Effect of residual slow pathway function on the time course of recurrences of atrioventricular nodal reentrant tachycardia after radiofrequency ablation of the slow pathway.
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OBJECTIVES: Herein we present the final results of a prospective randomized study comparing two prophylactic treatment modalities for superficial bladder tumors: chemotherapy with mitomycin C and immunotherapy with interferon. METHODS: The study comprised 65 patients. Mitomycin C was utilized in 34 and interferon in 31 patients. RESULTS: The mitomycin C-treated patients had 41% recurrence, 1.7 recurrence/100 patients-month, 17 months mean time to recurrence and 8.8% tumor progression. The patients receiving interferon had 45% recurrence, 2.4 recurrence/100 patients-month, 12 months mean time to recurrence and 22.2% tumor progression rate. No significant differences were observed between the two groups of patients. Treatment was well-tolerated by both groups and the cost:efficacy ratio was higher for the interferon-treated patients. CONCLUSIONS: Immunoprophylaxis with interferon is as effective, but costs more than chemoprophylaxis with mitomycin C. Both agents have a moderate effect relative to control of recurrence, time to recurrence and tumor progression.
OBJECTIVE: To compare use of doxorubicin, surgery, and radiation versus surgery and radiation alone for treatment of cats with vaccine-associated sarcoma. DESIGN: Retrospective study. ANIMALS: 25 cats with vaccine-associated sarcomas. PROCEDURE: Time to first recurrence and survival time were compared between the 2 treatment groups. The number of surgeries (1 or > 1) were compared with respect to time to first recurrence and survival time. RESULTS: Median time to first recurrence was 661 days for the group that received doxorubicin, surgery, and radiation. Median time to first recurrence has not yet been attained for the group treated with surgery and radiation alone. Median survival time was 674 days for the group treated with doxorubicin, surgery, and radiation and 842 days for the group treated with surgery and radiation alone. For time to first recurrence and survival time, significant differences were not detected between cats that had 1 surgery and those that had > 1 surgery. CONCLUSIONS AND CLINICAL RELEVANCE: Significant differences between the 2 treatment groups were not detected. The efficacy of doxorubicin in the treatment of vaccine-associated sarcomas is uncertain.
Learning to store information over extended time intervals by recurrent backpropagation takes a very long time, mostly because of insufficient, decaying error backflow. We briefly review Hochreiter's (1991) analysis of this problem, then address it by introducing a novel, efficient, gradient-based method called long short-term memory (LSTM). Truncating the gradient where this does not do harm, LSTM can learn to bridge minimal time lags in excess of 1000 discrete-time steps by enforcing constant error flow through constant error carousels within special units. Multiplicative gate units learn to open and close access to the constant error flow. LSTM is local in space and time; its computational complexity per time step and weight is O(1). Our experiments with artificial data involve local, distributed, real-valued, and noisy pattern representations. In comparisons with real-time recurrent learning, back propagation through time, recurrent cascade correlation, Elman nets, and neural sequence chunking, LSTM leads to many more successful runs, and learns much faster. LSTM also solves complex, artificial long-time-lag tasks that have never been solved by previous recurrent network algorithms.
The control of early glottic cancer is equally satisfactory with either surgical resection or radiation therapy; this last method gives the patient good functional results. During the period from 1/1978 to 12/1985, 73 patients with early glottic carcinoma (T1 N0 M0) were treated in the Institute of Radiotherapy L. Galvani, University of Bologna; 45 were stage T1a (tumour limited to one vocal cord) and 28 were stage T1b (tumour of both vocal cords or involving anterior commissure); radiation treatment utilised a 60Co machine and 5 x 5 cm fields; the median dose was 67.2 Gy (range 50-76) with conventional fractionation. Ten patients had local recurrence; the median time of recurrence was 13.4 months; 9/10 were treated by surgery and 2/10 died, so the overall control by radiotherapy with surgery in reserve was 100% in T1a tumours and 90.6% in T1b ones. The 5-years disease free survival rate was 93.1% in T1a tumours and 69% in T1b; lesions involving anterior commissure had the worst prognosis, independent of the dose and time-dose factor (3/10 recurrences in the group treated with TDF less than 110 and 4/18 recurrences in the group with TDF more than 110).
