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Biomedical subjects

O Eremin

Publications and source records attributed to O Eremin.

At least 37 records · Page 2Linked to original sources

Positron emission tomography using [(18)F]-fluorodeoxy-D-glucose to predict the pathologic response of breast cancer to primary chemotherapy.

PURPOSE: To determine whether [(18)F]-fluorodeoxy-D-glucose ([(18)F]-FDG) positron emission tomography (PET) can predict the pathologic response of primary and metastatic breast cancer to chemotherapy. PATIENTS AND METHODS: Thirty patients with noninflammatory, large (> 3 cm), or locally advanced breast cancers received eight doses of primary chemotherapy. Dynamic PET imaging was performed immediately before the first, second, and fifth doses and after the last dose of treatment. Primary tumors and involved axillary lymph nodes were identified, and the [(18)F]-FDG uptake values were calculated (expressed as semiquantitative dose uptake ratio [DUR] and influx constant [K]). Pathologic response was determined after chemotherapy by evaluation of surgical resection specimens. RESULTS: Thirty-one primary breast lesions were identified. The mean pretreatment DUR values of the eight lesions that achieved a complete microscopic pathologic response were significantly (P =.037) higher than those from less responsive lesions. The mean reduction in DUR after the first pulse of chemotherapy was significantly greater in lesions that achieved a partial (P =.013), complete macroscopic (P =.003), or complete microscopic (P =.001) pathologic response. PET after a single pulse of chemotherapy was able to predict complete pathologic response with a sensitivity of 90% and a specificity of 74%. Eleven patients had pathologic evidence of lymph node metastases. Mean pretreatment DUR values in the metastatic lesions that responded did not differ significantly from those that failed to respond (P =.076). However, mean pretreatment K values were significantly higher in ultimately responsive cancers (P =.037). The mean change in DUR and K after the first pulse of chemotherapy was significantly greater in responding lesions (DUR, P =.038; K, P =.012). CONCLUSION: [(18)F]-FDG PET imaging of primary and metastatic breast cancer after a single pulse of chemotherapy may be of value in the prediction of pathologic treatment response.

Adult↗

Tumour-associated macrophages (TAMS): disordered function, immune suppression and progressive tumour growth.

Evidence currently available suggests that in established, progressively growing solid tumours, tumour associated macrophages (TAMs) are reprogrammed to induce immune suppression of host defenses in situ, through release of specific cytokines, prostanoids and other humoral mediators. This disordered response, results in the inhibition of effective anti-cancer cell-mediated immune mechanisms. Concurrently, TAMs produce tumour growth promoting factors. The summation of this complex interplay of biological factors results in progressive tumour growth and tumour cell dissemination. A better understanding of these complex inter-relationships should form the basis of novel strategies designed to eradicate tumour cells in man and animals. These various biological aspects and processes are discussed in detail and critically evaluated in this review article.

Apoptosis↗

Apoptosis and prognosis in cancer: rationale and relevance.

Apoptosis is the biological process by which cells in tissues undergo programmed death. This process is morphologically identifiable and characterised by light and electron microscopy. However, the biological mechanisms underlying this process, as yet, are poorly understood and in need of elucidation. As apoptotic tumour cells can be identified and counted by light microscopy, there has been interest in the application of the enumeration of apoptosis in malignant growths as a putative prognostic marker. This review outlines the rationale for and discusses the relevance of using such an approach in clinical practice.

Animals↗

Minimal modulation of lymphocyte and natural killer cell subsets following minimal access surgery.

