Predictor Of Better Survival Research Articles

Disseminated M. avium complex infection in the Swiss HIV Cohort Study: declining incidence, improved prognosis and discontinuation of maintenance therapy.

Introduction of potent antiretroviral combination therapy (ART) has reduced overall morbidity and mortality amongst HIV-infected adults. Some prophylactic regimes against opportunistic infections can be discontinued in patients under successful ART. (1) The influence of the availability of ART on incidence and mortality of disseminated M. avium Complex infection (MAC). (2) The safety of discontinuation of maintenance therapy against MAC in patients on ART. The Swiss HIV-Cohort Study, a prospective multicentre study of HIV-infected adults. Patients with a nadir CD4 count below 50 cells/mm3 were considered at risk for MAC and contributed to total follow-up time for calculating the incidence. Survival analysis was performed by using Kaplan Meier and Cox proportional hazards methods. Safety of discontinuation of maintenance therapy was evaluated by review of the medical notes. 398 patients were diagnosed with MAC from 1990 to 1999. 350 had a previous CD4 count below 50 cells/mm3. A total of 3208 patients had a nadir CD4 count of less than 50 cells/mm3 during the study period and contributed to a total follow-up of 6004 person-years. The incidence over the whole study period was 5.8 events per 100 person-years. In the time period of available ART the incidence of MAC was significantly reduced (1.4 versus 8.8 events per 100 person-years, p < 0.001). Being diagnosed after 1995 was the most powerful predictor of better survival (adjusted hazard ratio for death: 0.27; p < 0.001). None of 24 patients discontinuing maintenance therapy while on ART experienced recurrence of MAC during a total follow-up of 56.6 person-years (upper 95% confidence limit 5.3 per 100 person-years). Introducing ART has markedly reduced the risk of MAC for HIV-infected individuals with a history of very low CD4 counts. Survival after diagnosis of MAC has improved after ART became available. In patients responding to ART, discontinuation of maintenance therapy against M. avium may be safe.

The influence of environmental conditions on immune responses, morphology and recapture probability of nestling house martins (Delichon urbica).

Nestling birds produced later in the season are hypothesized to be of poor quality with a low probability of survival and recruitment. In a Spanish population of house martins (Delichon urbica), we first compared reproductive success, immune responses and morphological traits between the first and the second broods. Second, we investigated the effects of an ectoparasite treatment and breeding date on the recapture rate the following year. Due probably to a reverse situation in weather conditions during the experiment, with more rain during rearing of the first brood, nestlings reared during the second brood were in better condition and had stronger immune responses compared with nestlings from the first brood. Contrary to other findings on house martins, we found a similar recapture rate for chicks reared during the first and the second brood. Furthermore, ectoparasitic house martin bugs had no significant effect on the recapture rate. Recaptured birds had similar morphology but higher immunoglobulin levels when nestlings compared with non-recaptured birds. This result implies that a measure of immune function is a better predictor of survival than body condition per se.

Natural infection of Sitka spruce thinning stumps in Britain by spores of Heterobasidion annosum and long-term survival of the fungus

Summary On 48 sites throughout Scotland and north England freshly cut stumps were either inoculated with basidiospores of H. annosum or allowed to become infected naturally. Sites were in first rotation plantations growing in high rainfall or low rainfall areas on either peat or mineral soils. After 2 years, infection varied greatly between sites. It was generally much higher following inoculation, but otherwise little of the variation can be explained. Overall, only 10.5 per cent of stumps became infected naturally; colonies were generally small and almost half the stumps contained only homokaryons. Colonization took place principally in the heartwood but stumps sampled 8 years after inoculation showed that in contrast to previous findings this did not prejudice long-term survival. The cross-sectional area of each stump occupied by H. annosum at two years was also not a good predictor of survival. There was a marked decline in survival of H. annosum in stumps sampled after 8 years, which implied a corresponding decline in the overall level of incidence to only 2.8 per cent across all sites. Even in those stumps in which the fungus survived, it failed to colonize two-thirds of the available roots. These results reinforce the conclusions of earlier work that there is a low risk of serious disease on peat soils in the uplands. It is suggested that for Sitka spruce stumps on wet sites, the risk of successful colonization is so low, particularly on peaty soils, that H. annosum may not become permanently established in stands on these site types, even if ambient spore loads increase. By contrast, on mineral soils in low rainfall areas, the risk of a build-up of inoculum in unprotected thinning stumps and the transfer of infection to residual trees in the stand is much higher.

