameters was not demonstrated in a single tumor type of this group until now. We compared the Ki-67 LI of 20 primary glioblastomas and their recurrent tumors with the time to reoperation for recurrence. Regression analyses showed (1) a high reproducibility of the LIs at the second versus the first operation corresponding to an inherent growth potential of a given individual tumor and (2) a strong inverse correlation of LI to time to recurrence (TR) (r = -0.92). Additionally to a lower LI (corresponding to a smaller growth fraction), a longer cycle time could be derived in slowly growing as compared to rapidly growing tumors. A direct relationship of the Ki-67 LI to a clinical time parameter (the TR) was obtained, and a predictive significance of individual LIs in glioblastomas could be defined.

Adult↗

Time to recurrence of squamous cell carcinoma of the head and neck.

A personal series of 3,215 patients with proven squamous cell carcinoma of the mucosal surfaces of the upper aerodigestive tract is presented. Of these patients, 515 suffered a recurrence of their primary tumor after a course of radiotherapy. The time from the end of radiotherapy to diagnosis of a primary recurrence was not related to any known host factors, nor to tumor factors except site. However, it was the most significant predictor of survival, both from initial presentation and from the date of recurrence. The time to recurrence did not relate to the size of the tumor at recurrence, suggesting that large recurrences are multicentric. The time to recurrence also predicted response and survival of 67 patients with end-stage disease treated by chemotherapy. The response and survival were better in tumors with a time to recurrence longer than the median; the increased survival was not significant, but the increased response was.

Carcinoma, Squamous Cell↗

Clinical responsiveness of glioblastoma multiforme to chemotherapy after vaccination.

PURPOSE: Although the development of immune-based therapies for various cancers including malignant glioma has been heralded with much hope and optimism, objective clinical improvements in most vaccinated cancer patients have not been realized. To broaden the search for vaccine-induced benefits, we examined synergy of vaccines with conventional chemotherapy. EXPERIMENTAL DESIGN: Survival and progression times were analyzed retrospectively in 25 vaccinated (13 with and 12 without subsequent chemotherapy) and 13 nonvaccinated de novo glioblastoma (GBM) patients receiving chemotherapy. Immune responsiveness and T-cell receptor excision circle (TREC) content within CD8+ T cells (CD8+ TRECs) was determined in vaccinated patients. RESULTS: Vaccinated patients receiving subsequent chemotherapy exhibited significantly longer times to tumor recurrence after chemotherapy relative to their own previous recurrence times, as well as significantly longer postchemotherapy recurrence times and survival relative to patients receiving isolated vaccination or chemotherapy. Patients exhibiting objective (>50%) tumor regression, extremely rare in de novo GBM, were also confined to the vaccine + chemotherapy group. Prior tumor behavior, demographic factors, other treatment variables, distribution of vaccine responders, and patients with high CD8+ TRECs all failed to account for these differences in clinical outcome. Within all GBM patients receiving post-vaccine chemotherapy, however, CD8+ TRECs predicted significantly longer chemotherapeutic responses, revealing a strong link between the predominant T-cell effectors in GBM and tumor chemosensitivity. CONCLUSIONS: We propose that therapeutic vaccination synergizes with subsequent chemotherapy to elicit tangible clinical benefits for GBM patients.

Adult↗

[Early characters of recurred vocal cord cancers after laser cordectomy and treatment].

OBJECTIVE: To explore the characters of recurred vocal cord cancer in early phase after laser cordectomy and selection of the second treatment. METHOD: Five cases who had recurrence after laser cordectomy was selected and analyzed according to the scope of the tumor, operation type, recurrence time, site of recurrence. RESULT: One case's had the first recurrence two months after the first operation and was treated by laser once more, and the second recurrence happened three months after the second operation and no recurrence was found within the 4 years after the third operation-extended vertical hemilaryngectomy. Two cases had recurrence 3 months after the first operation and one case 6 months later. The three cases had extended vertical hemilaryngectomy for remedy and had no recurrence within 4 years. The last one had recurrence 1 year after operation, and received a total laryngectomy. The site of recurrence was the anterior commission in 4 cases and median part of vocal cord in one case. The 5 cases included 3 T1a and 2 T1b. The recurrence rate of T1a and T1b were 3.1% and 50.0% respectively. CONCLUSION: The recurrence time after laser cordectomy is often within half a year. The most common site of recurrence is anterior commission. Extended partial laryngectomy should be the first choice remedy. Strict selection of indication and skillful technique are the base of good efficacy.

Adult↗

Isolated vaginal recurrences of endometrial carcinoma.

PURPOSE: The authors undertook this study to evaluate the results of radiation therapy (RT) for vaginal recurrence in early stage endometrial carcinoma. MATERIALS AND METHODS: Between 1964 and 1987, 34 patients with isolated vaginal recurrences of endometrial carcinoma were treated with RT. The records were reviewed for outcome and prognostic factors, such as location of tumor recurrence, time to recurrence, size of tumor at recurrence, tumor differentiation, and total radiation dose delivered at RT. RESULTS: With a median follow-up of 48 months, the 5-year actuarial survival and disease-free survival rates were 68% +/- 4 and 60% +/- 3, respectively. Results were statistically significant for some prognostic factors, including time to tumor recurrence and total radiation dose delivered at RT to the recurring tumor. CONCLUSION: Long-term survival can be obtained for patients with an isolated vaginal recurrence of endometrial cancer treated with aggressive local-regional radiation therapy.