BACKGROUND: Trauma, whether accidental or surgically induced, is known to cause significant modulation of the cell-mediated immune response. Minimal access surgery (MAS) has been shown to improve postoperative recovery and enhance rehabilitation. The degree of immunosuppression resulting from two MAS techniques was studied and compared by measuring the circulating T lymphocyte and natural killer (NK) cell subsets. METHOD: This investigation was a randomized prospective study of patients admitted to the Professorial Surgical Unit, Aberdeen Royal Infirmary for elective cholecystectomy. Two methods of MAS were studied-laparoscopy and minilaparotomy. RESULTS: Laparoscopy was found to cause significantly less reduction in the number of cells expressing T lymphocyte phenotypic surface markers (CD2, CD3, CD8, CD4:CD8 ratio), activation markers (CD71 and HLA-DR), and NK cell subsets (CD11b, CD16, CD56 and CD57), when compared with the minilaparotomy technique. CONCLUSIONS: These data show that host defences are less suppressed after laparoscopic cholecystectomy, and this may have important implications for the use of laparoscopic techniques in major surgical resections, especially for malignant disease.

Adult↗

Minimal access surgery for cholelithiasis induces an attenuated acute phase response.

BACKGROUND: Some benefits of laparoscopic (LC) and minilaparotomy (MC) cholecystectomy may reflect attenuation of the acute phase response. The authors examined components of this response. METHODS: Patients were randomized to LC (n = 11) or MC (n = 11). C-reactive protein (CRP), alpha-1-antitrypsin (AAT), retinol-binding protein (RBP), transferrin, and albumin were measured preoperatively and on postoperative days 1, 2, 4, and 7. Interleukin-1 receptor antagonist (IL-1ra), IL-6, and tumor necrosis factor (TNF-alpha) were measured more frequently perioperatively. Peak expiratory flow rate, forced expiratory volume in 1 second, and forced vital capacity were measured daily. RESULTS: The IL-6 increase was more persistent and marked in the MC patients from hour 8 to day 7 postoperatively (P < 0.05). Alterations in CRP, AAT, and albumin were similar. Postoperative deficits of respiratory function correlated with the magnitude of acute phase protein alteration. CONCLUSIONS: Minimal access surgery induces an acute phase response that is less prominent after a laparoscopic technique.

Acute-Phase Proteins↗

Psychological factors can predict the response to primary chemotherapy in patients with locally advanced breast cancer.

This study evaluated the possible value of psychological variables in predicting clinical and pathological response to primary chemotherapy. 96 women with newly diagnosed large, or locally advanced, breast cancer (T2 > 4 cm, T3, T4, N2 and M0) participated in a prospective, randomised trial to evaluate the effects of relaxation training with guided imagery and L-arginine on response to primary chemotherapy. Before the first of six cycles of primary chemotherapy, women were assessed using the Hospital Anxiety and Depression Scale (HADS) and the Eysenck Personality Questionnaire (EPQ). The primary outcomes were clinical response (evaluated using standard International Union Against Cancer (UICC) criteria) and pathological response (graded by means of a previously published 5-point scale) following primary chemotherapy. Stepwise linear regressions were used to estimate the predictive value of age, menopausal status, clinical nodal status, tumour size at diagnosis, oestrogen receptor status, dietary supplementation (L-arginine versus placebo), personality (EPQ-L scores), mood (HADS scores) and a psychological intervention. HADS depression score was a significant independent predictor of pathological response to chemotherapy. HADS anxiety score was a significant independent predictor of clinical response. Because the original tumour size before chemotherapy (also a significant predictor of clinical and pathological responses) was taken into account in the analyses, the results cannot be explained in terms of psychobiological factors related to tumour size. This study supports the importance of psychological factors as independent predictors of response to primary chemotherapy in patients with breast cancer. If they can be replicated, these findings have major implications for the management of women with breast cancer. Psychological factors need to be assessed and evaluated in future trials of chemotherapy.

Adult↗

In pursuit of excellence for patients with cancer: the Scottish Cancer Therapy Network model.