Epidemiologic aspects of pediatric multiple trauma in a Spanish urban population

Background/Purpose: Trauma is still the most frequent cause of mortality and disability in childhood and adolescence. An epidemiologic prospective study on children under 16 years of age with multiple trauma (MT) was conducted in a large Spanish urban university hospital over a 6-year period. Methods: Of 1,937 children admitted at the pediatric trauma unit for musculoskeletal injuries from March 1988 until March 1994, 56 patients including 37 boys and 19 girls had MT. MT was considered when at least 2 long bones were fractured or there was a fracture of 1 long bone combined with an injury of 4 other major anatomic regions (face and neck, thorax, abdomen, or neural system). The severity of injuries was evaluated according to the modified injury severity score (MISS). Results: Injury to pedestrians was the most frequent cause of MT (54%). The overall mortality rate of the series, including those children dying during transport to the hospital was 11.5%. The average MISS for the whole group was 15 (range, 5 to 59). Head trauma was the most frequent associated injury (52%), two thirds of which were considered minor injuries (Glasgow Coma Scale >15). Seventy-seven fractures were registered, 10% of which were open fractures. External fixation was the most common surgical technique among operated fractures. The average hospitalization period was 16 (median, 13; range, 1 to 150) days. Children with a MISS above 18 points showed a significant longer hospitalization period (mean, 31 ± 45 days) as compared with those with MISS below 18 points (mean, 10 ± 7 days; P <.05). There was a strong correlation between the MISS and both the period of hospitalization at the pediatric intensive care unit and the total length of hospital stay. Conclusions: Pedestrian accidents caused by motor vehicles in children playing at the street contributed most significantly to MT in the urban pediatric population. Special care for prevention must be taken in the age group of 6 to 10 years. Head injury was the main cause of death in children with multiple trauma. MISS was found to be a good predictor of survival and duration of hospital stay in pediatric MT. J Pediatr Surg 35:1478-1481. Copyright © 2000 by W.B. Saunders Company.

Predictors of physical outcomes in pediatric bone marrow transplantation

The purpose of the present study was to investigate the hypothesis that family factors, in conjunction with clinical factors, are associated with physical outcomes in pediatric BMT. A prospective study of 68 pediatric patients (mean age = 7.5 years; ranging from 4 months to 18 years) undergoing BMT was carried out over a 6.5 year period. Physicians rated initial prognosis on a (0-5) scale which incorporated the child's diagnosis, known risk factors, and type of donor. Both parents individually completed two psychometrically sound questionnaires assessing family well-being and marital satisfaction. Cox proportional hazards survival analyses were performed to determine predictors of death (44% of the patients died). Potential predictor variables included were: initial prognosis, type of transplant, patient's age, socioeconomic status, marital satisfaction and family status, and family stress. Initial prognosis, as estimated by the physician, (RR = 0.62, 95% CI = 0.40, 0.97) was the best predictor of survival. Initial clinical factors are clearly critical in outcomes for pediatric BMT patients.

Variations in the low levels of cyclin D1/BCL1 have prognostic value in chronic lymphocytic leukemia

