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Pathological Response (pathological + response)

Distribution by Scientific Domains

Medical Sciences	94%

Kinds of Pathological Response

complete pathological response

Selected Abstracts

Trastuzumab in Primary Inflammatory Breast Cancer (IBC): High Pathological Response Rates and Improved Outcome

THE BREAST JOURNAL, Issue 5 2010
Shaheenah Dawood MRCP (UK)
Abstract:, Inflammatory breast cancer (IBC) represents a rare but aggressive and lethal form of locally advanced breast cancer (LABC) and frequently with HER-2 neu overexpressed or amplified. We retrospectively identified 16 newly diagnosed HER-2/neu-positive IBC patients who were treated with preoperative trastuzumab. We determined the pathological complete response rate (pCR) when trastuzumab was added to preoperative chemotherapy in patients with HER2/neu-positive IBC. Furthermore, we assessed the expression of CXCR4 in metastatic recurrence sites. Ten patients (62.5%) achieved a pCR. Six patients (37.5%) achieved a partial response. Median follow-up of all patients was 24.2 months. Four (25%) patients have experienced a progression, of which three were in the brain. Two-year progression-free survival was 59.4% (95% CI 35,100). High expression of CXCR4 was detected in the brain metastases. We conclude that in spite of high pCR rates among women with HER-2/neu-positive IBC treated with neoadjuvant trastuzumab-based regimens the outcome remains dismal and brain recurrences are frequent. CXCR4 may represent a novel therapeutic target. [source]

Assessment of the predictive value of clinical and histopathological factors as well as the immunoexpression of p53 and bcl-2 proteins in response to preoperative chemotherapy for esophageal squamous cell carcinoma

DISEASES OF THE ESOPHAGUS, Issue 3 2000
J. Szumilo
The aim of the study was to determine the predictive value of selected clinical and histopathological factors as well as the immunohistochemical expression of p53 and bcl-2 proteins in the prediction of the pathological response to preoperative chemotherapy in esophageal squamous cell carcinoma. Thirty-four patients with advanced squamous cell carcinoma of the thoracic esophagus (T2,4 N0,1 M0), who underwent one cycle of cisplatin and 5-fluorouracil therapy followed by subtotal esophagectomy, were studied. All clinical factors (tumor longitudinal diameter in a computed tomographic scan, invasion depth, the presence of lymph node metastasis and clinical tumor staging) were evaluated before the onset of the therapy. The histopathological features (grade of differentiation, degree of keratinization, nuclear polymorphism, mitotic index, pattern of cancer invasion and inflammatory response), and the expression of p53 and bcl-2 proteins were also estimated in prechemotherapy endoscopic biopsy specimens. Pathological response to chemotherapy was assessed in surgically resected specimens. Of 34 patients, two (5.9%) showed complete response (CR), six patients (17.6%) exhibited major histological changes (partial response 1; PR1), 24 (70.6%) showed minor histological changes (partial response 2; PR2), and two patients (5.9%) exhibited no response to chemotherapy (stable disease; SD). There were no significant relationships between the response to preoperative chemotherapy (CR + PR1 vs. PR2 + SD) and the majority of the clinical and all the histopathological features. Deeper cancer invasion before chemotherapy was the only factor that tended to worsen the therapy effect (p < 0.01). The pathological response to treatment had no significant associations with the expression of p53 and bcl-2 proteins in esophageal squamous cell carcinoma. It should be noted, however, that both patients in CR were p53 and bcl-2 protein-negative. [source]

USEFUL ENDOSCOPIC ULTRASONOGRAPHY TO ASSESS THE EFFICACY OF NEOADJUVANT THERAPY FOR ADVANCED ESOPHAGEAL CARCINOMA: BASED ON THE RESPONSE EVALUATION CRITERIA IN SOLID TUMORS

