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Combination transcatheter hepatic arterial chemoembolization with thymosin alpha1 on recurrence prevention of hepatocellular carcinoma.

BACKGROUND/AIMS: To observe recurrence prevention on hepatocellular carcinoma after hepatectomy by using TACE (transcatheter hepatic arterial chemoembolization) with thymosin alpha1 postoperatively. METHODOLOGY: From January 2000 to December 2002, 57 patients with hepatocellular carcinoma were randomly divided into three groups: Group A (n=18) received hepatectomy plus TACE and thymosin alpha1 postoperatively, group B (n=23) received hepatectomy plus TACE postoperatively and group C (n=16) received hepatectomy only. The recurrent rate, recurrent time and median survival period for the three groups were observed and measured. RESULTS: For group A, B and C, one-year recurrent rates were 83.3%, 87.0% and 87.5% (p=0.926), respectively. The recurrent time were 7.0, 5.0 and 4.0 months (p=0.039), respectively, and the median survival were 10.0, 7.0 and 8.0 months (p=0.002), respectively. CONCLUSIONS: Comprehensive therapy combining TACE plus Talpha1 postoperatively could not decrease the recurrent rate, but it might delay the recurrent time and prolong survival periods for hepatocellular carcinoma patients after hepatectomy.

Adjuvants, Immunologic↗

Clinical risk factors and timing of recurrent venous thromboembolism during the initial 3 months of anticoagulant therapy.

BACKGROUND: In patients with venous thromboembolism (VTE), identifying clinical risk factors for recurrence during the initial 3 months of anticoagulant therapy and knowledge of the time course of recurrence may help clinicians decide about the frequency of clinical surveillance and the appropriateness of outpatient treatment. METHODS: Analysis of a randomized controlled trial database involving 1021 patients with VTE (750 with deep vein thrombosis [DVT] and 271 with pulmonary embolism [PE]) who were followed up for 3 months after the start of anticoagulant therapy. All patients received initial treatment with unfractionated heparin or a low-molecular-weight heparin (reviparin) and a coumarin derivative starting the first or second day of treatment, with a target international normalized ratio of 2.0 to 3.0. RESULTS: Four independent clinical risk factors for recurrent VTE were identified: (1) cancer (odds ratio [OR], 2.72; 95% confidence interval [CI], 1. 39-5.32), (2) chronic cardiovascular disease (OR, 2.27; 95% CI, 1. 08-4.97), (3) chronic respiratory disease (OR, 1.91; 95% CI, 0.85-4. 26), and (4) other clinically significant medical disease (OR, 1.79; 95% CI, 1.00-3.21). Older age was associated with a decreased risk for recurrent VTE (OR, 0.76; 95% CI, 0.64-0.92). Previous VTE, sex, and idiopathic VTE were not risk factors for recurrence. In patients with DVT or PE, there was no significant difference in the rates of recurrent nonfatal VTE (4.8% vs 4.1%; P =.62), major bleeding (2.9% vs 2.2%; P =.53), and non-VTE death (6.4% vs 7.8%; P =.45), but recurrent fatal PE was more frequent in patients with PE than DVT (2. 2% vs 0%; P<.01). There was a clustering of recurrent VTE episodes during the initial 2 to 3 weeks after the start of treatment. CONCLUSIONS: During the initial 3 months of anticoagulant therapy, recurrent VTE is more likely to occur in patients with cancer, chronic cardiovascular disease, chronic respiratory disease, or other clinically significant medical disease. Patients with PE are as likely to develop recurrent VTE as those with DVT; however, recurrence is more likely to be fatal in patients who initially present with PE. Arch Intern Med. 2000;160:3431-3436.

Adult↗

The value of postoperative radiotherapy in advanced renal cell cancer.