Cyclin D1 (CyD1)/BCL1 (PRAD1) is expressed at high levels in almost all cases of mantle cell leukemia/lymphoma (MCL) and in rare cases of chronic lymphocytic leukemia (CLL). The CyD1/BCL1 protein plays an important role in the progression of cells through the G1 phase of cell cycle. Most of the CyD1/BCL1 protein expression studies are performed using immunohistochemistry. We used a sensitive solid-phase radioimmunoassay (RIA) to quantify CyD1 protein expression in 199 patients with CLL. Of these 137 patients were previously untreated with the rest having had standard chemotherapeutic regimens including alkylating agents and fludarabine before being referred to our center. Median white cell count in these patients was 49×10 3 /μl (range 3.0–438.5×10 3 /μl), hemoglobin level 13.1 g/dl (range 5.2–17.3 g/dl), platelet count 157×10 3 /μl (range 10–377×10 3 /μl), age 58 (range 26–89), and β2-microglobulin 2.75 mg/dl (range 1.1–14.3). The median radioactivity (CPM) of mononuclear cells obtained from 56 normal individuals was assigned a value of 1. There was no significant variation in CyD1 levels among normal individuals (SD=0.12). While most CyD1 levels in MCL varied from 6.5 to 15.6, the median CyD1/BCL1 in CLL was 1.4 with 75th percentile under 2.12. Rare CLL cases (3.5%) showed levels between 4 and 8.83. When divided into two groups at the median level, patients with higher CyD1/BCL1 expression had shorter survival ( P=0.03). This remained true when applied only to the previously untreated patients ( P=0.05). Despite the relatively low expression, the CyD1/BCL1 levels in univariate analysis were as good or better predictors of survival than Binet ( P=0.03) or Rai ( P=0.05) staging. Furthermore, CyD1/BCL1 levels correlated with serum β2-microglobulin ( P=0.001), white blood cell count ( P=0.004) and hemoglobin levels at the time of collection ( P=0.0003) but not with lymphocyte count, platelet count or age. The data demonstrate that CyD1/BCL1 is likely to play a significant role in the biology of CLL and can be used as a prognostic indicator. Further studies to clarify the role of CyD1 in the biology of CLL and its value as a prognostic indicator at the time of diagnosis are encouraged.

Primary systemic therapy in operable breast cancer.

Laboratory studies suggest that primary systemic therapy (PST) could improve control of micrometastatic disease and impact on overall survival (OS). This article examines the rationale for and preclinical and clinical data of PST in operable breast cancer and the potential role of intermediate biomarkers as predictive and/or prognostic factors for response and survival. We conducted an extensive literative review (including MEDLINE) on preclinical studies, single-arm feasibility studies, large randomized single- and multi-institutional trials, and laboratory correlate studies of PST in breast cancer. Small trials in locally advanced disease showed high initial rates of response and local control. Six randomized clinical trials (RCTs) of PST for palpable, operable breast cancer have been reported since 1991 (from 204 to 1,523 patients each). These data clearly show a small but significant (less than 10%) absolute increase in the use of breast-conservation treatment (BCT) with similar rates of local control. Although one study showed better disease-free survival (DFS) and another showed better OS, most studies did not show any survival advantage of primary versus adjuvant systemic therapy. Thus far, pathologic complete response seems to be the best predictor of survival, but clinical response assessment correlates poorly with pathologic response. Pilot studies demonstrated feasibility of procuring tissue at diagnosis and after treatment for assays of potential intermediate biomarkers. Initial data suggest a potential correlation between markers of proliferation and apoptosis and in vivo chemotherapy sensitivity. Thus far, RCTs of PST versus standard adjuvant therapy have not shown any clear benefit for DFS or OS in early breast cancer. Ongoing trials should determine if specific subsets of patients at risk would benefit from additional systemic therapy and the potential role of intermediate biomarkers in identifying such women. Although PST results in a small increase in the rate of BCT with similar rates of local control, current PST strategies should not replace standard adjuvant approaches. Rather, they represent an acceptable alternative to women with palpable, operable tumors and an excellent arena for clinical trials.

Cell-mediated immunity to tumor-associated antigens is a better predictor of survival in early stage breast cancer than stage, grade or lymph node status.

Cell-mediated immune (CMI) responses to tumor-associated antigens (TAA) in the early postoperative period were examined for correlations with disease recurrence and survival in a 13-year-prospective study of 77 stage 1 and 2 breast cancer patients treated with modified radical or radical mastectomy alone. Among the 21 patients who had positive lymphoproliferative tests using patients' peripheral blood mononuclear cells and autologous TAA of breast cancer cells, only one died from metastatic disease (5%). Among the 56 patients who had a negative test, 23 died from metastatic disease (41%). This difference is statistically significant (p = 0.002) Three other risk factors including tumor size, nodal status and cell differentiation patterns were also analyzed. When these three clinical-pathologic criteria were analyzed individually, none reliably predicted disease recurrence and survival. Nodal status was the most predictive clinical-pathologic risk factor, but was not significant (p = 0.089). The results of this study demonstrate the detection of CMI responses against autologous TAA by lymphoproliferative assays identifies a sub-set of stage 1 and 2 breast cancer patients who are at minimal risk of developing metastatic disease. This testing also identifies immunologically unreactive patients who are at risk for disease recurrence.

