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[A comparative study between clinical response and pathologic changes to preoperative chemotherapy in non-small cell lung cancer].

OBJECTIVE: To study the clinical response to preoperative chemotherapy in relation to pathologic changes in non-small cell lung cancer (NSCLC). METHODS: Forty-six stage I-IIIa NSCLC patients were given 1-2 courses of preoperative chemotherapy with mitomycin C (MMC) 6 mg.M-2 on day 1, vindesine (VDS) 2.5-3 mg.M-2 on day 1, day 8 and/or day 15, and cisplatin (DDP) 90 mg.M-2 on day 1 (MVP regimen). 'The treatment was recycled every 28 days. Clinical response was assessed according to WHO criteria. Pathologic changes of the resected tumor were categorized to 3 grades. Grade I: No tumor under gross and microscopic observation. Grade II: Grossly no tumor present but residual tumor cells under microscopic observation. Grade III: Tumor reduced in size with clear margins; marked tumor cells degeneration and necrosis accompanied with fibrosis. Grade IV: Active proliferation of tumor cells with invasion. Grade I-II was considered to be chemotherapeutically effective. RESULTS: (1) The clinical response rate was higher in patients who had received 2 courses than those received 1 course of treatment. More patients treated with 2 courses had their pathologic changes in Grade I-II than those treated with 1 course of chemotherapy but the response rate was not fully consistent with pathologic grading. (2) Pathologic grading significantly correlated with the extent of tumor involvement but not with the lymph node status. (3) Efficacy of chemotherapy should be evaluated jointly by the clinical response and grading of pathologic changes. (4) Chemotherapy with MVP regimen did not elicit severe toxic side effect. Nor did it lead to operative morbidity, operative mortality and a delay in postoperative recovery. CONCLUSION: Preoperative chemotherapy with MVP regimen is effective in the treatment of NSCLC in stage I-IIIa.

Adult↗

Preoperative chemoradiation in fixed distal rectal cancer: dose time factors for pathological complete response.

PURPOSE: Preoperative chemoradiation is being utilized extensively in the treatment of rectal cancer. However, a variety of dose time factors in both delivery of chemotherapy and irradiation remain to be established. This study was undertaken to examine the impact of dose time factors on pathological complete response (pCR) rates following preoperative chemoradiation for fixed rectal cancer. METHODS AND MATERIALS: Thirty-three patients with fixed rectal cancers were treated with combined 5-fluorouracil (5-FU) chemotherapy and pelvic radiation. Twenty-one patients received bolus 5-FU during the first 3-5 days of radiation and repeated on days 28-33 of their radiation treatment. Twelve patients were treated with continuous infusion (CI) 5-FU, 225 mg/m(2) for the duration of the pelvic radiation. Fifteen patients received a planned total radiation dose of 45 to 50 Gy and 18 patients received a dose of 55 to 60 Gy. Surgical resection was then carried out 6-8 weeks after completion of treatment. RESULTS: Diarrhea was the most frequent acute toxicity. Grade 3 diarrhea was observed in 6 patients requiring treatment interruption and was not related to the chemotherapy regimen. There was no Grade 4 or 5 toxicity. pCR was observed in 2 of 21 (10%) patients treated with bolus 5-FU as compared to 8 of 12 (67%) for patients treated with CI (p = 0.002). pCR were observed in 8 of 18 (44%) patients receiving radiation dose > or = 5500 cGy as compared to 2 of 15 (13%) patients treated to a dose < or = 5000 cGy (p = 0.05). In the high-dose radiation (> or = 5500 cGy) group, a significant difference in pCR rate was observed in patients treated with CI, 8 of 12 (67%) (p = 0.017) as compared with bolus 5-FU (0 of 6). There was no significant difference in operative morbidity or in wound healing between patients treated with bolus 5-FU or CI or within the groups treated with low or high doses of radiation. Three patients have developed local recurrence at 14 and 24 months, two in the low-dose group treated with bolus 5-FU and one patient in the CVI group. The overall 5-year survival for the whole group is 71%. CONCLUSION: Dose intensity of 5-FU and dose of radiation correlate significantly with the likelihood of achieving a pCR. Continuous infusion 5-FU (CI) and a preoperative radiation dose of 5500 cGy or higher can achieve pCR rates of approximately 50%, even in fixed cancers of the rectum.