DIGESTIVE ENDOSCOPY, Issue 1 2005
Masaho Ota
Objective:, The aim of the present study was to assess the usefulness of endoscopic ultrasonography (EUS) for evaluating the efficacy of neoadjuvant therapy for advanced esophageal carcinoma based on the Response Evaluation Criteria in Solid Tumors (RECIST). Patients and Methods:, Sixty-two patients with advanced esophageal carcinoma underwent surgical resection after neoadjuvant therapy. The maximal tumor thickness was measured by EUS before and after neoadjuvant therapy, and the percent reduction was compared with the pathological response. Based on the RECIST, PD-SD (progressive disease-stable disease) was defined as < 30% reduction of tumor thickness on EUS, PR (partial response) as , 30% reduction of tumor thickness, and CR (complete response) as no detectable tumor (100%). Results:, The percent reduction of the thickness of Grade 0,1, Grade 2 and Grade 3 tumor was 11.5 ± 21.0%, 48.2 ± 17.0% and 74.9 ± 21.1%, respectively. There were significant differences in the extent of reduction among the three groups. Based on the RECIST, 80% of Grade 0,1 cases, 91% of Grade 2 cases and 22% of Grade 3 cases were PD-SD, PR, and CR according to EUS, respectively. EUS correctly identified 80% of non-responders and 94% of responders. Conclusions:, The percentage reduction of tumor thickness on EUS closely reflected the pathological evaluation. EUS evaluation based on the RECIST seems to be useful for monitoring neoadjuvant therapy in patients with esophageal carcinoma. [source]

Assessment of the predictive value of clinical and histopathological factors as well as the immunoexpression of p53 and bcl-2 proteins in response to preoperative chemotherapy for esophageal squamous cell carcinoma

Periventricular leukomalacia, inflammation and white matter lesions within the developing nervous system

NEUROPATHOLOGY, Issue 3 2002
Payam Rezaie
Periventricular leukomalacia (PVL) occurring in premature infants, represents a major precursor for neurological and intellectual impairment, and cerebral palsy in later life. The disorder is characterized by multifocal areas of necrosis found deep in the cortical white matter, which are often symmetrical and occur adjacent to the lateral ventricles. There is no known cure for PVL. Factors predisposing to PVL include birth trauma, asphyxia and respiratory failure, cardiopulmonary defects, premature birth/low birthweight, associated immature cerebrovascular development and lack of appropriate autoregulation of cerebral blood flow in response to hypoxic-ischemic insults. The intrinsic vulnerability of oligodendrocyte precursors is considered as central to the pathogenesis of PVL. These cells are susceptible to a variety of injurious stimuli including free radicals and excitotoxicity induced by hypoxic-ischemic injury (resulting from cerebral hypoperfusion), lack of trophic stimuli, as well as secondary associated events involving microglial and astrocytic activation and the release of pro-inflammatory cytokines TNF-, and IL-6. It is yet unclear whether activated astrocytes and microglia act as principal participants in the development of PVL lesions, or whether they are representatives of an incidental pathological response directed towards repair of tissue injury in PVL. Nevertheless, the accumulated evidence points to a pathological contribution of microglia towards damage. The topography of lesions in PVL most likely reflects a combination of the relatively immature cerebrovasculature together with a failure in perfusion and/or hypoxia during the greatest period of vulnerability occurring around mid-to-late gestation. Mechanisms underlying the pathogenesis of PVL have so far been related to prenatal ischemic injury to the brain initiated within the third trimester, which result in global cognitive and developmental delay and motor disturbances. Over the past few years, several epidemiological and experimental studies have implicated intrauterine infection and chorioamnionitis as causative in the pathogenesis of PVL. In particular, recent investigations have shown that inflammatory responses in the fetus and neonate can contribute towards neonatal brain injury and development-related disabilities including cerebral palsy. This review presents current concepts on the pathogenesis of PVL and emphasizes the increasing evidence for an inflammatory pathogenic component to this disorder, either resulting from hypoxic-ischemic injury or from infection. These findings provide the basis for clinical approaches targeted at protecting the premature brain from inflammatory damage, which may prove beneficial for treating PVL, if identified early in pathogenesis. [source]