The Scottish Cancer Therapy Network (SCTN) was created against a background of rising concerns about perceived variation in the quality of care available to patients with cancer. SCTN has established itself as a major organization with the necessary recognition and infrastructure to provide leadership, support and impetus in the field of clinical guidelines, clinical audit and clinical trials of cancer therapy in Scotland. Since being formed in 1993, SCTN has been instrumental in the development of three evidence-based, clinical guidelines and in the completion of detailed, national, retrospective audits of the treatment of five major tumour sites. The infrastructure has been used successfully to support and encourage trial participation. Challenges for the future are a re-orientation towards prospective audit, widening the constituency and sense of ownership of SCTN as a resource for practising clinicians, and further increasing recruitment into clinical trials.

Clinical Trials as Topic↗

Psychological, clinical and pathological effects of relaxation training and guided imagery during primary chemotherapy.

The diagnosis and treatment of breast cancer are stressful, and stress may be associated with a poorer response to chemotherapy. There is a need, therefore, to develop and evaluate interventions that might enhance quality of life and, possibly, improve treatment response. The effects of relaxation combined with guided imagery (visualizing host defences destroying tumour cells) on quality of life and response to primary chemotherapy, to date, have not been adequately evaluated. Ninety-six women with newly diagnosed large or locally advanced breast cancer (T2 > 4 cm, T3, T4, or TxN2 and M0) took part in a prospective, randomized controlled trial. Patients were randomized following diagnosis to a control condition (standard care) or to the experimental condition (standard care plus relaxation training and imagery). Psychometric tests to evaluate mood and quality of life were carried out before each of the six cycles of chemotherapy and 3 weeks after cycle 6: tests of personality and coping strategy were carried out prior to cycles one and six. Clinical response to chemotherapy was evaluated after six cycles of chemotherapy using standard UICC criteria and pathological response was assessed from the tissue removed at surgery. As hypothesized, patients in the experimental group were more relaxed and easy going during the study (Mood Rating Scale). Quality of life was better in the experimental group (Global Self-assessment and Rotterdam Symptom Checklist). The intervention also reduced emotional suppression (Courtauld Emotional Control Scale). The incidence of clinically significant mood disturbance was very low and the incidence in the two groups was similar. Finally, although the groups did not differ for clinical or pathological response to chemotherapy, imagery ratings were correlated with clinical response. These simple, inexpensive and beneficial interventions should be offered to patients wishing to improve quality of life during primary chemotherapy.

Antineoplastic Combined Chemotherapy Protocols↗

Peri-operative acute phase response and cytokine releasein women with breast cancer: modulation bypolyadenylic-polyuridylic acid.

AIMS: Acute phase reactants (APRs) are believed to play an important biological role in trauma, sepsis and malignant disease. We have investigated the induction of the APR, C-reactive protein (CRP), by the biological response modifier, polyadenylic-polyuridylic acid (PAPU) during the peri-operative period. METHODS: Twenty post-menopausal women with breast cancer undergoing mastectomy were randomized into a double blind, placebo-controlled, parallel group pilot study. PAPU (150 mg) or placebo was given intravenously the day prior to surgery (D -1), the day of surgery (D 0) and post-operatively on days (D 1, 3, 5, 7 and 14). Blood samples were collected on eight different days (D -2, -1, 0, 1, 2, 4, 6 and 18). CRP was significantly elevated in the PAPU group (P<0.05) on days 2 and 4, when compared with patients receiving placebo. The serum levels of cytokines believed to induce hepatic APRs, were also measured. RESULTS: The serum concentration of IL-6 was elevated on days 1, 2, 4 and 6 (P<0.05), TNF- alpha and IL-1 beta levels were increased on days 1 and 2 (P<0.05), respectively, while the serum level of soluble interleukin-2 receptor (sIL-2R) was elevated above the baseline on days 0, 2, 4, 6 and 18 in the PAPU group, when compared with the baseline. CONCLUSIONS: This modulation of acute phase response may have important implications for patients with cancer undergoing surgery.