Adult↗

A pathologic complete response of rectal cancer to preoperative combined-modality therapy results in improved oncological outcome compared with those who achieve no downstaging on the basis of preoperative endorectal ultrasonography.

BACKGROUND: Preoperative combined-modality therapy (CMT) is the preferred treatment for locally advanced rectal cancer (endorectal ultrasonography [ERUS] T3-4, N1, or clinically bulky) and achieves a pathologic complete response (pCR) in 4% to 33% of patients. However, the prognostic significance of pCR remains unclear. METHODS: A prospectively collected database was queried to identify 200 patients with locally advanced disease treated from 1992 to 2002. The pCR group was defined as having no evidence of viable tumor on pathologic analysis. The no-downstaging group was defined as no difference between the pre-CMT ERUS stage and the pathologic stage. Those achieving some downstaging but not pCR were excluded. Patients were treated with CMT (5040 cGy of radiation and 5-fluorouracil-based chemotherapy) followed by surgery, and 51 (85%) in the pCR group and 129 (92%) in the no-downstaging group (P = .1) received postoperative chemotherapy. Recurrence-free survival (RFS) and overall survival (OS) were determined by using the Kaplan-Meier method. RESULTS: The median follow-up was 38.6 months (range, 18.2-124.9 months). The pCR (n = 60) and control (n = 140) groups were similar in age (P = .6), sex (P = .4), distance of the tumor from the anal verge (P = .3), pre-CMT ERUS stage (P = .2), and comorbidities (P = .2). The 5-year RFS was 96% and 54% in the pCR and control groups, respectively (P < .00001); the 5-year OS was 90% and 68% (P = .009). Sphincter-preservation rates were higher in the pCR group (P = .01). CONCLUSIONS: Rectal cancer patients with pCR after preoperative CMT have improved RFS, OS, and sphincter preservation compared with patients without downstaging. Because pCR seems to be associated with better outcome, an understanding of the factors governing the response to CMT should be pursued.

Adenocarcinoma↗

Complete axillary conversion after neoadjuvant chemotherapy in locally advanced breast cancer: a step towards conserving axilla?

OBJECTIVES: This study was designed to assess the clinical, sonographic and histopathological response of axillary lymph node metastasis to neoadjuvant chemotherapy in patients with locally advanced breast cancer. MATERIAL AND METHODS: Forty patients with locally advanced breast cancer (LABC) with clinically palpable or sonographically detectable axillary nodes were studied. FNAC of the primary tumor and axillary nodes was done and patients were started on neoadjuvant chemotherapy. Axillary nodes were assessed clinically and sonographically for response after 3 cycles of chemotherapy. All patients underwent total mastectomy with axillary clearance and the lymph nodes in the specimen were examined for metastasis. RESULTS: 47% patients had complete clinical nodal response, while 19% showed complete sonographic response. Complete pathological nodal response was documented in 22% of patients. Ultrasonography was found to be more sensitive than clinical examination in assessing complete nodal response. 10% of the patients had complete pathological response of both primary tumor and axillary nodes. There was significant correlation between pathological response of primary tumor and lymph nodes (P=0.004). Patients with complete sonographic or clinical response were found to have no or minimal residual disease in axilla and hence axillary dissection may be avoided in them.

Analysis of Variance↗

Pathologic complete response of advanced ovarian mixed mesodermal tumor to cisplatin, adriamycin and dacarbazine: a case report.

Presented is a case report of a stage IIIC primary ovarian mixed mesodermal tumor with gross residual disease following aggressive cytoreductive surgery. Following twelve courses of Cisplatin, Adriamycin and Dacarbazine, second-look laparotomy confirmed a pathologic complete response. The patient is now free of disease at 17+ months.