The study reviews experience with the treatment of advanced renal cell cancer at Bydgoszcz Regional Cancer Center within a 10-year period from 1985 to 1996. The aim of this paper was to evaluate the value of postoperative radiotherapy. The medical records of 186 patients with locally advanced renal cell cancer were reviewed retrospectively. Postoperative radiation therapy with a median dose of 50.0 Gy/t was given in 114 patients. The overall and disease-free survival, the pattern of recurrences, time interval to recurrence were assessed. For all patients, the 5-year overall and disease-free survival rates were 36.2% and 30.5%, respectively. Non significant difference was observed in terms of 5-year overall and disease-free survival between the group of patients with postoperative radiotherapy and without, 37.9%/29.5% vs. 35.5%/31.3%, respectively. A total of 29 patients (15.6%) developed local recurrences. Local failure by stage was as follows: T3N0 without postoperative radiation therapy--15.8%, with irradiation--8.8%; T3N(+) without radiation therapy--33.3%, with irradiation--33.3%; T4N0 without radiation therapy--33.3%, with irradiation--33.3%, T4N(+) without radiation therapy--33.3%, with irradiation--25.0%. 73 patients (39.3%) had distant metastases as a first symptom of renal cell cancer relapse. The median time to relapse for local recurrence or distant metastases were approximately two times longer in patients with adjuvant radiotherapy compared to those without, 27.0/21.0 months vs. 16.0/12.5 months, respectively. In our opinion postoperative radiotherapy reduces the probability of local recurrences in selected patients, mainly with pathologic stage T3N0, but its impact on survival is minimal.

Adult↗

Postoperative radiotherapy of squamous cell carcinoma of the tonsil. Factors influencing survival and time to recurrence.

From 1970 to 1988, 40 patients with squamous cell carcinoma of the tonsillar region were treated with surgery and postoperative split-course radiotherapy. The 5-year survival rate for all the patients was 52.5%; the corresponding figure was 100% in stage I, 75% in stage II, 63% in stage III and 15% in stage IV. The local control rate was 100% in stage I, 89% in stage II, 87% in stage III and 38% in stage IV. In the proportional hazards regression analysis T- and N-category and pretreatment Karnofsky index had the strongest association to survival, whereas T- and N-category and total radiation dose were most strongly associated to time to recurrence.

Carcinoma, Squamous Cell↗

Collins' law revisited: can we reliably predict the time to recurrence in common pediatric tumors?

Collins' law states that the period of risk for tumor recurrence is the age of the child at diagnosis plus 9 months. The purpose of this study is to validate this rule through a retrospective review of common pediatric tumors seen at 1 institution. Inclusion criteria for this study included an age at diagnosis of < 16 years old, minimum follow-up time of the Collins risk period (CRP) if child did not relapse and treatment with curative intent. The records of 424 children seen and treated for neuroblastoma (n = 98), Wilms tumor (n = 86), rhabdomyosarcoma (n = 82), medulloblastoma (n = 59), Ewing sarcoma (n = 43), ependymoma (n = 25), supratentorial PNET (n = 22), and synovial sarcoma (n = 9) from 1960 to 2001 were reviewed. CRP was calculated using the age of child at initial diagnosis plus 9 months. The median follow-up time was 164 months (range, 11-484 months), while the median follow-up/CRP ratio was 4.89 (range, 1.0-48.0). A total of 183 of 424 (43.2%) patients relapsed, with 180 (98.4%) relapses occurring during the CRP. Relapses beyond the CRP were seen in 3 young children (ages 7 months, 24 months, and 2 weeks at initial diagnosis) with a diagnosis of Wilms tumor (n = 2) and supratentorial PNET (n = 1) at 1, 3, and 26 months post-CRP. Collins' law is a useful and simple way of predicting risk period for relapse in the tumor types studied.

Adolescent↗

Markov chain analysis of succession in a rocky subtidal community.

We present a Markov chain model of succession in a rocky subtidal community based on a long-term (1986-1994) study of subtidal invertebrates (14 species) at Ammen Rock Pinnacle in the Gulf of Maine. The model describes successional processes (disturbance, colonization, species persistence, and replacement), the equilibrium (stationary) community, and the rate of convergence. We described successional dynamics by species turnover rates, recurrence times, and the entropy of the transition matrix. We used perturbation analysis to quantify the response of diversity to successional rates and species removals. The equilibrium community was dominated by an encrusting sponge (Hymedesmia) and a bryozoan (Crisia eburnea). The equilibrium structure explained 98% of the variance in observed species frequencies. Dominant species have low probabilities of disturbance and high rates of colonization and persistence. On average, species turn over every 3.4 years. Recurrence times varied among species (7-268 years); rare species had the longest recurrence times. The community converged to equilibrium quickly (9.5 years), as measured by Dobrushin's coefficient of ergodicity. The largest changes in evenness would result from removal of the dominant sponge Hymedesmia. Subdominant species appear to increase evenness by slowing the dominance of Hymedesmia. Comparison of the subtidal community with intertidal and coral reef communities revealed that disturbance rates are an order of magnitude higher in coral reef than in rocky intertidal and subtidal communities. Colonization rates and turnover times, however, are lowest and longest in coral reefs, highest and shortest in intertidal communities, and intermediate in subtidal communities.