Adjuvants, Immunologic↗

Enteral nutritional supplementation with key nutrients in patients with critical illness and cancer: a meta-analysis of randomized controlled clinical trials.

OBJECTIVE: To conduct a meta-analysis of 11 randomized controlled trials comparing enteral nutritional support supplemented with key nutrients versus standard enteral nutritional support to determine effects on morbidity and mortality rates and hospital stay. BACKGROUND DATA: Recent studies have shown that malnutrition occurs in up to 30% of patients undergoing gastrointestinal surgery, resulting in an increased risk of postoperative complications and death. With the realization that key nutrients can modulate inflammatory, metabolic, and immune processes, enteral nutritional regimens (supplemented with large amounts of key nutrients) have been developed for clinical use. METHODS: Eleven prospective, randomized controlled trials evaluating 1009 patients treated with combinations of key nutrients (Impact, Immun-Aid) were evaluated. Outcome measures examined were the incidences of pneumonia, infectious complications, and death, and length of hospital stay. Meta-analyses were undertaken to obtain the odds ratio and 95% confidence interval for incidences of infectious complications, pneumonia, and death, and the weighted mean difference and 95% confidence interval for length of hospital stay. RESULTS: The provision of nutritional support supplemented with key nutrients to patients with critical illness resulted in a decrease in infectious complications when compared with patients receiving standard nutritional support and a significant reduction in overall hospital stay. Similar results were documented in patients with gastrointestinal cancer. However, there were no differences between patient groups for either pneumonia or death. CONCLUSIONS: This meta-analysis has demonstrated that nutritional support supplemented with key nutrients results in a significant reduction in the risk of developing infectious complications and reduces the overall hospital stay in patients with critical illness and in patients with gastrointestinal cancer. However, there is no effect on death. These data have important implications for the management of such patients.

Abdominal Abscess↗

The management of cancer in the elderly.

The treatment of elderly patients with cancer requires a multidisciplinary approach if optimal locoregional control of disease and survival are to be achieved. Wherever possible, the surgical, radiotherapeutic and chemotherapeutic regimens given to elderly patients with cancer should be comparable with those currently used for the treatment of younger patients with cancer. However, the morbidity (physical and psychological) of therapy must be evaluated against the likely benefits to ensure that elderly patients with cancer receive both optimal management and quality of life.

Aged↗

The accuracy of "one-stop" diagnosis for 1,110 patients presenting to a symptomatic breast clinic.

UNLABELLED: To minimise delay in diagnosis and reduce patient anxiety, triple assessment with immediate reporting has been used in our symptomatic breast clinic since 1991. This article examines the accuracy of the diagnostic modalities used and the efficacy of the "one-stop" diagnostic policy. The data on 1,110 new patients presenting to the symptomatic breast clinic between January and July 1993, were analysed and subsequent three year follow-up and outcome established. Fine needle aspiration cytology (FNAC) gave the highest predictive value (97.3%) with a sensitivity of 93.5% and a specificity of 98.1%. Ultrasonography provided a 97.0% prediction with a sensitivity of 88.9% and a specificity of 97.4%, whereas mammography had a prediction of 96.4% with sensitivity of 93.2% and a specificity of 96.7%. When the mammogram or ultrasound scan were reported as unequivocally benign (M1), there were no missed cancers. The false positive and false negative rates for FNAC were 0% and 1.4%, respectively. Following assessment, a diagnosis was made in 96% of patients. Sixty-two percent of the patients were discharged at the first clinic visit. Four breast malignancies were subsequently diagnosed in the discharged group; two with new microcalcifications due to ductal carcinoma in situ, one with invasive disease in a different quadrant of the breast from that originally investigated, and in one patient the cancer was missed. CONCLUSION: A "one-stop" symptomatic breast clinic provides an accurate and effective means of establishing a correct diagnosis.

Adolescent↗

Urinary cytokines as markers of reflux nephropathy.