Antineoplastic Combined Chemotherapy Protocols↗

Using endosonography to assess the effects of neoadjuvant therapy in patients with advanced esophageal cancer.

OBJECTIVE: The aim of this study was to determine the usefulness of endosonography for evaluating the effect of neoadjuvant therapy for advanced esophageal carcinoma. MATERIALS AND METHODS: Thirty-four patients with esophageal carcinoma (stage II, 16 patients; stage III, 18 patients) underwent various preoperative treatment. In all patients, endosonography was performed before and after treatment, and the percentage reduction in tumor size was calculated from the maximum area of the tumor. In the 27 patients who underwent surgery, the percentage reduction was compared with the pathologic response. Also, the overall survival rates were compared with the percentage reduction in tumor area. RESULTS: Reduction in tumor area ranged from 0% to 47%. The patients were divided into three groups according to the percentage reduction in tumor area. Pathologic response was graded according to the number of viable cells in the entire lesion. Correlation between pathologic response and percentage reduction in tumor area was strong. We found a significant difference in survival rates among the three groups. CONCLUSION: The percentage reduction in tumor area estimated by means of endosonography reflects the histologic effectiveness of neoadjuvant therapy in patients with advanced esophageal carcinoma and may enable clinicians to predict the prognosis of the disease.

Aged↗

Survival outcomes of resected patients who demonstrate a pathologic complete response after neoadjuvant chemoradiation therapy for locally advanced esophageal cancer.

A variety of strategies, using chemotherapy, radiation therapy, and surgical resection have been employed in the treatment of locally advanced esophageal cancer. No strategy has proven superior, and poor long-term survival is anticipated. A survival benefit has been suggested for patients who achieve a pathologic complete response (pCR) following neoadjuvant chemoradiation therapy. We examined the collective results at three institutions of patients who achieved a pCR following neoadjuvant chemoradiation therapy. A retrospective, chart-based review was conducted. Kaplan-Meier calculations were used to determine overall and disease-free survival. Between 1995 and 2002, 229 patients were treated with neoadjuvant chemoradiation followed by surgery as a planned approach for locally advanced esophageal cancer. Forty-one patients (18%) demonstrated pCR and were the focus of this study. Histology was adenocarcinoma in 29, squamous in 10, and adenosquamous/undifferentiated in two patients. Forty patients were staged by endoscopic ultrasound prior to neoadjuvant therapy and all demonstrated a T-stage of 2 or higher, while 19 had evidence of nodal metastasis. Four patients died in the perioperative period. The remaining patients have been followed for an average of 46 months. Overall survival at 5 years was 56.4% and a median survival has not been reached. Esophageal cancer patients who demonstrate a pCR following neoadjuvant chemoradiation are a select subset who demonstrate excellent long-term survival. Identification of clinical variables or biomarkers predictive of pCR may therefore optimize treatment strategies of patients with locally advanced esophageal cancer.

Adenocarcinoma↗

Vaccination studies against experimental bovine Pasteurella pneumonia.

Vaccination-challenge experiments were conducted in colostrum-deprived calves to evaluate the efficacy of Pasteurella bacterins and vaccines against experimental pneumonic pasteurellosis. Calves were vaccinated with formalin-killed bacterins and live vaccines, then challenge exposed intratracheally with P. haemolytica or P. multocida. Infectious bovine rhinotracheitis virus was inoculated intranasally three to four days prior to P. haemolytica challenge-exposure. All calves were examined for macroscopic and microscopic lesions after being found dead or following euthanasia four to seven days after challenge exposure with the bacterial pathogen. Clinical, hematological, and pathological responses to challenge exposure in aluminum hydroxide absorbed P. haemolytica and P. multocida bacterin-treated calves were consistent with the pneumonic lesions of pulmonary pasteurellosis in the control calves. An oil-adjuvanted P. haemolytica bacterin limited clinical and pathological responses in the affected calves whereas a P. multocida oil-adjuvanted bacterin did not. Both clinical and pathological responses to challenge exposure in calves vaccinated with live Pasteurella vaccines were less severe than those of the control calves. Vaccine effectiveness appeared to be dose dependent.