BACKGROUND: Complete surgical resection is the mainstay of treatment for patients with hepatocellular carcinoma (HCC). Unfortunately, most patients ultimately develop disease recurrence and the median survival from the time of recurrence is <1 year. The purpose of the current study was to review the authors' experience using bland hepatic arterial embolization to treat recurrent HCC after definitive surgical resection. METHODS: The authors reviewed their single-center hepatic embolization database from 1995 through 2004 to identify patients who underwent bland hepatic arterial embolization for disease recurrence. Data analyzed included patient demographics, Okuda stage and Child score, imaging findings, and embolization variables. Recurrence-free survival (from surgery to disease recurrence) and survival time (from recurrence to last follow-up) were calculated using the Kaplan-Meier method. RESULTS: The authors identified 45 patients treated with bland embolization for recurrent HCC after resection. Six patients also underwent ablative therapy after embolization. Of the 45 patients, 42 (93.3%) patients had Okuda Stage 1 disease. The median time to recurrence was 13 months. The median survival after embolization was 46 months, and actuarial survival rates at 1 year, 2 years, and 5 years after recurrence were 86%, 74%, and 47%, respectively, with a median follow-up of 31 months. Patients who developed disease recurrence with a solitary lesion had a significantly improved survival (P = .03) At the time of last follow-up, 3 patients (6.6%) were alive with no evidence of viable disease. CONCLUSIONS: Bland arterial embolization was found to be an effective method of salvage therapy for patients with good liver function with recurrent HCC after prior surgical resection. Patients whose disease recurred with a solitary lesion appear to have a significantly increased survival compared with patients who develop disease recurrence with multiple tumors. A small proportion of patients can be rendered without evidence of viable disease.
Retransplantation (re-LT) of patients with recurrent hepatitis C virus (HCV) carries significant morbidity and mortality, negatively impacting on an already scarce donor allograft pool. In this study, we investigated the outcome of allografts and patients after re-LT due to recurrent HCV. Between 1989 and 2002, 47 patients were retransplanted at our institution due to HCV-related graft failure. Clinical HCV recurrence after re-LT was diagnosed when patients had acute liver enzyme elevation correlated with histological recurrence. The independent influence of these variables on survival was tested using Cox regression model. Chi-squared tests were used to examine the influence of individual demographic and pre/perioperative variables on recurrence. Thirty-one (66%) patients died after re-LT (median 2.2 months). Donor age >60, clinical HCV recurrence, and graft failure due to cirrhosis were significant risk factors for mortality (risk ratios of 3.6, 3.3, and 2.4, respectively). Pre-LT MELD score was lower among survivors (22+/- 5 vs. 27+/- 8). Following re-LT, 38 patients had at least one biopsy due to acute liver dysfunction; 19 of them (50%) had recurrence within the first 3 months. High-dose solumedrol was correlated with early recurrence. No association was found between time of recurrence after the first LT and time of recurrence after re-LT. In conclusion, patients with cirrhosis due to recurrent HCV undergoing re-LT have an extremely high mortality rate; older allografts should be avoided in retransplanting these patients. The timing of clinical recurrence after initial liver transplantation is not predictive of the timing of recurrence after re-LT. Patients experiencing early graft failure due to accelerated forms of HCV should not be denied re-LT with the expectation that a similar disease course will occur after re-LT.
Time-dose factor (TDF) value at point A was evaluated in 75 patients with central recurrence and 100 patients free of cancer for more than 5 years after radiotherapy serving as control. The results showed that the mean TDF at point A was 131 +/- 16 and, 139 +/- 15 in patients with Stage II lesions in central recurrence and control groups and 134 +/- 18 and 144 + 14 in patients with Stage III lesions in both groups, respectively. The TDF was all lower in the recurrence groups than those in the control groups. There was significant difference between the two groups (P less than 0.02 and P less than 0.01). The results also showed that the TDF at point A was significantly different between the recurrent and control groups (P less than 0.05) when it was more than 135 and 140 in Stage II and III lesions. It is pointed out that, even with same dose delivered to point A, the lower TDF value at point A is possibly the reason of central failure in cervical cancer treatment. The authors suggest that total TDF value at point A in Stage II and III lesions be no less than 135 and 140.
