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Growth rates of small cell bronchogenic carcinomas.

In reviewing a series of 144 patients with small cell bronchogenic carcinoma, 12 were found to have serially measurable roentgenographic lesions prior to therapy. Although caliper-based measurements and a silhouette cutout method gave comparable sets of tumor doubling time data, inter-observer variability was less with the silhouette cutout method. Tumor doubling times in small cell bronchogenic carcinoma ranged between 25 and 160 days, with a median of 77 days, a log mean of 81 days, and an arithmetic mean of 91 days. There was no apparent relation between tumor doubling time and tumor location, histologic subtype, response to therapy, or patient survival. The data indicate that small cell bronchogenic carcinoma of the lung is a relatively slowly growing tumor. Assuming that late subclinical disease exhibits growth characteristics that are similar to those seen in the clinical stages of growth, it can be estimated that residual body tumor burdens of 1 X 10(6) cells may be followed by tumor recurrence times of 2 years or longer; the likelihood of "cure" should not be entertained in patients with disease-free intervals shorter than 4-5 years.

Carcinoma, Bronchogenic↗

Efficient Training of Recurrent Neural Network with Time Delays.

Training recurrent neural networks to perform certain tasks is known to be difficult. The possibility of adding synaptic delays to the network properties makes the training task more difficult. However, the disadvantage of tough training procedure is diminished by the improved network performance. During our research of training neural networks with time delays we encountered a robust method for accomplishing the training task. The method is based on adaptive simulated annealing algorithm (ASA) which was found to be superior to other training algorithms. It requires no tuning and is fast enough to enable training to be held on low end platforms such as personal computers. The implementation of the algorithm is presented over a set of typical benchmark tests of training recurrent neural networks with time delays. Copyright 1996 Elsevier Science Ltd.

Journal Article↗

Testing time-predictable earthquake recurrence by direct measurement of strain accumulation and release.

Probabilistic estimates of earthquake hazard use various models for the temporal distribution of earthquakes, including the 'time-predictable' recurrence model formulated by Shimazaki and Nakata (which incorporates the concept of elastic rebound described as early as 1910 by H. F. Reid). This model states that an earthquake occurs when the fault recovers the stress relieved in the most recent earthquake. Unlike time-independent models (for example, Poisson probability), the time-predictable model is thought to encompass some of the physics behind the earthquake cycle, in that earthquake probability increases with time. The time-predictable model is therefore often preferred when adequate data are available, and it is incorporated in hazard predictions for many earthquake-prone regions, including northern California, southern California, New Zealand and Japan. Here we show that the model fails in what should be an ideal locale for its application -- Parkfield, California. We estimate rigorous bounds on the predicted recurrence time of the magnitude approximately 6 1966 Parkfield earthquake through inversion of geodetic measurements and we show that, according to the time-predictable model, another earthquake should have occurred by 1987. The model's poor performance in a relatively simple tectonic setting does not bode well for its successful application to the many areas of the world characterized by complex fault interactions.

Journal Article↗

Effects of rapid cycling on response to lithium maintenance treatment in 360 bipolar I and II disorder patients.

INTRODUCTION: Rapid cycling (RC) in bipolar disorders is widely believed to predict future morbidity and poor treatment response, although empirical testing of its predictive utility remains limited. METHODS: In 360 DSM-IV bipolar I (N=218) and II (N=142) disorder subjects (64% women) followed over an average of 13.3 years, we evaluated factors associated with RC status with bivariate and multivariate techniques, and response to lithium maintenance treatment (recurrence rates, time ill, survival analysis of time to recurrence on lithium). RESULTS: RC risk (15.6% of cases) was 5. 1-times greater in bipolar II vs. I subjects (30.3%/6.0%), in minor excess in women vs. men (17.9%/11.5%), and associated with premorbid cyclothymia, depressive first episodes, older onset age, and being employed or married. Before lithium, RC vs. non-RC cases had more mean total (3.9/1.2), manic, and depressive episodes/year, and greater percent time ill (60%/38%). During treatment, prior RC status was unrelated to time to first recurrence and other measures of morbidity and improvement including percent time ill, although depressive episodes were 2.7-times more frequent, and there was 13.7% less chance of full protection from all recurrences in RC cases. LIMITATIONS: The study is naturalistic, without random assignment or blind assessment. CONCLUSIONS: The RC bipolar subtype was strongly associated with type II diagnosis, higher average prelithium episode frequency and percent time ill, and weakly with female sex, but not with greater overall morbidity during treatment.