Animals↗

Anxiety and depressive symptoms measured by the Hospital Anxiety and Depression Scale as predictors of time to recurrence in localized cutaneous melanoma.

The purpose of this study was to investigate anxiety and depression as predictors for recurrence-free survival in cutaneous melanoma, when corrected for known prognostic factors. The association between known prognostic factors and anxiety and depression were also studied. Consecutive patients (n = 437) completed the Hospital Anxiety and Depression Scale (HAD) approximately three months after diagnosis of melanoma. Neither anxiety, nor depression turned out to be prognostic factors for time to recurrence. A higher proportion of young patients, women, patients without ulcerated tumours, patients with tumours with low mitotic index and Clark's level II tumours scored > or = 8 (possible clinical levels of anxiety) on the anxiety scale. Furthermore, on the depression scale, a higher proportion of young patients scored > or = 8 (possible clinical level of depression). Using the HAD scale, a well-validated instrument for assessing anxiety and depression in patients with somatic diseases, our data did not show any associations between anxiety or depression and outcome in terms of recurrence in patients with localized disease.

Age Factors↗

Tumor markers at the time of recurrence in patients with germ cell tumors.

BACKGROUND: alpha-fetoprotein (AFP), human chorionic gonadotropin (HCG), and lactate dehydrogenase (LDH) closely follow the course of germ cell tumors (GCTs) and are widely used for diagnosis, prognosis, and follow-up purposes. The objective of this study was to assess the concordance of tumor markers at the time of diagnosis and recurrence. METHODS: The authors reviewed the records of 794 patients with GCTs treated in three Spanish hospitals from 1977-1996 and analyzed the concordance between AFP, HCG, and LDH levels at diagnosis and first and second recurrence. A positive marker was defined as a level of AFP > 10 ng/mL, HCG > 5 IU/L, or LDH > the upper limit of normal. One hundred twenty-five patients were identified who developed a first recurrence (123 had marker levels recorded). The median age was 27 years (range, 14-78 years). Histology was seminoma in 36 patients (29%) and nonseminomatous GCT (NSGCT) in 87 patients (71%). RESULTS: Seventy-nine patients (64%) had elevated tumor markers at diagnosis and 76 (62%) at first recurrence. An elevated marker was present at first recurrence in 58 of 79 patients (73%) with initially positive markers and in 18 of 44 patients (41%) with initially negative markers. In 84 of 123 patients (68%), the same marker pattern (positive or negative) was present at the time of diagnosis and at first recurrence, 78% in seminomas and 64% in NSGCTs. The earliest indicator of recurrence was an elevated marker in patients with NSGCTs and a radiologic finding in patients with seminomas. Thirty patients developed a second recurrence, 27 of whom (90%) had the same marker pattern as at first recurrence. CONCLUSIONS: Tumor marker pattern at diagnosis is not a good predictor of the pattern at recurrence, particularly in patients with NSGCTs. Marker assessment should be included in the follow-up schedule regardless of levels at the time of diagnosis. Early detection of recurrence should not rely only on marker levels, even in patients with elevated levels at presentation.

Adolescent↗

Primary malignant melanoma of the vagina: a clinicopathological analysis of 10 cases.

We retrospectively analyzed clinicopathological findings in 10 cases of primary malignant melanoma of the vagina. The main presenting symptoms were vaginal bleeding, vaginal discharge, and feeling of a mass. The tumors were predominantly located in the lowest one-third and in the anterolateral aspect of the vagina. Patients underwent various surgical procedures, radiation therapy, and chemotherapeutic modalities. The mean survival time and the recurrence time from the time of diagnosis were 15 and 8 months, respectively. The tumors were examined for histological characteristics of cell type, presence of melanin pigment, depth of invasion, vascular invasion, intraepithelial spread, junctional activity, and mitotic count. Of all these histological variables, the mean survival time had a significant correlation to mitotic count (P less than 0.04). We concluded that patients with lower mitotic counts (less than 6 per 10 HPF) had better survival (21 months) compared to patients with mitotic counts greater than 6 per 10 HPF who had a mean survival of only 7 months.

Female↗

The distribution of slow-wave sleep across the night: a comparison for infants, children, and adults.

