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Results for “Pathologic response”

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At least 649 records · Page 36Linked to original sources

PubMed1986

Intra-arterial chemotherapy as an adjuvant to surgery in transitional cell carcinoma of the bladder.

Regional chemotherapy with intra-arterial cis-platinum and doxorubicin as an adjuvant to total cystectomy and urinary diversion has been evaluated in a phase I to II study. In the first 17 patients chemotherapy consisted of 40 to 75 mg. per m. cis-platinum intra-arterially during 30 minutes, 30 to 40 mg. per m. doxorubicin intra-arterially during 60 minutes (11 patients) or 12 hours (6 patients) and 400 to 500 mg. per m. cyclophosphamide intravenously. The remaining 8 patients received 70 to 100 mg. per m. cis-platinum intra-arterially during 30 minutes. Intra-arterial chemotherapy was administered through a percutaneous catheter placed in the hypogastric artery before each course. Courses were repeated at 4-week intervals. A total of 25 patients received 58 courses (median 2 per patient). Clinical stages of disease in the patients entering the protocol were T3aNxMo (8), T3bNx-2Mo (12) and T4a-bNxMx-1 (5). Clinical response was assessed in 24 of 25 patients: 6 achieved a complete clinical response, 12 had a partial response and 7 had no response. Of 25 patients 16 underwent total cystectomy and urinary diversion with pathological staging as follows: ToNoMo in 3, T1NoMo in 1, T3aNoMo in 5, T3bNo-2Mo in 6 and T4NoMo in 1. Intra-arterial chemotherapy can produce a complete pathological response in patients with locally advanced bladder cancer and is tolerated well by most patients.

Aged↗

PubMed2002

Surgical results of maximal local-regional treatment (cisplatin-enhanced high-dose radiotherapy and adjuvant surgery) in initially non-resectable stage III lung cancer.

We report the surgical short- and long-term results in 42 patients treated in a phase II trial with 50-60 Gy cisplatin-enhanced radiotherapy (RT) and adjuvant resection, for initially non-resectable stage III non-small cell lung cancer. Six of the 42 patients had a complete response, 31 a partial response and five stable disease at the presurgical clinical restaging. A complete pathologic response was observed in 19 cases (R0a surgery); 15 complete resections were performed due to persistent disease (R0b). There were eight non-radical operations (R+). Operative deaths were seen after right pneumonectomy (five cases) and in case of a non-radical operation after no response following the chemo-radiotherapy schedule (two cases). Surgery should be contraindicated in these cases. Overall eight-year-survival was 26% (37% in R0a and 27% in R0b patients). No patient with R+ surgery survived at the eighth year. A local progression as initial failure occurred in four of the 34 R0 patients, and in five of the eighth with a R+ procedure. Resection seems to improve local control, but its role needs further definition. However, advanced stage III patients treated only with a local therapy were not precluded from a long-term survival.

Aged↗

PubMed1984

Dependency of blood flow velocity in the middle cerebral artery on end-tidal carbon dioxide partial pressure--a transcranial ultrasound Doppler study.

The end-tidal carbon dioxide partial pressure (PCO2) response curves for the flow velocity in the middle cerebral artery were studied in 31 normal subjects with transcranial Doppler techniques. An exponential curve with an exponent of 0.034 mm Hg-1 was found to be a good fit to the recorded data. By means of this relationship, recordings of flow velocity in cerebral arteries can be normalized to a standard value of PCO2. Physiological aspects of cerebrovascular reactivity to PCO2 and the clinical implications of the PCO2 response curve are discussed. The normal material provides a reference for assessing pathological responses.

Adolescent↗

PubMed2002

Positron emission tomography for assessment of the response to induction radiochemotherapy in locally advanced oesophageal cancer.