Gene Therapy for Head and Neck Cancer ,

THE LARYNGOSCOPE, Issue 5 2000
Lyon L. Gleich MD
Abstract Objectives/Hypothesis New treatment methods are needed for head and neck cancer to improve survival without increasing morbidity. Gene therapy is a potential method of improving patient outcome. Progress in gene therapy for cancer is reviewed with emphasis on the limitations of vector technology and treatment strategies. Given the current technological vector limitations in transmitting the therapeutic genes, treatments that require the fewest number of cells to be altered by the new gene are optimal. Therefore an immune-based gene therapy strategy was selected in which the tumors were transfected with the gene for an alloantigen, human leukocyte antigen (HLA),B7, a class I major histocompatibility complex (MHC). This would restore an antigen presentation mechanism in the tumor to induce an antitumor response. This gene therapy strategy was tested in patients with advanced, unresectable head and neck cancer. Study Design Prospective trial. Methods Twenty patients with advanced head and neck cancer who had failed conventional therapy and did not e-press HLA-B7 were treated with gene therapy using a lipid vector by direct intratumoral injection. The gene therapy product contained the HLA-B7 gene and the ,2-microglobulin gene, which permits complete e-pression of the class I MHC at the cell surface. Patients were assessed for any adverse effects, for changes in tumor size, for time to disease progression, and for survival. Biopsy specimens were assessed for pathological response, HLA-B7 e-pression, apoptosis, cellular proliferation, CD-8 cells, granzyme, and p53 status. Results There were no adverse effects from the gene therapy. At 16 weeks after beginning gene therapy, four patients had a partial response and two patients had stable disease. Two of the tumors completely responded clinically, but tumor was still seen on pathological examination. The time to disease progression in the responding patients was 20 to 80 weeks. The median survival in patients who completed gene therapy was 54 weeks, compared with 21 weeks in patients whose tumors progressed after the first cycle of treatment. One patient survived for 106 weeks without any additional therapy. HLA-B7 was demonstrated in the treated tumors, and increased apoptosis was seen in the responding tumors. Conclusion Significant advances have been made in the field of gene therapy for cancer. Alloantigen gene therapy has had efficacy in the treatment of cancer and can induce tumor responses in head and neck tumors. Alloantigen gene therapy has significant potential as an adjunctive treatment of head and neck cancer. [source]

Specific immunotherapy of experimental myasthenia gravis by a novel mechanism

ANNALS OF NEUROLOGY, Issue 4 2010
Jie Luo PhD
Objective Myasthenia gravis (MG) and its animal model, experimental autoimmune myasthenia gravis (EAMG), are antibody (Ab)-mediated autoimmune diseases, in which autoantibodies bind to and cause loss of muscle nicotinic acetylcholine receptors (AChRs) at the neuromuscular junction. To develop a specific immunotherapy of MG, we treated rats with ongoing EAMG by intraperitoneal injection of bacterially-expressed human muscle AChR constructs. Methods Rats with ongoing EAMG received intraperitoneal treatment with the constructs weekly for 5 weeks beginning after the acute phase. Autoantibody concentration, subclassification, and specificity were analyzed to address the underlying therapeutic mechanism. Results EAMG was specifically suppressed by diverting autoantibody production away from pathologically relevant specificities directed at epitopes on the extracellular surface of muscle AChRs toward pathologically irrelevant epitopes on the cytoplasmic domain. A mixture of subunit cytoplasmic domains was more effective than a mixture containing both extracellular and cytoplasmic domains or than only the extracellular domain of ,1 subunits. Interpretation Therapy using only cytoplasmic domains, which lack pathologically relevant epitopes, avoids the potential liability of boosting the pathological response. Use of a mixture of bacterially-expressed human muscle AChR cytoplasmic domains for antigen-specific immunosuppression of myasthenia gravis has the potential to be specific, robust, and safe. ANN NEUROL 2010;67:441,451 [source]