Antimanic Agents↗

[Are expanded tumor resection and reconstruction of soft tissue sarcoma justified by recurrence rate and survival time?].

The outcome of two groups of patients treated for soft tissue sarcoma either by a "limited resection" or by a radical procedure, including reconstructive techniques to vessels and soft tissues coverage, was compared. The latter group showed a higher rate of R0 resections, prolonged time to recurrence and a significantly decreased recurrence rate. Also, fewer patients developed distant metastases. From these data all efforts to achieve a radical resection seem to be worthwhile.

Combined Modality Therapy↗

Recurrence after radiotherapy for glottic carcinoma.

A series of 478 patients with T1-3N0 glottic carcinoma treated by irradiation is presented. Of these patients, 320 were previously untreated, whereas 158 patients were referred for treatment of a recurrence after receiving radiotherapy elsewhere. The primary recurrence rate in the previously untreated patients was 10%. The rate was higher in T2 and T3 tumors, poorly differentiated tumors, and in patients who were in poor general condition. Over 80% of the recurrent tumors were Stage pT3 or pT4, whereas 12% of total laryngectomy specimens showed necrosis only with no evidence of tumor. The necrosis rate in previously untreated patients was 1% for T1 tumors, 4% for T2 tumors, and 3% for T3 tumors. Of all tumors, 60% were transglottic when they recurred, whereas only 29% were confined to the glottis at recurrence. Histologic diagnosis had a high sensitivity but a low specificity, indicating that a negative histologic report is unreliable. Of patients with a recurrent primary tumor, 13% were untreatable. The 5-year survival after a primary recurrence was 39%, and the main prognostic factors were sex, T stage at recurrence, and time to recurrence. Of patients available for follow-up at 5 years 49% were alive with a larynx, 5% were alive without a larynx, 13% were dead of the original cancer, and 33% had died of other causes. In those suffering a primary recurrence, the commonest cause of death was a subsequent lymph node metastasis, followed in order of frequency by stomal recurrence and recurrence in the pharyngeal remnant. The hospital mortality rate after laryngectomy was 3%, and 30% of patients undergoing laryngectomy developed a pharyngocutaneous fistula. The recurrence rate in lymph nodes was 14% at 5 years, general condition and T stage being the only significant predictors of recurrence. Only 17% of patients had small (N1) nodes by the time the diagnosis of cervical lymph node recurrence was made, and 27% of all patients were unsuitable for treatment. Host, tumor factors, and time to recurrence were not significant predictors of survival after node recurrence. The survival rate 5 years after node recurrence was 16%, and the main cause of death in those who died was uncontrolled disease in the neck. The hospital mortality after salvage neck dissection was 4.7%.

Adolescent↗

Acinic cell carcinoma of salivary glands. Prognostic relevance of DNA flow cytometry and nucleolar organizer regions.

OBJECTIVE: To test the prognostic ability of flow cytometry and counts of silver-enhanced intranuclear nucleolar organizing regions (AgNORs) in acinic cell carcinoma. DESIGN: Using statistical methods to establish if analysis of DNA content, percentage DNA synthetic (S)-phase, and the AgNOR counts on 45 cases of acinic cell carcinoma with clinical follow-up ranging from 10 to 379 months are predictors of time to recurrence or time to death due to acinic cell carcinomas. MAIN OUTCOME MEASURES: Whether tumors with low AgNOR counts and diploid DNA are favorable acinic cell carcinomas and the converse, aneuploid DNA and elevated AgNOR count, predict unfavorable neoplasms. RESULTS: Tumors with a diploid DNA content had as unfavorable a clinical course as aneuploid acinic cell carcinomas. Similarly, S-phase and AgNOR count results showed considerable overlap when separated into carcinomas with or without local recurrence, metastasis, or death due to tumor. Statistical evaluation also failed to provide predictors of clinical course based on ploidy, percentage S-phase, or AgNOR counts. CONCLUSION: The results, although negative, are important in showing that data on DNA content, cell cycle, and nuclear limits useful in other neoplasms are of limited practical application in establishing predictors of time to recurrence or time to death in acinic cell carcinomas. Solving the enigmas, for clinicians and pathologists, associated with acinic cell carcinomas will require further information about the biology of this neoplasm.