Actuarial Analysis↗

Influence of quantity of lymph vascular space invasion on time to recurrence in women with early-stage squamous cancer of the cervix.

OBJECTIVE: To determine if the quantity of lymph vascular space invasion (LVSI) correlates with time to recurrence in women with early-stage squamous carcinoma of the cervix. METHODS: 101 consecutive women with Stages IA2, IB, and IIA squamous carcinoma of the cervix who had undergone radical hysterectomy between 1991 and 1997, with previously reported histopathologic quantification of LVSI by four methods, were prospectively followed. The outcome measure was time to recurrence. Univariate and stratified log-rank test analysis was performed to test the association of time to recurrence with prognostic factors. Further analysis was focused on recurrence in those patients who had negative surgical margins and whose tumors contained LVSI, incorporating the four quantification measures. RESULTS: Nineteen (19%) women had cancer recurrence. The presence of LVSI (P = 0.05), cervical stromal invasion (P = 0.01), parametrial involvement (P < 0.001), and positive margins (P < 0.0001) were significantly related to time to recurrence on univariate analysis. In patients whose tumors had negative surgical margins and contained LVSI (65%), percentage of all sections with LVSI >29% and total number of foci with LVSI >5 were significantly related to time to recurrence (P = 0.006). When stratifying for cervical stromal invasion, lymph node status, and parametrial involvement in this group, percentage of all sections with LVSI >29% and total number of foci with LVSI >5 were significantly related to time to recurrence (P = 0.05). CONCLUSION: The quantity of LVSI, as defined by the percentage of all sections with LVSI and total number of foci with LVSI, is an independent prognostic factor for time to recurrence in women with early-stage squamous carcinoma of the cervix.

Carcinoma, Squamous Cell↗

Major depression in community adolescents: age at onset, episode duration, and time to recurrence.

OBJECTIVE: This paper presents retrospective and prospective data regarding time course parameters of major depressive disorder (MDD) in community adolescents (14 to 18 years old): time to onset and recovery and, among those who recovered, time to recurrence. METHOD: Diagnostic interviews were conducted with 1,508 randomly selected high school students. Three hundred sixty-two had experienced at least one past or current episode of MDD. RESULTS: Mean age at onset of first episode was 14.9 (SD = 2.8). Early MDD onset was associated with female gender and suicidal ideation. MDD episode duration ranged from 2 to 520 weeks, with a mean of 26.4 weeks (SE = 3.3) and a median of 8.0 weeks. Longer episodes were observed in those whose depression occurred early (at or before age 15), whose depression had been accompanied by suicidal ideation, and for whom treatment was sought. Of the adolescents who recovered, 5% relapsed within 6 months, 12% within 1 year, and approximately 33% within 4 years. Shorter time to recurrence was associated with prior suicidal ideation and attempt and with later first onset. CONCLUSIONS: Risk of MDD is low in childhood, increasing substantially with adolescence. The majority of episodes in community adolescents are relatively brief, although the risk of recurrence is substantial. Suicidal behaviors are important mediators of episode duration and of recurrence.

Adolescent↗

Cost-effectiveness of video-assisted thoracoscopic surgery versus conservative treatment for first time or recurrent spontaneous pneumothorax.

The aim of this study was to analyse differences in efficacy and costs in treating first time or recurrent spontaneous pneumothorax by conservative therapy (pleural drainage or observation) and video-assisted thoracoscopic surgery (VATS). Retrospectively, 112 patients treated by conservative therapy during 1985-1989 (Period 1) were compared with 97 patients treated by VATS during 1991-1994 (Period 2). Mean follow-up time in each period was more than 2 yrs. Patients in both periods had comparable clinical characteristics. Irrespective of first time or recurrent spontaneous pneumothorax at presentation, drainage and hospitalization times were longer, and complication and recurrence rates were higher in Period 1. When costs due to the waiting time before VATS were excluded, the total costs in Period 1 were higher than in Period 2. Video-assisted thoracoscopic surgery is more effective in treating patients with first time or recurrent spontaneous pneumothorax, with less morbidity and total costs compared to conservative therapy. In view of cost-effectiveness, we feel that a different management of first time or recurrent spontaneous pneumothorax is not justified.

Adult↗

Time to recurrence varies inversely with thickness in clinical stage 1 cutaneous melanoma.

The thickness of a tumor has been identified as the principal prognostic factor in cutaneous malignant melanoma. However, time to recurrence has not conclusively been related to thickness. A retrospective study of 216 patients with a primary cutaneous malignant melanoma that recurred was conducted to clarify this relationship and investigate possible independent relationships between age at diagnosis and sex of patients to time to recurrence. The results of analysis of linear regression revealed an inverse linear relationship between thickness and time to recurrence (p less than 0.001). Patients more than 50 years of age at the time of diagnosis were shown to relapse sooner than those less than 50 years of age (p = 0.014). Sex was not a significant factor in predicting time to recurrence (p greater than 0.10). These results suggest that thickness of tumor provides an indication of time to recurrence in those patients destined to recur and stress the need for long term surveillance in patients with a history of malignant melanoma because of the possibility of late relapse even with thin lesions.

Female↗