A population-based study of congenital diaphragmatic hernia: Impact of associated anomalies and preoperative blood gases on survival

Background/Purpose: Although neonatal care has improved over the past 20 years, mortality rate with congenital diaphragmatic hernia (CDH) remains 50% to 60%, possibly reflecting defferences in management or selection biases. The authors determined the incidence, outcome, effect of coexisting anomalies, and prognostic indicators for neonates with CDH in a single inborn population older than 13 years. Methods: Forty-three neonates with CDH, those symptomatic within the first 6 hours of life, were identified using a validated neonatal database and diagnosis coding data from medical records among 180,643 live inborn neonates delivered at Parkland Memorial Hospital between 1983 and 1995. Charts were reviewed for prenatal history, demographic variables, presence of coexisting malformations, preoperative arterial blood gases, surgical findings, and outcome. Survival to hospital discharge was the primary outcome variable. Results: The incidence of CDH was 1 in 4,200 live births; overall survival rate was 51%. Thirty-two (74%) neonates underwent surgical repair, often at less than 8 hours of life; postoperative mortality rate was 31%. Eighteen (42%) had coexisting major anomalies or chromosomal abnormalities. Eighty percent of neonates with isolated CDH survived, whereas 89% with CDH and associated defects died. Nonsurvivors had lower birth weights and Apgar scores, were more acidotic, and had more severe respiratory compromise. When best preoperative pH was ≥7.25 or Pa co 2 ≤ 50 mm Hg, 80% of neonates survived. Conclusion: In this inborn population-based review of neonatal CDH between 1983 and 1995, the best predictors of survival were the presence or absence of other anomalies and the best preoperative Pa co 2 and pH.

GENETIC RESPONSES TO CLIMATE INPINUS CONTORTA: NICHE BREADTH, CLIMATE CHANGE, AND REFORESTATION

Fundamental plant–environment relationships were revealed by analyses of 20-yr height and survival of 118 populations representing two subspecies of Pinus contorta growing in common gardens at 60 environmentally disparate test sites in British Columbia. The approach involved (1) preparing models that described the general climate of British Columbia, (2) developing population-specific response functions driven by predicted climate variables, (3) developing general transfer functions that predict performance from the climatic distances over which populations were transferred, and (4) interpreting the results in terms of niche breadth, effects of climate change on adaptedness of populations, and reforestation in a changing environment. Polynomial regression models used physiographic descriptors to predict seven climate variables from normalized records of 513 weather stations. Values of R2 ranged over 0.80–0.97 for thermal variables and 0.54–0.61 for precipitation variables. Validations with independent data from 45 stations were strong and suggested that the models were generally free of bias within the limits of the original data. Response functions describing the height or survival of each population were developed from quadratic regressions using predicted climate variables for each test site. Mean annual temperature and mean temperature in the coldest month were the most effective variables for predicting population height, while the ratio of summer temperature to summer moisture was the best predictor of survival. Validation of the response functions with independent data from two additional test sites produced values of R2 between actual and predicted values that were as high as 0.93 for height and 0.73 for survival. The results demonstrated that natural populations have different climatic optima but tend to occupy suboptimal environments. Nevertheless, the general transfer functions showed that optimal growth and survival of the species as a whole is associated with the null transfer distance. These seemingly anomalous results suggest that the same processes thought to determine the distribution of species control the distribution of genotypes within species: (1) environmental selection to produce a broad fundamental niche, and (2) density-dependent selection to produce a relatively narrow realized niche within which most populations are relegated to suboptimal environments. Consequently, the steep geographic clines typical of P. contorta seem to be driven more by density-dependent selection than by environmental selection. Asymmetric gene flow from the center of distribution toward the periphery is viewed as a primary regulator that provides the fuel for both environmental and density-dependent selection and thereby indirectly perpetuates suboptimality. The response functions predict that small changes in climate will greatly affect growth and survival of forest tree populations and, therefore, that maintaining contemporary forest productivities during global warming will require a wholesale redistribution of genotypes across the landscape. The response functions also provide the climatic bases to current reforestation guidelines and quantify the adjustments necessary for maintaining adaptedness in planted trees during periods of small (∼1°C) temporal temperature shifts.