Outcome following surgery for squamous cell carcinoma of the oesophagus

ANZ JOURNAL OF SURGERY, Issue 10 2009
En Loon C. Yong
Abstract Introduction:, This study was undertaken to determine the outcomes of patients treated for squamous cell carcinoma (SCC) of the oesophagus. Methods:, The study group consisted of 61 patients (median age: 64 years) with invasive SCC of the oesophagus who underwent resection between 1987 and 2007 in Adelaide, South Australia. Thirty-two (52%) were female. Survival data were available for all patients. The log rank test was performed to identify prognostic factors for survival. Results:, The 5-year overall survival rate was 33% (median: 24 months). Of 61 patients, 42 (69%) received neoadjuvant therapy prior to surgery. The overall resection rate was 95%. Significant post-operative morbidity occurred in 47%, and the in-hospital mortality was 5% (30-day mortality: 3%). No overall survival benefit was seen in patients undergoing neoadjuvant therapy prior to surgical resection. However, patients who had a complete pathological response to neoadjuvant therapy had a better 5-year survival than patients who did not receive neoadjuvant therapy: 47% versus 30%, respectively. Conclusions:, Oesophagectomy following neoadjuvant therapy for SCC of the oesophagus can be performed with low perioperative mortality. A complete response to neoadjuvant therapy was followed by an improved survival outcome. [source]

Complete pathologic response after preoperative rectal cancer chemoradiotherapy

ANZ JOURNAL OF SURGERY, Issue 6 2009
Anthony Ciccocioppo
Abstract Background:, Following preoperative treatment of rectal cancer with chemoradiotherapy (CRT), a complete pathological response (CPR) can be seen in the surgical specimen. The aim of this study was to assess the outcome of these patients as compared with those who did not have a complete response. Methods:, A retrospective study of the outcome of patients managed with preoperative CRT for their rectal cancer was conducted. Results:, Between November 1998 and July 2004, there were 530 new presentations of rectal cancer at The Queen Elizabeth and Royal Adelaide hospitals. Forty of these patients (7.5%) were treated with long-course preoperative CRT. After resection, a CPR was seen in seven patients (17.5%). These patients were all disease free at January 2006 after a median follow-up of 6.0 years (range 1.42,7.02 years). One patient had died from non-tumour-/surgery-related causes. Tumour recurrence, but not mortality, in this group was superior to the comparison group of patients without a CPR. Conclusions:, None of our patients who had a CPR after preoperative CRT have recurred or died from their disease. [source]

Induction concurrent chemoradiotherapy compared with induction radiotherapy for superior sulcus non-small cell lung cancer: a retrospective study

ASIA-PACIFIC JOURNAL OF CLINICAL ONCOLOGY, Issue 1 2010
Jian LI
Abstract Aim: To evaluate the efficacy of current chemoradiotherapy on improvement of survival in patients with superior sulcus non-small cell lung cancer (NSCLC). Methods: We retrospectively reviewed the data of 39 patients with superior sulcus NSCLC treated with induction therapy followed surgery. The patients were divided into two groups according to the induction approach: the induction radiotherapy (RT) group (1993,1999), and the induction chemoradiotherapy (CT/RT) group (since 1999). Results: The rate of complete resection was 65 percent in the RT group (n = 17) compared with 91 percent in the CT/RT group (n = 22, P = 0.024). Complete pathological responses from induction therapy were 12 percent in the RT group and 45 percent in the CT/RT group (P = 0.032). Overall survival (OS) was significantly longer in patients who received CT/RT than that in those who received RT, with 2- and 5-year survival rates of 77.3 percent and 36.4 percent versus 41.2 percent and 11.8 percent, respectively (P = 0.007). CT/RT also associated with a markedly longer tumor-free survival (TFS), with a median TFS of 40 and 17 months, respectively (P = 0.007). Patients achieved complete resection or complete pathological response had a significantly better survival than those with incomplete resection or pathological partial responses and no change (P < 0.0005 and P = 0.001, respectively). Conclusion: Our results indicate that CT/RT followed by surgery can significantly improve OS and TFS, and may be considered as an optimal option in treatment of patients with superior sulcus NSCLC. [source]

Impact of preoperative radiochemotherapy on postoperative course and survival in patients with locally advanced squamous cell oesophageal carcinoma,