BACKGROUND: Although the prognosis of patients with early gastric carcinoma has improved, we still sometimes encounter recurrences following curative resection. Which carcinomas will recur and when a patient will die of recurrence are difficult to predict. PATIENTS AND METHODS: We retrospectively analyzed clinicopathological findings in 552 patients with early gastric carcinoma in terms of predicting recurrent cases and postoperative intervals to death from tumor recurrence. Predictive factors for postoperative recurrence were examined by multivariate analysis. RESULTS AND CONCLUSION: Patients developing recurrence were significantly older, and regional lymph node metastasis, lymphatic invasion and limited surgery were significantly more frequent. Two-thirds of patients who died of tumor recurrence survived more than 2 years after gastrectomy. The predictive factors for recurrence of early gastric carcinoma were regional lymph node metastasis, limited lymphadectomy and invasion of carcinoma into the submucosa. Extended radical lymphadectomy with gastrectomy and long-term intensive follow-up are needed for patients showing these factors.
OBJECTIVES: To determine whether in the prostate-specific antigen (PSA) era stage and/or grade migration of patients treated with radical prostatectomy (RP) has occurred. We also examined whether the biochemical recurrence rates after RP have changed with time. METHODS: A total of 1654 patients from the Shared Equal Access Regional Cancer Hospital (SEARCH) database were analyzed for time trends in age, preoperative PSA level, clinical stage, biopsy Gleason score, prostatectomy Gleason grade, pathologic stage, margin status, and recurrence rates after RP. Results were stratified into three 4-year blocks of time between 1988 and 2002 for analysis. RESULTS: The preoperative PSA level, patient age, tumor stage, rate of capsular penetration, and lymph node involvement decreased with time. Both biopsy and pathologic Gleason grade steadily increased with time. The positive margin rate and incidence of seminal vesicle involvement remained stable. On multivariate analysis, only serum PSA level (P <0.001) and biopsy Gleason score (P <0.001) were significant independent predictors of the time to recurrence after RP. The year of surgery was not a significant independent predictor of biochemical recurrence after RP in multivariate analysis. CONCLUSIONS: Despite lower stage and lower PSA levels with time, we found no improvement in PSA recurrence rates over time. This may reflect lead-time bias in detecting PSA recurrence by the use of more sensitive PSA assays in recent years.
BACKGROUND: Salvage surgery is often the only curative option for recurrent cancer. In patients whose initial tumor is stage T3 or T4, the primary therapy often makes salvage even more difficult. We therefore analyzed the outcome in patients who were originally treated for T3 or T4 squamous cell carcinoma of the oral cavity, larynx, oropharynx, or hypopharynx and who then had a recurrence and chose to undergo further therapy for cure. PATIENTS AND METHODS: From 1980 to 2000, a total of 940 patients were treated for stage T3 or T4 cancer. Forty-eight patients underwent salvage therapy for recurrence: 24 for primary site recurrence, 20 for regional recurrence, and 4 for locoregional recurrence. RESULTS: The mean time to recurrence was 14.0 months, and the mean survival time was 26.2 months. Among the 28 patients treated for primary site recurrence, the mean time to rerecurrence was 12.6 months, and the mean survival time was 27.3 months. Only 5 of the 28 patients had prolonged survival. The stage of the recurrent disease did not influence outcome. Among the 20 patients treated for neck recurrence, the mean time to recurrence was 14.0 months, and the mean survival time was 25.0 months. Six of the 20 patients had prolonged survival, but none had a recurrence in a previously dissected and irradiated neck. CONCLUSIONS: These results show the limited potential for survival in patients who have a recurrence after treatment for advanced primary site head and neck cancer. Patients who have not undergone all modalities of therapy have the potential for salvage, but even then the chances are limited. Given the morbidity of salvage therapy, and the limited chance for cure, physicians must cautiously counsel patients who are contemplating treatment of recurrent cancer after therapy for advanced disease.
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BACKGROUND: The diagnosis and treatment of recurrent gastric cancer remains difficult. The aim of this study was to determine the risk factors for recurrence of gastric cancer and the prognosis for these patients. METHODS: Of 2328 patients who underwent curative resection for gastric cancer from 1987 to 1995, 508 whose recurrence was confirmed by clinical examination or reoperation were studied retrospectively. The risk factors that determined the recurrence patterns and timing were investigated by univariate and multivariate analysis. RESULTS: The mean time to recurrence was 21.8 months and peritoneal recurrence was the most frequent (45.9 per cent). Logistic regression analysis showed that serosal invasion and lymph node metastasis were risk factors for all recurrence patterns and early recurrence (at 24 months or less). In addition, independent risk factors involved in each recurrence pattern included younger age, infiltrative or diffuse type, undifferentiated tumour and total gastrectomy for peritoneal recurrence; older age and larger tumour size for disseminated, haematogenous recurrence; and older age, larger tumour size, infiltrative or diffuse type, proximally located tumour and subtotal gastrectomy for locoregional recurrence. Other risk factors for early recurrence were infiltrative or diffuse type and total gastrectomy. Reoperation for cure was possible in only 19 patients and the mean survival time after conservative treatment or palliative operation was less than 12 months. CONCLUSION: The risk factors for each recurrence pattern and timing of gastric cancer can be predicted by the clinicopathological features of the primary tumour. Since the results of treatment remain dismal, studies of perioperative adjuvant therapy in an attempt to reduce recurrence are warranted.