Results of external beam radiotherapy alone for incompletely resected carcinoma of rectosigmoid or rectum: peter maccallum cancer institute experience 1981–1990

Purpose: To study the results of external beam radiotherapy treatment for incompletely resected nonmetastatic rectosigmoid and rectal carcinoma. Methods and Materials: A retrospective review was carried out of all patients (57) presenting to Peter MacCallum Cancer Institute from 1981 to 1990 with incompletely resected nonmetastatic rectosigmoid or rectal cancer who were treated with external beam radiotherapy. Three radiotherapy schedules were used: radical (50 to 60 Gy, 27 patients), high-dose palliative (45 Gy, 25 patients), and low-dose palliative (less than 45 Gy, 5 patients). Symptomatic response, overall survival, and the effect of prognostic factors on treatment outcome were evaluated. The median follow-up period for survivors was 49 months. Results: Symptomatic response rates were 83% and 79% for the radical and high-dose palliative groups respectively. The estimated median survival time from presentation for all patients was 16.4 months (radical 26.1 months, high-dose palliative 15.7 months). Patients with microscopic residual disease survived significantly longer than patients with macroscopic residual disease (estimated median survival time 30.7 months vs. 14.3 months, p = 0.013). Conclusions: No dose response effect was seen between the radical group and high-dose palliative group. Microscopic residual disease at presentation was the only significant predictor of better survival. The conventionally fractionated course of 50 to 60 Gy was not significantly better in terms of palliation and overall survival than a shorter palliative course of 45 Gy. In future, preoperative chemoradiation should improve outcome by reducing the number of patients with incompletely resected cancer.

Long-term survival of patients with coronary artery disease and left ventricular dysfunction: Implications for the role of myocardial viability assessment in management decisions

Objectives: Our purpose was to evaluate the long-term benefit of myocardial viability assessment for stratifying risk and selecting patients with low ejection fraction for coronary artery bypass grafting and to determine the relation between the severity of anginal symptoms, the amount of ischemic myocardium, and clinical outcome. Methods: We studied 93 consecutive patients with severe coronary artery disease and low ejection fraction (median, 25%) who underwent positron emission tomography to delineate the extent of perfusion-metabolism mismatch (reflecting hibernating myocardium) for potential myocardial revascularization. Median follow-up was 4 years (range, 0 to 6.2 years). Results: Fifty patients received medical therapy, and 43 patients underwent bypass grafting. In Cox survival models, heart failure class, prior myocardial infarction, and positron emission tomographic mismatch were the best predictors of survival. Patients with positron emission tomographic mismatch receiving bypass grafting had improved 4-year survival compared with those on medical therapy (75% versus 30%; P = .007) and a significant improvement in angina and heart failure symptoms. In patients without positron emission tomographic mismatch, bypass grafting tended to improve survival and symptoms only in those patients with severe angina (100% versus 60%; P = .085), whereas no survival advantage was apparent in patients with minimal or no anginal symptoms (63% versus 52%; P = .462). Conclusions: Patients with low ejection fraction and evidence of viable myocardium by positron emission tomography have improved survival and symptoms with coronary bypass grafting compared with medical therapy. In patients without evidence of viability, survival and symptom improvement with bypass grafting are apparent only among those patients with severe angina. (J Thorac Cardiovasc Surg 1998; 116:997-1004)

Reversible Restrictive Left Ventricular Diastolic Filling With Optimized Oral Therapy Predicts a More Favorable Prognosis in Patients With Chronic Heart Failure

Objectives. We sought to assess whether in clinically stable patients with chronic heart failure (CHF) the prolongation (i.e., increase) of an initially short (≤125 ms) Doppler transmitral deceleration time (DT) of early filling obtained with long-term optimal oral therapy predicts a more favorable prognosis.Background. It has been recently demonstrated that transmitral early DT is a powerful independent predictor of poor prognosis in patients with left ventricular dysfunction. However, DT may change over time according to loading conditions and medical treatment.Method. One hundred forty-four patients with CHF and a short DT (≤125 ms) underwent repeat Doppler echocardiographic study 6 months after the initial examination, while clinically stable with optimal oral therapy, and were then followed up for a mean period of 26 ± 7 months.Results. After 6 months, DT had not changed in 80 patients (group 1), whereas it was significantly prolonged (>125 ms) in the remaining 64 patients (group 2). Baseline Doppler echocardiographic features were similar in the two groups. No changes were found after 6 months in group 1, whereas group 2 showed a slight but significant (p < 0.01) reduction in end-systolic volume, an improvement in left ventricular ejection fraction (p < 0.01) and a decrease (p < 0.01) in the degree of tricuspid regurgitation. During follow-up, 37% of patients in group 1 experienced cardiac death versus 11% in group 2 (p < 0.0005). By Cox model analysis, prolongation of a short DT emerged as the single best predictor of survival (chi-square 15.70).Conclusions. The prolongation of an initially short DT obtained with long-term optimal oral therapy predicts a more favorable outcome in clinically stable patients with CHF.

