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PubMed2005

Comparison of clinical stage, therapy response, and patient outcome between squamous cell carcinoma and adenocarcinoma of the esophagus.

PURPOSE: To analyze the differences in clinical stage, pathologic response to chemoradiotherapy, patterns of failure, and overall survival (OS) between patients with squamous cell carcinoma (SCC) and adenocarcinoma (ACA) of the esophagus. PATIENTS AND METHODS: We stratified patients by two histologies, ACA and SCC, and statistically compared their clinical stage, post-therapy pathologic response, patterns of failure, and OS. RESULTS: Of the 235 patients who underwent preoperative chemoradiotherapy, 42 (18%) had SCC and 193 (82%) had ACA. Among the ACA patients, a significantly larger proportion was male (93% vs 7%; p <0.001), whereas sex was distributed similarly among SCC patients (55% male vs 45% female; p = 0.5). A significantly larger percentage of SCC patients were classified as lower TN and overall stage than ACA patients (T2 = 41% vs 28%, p <0.0001; N0 = 69% vs 48%, p = 0.01; stage II = 76% vs 55%, p <0.001). A significantly greater portion of SCCs was categorized as pathologic N0 after treatment (71% vs 65%; p = 0.02). Among the pathCR patients in clinical stage II, there were significantly greater proportion of SCC patients (77% vs 63%; p <0.001) than ACA patients. Among the pathCR patients in clinical stage III patients, a significantly greater proportion were ACA patients (38% vs 23%; p <0.001) than SCC patients. The median and 5-yr OS was 53 +/- 11 mo and 39% for ACA patients and 35 +/- 14 mo and 37% for SCC (median OS, p = 0.3). Among pathCR patients, median OS of ACA patients (133 mo) was longer than that of SCC patients but nonsignificant (29 mo; p = 0.07); results were similar for non-pathCR patients. DFS results were similar in all subgroups. Among the whole cohort, incidence of local-regional recurrence and distant metastases did not vary significantly. The median time to distant metastases did not vary significantly for pathCR and non-pathCR patients. CONCLUSIONS: We believe this is the first study that compares failure outcome of ACA and SCC patients with similar clinical stage after trimodality therapy. Our data suggest that significant differences in clinical stage and post-therapy pathologic stage exist between ACA and SCC. Frequent presence of malignant nodes in the resected specimens of ACA patients resulted in a shorter time-to-metastases suggesting that ACA patients need better systemic control.

Adenocarcinoma↗
PubMed2006

A phase II study of docetaxel, doxorubicin, and infusional 5-fluorouracil in the treatment of patients with locally advanced breast cancer.

OBJECTIVE: The primary aim of this study was to estimate the rate of clinical and pathologic response to preoperative docetaxel, doxorubicin, and infusional 5-fluorouracil in patients with locally advanced breast cancer. Secondary objective included the determination of toxicity profile. PATIENTS AND METHODS: Thirty-nine patients (median age 49 years) with histologically confirmed locally advanced breast cancer (stage IIIA or IIIB) were studied. Patients received 4 courses of chemotherapy with docetaxel (75 mg/m2 iv over 1 hour), doxorubicin (50 mg/m2 iv bolus), and 5-fluorouracil (300 mg/m2/d as continuous iv infusion on days 1-5). Treatment cycles were repeated every 21 days. Prophylactic filgastrim 5 microg/kg s/c QD was administered to all patients. Definitive surgery was performed after the completion of 4 cycles of therapy. Pathologic complete response was defined as the absence of invasive cancer in both the breast and ipsilateral axillary lymph nodes. RESULTS: The clinical objective response rate (partial plus complete) was 87% (95% confidence interval [CI]: 76-98%). Three patients (8%) had complete pathologic response. Two patients progressed preoperatively. Thirteen patients (33%) developed neutropenic fever. Fifty-three percent of the patients were hospitalized for treatment related complications. No cardiotoxicity or treatment related deaths were observed. CONCLUSIONS: Triple cytotoxic therapy based on concurrent doxorubicin and docetaxel with infusional 5-flourouracil (5-FU) does not appear to significantly improve the pathologic response in patients with locally advanced breast cancer.

Adult↗
PubMed1971

Vasopressin test in cases of optic atrophy and optic neuritis.