Studies of adolescent and young adult males sustaining primary anterior shoulder dislocations reveal the likelihood of recurrence to be virtually always above 50% and as high as 79% to 94%. Common among these investigations is the lack of a specific, rigidly adhered to rehabilitation program. During a 3 1/2 year period, 20 midshipmen at the United States Naval Academy sustained primary anterior shoulder dislocations. All participated in an identical treatment regimen which included a restrengthening program emphasizing the muscles of internal rotation and adduction, plus rigid restrictions of activities until the goals of their rehabilitation program were satisfied. Exercises progressed from isometrics through isotonics and isokinetics. Goals included return to full active, unrestricted duty and athletic participation which included participation in the sport that resulted in the original dislocation. Patients were followed for an average of 35.8 months (with a range of 17 to 45 months). During the period of study there were five recurrences (25%). A success rate of 75% would suggest that adherence to a specific, aggressive postdislocation rehabilitation program, plus rigid restrictions of activities until the goals of the program are satisfied, can substantially improve the likelihood of a full return to activity without recurrent shoulder dislocation.
The first 100 consecutive patients at our center receiving subcutaneous sumatriptan (6 mg) were evaluated over a total of 455 migraine attacks. Parameters included overall efficacy, average time to relief, recurrence rate, average time to recurrence, adverse events, comparison to previous abortive agents, and subjective global ratings. Overall efficacy (defined as headache severity reduction from severe or moderate to mild or none) was 84%. Average time to relief was 40 minutes. Nine percent failed to respond at all. Recurrence rate was 46.5% with 36% of patients having no recurrence. Fourteen percent of patients reported 100% recurrence (minimum 3 attacks; average 5.4 attacks). Time to recurrence varied widely, but averaged 9.1 hours. Eighty-one percent rated the drug better or much better than previous abortive medications in terms of sumatriptan's ability to abort the attack. Seventy-seven percent reported some adverse event (generally mild and transient) with 23% reporting no adverse events. Sixty-nine percent reported a global rating of Good to Excellent and 31% rated Poor or Fair. The rate of recurrence and average time to recurrence were the most significant factors affecting the global ratings. These parameters were further evaluated with respect to a variety of subgroups: 1) migraine alone 2) migraine with co-existent tension-type headache 3) drug-induced headache (analgesic rebound headache) 4) posttraumatic headache 5) preventive versus no preventive medication 6) presence or absence of adverse events 7) presence or absence of recurrence and 8) average duration of migraine with no medication.
BACKGROUND: Recurrent disease after liver transplant is a significant problem. Recurrent primary biliary cirrhosis (RPBC) is a histologic diagnosis. Clinical data is unreliable in predicting or diagnosing recurrence. RPBC appears to have a changing clinical presentation in recent years. MATERIALS AND METHODS: The diagnosis of RPBC after liver transplantation was made histologically. Data were obtained from our prospectively maintained liver-transplant database and evaluated statistically. RESULTS: Between 1985 and 1999, 1,835 liver transplants were performed, 169 for PBC. One hundred fifty-six patients were evaluated (one patient received retransplantation, and 13 were excluded). Seventeen (10.9%) experienced recurrence. Median posttransplantation follow-up time was 72.1 months. Median time to recurrence was 49.6 months. Median follow-up time after recurrence was 11.5 months. Neither acute rejection episodes (P=0.34) nor OKT3 use (P=0.36) before diagnosis of recurrence was significant. The combination of cyclosporine, azathioprine, and prednisolone demonstrated recurrence in 6 of 71 (8.4%). Six of 49 (12.2%) patients treated with cyclosporine with or without mycophenolate mofetil and prednisolone experienced recurrence. Six of 36 (16.7%) patients treated with tacrolimus and prednisolone with or without mycophenolate mofetil experienced recurrence. Patients treated with cyclosporine had numerically fewer recurrences than those treated with tacrolimus (P=0.11). CONCLUSIONS: Patients with RPBC demonstrated prolonged survival. Clinical factors did not aid in predicting RPBC. The clinical course of RPBC appears to be different than in the earlier years of liver transplantation. Immunosuppression may play a role. The use and type of antimetabolite drugs had no affect on recurrence. RPBC demonstrated a different clinical course with tacrolimus treatment (shorter time to recurrence) and increased incidence when compared with cyclosporine treatment. Controlled randomized studies are necessary to determine differences between tacrolimus and cyclosporine treatment, if any.