PURPOSE: We established whether the urinary cytokines interleukin-6 (IL-6), tumor necrosis factor (TNF)-alpha and soluble TNF receptor-1 have a role as noninvasive markers of renal damage in children with vesicoureteral reflux. MATERIALS AND METHODS: We performed an observational study in a surgical and urological unit at a pediatric teaching hospital. Urine cytokine levels of IL-6, TNF-alpha and soluble TNF receptor-1 were measured using a standard enzyme-linked immunosorbent assay technique in children stratified into group 1--11 with vesicoureteral reflux and reflux nephropathy, group 2--6 with vesicoureteral reflux only and no associated nephropathy, and group 3--15 age and sex matched controls. RESULTS: Urinary levels of the cytokines IL-6 and soluble TNF receptor-1 were significantly elevated in group 1 versus group 3 (0.048 to 13.25 pg./micromol. creatinine, mean 3.658 versus 0.027 to 0.677, mean 0.247 and 102.89 to 4,502.9 pg./micromol. creatinine, mean 1,395.3 versus 13.06 to 569.6, mean 145.357, respectively). Neither cytokine in group 2 (0.074 to 10.96 pg./micromol. creatinine, mean 2.94 and 51.52 to 1,115.48, mean 413.137, respectively) was elevated compared to that in group 3. TNF-alpha was not elevated in group 1 or 2 compared to that in group 3 (0.104 to 2.518 pg./micromol. creatinine, mean 0.56, 0.094 to 1.278, mean 0.334 and 0.065 to 0.694, mean 0.241, respectively). CONCLUSIONS: Measuring the urinary levels of the cytokines IL-6 and soluble TNF receptor-1 may be useful as a noninvasive marker of reflux associated renal damage. Further studies with larger patient groups are necessary to locate the source of production of the elevated urinary cytokines measured in our study.

Adolescent↗

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.

Adult↗

Self-expanding metal stents in the management of colorectal carcinoma--a preliminary report.

AIMS: The role of diagnostic imaging in colorectal carcinoma is in the initial diagnosis, staging and detection of complications of the disease. Seven cases of colorectal carcinoma are presented where expandable metallic stents were placed for the management of stenosing lesions in patients with advanced metastatic disease or with serious medical complications which prevented immediate surgery. RESULTS: Seven patients (five male, two female) with an age range of 51-76 years had expandable metallic stents placed over a 9-month period. All stents were placed successfully with no immediate complications. The stents remained in situ for a range of 7-210 days. CONCLUSION: Expandable metallic stents can be successfully and safely placed in the colon. These stents may be useful in the management of patients with advanced metastatic disease or in those presenting with large bowel obstruction in which decompression by a stent allows treatment of coexisting medical complications to enable surgery to be carried out at a later date.

Adenocarcinoma↗

Gamma emission imaging in the management of breast disorders.

Breast cancer is the commonest malignancy to affect women. The malignant process may present clinicians with problems in establishing the diagnosis expeditiously, accurately staging the disease and assessing tumour response to primary systemic chemotherapy. Considerable recent interest has focused on the application of imaging techniques that utilize tumour-specific gamma-ray-emitting radiopharmaceuticals to resolve these problems. The wide availability of gamma camera systems makes single photon-imaging techniques, using radiopharmaceuticals incorporating conventional isotopes, attractive options. However, results concerning the detection of the primary breast cancer and the staging of axillary lymph nodes suggest that these techniques would appear to offer no significant advantages, when compared with those obtained using standard diagnostic methods. Dual gamma-ray-emission imaging by positron emission tomography (PET) may offer an alternative solution. Studies performed show that PET can accurately detect primary breast cancers, stage locoregional lymph nodes and visualize distant tumour metastases. Furthermore, PET may be able to monitor early tumour response to chemotherapy agents. It would appear, therefore, that dual gamma emission might have an important role to play in the management of patients with breast cancer.

Bone Neoplasms↗