Animals↗

Early nodal response as a predictor for necessity of functional neck dissection after chemoradiation.

PURPOSE: Chemoradiation is increasingly becoming the standard of care for node-positive squamous cell cancer of the head and neck. Response to chemoradiation for clinically node-positive disease in the neck is often difficult to ascertain because clinical response may or may not be predictive of pathological response. This often leads to uncertainty about the necessity of a functional neck dissection after chemoradiation. In this study, we retrospectively analyzed a cohort of node-positive patients to examine pathological response as well as clinical outcome after chemoradiation with or without functional neck dissection. METHODS: Using the radiation oncology records from 1993 until 2003, a population of 420 patients with squamous cell cancer of the head and neck were identified. Of these, 34 patients were clinically node positive at the time of diagnosis and under went chemoradiation as their primary therapy. All patients received a concurrent platinum-based regimen. Median radiation dose to gross neck disease was 68.4 Gy (range: 50.4-73.8 Gy). RESULTS: Median follow-up time was 25 months (range: 4-88 months). Patients with a complete response (17/34, 50%) after receiving 50 Gy finished the full course of therapy but did not undergo functional neck dissection. Only one patient (1/17) in this observation group experienced relapse in the neck. Patients with a partial response who received 50 Gy (17/34) completed therapy and under went functional neck dissection, regardless of response at the end of therapy. Fifty percent (3/6) with positive pathology had a regional relapse in the neck, whereas only 1/11 patients with negative pathology relapsed in the neck. This result compared favorably with those who were observed after chemoradiation. CONCLUSIONS: Clinical response at 50 Gy can be an effective means of selecting patients for functional neck dissection. Patients with complete response at 50 Gy may be observed with a low regional recurrence rate. Those patients with a partial response should undergo adjuvant neck dissection.

Antineoplastic Combined Chemotherapy Protocols↗

Relation between serologic response and pathologic findings in sheep with naturally acquired paratuberculosis.

OBJECTIVE: To investigate the relation between lesions and serologic response in sheep with naturally acquired paratuberculosis and to evaluate the efficacy of agar gel immunodiffusion (AGID) and ELISA as diagnostic tests. ANIMALS: 134 adult sheep, culled by the owner from flocks with history of severe chronic weight loss. PROCEDURE: Before euthanasia, blood samples were collected and serum was obtained. AGID and ELISA were performed, using a protoplasmic antigen of Mycobacterium paratuberculosis. Sensitivity and specificity of these techniques were evaluated, using histopathologic findings as a reference. Histologic studies were carried out focusing on specimens containing intestinal organized lymphoid tissue. RESULTS: Of the sheep examined, 46.3% had lesions that were classified in 5 categories, according to their location, extension, cellular types, and presence of acid-fast bacilli. Regarding serologic test results, 37.1% of sheep with lesions had a positive AGID result, and all sheep without lesions had negative results. However, ELISA positivity was slightly greater--48.4% of sheep with lesions; however, by use of ELISA, 11.1% of sheep without lesions had positive results. CONCLUSION: A close relation between pathologic findings and serologic response was determined, especially between presence of acid-fast bacilli (potentially heavily shedding sheep) in the intestinal lesions and positivity to serologic tests, especially AGID. CLINICAL RELEVANCE: On the basis of these results, together with its high specificity, reliability, and the difficulty of fecal specimen culture in sheep, AGID is proposed as a useful tool for seeking evidence of paratuberculosis in live sheep, and therefore, is suggested as the basis for control programs in areas in which the disease is a serious threat to sheep production.