The vasopressin test gave pathological results in 12 cases of optic atrophy and normal results in three cases. One of the patients with a pathological response had Leber's disease and three had tobacco-alcholic amblyopia, while in the rest the optic atrophy was of uncertain origin. In the cases with normal results the aetiology was also unclear. The Metopirone test was normal in 13 cases and pathological in only one case of optic atrophy. In three out of five patients with optic neuritis the vasopressin test gave pathological responses. The high frequency of pathological vasopressin tests in patients with optic lesions indicates a simultaneous disturbance of the hypothalamo-hypophyseal function. The background to this might be a disturbed vascular supply. The vasopressin test was of no help in diagnosing tumours as a cause of optic atrophy.

Adolescent↗
PubMed1999

Phase II trial of neoadjuvant chemotherapy in early-stage small cell cervical cancer.

Clinical complete response (CR) to chemotherapy is not uncommon in small cell carcinoma. To understand its pathologic response, we conducted a phase II trial with neoadjuvant chemotherapy followed by hysterectomy in patients with small cell cervical cancer and reviewed all reported cases receiving neoadjuvant chemotherapy followed by hysterectomy through a MEDLINE search. From December 1993 to December 1997, the enrolled patients were treated with two to three courses of vincristine, adriamycin and cyclophosphamide alternating with cisplatin and etoposide (VAC/PE) before hysterectomy. Another three courses of chemotherapy were added after surgery. A total of seven patients was enrolled. Clinical CR was observed in six patients, but microscopic residual tumor was present in all. Lymphatic permeation, scattered residual tumor clusters and residual superficial invasive adenocarcinoma over the cervix presented in five cases, and another had a metastatic pelvic node with no residual cervical tumor. Three of these seven patients have been alive with no evidence of disease for 16.2, 45.2 and 56.6 months, respectively. The other four died from disease 10.3-23.6 months after diagnosis. These findings indicate the discrepancy between clinical and pathologic responses in small cell cervical cancer after chemotherapy and emphasize the necessity of local treatment.

Adult↗
PubMed1982

A spectrum of immune responses and pathological conditions between certain animal species to experimental Mycobacterium bovis infection.

Guinea-pigs, rabbits, rats, ferrets and hedgehogs were infected with a recent field isolate of Mycobacterium bovis. The cell-mediated and antibody responses were studied up to 8 weeks after infection at which time the animals were killed and pathological, histological and bacteriological examinations were carried out. Guinea-pigs and rabbits produced an intense cell-mediated response and strong tissue reactions around the lesions. This appears, in part, to be responsible for the susceptibility of these animals to M. bovis. The strong cell-mediated response was also related to the small numbers of organisms in the tissues. Ferrets produced very little cell-mediated response and only minor tissue reactions. The lack of any cell-mediate response was related to the large numbers of organisms in the tissues which produced an acute disseminated disease. The antibody response produced by ferrets, rabbits and guinea-pigs was variable within an between the species and could not be related to numbers of organisms in the tissues. In rats and hedgehogs a specific cell-mediated and humoral response was difficult to detect but the growth of the organism was controlled by the host resulting in a persistent subclinical infection with no mortality.

Animals↗
PubMed2005

The surgical management of superior sulcus tumors: a retrospective review with long-term follow-up.

BACKGROUND: We reviewed our experience with multimodality therapy for superior sulcus tumors to identify aspects of treatment that impact survival. METHODS: We retrospectively analyzed the records of 39 consecutive patients who underwent surgical resection in a single institution between 1993 and 2000. RESULTS: Median age at presentation was 59 years (range, 40 to 77). Twenty-five patients (64%) were men. At presentation, 36 patients (92%) had clinical T3 tumors and 3 (8%) had clinical T4 tumors. Mediastinoscopy was negative in all patients. Thirty-one patients (79%) received preoperative radiotherapy (median dose, 4500 cGy). Chemotherapy was administered concurrently with radiotherapy in 27 patients (69%). Complete surgical resection was performed in 34 patients (87%). There were 2 (5%) postoperative deaths. Of the 31 patients who received preoperative therapy, 14 (45%) had their tumors downstaged and 9 (29%) demonstrated a complete pathologic response. Median follow-up (100%) was 69 months. Overall 5-year survival was 47.9%. Five-year survival was 52.1% in patients with negative resection margins (p = 0.005), and 60.6% in patients who demonstrated a response to induction chemoradiation therapy (p = 0.008). Independently, margin status and response to induction therapy are predictors of overall survival (p = 0.01 and p = 0.02, respectively). Multivariable analysis identified margin status as the only factor significantly associated with overall survival. Negative margins strongly correlated with the response to preoperative therapy (p = 0.004). Disease-free survival correlated well with the response to induction therapy (p = 0.03). The chemotherapy regimen, T status, operative procedure, and complete pathologic response did not correlate with survival. CONCLUSIONS: The use of chemoradiation induction therapy may downstage tumors, enhance the ability to obtain a complete surgical resection, and prolong survival.