AIMS: This prospective study was designed to determine the utility of 18F-labelled deoxyglucose (FDG) in positron emission tomography (PET) (FDG-PET) for assessing the response to neoadjuvant chemoradiation therapy (CRT) in locally advanced oesophageal tumours. PATIENTS AND METHODS: Thirty-six patients with locally advanced oesophageal cancer (clinical T4 stage) without organ metastases, underwent FDG-PET before and 1 month after CRT. Patients were classified as major responders by serial FDG-PET when the post-CRT PET demonstrated a strong reduction of FDG uptake at the primary tumour site (>80% reduction of tumour-to-liver uptake ratio) without any abnormal FDG uptake elsewhere in the body. PET response was compared with histology obtained during post-induction transthoracic oesophagectomy. RESULTS: A strong correlation was found between the extent of lymph node (LN) involvement as shown by the pre-CRT PET and the major response rate (P = 0.001): such response occurred in nine of 11 N0M0 patients (82%), in three of nine N(1-2)M0 patients (33%) and in two of 16 patients (13%) with distant lymphatic spread. Such a correlation was not found for computed tomography or endoscopic ultrasonography. The sensitivity of serial FDG-PET for a major CRT response was 10 of 14 (71%), its specificity 18 of 22 (82%). The concordance between the response assessment by PET and histopathology was 78%. The median survival time after CRT of PET major responders compared with PET non-major responders was 16.3 months and 6.4 months, respectively. The metabolic response as measured by serial FDG-PET is a stronger prognostic factor for overall survival (P = 0.002) than the extent of LN involvement seen on the pretreatment FDG-PET (P = 0.087). CONCLUSIONS: These data indicate that CRT response as assessed by serial FDG-PET is strongly correlated with pathological response and survival.

Adenocarcinoma↗

PubMed2003

Neoadjuvant chemotherapy for cervical cancer.

None of the current surgical or radiation treatment strategies for cervical cancer satisfactorily leads to a high disease-free survival and a low risk for treatment-related complications in patients with bulky or locally-advanced disease. Neoadjuvant chemotherapy (NACT) prior to surgery or radiation therapy has been studied as a means to reduce tumour bulk and thereby rendering subsequent therapy more effective. Impressive clinical response rates to cisplatin-based NACT have been achieved with acceptable toxicity and survival. Of the patients treated, approximately 20% will achieve a complete clinical response and many of these patients will prove to have a complete pathological response. Although there are too few randomised controlled studies to determine the effectiveness of NACT approaches, relative to standard treatments.

Antineoplastic Agents↗

PubMed1990

[Clinical and electrophysiological investigations of hearing in neonates. I. Behavioral audiometry and auditory brainstem response in evaluation of the auditory apparatus in pre- and full-term neonates].

Auditory Brain stem Responses (ABRs) and behavioural thresholds were studied in 130 neonates born between 25 to 42 weeks of gestational age. ABR thresholds were determined by the weakest stimulus that elicited a recognizable and replicable wave V. Behavioural audiometric thresholds for 1 and 2 kHz pure tones were determined by taking the lowest of threshold for eliciting auro-palpebral reflex. In 130 tested neonates ABR responses were normal in 102 (78.5%) while 28 babies (21.5%) elicited a pathological response. In the normal ABR group mean thresholds values ranged between 24.7-35 dBHL, and it was observed that the thresholds diminished with neonatal maturation. Behavioural audiometry disclosed that 77.5% normal full-term neonates responded to pure tone 1000 Hz, with mean threshold of 92.83 dBHL, while only 59.09% of pre-term neonates responded to pure tone stimuli at 101 dBHL.

Audiometry↗

PubMed1983

Genetic control of eosinophilia. Mouse strain variation in response to antigens of parasite origin.

Strain variation in capacity to develop peripheral blood eosinophilia was observed in inbred NIH and C57BL/10 (B10) mice exposed to parasite antigens by infection or by parenteral injection in Freund's complete adjuvant. NIH mice were good responders, showing rapid development of high eosinophil counts, B10 mice were low responders. The difference in response phenotype was independent of the parasite used for infection (Trichinella spiralis or Nematospiroides dubius) and of the antigen used for injection (T. spiralis larval antigen or Limulus haemocyanin). Pre-treatment of T. spiralis infected mice with low doses of cyclophosphamide (150 mg/kg) or restriction of the duration of infection to 7 days by anthelmintic treatment did not enhance the response of B10 mice. Thus no evidence was found that the poor response phenotype of B10 during T. spiralis infection reflected any active suppressive mechanisms developed during the adult or muscle larval phases of infection. Demonstration that eosinophilia is induced primarily by the intestinal phase allows comparison with other parameters of the immune response induced by the adult worms, namely intestinal mastocytosis and worm expulsion. From this comparison it is concluded that the low eosinophil response phenotype of B10 mice may reflect a generalized deficiency in the response of bone marrow derived precursor cells to factors of T lymphocyte origin. The significance of genetically determined variation in eosinophil responsiveness is discussed in relation to the development of protective immune or pathological responses to parasite infection.