Animals↗

Aberrant p53 expression predicts clinical resistance to cisplatin-based chemotherapy in locally advanced non-small cell lung cancer.

The development of cisplatin-based induction chemotherapy followed by surgical resection or radiation has improved the poor prognosis of stage III non-small cell lung cancer (NSCLC). In vitro studies indicate that p53 can modulate cisplatin-induced cytotoxicity, but the molecular genetic features determining response or resistance to cisplatin in vivo must be defined. For this reason, tumor specimens from 52 patients with stage IIIA NSCLC entered in a prospective clinical trial of cisplatin-based induction chemotherapy followed by surgical resection were examined for p53 expression by immunohistochemical staining before and after induction chemotherapy. p53 expression was correlated with clinical and pathological response using Fisher's exact test. No correlation was established between p53 expression and clinical response because 47 of the 52 patients studied had a major response. However, a significant association was observed between aberrant p53 expression and resistance to chemotherapy as assessed by pathological response. Only 3 of the 20 patients whose tumors exhibited a high level (+ + to + + + +) of p53 staining experienced a major (+ + + to + + + +) pathological response to chemotherapy. Only 7 of 52 cases examined before and after chemotherapy treatment exhibited a change in the level of p53 expression after cisplatin-based chemotherapy. These results indicate that cisplatin alters p53 expression infrequently and suggest a direct link between aberrant p53 expression and resistance to cisplatin-based chemotherapy in NSCLC.

Carcinoma, Non-Small-Cell Lung↗

A combined modality approach to the management of oesophageal cancer.

This study aims to update the experience of multimodality approaches in the management of oesophageal cancer that have been adopted in several Australian and New Zealand hospitals. Between 1984 and 1985, 92 patients received pre-operative radiotherapy (30-36 Gy over 3 weeks) and one of two chemotherapy regimes (one or two courses of i.v. cisplatin 80 mg/m2 plus a 4-5 day continuous i.v. of fluorouracil 5-800 mg/m2/day) concurrently prior to surgery. Eighty-two patients (89%) underwent resection as planned. Operative specimens were microscopically free of residual tumour in 18 patients. Eight patients (9%) had treatment-related deaths: seven from surgery and one due to pre-operative chemoradiation. The Kaplan-Meier 5-year cause-specific survival estimates were 32.9 +/- 7.8% for the 58 patients with squamous cancer and 0% for the 32 with adenocarcinoma. Complete pathological response to the pre-operative regime was more common in females and was associated with a survival advantage. Five-year cause-specific survival expectation in patients who experienced a complete pathological response was 71.5 +/- 12.4%, whereas it was only 15.9 +/- 5.6% in patients who had residual cancer in their surgical specimens. Although less toxic the pre-operative regime utilizing only one cycle of chemotherapy was no less efficacious either in producing a complete pathological response or in terms of survival expectation. This uncontrolled pilot study has produced encouraging long-term results, especially for patients with squamous carcinoma that experienced a complete response to pre-operative synchronous chemoradiotherapy. A randomized controlled study comparing surgery alone with (one cycle) chemoradiation followed by surgery is now underway.

Adult↗

Overexpression of p53 protein associates decreased response to chemoradiotherapy in patients with esophageal carcinoma.