This study describes the temporal distribution of slow-wave sleep (SWS) (defined as the visually scored stages 3 + 4) across the night for 16 infants aged between 20 weeks and 1 year, 17 children between 1 and 6 years, and 17 adults between 20 and 36 years. In all three groups the amounts of SWS peaked during the first nonrapid eye movement (NREM) episode. SWS decreased across the night for adults and children, but not for infants. In infants the amounts of SWS remained at a fairly constant level from the second cycle onward, although many cycles were observed with zero SWS. The latter was evident from the very low tendency for SWS to appear in consecutive NREM/REM cycles. Rather, SWS was observed in alternate cycles. In children this phenomenon was less prominent but still well visible, and the tendency for SWS to appear in consecutive cycles had increased. In adults SWS occurred predominantly in consecutive cycles. The results suggest that whereas REM recurrence time increases twofold from infancy to adulthood, SWS recurrence time remains of similar length in infants, children, and adults.

Adult↗

[Pelvic recurrence of cervical cancer: the prognostic relationship to the retreatment modalities].

OBJECTIVE: To investigate the prognostic factors in relation to retreatment modalities in patients with recurrent cervical carcinoma. METHODS: According to initial therapy, 194 patients with recurrence were grouped as: (1) surgery, 22 cases; (2) surgery and radiotherapy, 24 cases, and (3) radiotherapy alone, 148 cases. Factors such as clinical stage, sites of recurrence, time of diagnosis of recurrence after initial therapy and modalities of retreatment were analyzed. RESULTS: There were 19 cases alloted to stage I, 51 cases to stage II (IIa 23 and IIb 28) and 124 cases to stage III (IIIa 21 and IIIb 103); histopathologically confirmed squamous cell carcinoma in 181 cases and adenocarcinoma 13 cases. Central recurrences were found in 91 cases and lateral or pelvic recurrences in 103 cases. Time of diagnosis of recurrence within 2 years from initial treatments was shown in 118 patients and above 2 years in 76 patients. In 147 of the 194 patients retreated, those of the group 1 obtained a median survival rate of 24 months, which was significantly longer than that of group 2, and group 3. The sites of recurrence did not significantly affect the survival. CONCLUSION: Radiotherapy remains the treatment of choice for patients with pelvic recurrence after surgery. Previously irradiated patients retreated for recurrence by radiotherapy and (or) chemotherapy had lower response rates. The optimal therapy for these patients should be comprehensive managements including surgery, radiotherapy and chemotherapy.

Carcinoma, Squamous Cell↗

Instability versus nonlinearity in certain nonautonomous oscillators: A critical dynamical transition driven by the initial energy.

The equation of motion q+Omega(2)(t)q+alpha/q/(gamma-2)q=0 (gamma>2) for the real coordinate q(t) is studied, as an example of the interplay between nonlinearity and instability. Two contrasting mechanisms determine the behavior of q(t), when the time-varying frequency Omega(t) does produce exponential instability in the linear equation q (lin)+Omega(2)(t)q(lin)=0. At low energy, the exponential instability is the dominant effect, while at high energy the bounding effect of the autonomous nonlinear term prevails. Starting from low initial energies, the result of this competition is a time-varying energy characterized by quasiperiodic peaks, with an average recurrence time T(peak). A closed critical curve S(omega) exists in the initial phase space, whose crossing corresponds to a divergence of the recurrence time T(peak). The divergence of T(peak) has a universal character, expressed by a critical exponent a=1. The critical curve S(omega) is the initial locus of the solutions that vanish asymptotically. A close relationship exists between this dynamical transition and the transition from mobile to self-trapped polarons in one spatial dimension. The application to a number of physical problems is addressed, with special attention to the Fermi-Pasta-Ulam problem and to transitions to chaos.

Journal Article↗

The effect of extent of resection on recurrence in patients with low grade cerebral hemisphere gliomas.