Animals↗

PubMed2004

[Neoadjuvant chemotherapy for primary breast cancer].

OBJECTIVE: To evaluate the feasibility and effect of fluorouracil (5-Fu) in association with anthracycline-based regimen as neoadjuvant chemotherapy for primary breast cancer. METHODS: For one hundred and eleven primary breast cancer patients with 114 lesions who were to be operated, two to six cycles of 5-Fu (continuous infusion) in association with epirubicin or pirarubicin and cyclophosphamide (CEFci or CTFci regimen) were given before operation. The response rate, side effect and its relation with tumor characteristics were studied. RESULTS: The overall response rate was 87.7%, of which the complete clinical response was 39.5%, pathological complete response was 23.7%, only one patient (0.9%) showed progressive disease. The regimen containing pirarubicin was superior to epirubicin regimen in pathological complete response rate (P < 0.05). Alopecia was mild in pirarubicin regimen as compared with epirubicin regimen but neutropenia was more severe in pirarubicin regimen than that in epirubicin regimen. Hormonal receptor expressions were significantly related to treatment response, the pathological complete response rate was 33.3% in oestrogen or progestin receptor negative tumors, but it was 7.5% in the positive tumors (P < 0.005). No correlation was observed between treatment response and tumor size, as well as HER-2 expression. CONCLUSION: CTFci/CEFci regimen as neoadjuvant chemotherapy is effective and safe for primary breast cancer. CTFci regimen is superior to CEFci regimen in response rate. The patients with negative hormonal receptor are more sensitive to the neoadjuvant chemotherapy.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed2004

Are anti-interferon antibodies the cause of failure in: chronic HCV hepatitis treatment?

A follow-up study was made of 94 chronic hepatitis C patients at a hepatitis clinic in Brazil, after interferon alpha (IFN-alpha) therapy, to determine the influence of anti-interferon antibodies on treatment outcome. Patients diagnosed as having chronic hepatitis C, confirmed by PCR (HCV RNA) and liver biopsy, were treated with interferon alpha 2a or 2b for at least six months, and were followed up for 24 weeks after termination of treatment in order to assess biochemical, virological and clinical pathology responses. Only 6% of the 94 patients developed anti-IFN antibodies, 70% presented a biochemical response and 23% maintained a sustained virological response. Clinical evaluation revealed that in only 2 patients was there progression of fibrosis; the necro-inflammatory score indicated that 72% maintained the same activity, 12% had worsening necro-inflammatory activity, and the remaining 16% had decreased activity. There was no significant correlation of demographic and laboratory variables with levels of anti-interferon antibodies. Similarly, biochemical and virological responses were not influenced by anti-interferon antibodies. Multivariate analysis by logistic regression revealed that clinical pathological parameters, staging and necro-inflammatory activity did not influence the response to the virus.

Adolescent↗

PubMed2003

Early changes in pancreatic acinar cell calcium signaling after pancreatic duct obstruction.

Intracellular Ca(2+)-changes not only participate in important signaling pathways but have also been implicated in a number of disease states including acute pancreatitis. To investigate the underlying mechanisms in an experimental model mimicking human gallstone-induced pancreatitis, we ligated the pancreatic duct of Sprague-Dawley rats and NMRI mice for up to 6 h and studied intrapancreatic changes including the dynamics of [Ca(2+)](i) in isolated acini. In contrast to bile duct ligation, pancreatic duct obstruction induced intra-pancreatic trypsinogen activation, leukocytosis, hyperamylasemia, and pancreatic edema and increased lung myeloperoxidase activity. Although resting [Ca(2+)](i) in isolated acini rose by 45% to 205 +/- 7 nmol, the acetylcholine- and cholecystokinin (CCK)-stimulated calcium peaks as well as the amylase secretion declined, but neither the [Ca(2+)](i)-signaling pattern nor the amylase output in response to the Ca(2+)-ATPase inhibitor thapsigargin nor the secretin-stimulated amylase release were impaired by pancreatic duct ligation. On the single cell level pancreatic duct ligation reduced the percentage of cells in which submaximal secretagogue stimulation was followed by a physiological response (i.e. Ca(2+) oscillations) and increased the percentage of cells with a pathological response (i.e. peak plateau or absent Ca(2+) signal). Moreover, it reduced the frequency and amplitude of Ca(2+) oscillation as well as the capacitative Ca(2+) influx in response to secretagogue stimulation. Serum pancreatic enzyme elevation as well as trypsinogen activation was significantly reduced by pretreatment of animals with the calcium chelator BAPTA-AM. These experiments suggest that pancreatic duct obstruction rapidly changes the physiological response of the exocrine pancreas to a Ca(2+)-signaling pattern that has been associated with premature digestive enzyme activation and the onset of pancreatitis, both of which can be prevented by administration of an intracellular calcium chelator.