Adult↗

Serum tissue polypeptide specific antigen as a noninvasive prognostic indicator for early recurrence of hepatocellular carcinoma after curative resection.

BACKGROUND: Serum tissue polypeptide specific antigen (TPS) is a useful cell proliferation marker in diagnosing and monitoring patients with a variety of malignancies. The objective of this study was to determine the usefulness of serum TPS as a noninvasive prognostic factor for early recurrence of hepatocellular carcinoma (HCC) after patients undergo curative resection. METHODS: Serum TPS levels were measured by monoclonal TPS immunoradiometric assay in 54 patients shortly before they underwent curative resection for HCC. The recurrence time was correlated with the TPS level and with other prognostic factors using the log-rank test in univariate analysis and a Cox regression in multivariate analysis. Receiver operating characteristic analysis was performed to examine the power of the various prognostic factors to distinguish between patients with recurrent tumors and patients who were disease free. RESULTS: Patients who had higher levels of TPS (>or= 150 U/L) had earlier recurrences compared with patients who had lower levels of TPS (< 150 U/L; P = 0.016) in univariate analysis. Tumor size, the number of tumors, portal vein invasion, and the resection margins also were associated significantly with the time to tumor recurrence (P = 0.015, P = 0.004, P = 0.003, and P = 0.003, respectively). Serum alpha-fetoprotein was not a significant risk factor for tumor recurrence. In multivariate analysis, the TPS level, tumor size, and resection margins were independent prognostic factors (P = 0.025, P = 0.018, and P = 0.016, respectively). The inclusion of TPS in addition to tumor size and resection margins increased the rate of corrective prediction from 0.72 to 0.80. CONCLUSIONS: The current study demonstrated that the preoperative serum TPS level was a significant factor in predicting early recurrence of HCC after curative resection. Patients with high serum TPS levels warrant more aggressive treatment and close follow-up after they undergo tumor resection.

Adult↗

Radical hysterectomy for recurrent cervical cancer following radiation therapy.

In patients with small central recurrences following radiation therapy for cervical cancer the surgeon may have to make a judgment as to when radical hysterectomy is preferable to exenteration. During the years 1968-1984 there were 21 radical hysterectomies performed at Memorial Sloan-Kettering Cancer Center for recurrent cervical cancer. The original clinical stage distribution is as follows: IB-4, IIA-4, IIB-11, IIIB-1, IVA-1. The median interval from initial diagnosis to recurrence was 10 months. There were two operative deaths; both were from sepsis. Ten of the 21 patients developed postoperative fistulas, with 9 requiring surgical diversion of the urinary or both urinary and intestinal tracts. Thirteen of 21 patients (62%) have survived with a median follow-up of 73 months. Seven patients suffered recurrences following radical hysterectomy. All developed recurrence in the central pelvis. Four had sidewall disease as well, but none had distant disease at the time recurrence was diagnosed. Of 11 patients with cervical tumors of 2 cm or less in size at the time of radical hysterectomy, none experienced recurrence, while among 10 patients with tumor size of greater than 2 cm, 7 had recurrence. All patients whose initial clinical stage was IB or IIA have survived without recurrence. There was only 1 survivor among 5 patients with positive parametrial or vaginal margins. Six of the 13 survivors required urinary diversion, and 2 required colostomy as well. Radical hysterectomy for this indication is a morbid procedure which should be undertaken only by the most experienced of pelvic surgeons and limited to patients of early clinical stage with central recurrences of less than 2 cm in size.

Adult↗

Maxwell-type constructions for multiple nonequilibrium steady states.

A stochastic analysis is used to obtain Maxwell-type constructions for multiple nonequilibrium steady states in homogeneous systems. The stochastic theory shows that homogeneous molecular fluctuations can nucleate the Maxwell construction only on a time scale that is the order of a Poincaré recurrence time and indicates that hysteresis should be observed. The nonrelevance of homogeneous fluctuations for systems that undergo phase separation or in which spatial structures occur is discussed.