CARCINOSARCOMA AND SARCOMATOID CARCINOMA OF THE BLADDER: CLINICOPATHOLOGICAL STUDY OF 41 CASES

Purpose Carcinosarcoma of the bladder is a rare neoplasm characterized by an intimate admixture of carcinoma and malignant soft tissue neoplasm. The clinical usefulness of separating carcinosarcoma (carcinoma with sarcomatous component) from sarcomatoid carcinoma (carcinoma with spindle cell carcinomatous component) is uncertain, and it comprises the subject of this report. Materials and Methods We reviewed the clinical and pathological records of 10 men and 5 women a mean of 66 years old with carcinosarcoma, and 21 men and 5 women a mean of 66.5 years old with sarcomatoid carcinoma of the bladder, as documented in the files of the Mayo Clinic between 1936 and 1995. Results Of the 15 patients in the carcinosarcoma group 9 had urothelial carcinoma, small cell carcinoma, 3 had squamous cell carcinoma and 2 had more than 1 type. The sarcomatous component included chondrosarcoma in 3 cases, leiomyosarcoma in 3, malignant fibrous histiocytoma in 3, osteosarcoma in 2, fibrosarcoma in 1, rhabdomyosarcoma in 1 and more than 1 type in 2. All disease was high stage at presentation. Treatment included cystectomy in 11 patients with (4) and without (7) radiation therapy, and transurethral resection in 4 with (1) and without (3) radiation therapy. Mean followup available in 14 cases was 34 months (range 1 to 144). A total of 11 patients died of cancer at 1 to 48 months (mean 17.2) and 2 survived for 8 to 131 months. Of the 26 patients in the sarcomatoid carcinoma group 18 had urothelial carcinoma, 1 had squamous carcinoma, 2 had urothelial carcinoma combined with squamous cell carcinoma and 5 had spindle cells only with no recognizable epithelium. All but 1 case was high stage at diagnosis. Treatment included transurethral resection in 17 patients with (7) and without (10) radiation therapy, including 1 who also received chemotherapy, and only cystectomy in 5, including 2 who also underwent radiation therapy and 1 who also received chemotherapy. Mean followup available in 21 cases was 49 months (range 1 to 420). A total of 17 patients died of cancer at 1 to 73 months (mean 9.8), 1 was alive at 140 months and 3 died of unrelated causes. Conclusions Carcinosarcoma and sarcomatoid carcinoma of the bladder are highly aggressive malignancies with a similar outcome regardless of histological findings and treatment. Pathological stage is the best predictor of survival.

Nuclear p53 protein expression in resected hepatic metastases from colorectal cancer: an independent prognostic factor of survival.

An association has been reported between nuclear p53 protein expression in tumour cells and a poor outcome in patients with colorectal cancer (CRC). In this study we investigated the prognostic significance of nuclear p53 protein expression in CRC liver metastases after curative hepatic resection. The study population consisted of 69 consecutive patients who underwent curative hepatic resection for metastases from CRC at our Institution between February 1987 and October 1993. Immunohistochemical expression of p53 protein was evaluated in formalin-fixed paraffin-embedded sections of CRC liver metastases using the monoclonal antibodies (MAbs) D01 and Pab 1801. The Cox proportional hazards model was used in forward stepwise regression to assess the relative influence of different prognostic factors. Forty-four (63.8%) CRC liver metastases were p53-positive. Kaplan-Meier survival curves demonstrated that patients with p53-positive metastases had a median survival of 27 months versus 93 months for patients with p53-negative metastases (P < 0.01). The 3 and 5 years survival rates were 31.5 and 21.0% in patients with p53-positive metastases and 71.8 and 53.1% in patients with p53-negative metastases. At multivariate analysis p53 protein status was the single best predictor of survival (P = 0.0079); the odds ratio of death among patients with p53-positive tumours was 2.53. Nuclear p53 protein expression in hepatic metastases from CRC is an independent prognostic factor of survival following liver resection. These findings may be of clinical importance in the selection of patients more likely to benefit from liver resection and could be used as criteria for stratification in trials on adjuvant therapy.