Adenosine Triphosphatases↗

PubMed1990

Arthritis induced by interleukin-1 is dependent on the site and frequency of intraarticular injection.

Intraarticular injection of recombinant human interleukin-1 (IL-1) in rats resulted in varying degrees of inflammatory changes depending on the site and frequency of injections. (i) Much lower amounts of IL-1 were required to elicit an inflammatory response in the ankle joints (15-3000 ng) than the knee joints (90-150 micrograms). (ii) The inflammatory response was much greater if IL-1 was administered in multiple doses as compared to a single dose injection. One day after a single injection of IL-1 (90-150 micrograms), knee joints exhibited a mild increase in volume as a consequence of edema, but at the end of 1 week, no discernible change in volume was observed. However, when the same total amount of IL-1 was injected in three doses, there was a dramatic increase in joint volume at the end of 1 week that persisted for at least 3 weeks. The increase was dose dependent. (iii) The inflammatory response was dependent on the age/weight of the rats: the older the animals the greater the response. (iv) Under conditions where IL-1 induced inflammatory changes in knee joints, recombinant tumor necrosis factor failed to induce any significant response. (v) Histological examination of the knee joints revealed distinct differences in the pathological response to the two different protocols of IL-1 administration in the knee joints. The animals injected with a single dose of IL-1 showed a mild and transient inflammation that was resolved by 2 weeks postinjection, but exhibited degenerative changes associated with focal loss of chondrocytes and proteoglycan of the knee joint cartilage, which became progressively severe. The knee joints of animals given three injections of IL-1 showed evidence of marked acute synovitis, fibroplasia, loss of proteoglycan and chondrocytes, resorption of subchondral bone, and transition of hematopoeitic marrow cells into cells of mesenchymal morphology. (vi) Examination of proteoglycan synthesis by cartilage of IL-1-injected rats revealed that within 1 day after injection, a dramatic reduction in synthesis occurred which persisted for at least 2 weeks. These studies suggest that intraarticular injection of IL-1 provides a useful rodent model for the investigation of pathological changes occurring within a localized joint as a result of acute and chronic inflammatory stimuli. Relevant aspects of the pathology of joint erosion can be demonstrated depending on the frequency of IL-1 injection.

Aging↗

PubMed1995

[Clinical efficacy of neoadjuvant M-VAC chemotherapy for invasive bladder cancer].

We clinically evaluated the efficacy of neoadjuvant M-VAC (methotrexate, vinblastine, doxorubicin and cisplatin) therapy followed by radical cystectomy. A total of 21 patients with locally invasive bladder cancer received neoadjuvant M-VAC therapy with an average of 2.4 courses (range 2-4). Of the 21 patients, 4 had stage T2N0M0, 11 had stage T3aN0M0, 5 had stage T3bN0M0 and 1 had stage T4N0M0 at diagnosis. Of the 21 patients, 3 had clinically complete responses (cCR) and 12 had partial responses (cPR), for an overall response rate of 71.4%. The patients who responded to the chemotherapy (cCR + cPR) had a 2-year disease free rate of 80.0% in contrast to 50.0% for the remaining patients who did not respond. A pathological response (pT0, pT1) was achieved in 6 (28.6%) of the 21 patients. The 5 patients in this group remain free of disease for 15 to 79 months (mean 58.8 months). These preliminary results suggest that the patients who achieve either a complete or partial response, in particular those had pathological stage of pT0 or pT1, may have a favorable clinical course.