Journal Article↗

A discrete-time Lagrangian network for solving constrained quadratic programs.

A discrete-time recurrent neural network which is called the discrete-time Lagrangian network is proposed in this letter for solving convex quadratic programs. It is developed based on the classical Lagrange optimization method and solves quadratic programs without using any penalty parameter. The condition for the neural network to globally converge to the optimal solution of the quadratic program is given. Simulation results are presented to illustrate its performance.

Mathematics↗

Spontaneous pneumothorax. Long-term results with tetracycline pleurodesis.

The aim of this prospective study was to determine the rate of recurrence for spontaneous pneumothorax (SP) after tetracycline pleurodesis (TCP), using that of observation, tube thoracostomy alone, and thoracotomy as references. From 1985 to the end of 1991, 78 patients were treated with tetracycline pleurodesis and 135 patients served as control subjects. Pleurodesis was induced by instillation of tetracycline and ascorbic acid through the pleural drain. The indication was any SP treated with tube thoracostomy, without active pulmonary infection. Follow-up period was from 13 to 95 months (mean, 45 months); follow-up rate was 94 percent. Post-therapy surgery was necessary for eight patients in whom pleurodesis failed due to presence of a persistent air leak. The ipsilateral recurrence rate of patients treated with TCP was 9 percent (6/66) and recurrence time ranged from 2 days to 9 months. The recurrence rate for patients treated with observation was 36 percent, 35 percent for those having chest tube alone, and none for those undergoing surgery. No death occurred as a direct result of this procedure and all patients could be released from the hospital. Eleven subjects died during the follow-up period; the mean follow-up until death was 37 months (range, 2 to 87 months). Five deaths were due to respiratory causes and six were due to extrapulmonary causes. Tetracycline pleurodesis has been shown to be a good alternative for the prevention of recurrence of SP. Its recurrence rate is lower than that of tube drainage but higher than that of surgical treatment.

Adolescent↗

Recurrent neural networks with trainable amplitude of activation functions.

An adaptive amplitude real time recurrent learning (AARTRL) algorithm for fully connected recurrent neural networks (RNNs) employed as nonlinear adaptive filters is proposed. Such an algorithm is beneficial when dealing with signals that have rich and unknown dynamical characteristics. Following the approach from, three different cases for the algorithm are considered; a common adaptive amplitude shared among all the neurons; each layer has its own adaptive amplitude; different adaptive amplitude for each neuron. Experimental results show the AARTRL outperforms the standard RTRL algorithm.

Algorithms↗

Is time to first recurrence of atrial fibrillation correlated with atrial fibrillation burden?

The time to the first recurrence of atrial fibrillation (AF) and the AF burden have commonly been used as end points for AF therapy. We conducted a retrospective analysis of data from a large pacemaker registry to assess the relation between the time to the first recurrence and the AF burden. Although a statistical association exists, the small correlation coefficients limit the clinical value of the time to first recurrence as an indicator of AF burden.

Aged↗

Modeling two-state disease processes with random effects.

Many chronic medical conditions are manifested by alternating sojourns in symptom-free and symptomatic states. In many cases, in addition to their relapsing and remitting nature, these conditions lead to worsening disease patterns over time and may exhibit seasonal trends. We develop a mixed-effect two-state model for such disease processes in which covariate effects are modeled multiplicatively on transition intensities. The transition intensities, in turn, are functions of three time scales: the semi-Markov scale involving the backward recurrence time for the cyclical component, the Markov scale for the time trend component, and a seasonal time scale. Multiplicative bivariate log-normal random effects are introduced to accommodate heterogeneity in disease activity between subjects and to admit a possible negative correlation between the transition intensities. Maximum likelihood estimation is carried out using Gauss-Hermite integration and a standard Newton-Raphson procedure. Tests of homogeneity are presented based on score statistics. An application of the methodology to data from a multi-center clinical trial of chronic bronchitis is provided for illustrative purposes.

Anti-Infective Agents↗

Malignant tracheoesophageal fistula secondary to Hodgkin's disease. Successful surgical treatment with free fascia-muscle graft and left colon bypass.