A time discrete model of recurrent inhibition in the hippocampal dentate gyrus is made and analyzed. This model assumes that (1) each granule cell can generate only one action potential in response to a single stimulation of the perforant path, (2) each interneuron receives synaptic inputs from many granule cells, and (3) an output of the interneuron is inhibitory for granule cells. Although each granule cell generates an action potential in the all-or-none fashion, the population spike is shown to be approximated by a piecewise linear function of the population excitatory post-synaptic potential (EPSP). From this model six patterns in the population spike responses to the paired-pulse stimulation are deduced. Each pattern is composed of some broken lines whose slopes and intercepts are explicitly expressed by the average and variance of the microscopic parameters and the population size of the cells. This model clarifies the relation between the measured quantity in the field potential experiment and the microscopic quantities peculiar to the granule cell and to the interneuron.
OBJECTIVES/HYPOTHESES: Salvage surgery is widely viewed as a "double-edged sword." It is the best option for many patients with recurrent cancer of the upper aerodigestive tract, especially when original therapy included irradiation, yet it may provide only modest benefit at high personal cost to the patient. The stakes are high because alternatives are of limited value. The primary objective of this study was to fully assess the value of salvage surgical procedures in the treatment of local and regional recurrence. The following hypotheses were developed to focus the study design and data analysis. 1) The efficacy of salvage surgery correlates recurrent stage, recurrent site, and time to presalvage recurrence. 2) The economic and noneconomic costs of salvage surgery increase with higher recurrent stage. 3) Information relating the value of salvage surgery to recurrent stage and recurrent site will be useful to these patients and the physicians who treat them. STUDY DESIGN: Two complimentary methods of investigation were used: a meta-analysis of the published literature and a prospective observational study of patients undergoing salvage surgery for recurrent cancer of the upper aerodigestive tract. METHODS: The meta-analysis combined 32 published reports to obtain an estimate of average treatment effect for salvage surgery with regard to survival, disease-free survival, surgical complications, and operative mortality. The prospective observational study included detailed data in 109 patients who underwent salvage surgery. In addition to parameters studied in the meta-analysis, we obtained baseline and interval quality of life data (Functional Living Index for Cancer [FLIC] scores), baseline and interval performance status evaluations (Performance Status Scale for Head and Neck Cancer Patients [PSS head and neck scores]), length of hospital stay, and hospital and physician charges, and related this data primarily to recurrent stage, recurrent site, and time to presalvage recurrence. RESULTS: The weighted average of 5-year survival in the meta-analysis was 39% in 1,080 patients from 28 different institutions. In the prospective study, median disease-free survival was 17.9 months in 109 patients, and this correlated strongly with recurrent stage, weakly with recurrent site, and not at all with time to presalvage recurrence. Noneconomic costs for patients and economic costs correlated with recurrent stage, but not with site. Baseline FLIC and PSS head and neck scores correlated with recurrent stage, but not with site. After salvage surgery the percentage of patients reaching or exceeding baseline was 51% for FLIC scores, and this differed significantly with recurrent stage. Postoperative interval "success" in PSS head and neck subscale scores for diet and eating in public also correlated with recurrent stage. CONCLUSIONS: Overall, the expected efficacy for salvage surgery in patients with recurrent head and neck cancer was surprisingly good, but success was limited and costs were great in stage III and, especially, in stage IV recurrences. A strong correlation of efficacy and noneconomic costs with recurrent stage allowed the creation of expectation profiles that may be useful to patients. Additional systematic clinical research is needed to improve results. In the end, the decision to undergo salvage surgery should be a personal choice made by the patient after honest and compassionate discussion with his or her surgeon.