Treatment of large and locally advanced breast cancers using neoadjuvant chemotherapy

background Neoadjuvant (primary) chemotherapy is being used increasingly in the treatment of patients with large and locally advanced breast cancer with the aim of reducing the size of the primary tumor and eliminating micrometastatic disease. Response rates to, compliance with, and survival of patients following neoadjuvant chemotherapy have been variable. We report the results of a consecutive series of 77 patients with breast cancer who received neoadjuvant chemotherapy. methods Seventy-seven patients with locally advanced breast cancers were treated with multimodality therapy comprising up to six cycles of chemotherapy (cyclophosphamide, vincristine, doxorubicin, and prednisolone), radiotherapy, and then surgery. The median follow-up was 54 months. Clinical response rates to therapy and overall survival have been documented. In addition, prognostic factors for survival were identified using the Cox proportional hazards model. results The overall objective response rate of the primary tumor to chemotherapy alone was 87% (25% complete and 62% partial responses, UICC criteria). Following radiotherapy the response rate was 90% (52% complete and 38% partial responses). The overall 5-year survival for all patients was 0.48. However, the probability of survival at 5 years was 0.74 in those with a complete response, and 0.36 if there was a partial clinical response, but no patients who had either stasis of disease or progression survived for 5 years. Independent predictors of better survival that were identified were a complete histopathological response after chemotherapy and radiotherapy, a complete clinical response to chemotherapy, and five or six cycles of chemotherapy versus four or less. conclusions Neoadjuvant chemotherapy in patients with large and locally advanced breast cancers can result in satisfactory local control and overall survival rates, especially in patients with a complete clinical or histopathological response after treatment.

Nutritional and prognostic significance of serum hypothyroxinemia in hospitalized patients with liver cirrhosis

Background/Aims: A variety of severe illnesses can induce changes in thyroid hormone metabolism, leading to findings referred to as “sick euthyroid syndrome”. In several groups of patients the reduction of serum thyroxine concentration (T 4), characteristic of the low-T 4 variant of sick euthyroid syndrome, has been found to be a good predictor of survival. Although the pathophysiology of hormonal alterations has not yet been defined, nutritional deficits have been suggested to play a role. The study aimed to define the prognostic and nutritional significance of serum thyroxine in liver cirrhosis. Methods: Thyroid hormones and nutritional status were evaluated in a group of 75 consecutive hospitalized patients with cirrhosis, followed-up clinically for 12 months. Results: A low-T 4 variant of sick euthyroid syndrome was found in 23 of the 75 enrolled patients with cirrhosis (30.6%). Serum T 4, but not serum T 3, correlated with mid-arm muscle circumference ( p<0.01), an indicator of muscle protein compartment. While both serum T 3 and T 4 correlated directly with serum proteins and inversely with Child-Pugh score, only T 4 was predictive of outcome. Patients with the low-T 4 variant of sick euthyroid syndrome showed significantly lower short- and long-term survival rates compared to those with normal serum T 4 concentrations ( p<0.008 at 3 months, p<0.001 at 6 months and 1 year). A multivariate analysis using the proportional hazards Cox's regression procedure showed that serum T 4, but not serum T 3 or nutritional parameters, improves the prognostic capacity of Child-Pugh score ( p<0.01). Conclusions: These data indicate that the low T 4-variant of sick euthyroid syndrome distinguishes a subgroup of patients with cirrhosis at risk for decreased survival. The inclusion of T 4 in the Child-Pugh score, by improving its prognostic power, may otpimize the selection of patients with advanced cirrhosis to receive specific therapy such as transplantation.

The value of the Health Assessment Questionnaire and special patient-generated scales to demonstrate change in systemic sclerosis patients over time.