Adult↗

PubMed2005

Light and electron microscopic assessment of progressive atrophy following moderate traumatic brain injury in the rat.

The presence of progressive white matter atrophy following traumatic brain injury (TBI) has been reported in humans as well as in animal models. However, a quantitative analysis of progressive alterations in myelinated axons and other cellular responses to trauma has not been conducted. This study examined quantitative differences in myelinated axons from several white and gray matter structures between non-traumatized and traumatized areas at several time points up to 1 year. We hypothesize that axonal numbers decrease over time within the structures analyzed, based on our previous work demonstrating shrinkage of tissue in these vulnerable areas. Intubated, anesthetized male Sprague-Dawley rats were subjected to moderate (1.8-2.2 atm) parasagittal fluid-percussion brain injury, and perfused at various intervals after surgery. Sections from the fimbria, external capsule, thalamus and cerebral cortex from the ipsilateral hemisphere of traumatized and sham-operated animals were prepared and. estimated total numbers of myelinated axons were determined by systematic random sampling. Electron micrographs were obtained for ultrastructural analysis. A significant (P<0.05) reduction in the number of myelinated axons in the traumatized hemisphere compared to control in all structures was observed. In addition, thalamic and cortical axonal counts decreased significantly (P<0.05) over time. Swollen axons and macrophage/microglia infiltration were present as late as 6 months post-TBI in various structures. This study is the first to describe quantitatively chronic axonal changes in vulnerable brains regions after injury. Based on these data, a time-dependent decrease in the number of myelinated axons is seen to occur in vulnerable gray matter regions including the cerebral cortex and thalamus along with distinct morphological changes within white matter tracts after TBI. Although this progressive axonal response to TBI may include Wallerian degeneration, other potential mechanisms underlying this progressive pathological response within the white matter are discussed.

Animals↗

PubMed2004

Grammaticality sensitivity in children with early focal brain injury and children with specific language impairment.

Grammaticality judgments and processing times associated with violation detection were examined in typically developing children, children with focal brain lesions (FL) acquired early in life, and children with specific language impairment (SLI). Grammatical sensitivity in the FL group, while below typically developing children, was above levels seen in children with SLI. Age effects were noted with developmental changes in sensitivity extending into adolescence. Developmental delays in grammatical processing were particularly pronounced for children with SLI, who showed sensitivity levels below those of younger typically developing children. Sensitivity to agreement violations was also protracted in the SLI group providing further evidence of the vulnerability of morphology, a pattern not unlike that seen in adult aphasics. Findings for the FL group provide compelling evidence of neural and behavioral plasticity in children with early unilateral brain injury. Moreover, results from these children underscore how very different compensatory organization may be compared to profiles seen in adult aphasics who have comparable lesions. In contrast, although it was expected that the SLI children would perform below the typically developing children, the disadvantage seen with respect to the FL group suggests that the underlying pathology responsible for SLI may be more pervasive and less plastic than the focal pathology of children with early brain damage.

Age Factors↗

PubMed2005

Neoadjuvant chemotherapy for oesophageal cancer: the need for accurate response prediction and evaluation.

Primary surgical resection for locally advanced oesophageal cancer is associated with systemic failure and poor survival due to presence of micrometastatic disease at the time of diagnosis. Neoadjuvant chemotherapy prior to surgical resection aims to downstage these locally advanced tumours. A review of reported randomised controlled trials has shown only one sufficiently powered trial with a survival advantage for cisplatin-based chemotherapy. Published meta-analyses of neoadjuvant chemotherapy trials have shown little or no overall survival benefit. A subgroup of patients with biologically favourable tumours who respond to this treatment have been consistently shown to have a survival advantage. These patients need to be differentiated from non-responders preferably at an early stage of this potentially toxic treatment. Current clinical, endoscopic and radiological methods of response evaluation are all unreliable. Response evaluation with 18FDG-PET has been shown to accurately assess the pathological response and also to predict the risk of local recurrence and overall survival. The development of integrated PET/CT imaging may enhance the accuracy of this response evaluation. In the future, molecular markers of response prediction prior to initiation of treatment may allow the development of individualised treatment strategies. New emerging chemotherapeutic agents may prove to be more effective in eradicating micrometastatic disease.