BRITISH JOURNAL OF SURGERY (NOW INCLUDES EUROPEAN JOURNAL OF SURGERY), Issue 9 2006
C. Mariette
Background: The aim of this study was to determine the effect of neoadjuvant radiochemotherapy (RCT) on postoperative complications and survival after surgery for locally advanced oesophageal squamous cell carcinoma. Methods: Postoperative course and survival were compared in 144 patients who had neoadjuvant RCT and 80 control patients who had surgery alone for locally advanced oesophageal squamous cell carcinoma (radiological stage T3, N0 or N1, M0). Results: The two groups were comparable in terms of American Society of Anesthesiologists grade, age, sex, weight loss, tumour location, presence of lymph node metastasis and surgical approach. Postoperative mortality rates were 6·3 and 9 per cent (P = 0·481), with morbidity rates of 40·3 and 41 per cent (P = 0·887) in the RCT and control group respectively. Complete resection (R0) rates were 74·3 and 48 per cent respectively (P < 0·001). Significant downstaging was observed in the RCT group (P < 0·001), with 16·0 per cent of patients having a complete pathological response. Median survival was 29 versus 15 months, and the 5-year survival rate 37 versus 17 per cent (P = 0·002) in RCT and control groups respectively. Conclusion: Neoadjuvant RCT significantly enhanced R0 resection and survival rates in patients with stage T3 oesophageal squamous cell carcinoma, with no increase in postoperative mortality and morbidity rates. Copyright © 2006 British Journal of Surgery Society Ltd. Published by John Wiley & Sons, Ltd. [source]

Increased Cerebral Blood Flow And Cardiac Output Following Cerebral Arterial Air Embolism In Sheep

CLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY, Issue 11 2001
David J Williams
SUMMARY 1. The effects of cerebral arterial gas embolism on cerebral blood flow and systemic cardiovascular parameters were assessed in anaesthetized sheep. 2. Six sheep received a 2.5 mL injection of air simultaneously into each common carotid artery over 5 s. Mean arterial blood pressure, heart rate, end-tidal carbon dioxide and an ultrasonic Doppler index of cerebral blood flow were monitored continuously. Cardiac output was determined by periodic thermodilution. 3. Intracarotid injection of air produced an immediate drop in mean cerebral blood flow. This drop was transient and mean cerebral blood flow subsequently increased to 151% before declining slowly to baseline. Coincident with the increased cerebral blood flow was a sustained increase in mean cardiac output to 161% of baseline. Mean arterial blood pressure, heart rate and end-tidal carbon dioxide were not significantly altered by the intracarotid injection of air. 4. The increased cardiac output is a pathological response to impact of arterial air bubbles on the brain, possibly the brainstem. The increased cerebral blood flow is probably the result of the increased cardiac output and dilation of cerebral resistance vessels caused by the passage of air bubbles. [source]

Neoadjuvant chemo-radiotherapy and rectal cancer: can the UK watch and wait with Brazil?

COLORECTAL DISEASE, Issue 1 2010
S. M. Nyasavajjala
Abstract Objecive, It has recently been reported that up to one-third of patients with nonmetastatic distal rectal cancer managed with neoadjuvant chemoradiation therapy (CRT) had a complete clinical response (cCR) to treatment. In the selected cases, this has been used as the sole treatment. The aim of this study was to determine the frequency of complete pathological response for patients receiving CRT in one centre in the UK. Method, Patients receiving 6 weeks of neoadjuvant CRT were identified using the two cancer audit databases in two different tertiary hospitals from January 2002 to November 2007. Pathology was reviewed and the histopathological response of the resected specimen to CRT was evaluated using the Mandard classification (1 = complete response, 5 = no response) Results, One hundred and thirty-two consecutive patients [median age 61 (range 44,86) years, 90 men] with nonmetastatic locally advanced rectal cancer received neoadjuvant chemo radiotherapy between 2002 and 2007 followed by resection of the tumour. Data were available from 129 patients. Mandard classification Number of patients 1 13 2 14 3 31 4 47 5 24 Conclusion, Only 13 out of 132 (10%) of patients had a complete pathological response. This is one-third of the cCR previously reported. Nonsurgical therapy for rectal cancer using the Habr-Gama treatment algorithm may only be effective in a very small proportion of patients with rectal cancer in the UK and nonoperative treatment would not be recommended. [source]