A case of malignant tracheoesophageal fistula due to Hodgkin's disease at the mediastinum and mid-third of the esophagus is reported. The fistula developed after x-ray therapy (2,000 rads) to the medistinum. In another hospital, she had undergone two unsuccessful attempts to close the fistula surgically with muscle flap grafts, following tracheostomy and feeding gastrostomy. The third operation, performed successfully 2 months later at The Roosevelt Hospital, included division of the esophagus above the fistula with cervical esophagostomy. A free muscle graft was used to close the fistula in the trachea. One month later, subcutaneous antiperistaltic left colon bypass was performed in one stage to connect the cervical esophagus with the lower stomach. At the same time, distal closure of esophagus at the cardia, pyloroplasty, and splenectomy were done. These operations allowed that time, recurrence of the fistula necessitated a fourth operative repair. This time, a 2 inch square piece of fascia and its underlying muscle from the gluteus medius were used to reinforce the closure. The fistula remains closed to date.

Adult↗

[Analysis of the causes of recurrence of atrioventricular reentry tachycardia in patients treated with radiofrequency current ablation].

The recurrence rate of atrioventricular reentry tachycardia (AVRT) after radiofrequency current ablation (RFCA) of 124 accessory atrioventricular pathways (AP) in 122 patients were reported and the possible causes of recurrence of AVRT were analyzed. Of the 122 patients, 81 were male, 41 female. The average age of the patients was 46.3 +/- 14.4 (14-71) hears. There were 81 manifest AP in 80 patients, 43 concealed AP in 42 patients. 13 of the 124 AP were located in left anterior wall, 59 left lateral wall, 8 left posterior wall, 10 left posterior interventricular septum. 14 right anterior interventricular septum, 2 mid-septum, 14 righy posterior interventricular septum and 4 right free wall. All patients had no organic heart disease. The total recurrence rate of 124 AP in the 122 patients during a follow-up period of 2-25 (13.5 +/- 7.1) months was 4.03% (5/124), with manifest and concealed AP 1.23% (1/81) and 9.30% (4/43), respectively (P < 0.05); left free wall and interventricular septum AP were 2.5% (2/80) and 7.5% (3/40), respectively (P > 0.05); left and right AP were 3.3% (3/90) and 3.1% (1/32), respectively (P > 0.05). The recurrence time was from 0.5 to 60 (15.4 +/- 25.4) days. The recurrence may be related to inaccurate ablation target site, functional and anatomical characteristics of AP, locations of AP, and insufficient ablation energy, etc. It is suggested that AVRT patients receiving RFCA should be followed up for a certain period.

Adolescent↗

Preoperative immune status determines anal condyloma recurrence after surgical excision.

PURPOSE: Immunosuppression is an important risk factor for anal condyloma progression; however, its effects on postoperative outcomes remain unclear. In the present study, we investigated risk factors and recurrence rates in immunocompromised patients requiring surgery for medically intractable anal condyloma. METHODS: A retrospective review was performed on 63 consecutive patients who underwent surgical intervention for medically intractable anal condyloma at a single institution. Patient cohorts included immunosuppressed patients (e.g, HIV-seropositive, leukemia, idiopathic lymphopenic syndrome, or transplant patients; n = 45) and immunocompetent patients (n = 18). Recurrence rates and time to recurrence after surgery were determined for both groups. Preoperative CD4 count and viral load within the HIV subpopulation were also determined. The majority of the patients were male (90 percent), with a median age of 36 years. RESULTS: Anal condyloma recurred in 66 percent of the immunosuppressed patients compared with 27 percent of the immunocompetent group. Recurrence time expressed in months was shorter in immunosuppressed patients than in immunocompetent patients (6.8 +/- 1.5 vs. 15 +/- 5.7 months; P< 0.05). In the subpopulation of HIV-seropositive patients, no association was found between recurrence rates and viral loads; however, CD4 counts were significantly lower in those who had recurrence than in those who did not (226 +/- 31.7 vs. 401 +/- 51.2 cells/microl; P< 0.05). CONCLUSIONS: After surgery, anal condyloma in immunosuppressed patients recurs significantly more often and within a shorter period of time than in patients with a competent immune system. Additionally, in HIV-seropositive patients, CD4 counts should be maximized to prevent early recurrence of anal condyloma.

Adolescent↗