Antineoplastic Agents↗

PubMed1999

Pre-operative chemotherapy in early stage resectable non-small-cell lung cancer: a randomized feasibility study justifying a multicentre phase III trial.

Surgical resection offers the best chance for cure for early stage non-small-cell lung cancer (NSCLC, stage I, II, IIIA), but the 5-year survival rates are only moderate, with systemic relapse being the major cause of death. Pre-operative (neo-adjuvant) chemotherapy has shown promise in small trials restricted to stage IIIA patients. We believe similar trials are now appropriate in all stages of operable lung cancer. A feasibility study was performed in 22 patients with early stage (IB, II, IIIA) resectable NSCLC; randomized to either three cycles of chemotherapy [mitomycin-C 8 mg m(-2), vinblastine 6 mg m(-2) and cisplatin 50 mg m(-2) (MVP)] followed by surgery (n = 11), or to surgery alone. Of 40 eligible patients, 22 agreed to participate (feasibility 55%) and all complied with the full treatment schedule. All symptomatic patients achieved either complete (50%) or partial (50%) relief of tumour-related symptoms with pre-operative chemotherapy. Fifty-five per cent achieved objective tumour response, and a further 27% minor tumour shrinkage; none had progressive disease. Partial pathological response was seen in 50%. No severe (WHO grade III-IV) toxicities occurred. No significant deterioration in quality of life was detected during chemotherapy. Pre-operative MVP chemotherapy is feasible in early stage NSCLC, and this study has now been initiated as a UK-wide Medical Research Council phase III trial.

Adult↗

PubMed2003

Animal and in vitro models of alcoholic pancreatitis: role of cholecystokinin.

Although ethanol abuse is the major etiologic factor in the development of acute and chronic pancreatitis, the mechanisms of ethanol effects to cause pancreatitis are poorly understood. The major reason for the lack of progress is the relative lack of animal models that reproduce the deleterious effects of ethanol on the pancreas that are observed in human disease. We propose that the effect of ethanol on the pancreas is due to its ability to sensitize animals and humans to the potentially injurious effects of other stimuli. We have developed models of ethanol-induced acute and chronic pancreatitis in rats as well as pancreatic acinar cells in primary culture demonstrating that ethanol sensitizes the pancreas to the inflammatory, cell death, and fibrosing responses caused by cholecystokinin (CCK). Our results indicate that the ethanol-sensitized inflammatory response is the key or trigger event for the development of the other pathologic responses in both acute and chronic pancreatitis, such as cell death, intracellular digestive enzyme activation, and fibrosis. These findings suggest that experimental strategies designed to reveal the modulating effects of ethanol on the mechanisms underlying the inflammatory, cell death, and fibrosing responses stimulated by CCK will provide the key information needed to understand how ethanol abuse causes pancreatitis.

Animals↗

PubMed2004

Systemic treatment of oesophageal cancer.

Most patients with oesophageal cancer present with locally advanced or metastatic disease. In an effort to improve the results of surgery in patients with operable disease, strategies to incorporate radiotherapy and chemotherapy, preoperatively (neoadjuvant) and postoperatively (adjuvant), have been extensively investigated in numerous clinical trials. Meta-analyses of neoadjuvant trials did not demonstrate a survival advantage for neoadjuvant chemotherapy or concurrent chemoradiotherapy. Although local control seems to be improved with neoadjuvant treatment, the currently used chemotherapeutic agents are simply not effective enough to eradicate micro-metastatic disease. Patients who undergo neoadjuvant treatment and achieve a histologically confirmed complete response have a significant better survival than those who do not achieve such a response. Although neoadjuvant chemoradiotherapy is able to induce a higher rate of complete pathological responses compared to neoadjuvant chemotherapy (25-30% vs 5-15%), this advantage is counteracted by a higher incidence of operative mortality. In patients with metastatic disease there is no evidence that chemotherapy (cisplatin, 5-fluorouracil and anthracyclins) improves survival. Several new agents such as taxanes, irinotecan and vinorelbine in combination with cisplatin and carboplatin have shown promising activity in neoadjuvant settings and as palliative treatment of metastatic oesophageal cancer. However, the benefit of these new drugs in the treatment of oesophageal cancer has to be confirmed in randomized trials.

Antineoplastic Agents↗