B001 Multicentre Randomized Trial of Sphincter Preserving Surgery for Ultra-Low Rectal Carcinoma

COLORECTAL DISEASE, Issue 2006
E. Rullier
Objective, This randomized study compared two neoadjuvant treatments in patients with a low rectal cancer less than 2 cm from the anal verge that would have required APR before radiotherapy. Method, A total of 207 patients (71% uT3) with a rectal carcinoma at 0.5 cm from the anal verge were randomized in two groups. The group HDR received a high dose of radiotherapy (45 Gy + boost 18 Gy). The group RCT received 45 Gy with concomitant chemotherapy (5FU). Surgery was performed 6 weeks after treatment, surgeons were trained with TME, APR and intersphincteric resection. Results, The rate of sphincter preserving surgery was 83% after HDR and 86% after RCT (P = 0.69). There was no difference in morbidity, clinical tumour regression (80% vs. 87%) and complete pathological response (8% vs. 15%) between HDR and RCT. Overall, the rate of R0 resection was 78%. After a follow-up of 23 months, the rates of local and distant recurrence were 6% and 19% respectively and the disease-free survival was 77%. Survival was better after sphincter preservation than after APR. Conclusion, Sphincter preservation was achieved in 85% of ultra-low rectal carcinomas without compromising oncological prinicples. No difference was observed between HDR and RCT. Further follow-up is necessary to confirm this conservative approach. [source]

Response of vulval lichen sclerosus and squamous hyperplasia to photodynamic treatment using sustained topical delivery of aminolevulinic acid from a novel bioadhesive patch system

PHOTODERMATOLOGY, PHOTOIMMUNOLOGY & PHOTOMEDICINE, Issue 2 2009
Agnieszka A. Zawislak
This study evaluated the clinical and histopathological responses of vulval lichen sclerosus (LS) and squamous hyperplasia (SH) to photodynamic therapy (PDT). A novel bioadhesive patch containing aminolevulinic acid (ALA) at a dose of (38 mg/cm2) was used to treat 10 patients before irradiation with light of 630 nm. Clinical, histopathological and pathological responses to treatment were assessed at 6 weeks post-treatment. After 17 cycles of PDT, six patients reported significant symptomatic relief and no cutaneous photosensitivity. Histopathological differences were not demonstrated, but statistically significant induction of apoptosis was seen. It can be concluded that ALA-PDT patch-based formulation is pragmatic and primarily offers symptomatic management of vulval LS and SH. [source]

O -acetylation of sialic acids in N -glycans of Atlantic salmon (Salmo salar) serum is altered by handling stress

PROTEINS: STRUCTURE, FUNCTION AND BIOINFORMATICS, Issue 14 2008
Xin Liu
Abstract O -acetylation is one of the major modifications of sialic acids that significantly alters biological properties of the parent molecule. These O -acetylated forms are components of the cellular membrane and can affect physiological and pathological responses. Understanding the role of N -glycans in physiology is of increasing relevance to cellular biologists in various disciplines who study glycoproteomics yet lack information regarding the function of the attached glycans. It is well known that stress may decrease immune function in fish; however, there are only few suitable biomarkers available to monitor the physiological responses under the stress conditions. This study is the first report on the effect of stress on the profile of O -acetylation of sialic acids in fish serum. In order to preserve the relevant structural characteristics as much as possible, native N -glycans were directly analyzed using CE-MS. We have characterized the N -glycans in serum of salmon (Salmo salar) exposed to long-term handling stress (15,s out of the water, daily for 4,wk) and compared with the results obtained from sera of control fish. The results indicated that major N -glycans in salmon serum contained mono-acetylated sialic acids (83%), and that the O -acetylation pattern of sialic acids could be altered by long-term stress. [source]