BACKGROUND: To evaluate the role of radical resection for low grade cerebral hemisphere gliomas, the authors analyzed the preoperative and postoperative radiographic tumor volumes (computed tomography hypodensity, magnetic resonance imaging-T2 signal hyperintensity) in 53 patients. METHODS: Using a previously described method of computerized image analysis, the authors evaluated whether the percent of resection and volume of residual disease, postoperatively, influenced the incidence of recurrence, time to tumor progression, and histology of the recurrent tumor. Survival was not analyzed in this study. RESULTS: No recurrence was detected, regardless of percent of resection and volume of residual disease, in patients with preoperative tumor volumes less than 10 cm2 (mean follow-up, 41.7 months). Patients with tumors measuring 10-30 cm3 had an incidence of recurrence and time to tumor progression of 13.6% and 58 months, respectively, compared with tumors measuring greater than 30 cm3, which had an incidence of recurrence and time to tumor progression of 41.2% and 30 months, respectively (P = 0.016). All patients (n = 13) who underwent a 100% resection had a recurrence-free follow-up period (mean, 54 months). In the remaining patients (n = 40), as the percent of resection decreased, the incidence of recurrence increased along with a shorter time to tumor progression (P = 0.03). Patients with a volume of residual disease of greater than 10 cm3 had a higher incidence of recurrence (46.2%) and a shorter time to tumor progression (30 months) compared with patients with a tumor volume of residual disease of less than 10 cm3 (incidence of recurrence, 14.8% and time to tumor progression, 50 months) (P = 0.002). Forty-six percent of patients with a tumor volume of residual disease of more than 10 cm3 had a recurrence of higher histologic grade, and this was significantly more frequent than patients with a volume of residual disease less than 10 cm3 (3.7%) (P = 0.0009). Age, radiotherapy, and histologic subtype had no influence on recurrence patterns. CONCLUSION: For tumors greater than 10 cm3, the authors' data suggest that a greater percent of resection and a smaller volume of residual disease conveys a significant advantage, that is, terms of incidence of recurrence and the recurrent tumor phenotype, for patients with low grade cerebral hemisphere gliomas, compared with those who have a less aggressive resection or biopsy. While this may also be the case with tumors less than 10 cm3, further follow-up is necessary to determine the effect of surgery on recurrence patterns for this subset of patients.

Adolescent↗

Regression with frailty in survival analysis.

In studies of survival, the hazard function for each individual may depend on observed risk variables but usually not all such variables are known or measurable. This unknown factor of the hazard function is usually termed the individual heterogeneity or frailty. When survival is time to the occurrence of a particular type of event and more than one such time may be obtained for each individual, frailty is a common factor among such recurrence times. A model including frailty is fitted to such repeated measures of recurrence times.

Adolescent↗

Multi-drug resistant Plasmodium falciparum malaria in Assam, India: timing of recurrence and anti-malarial drug concentrations in whole blood.

The susceptibility of 23 cases of Plasmodium falciparum malaria from the Sonapur primary health center in the Kamrup district of Assam, India to different antimalarials was investigated using the 28-day World Health Organization in vivo test. Whole blood concentrations of chloroquine, sulfadoxine, and quinine were determined at different intervals and at the time of parasites recrudescence after completion of treatment with the respective drugs to confirm the status of drug sensitivity. A case of multi-drug resistant P. falciparum malaria was found where recrudescence occurred, despite standard oral treatment with chloroquine, sulfadoxine/pyrimethamine, and quinine sequentially. Whole blood concentrations of chloroquine, sulfadoxine, and quinine at the time of recrudescence were 0.35 microg/ml (day 7), 18 microg/ml (day 14), and 0.009 microg/ml (day 14), respectively. Therefore, monitoring of drug-resistant P. falciparum malaria and its proper treatment should be intensified to check the spread of multi-drug resistant strains in other parts of the country.

Adolescent↗

Statistical inference in stationary populations.

A fixed ensemble of alternating renewal processes is proposed as a model for stationary populations. This model is applied to explore the relationship between survival times and forward recurrence times. In addition, it is shown that ergodic theory can be applied to the model. An example is presented.

Biometry↗

Polypoidal rhinosinusitis in cystic fibrosis: a clinical and histopathological study.

The eosinophil may play a key role in the pathogenesis of nasal polyposis. Polyps in cystic fibrosis, however, have been described as neutrophilic. We compared the cell counts in polyps from 44 patients with cystic fibrosis to polyps from 50 patients without cystic fibrosis. The clinical profile, CT-scan and time to polyp recurrence were also compared with the cell counts in the patients with cystic fibrosis. No significant difference was detected in the number of patients with eosinophils (P > 0.25). Significantly more patients in the group with cystic fibrosis had polyp neutrophils (P < 0.01). Polyps from patients without cystic fibrosis contained more eosinophils (P < 0.001) whilst polyps from patients with cystic fibrosis contained more neutrophils (P = 0.001) and plasma cells (P = 0.038). Significant correlation was found between the neutrophil count and the CT score (P = 0.025) and between the recurrence time of polyps and the macrophage count (P = 0.01). Eosinophils are present in varying degrees in polyps from patients with and without cystic fibrosis and to classify polyps as eosinophilic or neutrophilic may be a false distinction.

Adolescent↗