Adult↗
PubMed1978

Analytical subcellular fractionation of jejunal biopsy specimens: enzyme activities, organelle pathology and response to corticosteroids in patients with non-responsive coeliac disease.

1. Jejunal biopsies from five patients with non-responsive coeliac disease have been subjected to analytical subcellular fractionation and enzymic microassay in order to compare the organelle pathology of this group with untreated but glutensensitive patients. 2. Compared with the gluten-sensitive group these non-responsive patients showed marked reduction of the endoplasmic reticulum enzymes, normal activities of lysosomal enzymes and slightly less severely reduced brush border activities. 3. It is suggested that the present biochemical studies in combination with previous clinical reports and measurements of DNA and protein synthesis by cultured mucosal biopsies delineate non-responsive coeliac disease as a distinct entity. 4. The patients were treated with oral prednisolone (20 mg daily) for between 5 and 9 weeks and the properties of the jejunal biopsies restudied. 5. Although morphologically there was only a partial restoration of the villus architecture the enzymic alterations and organelle abnormalities returned essentially to normal values.

Adult↗
PubMed2003

Preoperative mitomycin, ifosfamide, and cisplatin followed by esophagectomy in squamous cell carcinoma of the esophagus: pathologic complete response induced by chemotherapy leads to long-term survival.

PURPOSE: Squamous cell carcinoma of the esophagus remains an aggressive disease with a poor prognosis, even after curative-intent surgery. This article analyzes the impact of preoperative chemotherapy with mitomycin, ifosfamide, and cisplatin (MIC) on a cohort of 68 patients. PATIENTS AND METHODS: From 1988 to 1994, 68 patients with potentially operable squamous cell carcinoma of the esophagus were entered onto two phase II trials of neoadjuvant chemotherapy with mitomycin 6 mg/m2, ifosfamide 3 g/m2, and cisplatin 50 mg/m2 and received between two and four cycles of treatment at 3-weekly intervals. Two patients were removed from the analysis when they were found to have malignancy other than squamous cell carcinoma of the esophagus. RESULTS: Forty (61%) of 66 patients had a radiologic response to chemotherapy (18 complete responses and 22 partial responses), and 52 (79%) of 66 patients went on to have the primary tumor resected. There were nine pathologic complete responders, seven of whom remain fit and well after at least 60 months of follow-up. The overall median survival was 12.4 months (95% confidence interval, 9.6 to 18.8 months). The complete response and node-negative patients survived significantly longer than those in other categories (log-rank chi2 = 18.8; P <.001): on average 13 months longer than the node-positive or nonresected category (22.0 v 9.4 months). The toxicity of the regimen was low. CONCLUSION: MIC is an easily administered, well-tolerated, and efficacious regimen as neoadjuvant therapy for patients with squamous cell carcinoma of the esophagus. These results warrant further investigation.

Adult↗
PubMed2001

MRI phenotype is associated with response to doxorubicin and cyclophosphamide neoadjuvant chemotherapy in stage III breast cancer.

BACKGROUND: The preferred management for women with stage II or locally advanced breast cancer (LABC) is neoadjuvant chemotherapy. Pathologic response to chemotherapy has been shown to be an excellent predictor of outcome. Surrogates that can predict pathologic response and outcome will fuel future changes in management. Magnetic resonance imaging (MRI) demonstrates that patients with LABC have distinct tumor patterns. We investigated whether or not these patterns predict response to therapy. METHODS: Thirty-three women who received neoadjuvant doxorubicin and cyclophosphamide chemotherapy for 4 cycles and serial breast MRI scans before and after therapy were evaluated for this study. Response to therapy was measured by change in the longest diameter on the MRI. RESULTS: Five distinct imaging patterns were identified: circumscribed mass, nodular tissue infiltration diffuse tissue infiltration, patchy enhancement, and septal spread. The likelihood of a partial or complete response as measured by change in longest diameter was 77%, 37.5%, 20%, and 25%, respectively. CONCLUSIONS: MRI affords three-dimensional characterization of tumors and has revealed distinct patterns of tumor presentation that predict response. A multisite trial is being planned to combine imaging and genetic information in an effort to better understand and predict response and, ultimately, to tailor therapy and direct the use of novel agents.