To determine the validity and usefulness of a modified Health Assessment Questionnaire (HAQ) for measurement of disease status and changes in disease status over time in patients with systemic sclerosis (SSc). Since 1985, 1,250 patients attending the University of Pittsburgh Scleroderma Clinic have completed a modified HAQ annually. In addition to the standard HAQ questions about disability, the questionnaire includes visual analog scales (VAS) to evaluate SSc organ system symptoms, Raynaud's phenomenon, gastrointestinal (GI) tract and lung involvement, pain, and overall disease severity. In this study, the disability index (DI) (from the HAQ) and the VAS scores (on a 0-3 scale) were compared with various clinical and laboratory features recorded within 3 months of administration of the HAQ and VAS, using t-tests and Spearman's correlation tests. The HAQ DI correlated directly with skin involvement, scleroderma heart or kidney disease, tendon friction rubs, hand contractures, and proximal muscle strength. Over time, the DI correlated with changes in skin score and was a good predictor of survival. There was a significant improvement in the DI during a 2-year time period in patients treated with D-penicillamine. The VAS for digital ulcers, GI symptoms, and lung symptoms correlated very closely with subjective and objective findings for these organ systems. The presence of new digital ulcers or improvement in digital ulcers showed significant associations with the Vascular scale, new GI symptoms or improvement in GI symptoms and institution of H2-blockers showed appropriate strong correlations with the GI scale, and changes in the forced vital capacity had an excellent correlation with the Lung scale (r = 0.58, P < 0.001). By Cox regression analysis, the HAQ DI was one of the best predictors of survival. These data provide convincing evidence that a self-administered questionnaire is an accurate and inexpensive tool to measure disease status changes in SSc. Prospective studies with the HAQ administered at regular intervals, as in controlled trials, should be performed to further assess the benefits and limitations of this instrument.

Hope: critical therapy

According to a recent Time magazine article, a 1995 study at Dartmouth-Hitchcock Medical Center found that one of the best predictors of survival among 232 heart-surgery patients was the degree to which the patients said they drew comfort and strength from religious faith. Those who did not had more than three times the death rate of those who did (June 24, 1996, pp. 59-68) Likewise, according to the article, numerous studies have found lower rates of depression among the religiously committed.The article goes on to state that patients with chronic health problems are failing to find relief in a doctor's office, and the increasing use of high-tech scans and tests of modern medicine leave patients feeling uncared for and alienated.Dr. Herbert Benson, President of the Mind/Body Medical Institute at Boston's Deaconess Hospital and Harvard Medical School, in his book, Timeless Healing, demonstrated the role of meditation and spirituality in patients battling chronic illnesses. A 5-year study found that those who claimed to feel the intimate presence of a higher power had better health and more rapid recoveries.As clinicians, we were not trained to recognize or teach our patients how to act on the role of faith and hope in healing. However, as researchers, we cannot dismiss the possibility that there is a definite relationship.The following commentary is offered to you as food for thought. Today, as we continue to seek ways to reduce health care costs while still providing effective methods of treating illness, we must not rule out factors such as faith and hope in meeting our ultimate goal of healing the sick.

Nutritional and prognostic significance of insulin-like growth factor 1 in patients with liver cirrhosis

Most of the traditional parameters for nutrition assessment have important limitations in patients with chronic liver disease. Insulin-like growth factor 1 (IGF-1) has been found to be regulated by nutrition and proposed as a nutritional marker. Its nutritional significance in patients with liver cirrhosis, however, has not been investigated. Serum IGF-1 as well as traditional anthropometric, visceral, and immunologic parameters were evaluated in 64 hospitalized cirrhotics, followed up clinically for 2 y. IGF-1 z-score averaged −2.16 ± 1.08 and inversely correlated with Child-Pugh score ( P < 0.01), the most reliable composite score reflecting the severity of liver disease. IGF-1 z-score was not different in patients with or without signs of energy malnutrition, as defined by values of midarm muscle circumference (MAMC) and/or triceps skinfold (TSF) <5th percentile. Moreover, IGF-1 z-score did not correlate with MAMC or TSF. Despite its correlation with all visceral proteins, the reduction of IGF-1 was much greater and more frequent than that of visceral proteins. Patients with IGF-1 z-score < median values (−2.5) showed lower long-term survival rates compared with patients with IGF-1 z-score > −2.5 ( P < 0.01). These data indicate that serum IGF-1 is not related to energy malnutrition in cirrhotic patients, while it appears to be a good predictor of survival and an early marker of liver dysfunction. Multiple factors, most of which are related to the severity of the liver disease, may contribute to the reduction of IGF-1. This multifactorial pathogenesis probably accounts for its prognostic significance.