Adult↗
PubMed2002

[Option of the surgical mode for breast cancer based on the effect of neoadjuvant chemotherapy].

Neoadjuvant chemotherapy has become standard treatment for breast cancer patients to avoid mastectomy in larger tumors. Neoadjuvant chemotherapy permits more breast-conserving surgery to be performed. The treatment outcome is favorable in women whose tumors show a complete pathological response. Histological grade, HER-2, p53, and hormone receptor status are significant predictive factors of a good pathological response to neoadjuvant chemotherapy. In addition, computed tomography and/or magnetic resonance imaging are useful tools in determining the optimal resection area for breast cancer.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2005

Immune regulation of central nervous system functions: from sickness responses to pathological pain.

Classically, the central nervous system (CNS) and the immune system are thought to operate independently of each other. This simplistic view has been corrected in recent years, first with the recognition that the brain dynamically modulates the immune system, and later with the reverse; that is, that the immune system modulates the CNS as well. The evidence that the immune system regulates CNS functions is first reviewed. This immune-to-brain communication pathway triggers the production of a constellation of CNS-mediated phenomena, collectively referred to as 'sickness responses'. These sickness responses are created by immune-to-brain signals activating CNS glia to release glial proinflammatory cytokines. The most recently recognized member of this constellation of changes is enhanced pain responsivity. The hypothesis is then developed that pathological, chronic pain may result from 'tapping into' this ancient survival-oriented circuitry, including the activation of immune and glial cells and the release of immune/glial proinflammatory cytokines. This can occur at the level of peripheral nerves, dorsal root ganglia, spinal cord, and likely at higher brain areas. The implications of this model for human chronic pain syndromes and clinical resolution of these chronic pain states are then discussed.

Central Nervous System↗
PubMed2004

Lung pathology in response to repeated exposure to Staphylococcus aureus in congenic residual function cystic fibrosis mice does not increase in response to decreased CFTR levels or increased bacterial load.

OBJECTIVE: To establish the role of defects in murine Cftr in the susceptibility to Staphylococcus aureus lung disease using mouse models of cystic fibrosis (CF), congenic or inbred strains. METHODS: We describe the histopathological analyses of CF mice repeatedly exposed by aerosolisation to a CF isolate of S. aureus, using residual function Cftr mice and compound heterozygotes generated by intercrossing these with Cftr 'null' mice, all congenic on the C57Bl6/N background. RESULTS: We demonstrate that mice congenic on the C57Bl/6 background develop significantly more severe lung pathology than non-CF littermates in response to repeated exposure to the most frequent early CF lung pathogen S. aureus. Furthermore, reducing the level of Cftr by half in compound heterozygote mice does not impact upon disease severity, even in response to an increased bacterial dose. CONCLUSIONS: These results are consistent with an airway clearance defect, or abnormal inflammatory response secondary to Cftr mutation. These studies confirm the primary role for Cftr mutation in the development of this lung phenotype. In addition, these results demonstrate that a further 50% decrease in residual wild-type Cftr mRNA levels in this model does not impact the severity of the histopathological response to S. aureus, suggesting a critical threshold level for functional CFTR.

Animals↗
PubMed1997

Preoperative chemoradiation coupled with aggressive resection as needed ensures near total control in advanced head and neck cancer.

BACKGROUND: Preoperative chemotherapy or chemoradiation protocols are generally associated with high clinical response rates, but limited pathologic responses for large primary tumors. We have initiated a prospective phase II study of weekly paclitaxel 60 mg/M2, and carboplatin (AUC of 1) plus concurrent fractionated external beam radiation (45 Gy) followed by organ-preserving (or function restorative) surgery when applicable to maximize local-regional tumor control. PATIENTS AND METHODS: Operable patients staged by triple endoscopy received a percutaneous endoscopic gastrostomy and vigorous dental and nutritional support during therapy. Weekly paclitaxel 60 mg/M2, carboplatin (AUC of 1), and radiation 45 Gy were given with rebiopsy of the primary site at 5 weeks. Patients with positive biopsy had definitive surgery in 4 to 5 weeks. Patients with negative biopsy-results received 3 additional weeks of radiation, to a total dose of 72 Gy plus carboplatin and paclitaxel. RESULTS: The 35 patients were 29 men and 6 women, aged 40 to 71 years, with stage III (12) or stage IV (23) cancer. The site of the cancer was oral cavity, 10; base of tongue, 3; oropharynx, 3; hypopharynx, 4; larynx, 12 (glottic, 6; supraglottic, 6), unknown primary, 2; other, nasal cavity, 1. Of 34 evaluable patients, 16 (47%) had a complete clinical response (CR) and 18 (53%) had a partial response (PR); total clinical response rate was 100%. A pathologic CR at the primary site occurred in 23 of 34 patients (68%; 2 had an unknown primary) who went on to completion radiation at 67 to 72 Gy. After induction chemoradiation 21 patients with N1-3 nodes had neck dissection; 6 (31%) had positive nodes. Twelve patients had residual cancer at the primary site at time of rebiopsy: mandible, 4; maxilla, 1; base of tongue, 2; larynx, 4; floor of mouth, 1; and nasal cavity, 1. All were resected with function-preserving reconstruction. At median follow-up of >12 months, progression-free and overall survivals were 71% and 83%, respectively. CONCLUSION: Preoperative treatment with paclitaxel, carboplatin, and radiation is associated with high CR at the primary site and a high level of organ preservation or functional restoration if ablation is done.

Adult↗
PubMed2002

Pathologic changes related to CMF primary chemotherapy in breast cancer. Pathological evaluation of response predicts clinical outcome.

The pathologic changes associated to response to primary chemotherapy in a series of 303 operable breast cancers are evaluated and correlated to patients' follow-up (interval free of disease and survival). In our series, the incidence of microscopic changes related to chemotherapy is 43.9%. Tumor replacement by loose fibrosis is the most common pathologic event. In most cases, the intensity of fibrotic change is proportional to the degree of clinical-mammographic reduction of the tumor mass. However, some discrepancies exist in the sense of absence of microscopic changes in cases of well-documented mammographic reduction as well as in cases without clinical reduction but with large areas of chemotherapy-related fibrosis. The presence of pathologic response is significantly associated with better survival rate.

Adult↗
PubMed1981

A combination of spastic paraparesis, polyneuropathy and adrenocortical insufficiency-a childhood form of adrenomyeloneuropathy.

This report describes a combination of spastic paraparesis and symmetrical sensory motor polyneuropathy with a pathological response to the ACTH test in the case of a 16 year-old boy and a borderline response to the ACTH test in the case of his 8-year-old sister. Another sister, aged 14, showed only a pathological response to ACTH testing, the neurological status being unremarkable. The EEG was normal in all three children examined. Visually evoked potentials were borderline in the case of the boy and normal in the case of the clinically involved sister. Although on examination by light microscopy the sural nerve proved to be normal, the clinical diagnosis of adrenomyeloneuropathy (AMN) in its juvenile form may be assumed, in view of the clinical symptoms and the evidence of adrenocortical insufficiency revealed by the ACTH test.

Adolescent↗
PubMed2002

[Prospective phase II study of neoadjuvant radiochemotherapy in advanced operable carcinoma of the mouth cavity. 3-year outcome].

PURPOSE: The purpose of simultaneous chemoradiotherapy is to increase local-regional control and to decrease the incidence of distant metastases. Regimens containing cisplatin/5-FU chemotherapy are widely accepted as standard treatment in advanced head and neck cancer. Most studies reported promising response and survival data, but also severe mucosal toxicity. In recent years the newly developed drug Taxol demonstrated interesting activity in head and neck cancer as a single agent as well as in combination drug regimens. In the present outpatient phase II trial, we investigated the combination of Taxol/carboplatin with 40 Gy radiotherapy in a neoadjuvant setting of operable stage III/IV squamous cell carcinoma of the oral cavity and oropharynx. PATIENTS AND METHODS: Fifty-three patients were enrolled in this trial during the period from May 1998 to October 2000 and received five cycles weekly of Taxol (40 mg/m2) and carboplatin (AUC 1.5) with conventional radiotherapy (40 Gy). Within 3-4 weeks after chemoradiotherapy resection of the primary tumor and the regional neck nodes was performed. RESULTS: Fifty-two patients were evaluable for toxicity and response. Complete response was observed in 31 of 52 patients (CR 60%), and partial remission was seen in 21 of 52 patients (PR 40%). In 30 of 52 patients complete pathologic response (pCR 58%) was documented in the resection specimens. The 1-, 2-, and 3-year overall survival rate was calculated as 84%. CONCLUSION: Our present results demonstrated impressive clinical and pathological response rates of concurrent Taxol/carboplatin and radiotherapy as a preoperative treatment modality in advanced oral and oropharyngeal cancer.

Adult↗