Induction chemoradiotherapy before esophagectomy for esophageal carcinoma seems to improve patient survival. Given the toxicity of this regimen, it would be useful to predict those patients likely to benefit. p53 is known to mediate apoptosis in response to DNA damage, but there are few data evaluating the relationship between p53 expression and chemoradiosensitivity in human tissues. We immunohistochemically evaluated p53 protein expression in 95 biopsy specimens from patients with esophageal carcinoma before chemoradiotherapy. p53 expression was correlated to the pathologic response identified in subsequent esophagectomy specimens. p53 immunoreactivity was recorded semiquantitatively using the following scale: neg, < 5%; 1+, 5-25%; 2+, 26-50%; 3+, 51-75%; 4+, > or = 76%. Pathologic response in esophagectomy specimens was categorized as overt residual tumor (ORT), minimal residual tumor, and no residual tumor. Of the 95 patients, 64 had adenocarcinoma, and 31 had squamous cell carcinoma. Of those with adenocarcinoma, 46 (72%) of 64 were positive for p53. Thirty-seven (80%) of 46 p53+ patients had ORT, compared with 4 (22%) of 18 p53- patients (P < .001). There was no correlation between the degree of p53 staining and pathologic response. Of those with squamous cell carcinoma, 13 (42%) of 18 were positive for p53. Three (23%) of 13 p53+ patients had ORT, compared with 4 (22%) of 18 p53- patients (P = .96). Our data indicate that overexpression of p53 protein is associated with decreased responsiveness to induction chemoradiotherapy in patients with esophageal adenocarcinoma but that no such association exists in patients with esophageal squamous cell carcinoma.

Adenocarcinoma↗

Activated nuclear factor-kappa B and cytokine profiles in the esophagus parallel tumor regression following neoadjuvant chemoradiotherapy.

Esophageal adenocarcinoma is increasing in incidence; it relates to chronic gastroesophageal reflux, it is difficult to cure, and treatment modalities increasingly use chemotherapy and radiation therapy prior to resectional surgery. Nuclear factor-kappa B (NF-kappaB) is a pleiotropic transcription factor that regulates several genes for cytokines and enzymes involved in inflammation and immunity, and we have previously described sequential expression of NF-kappaB from the normal esophagus through Barrett's metaplasia to adenocarcinoma. The aim of this exploratory study was to assess the NF-kappaB status and cytokine profiles pre- and post-chemoradiotherapy for esophageal adenocarcinoma. Fresh biopsy specimens obtained from 20 patients with esophageal adenocarcinoma and normal adjacent squamous epithelium were obtained pre-, during and post-chemoradiotherapy, and NF-kappaB expression was analyzed by electrophoretic mobility shift assay. The cytokine protein content of interleukin-1 beta (IL-1beta) and interleukin-8 (IL-8) of tissue homogenates was measured using the ELISA technique. NF-kappaB was constitutively activated in tumor tissues from esophageal adenocarcinoma but was not detected in adjacent normal esophageal mucosa. Elevated levels of IL-1beta and IL-8 were significantly (P < 0.05) higher in tumor tissues compared to control tissues. Patients with a major or complete pathological response (responders) were associated with absence of activated NF-kappaB from nuclear extracts after treatment. Moreover, IL-1beta and IL-8 levels were significantly (P < 0.05) down-regulated in tumor tissues from patients who demonstrated a complete pathological response. No differences in NF-kappaB, IL-1beta and IL-8 levels were detected pre- and post-treatment in patients who did not have a major or complete pathological response (non-responders). The study suggests that monitoring of molecular and cytokine patterns in patients undergoing this neoadjuvant regimen may help subselect the cohort that derives most benefit from the multimodal approach.

Adenocarcinoma↗

Chemokine regulation of normal and pathologic immune responses.

Chemokines are small basic proteins that are the major mediators of all leukocyte migration. There are at least 46 distinct chemokines, and 19 chemokine receptors, making it easily the largest cytokine family. Chemokines can be both beneficial and harmful, by either stimulating an appropriate immune response to microbial invasion, or by mediating pathologic tissue destruction in many types of human disease. Chemokines have been implicated in the tissue destruction seen in autoimmune diseases, atherosclerosis, allograft rejection, and neoplasia. Chemokines also play essential roles in normal lymphocyte trafficking to primary and secondary lymphoid organs for antigen presentation and lymphocyte maturation. Chemokines also regulate hematopoietic stem and progenitor cell homing and proliferation. Therefore, it is likely that chemokines will become important targets for pharmacologic intervention in a wide variety of human diseases in the future.

Animals↗

Correlation of different 5-FU regimens and time to surgery with pathological complete response in locally advanced rectal cancer patients treated by pre-operative chemo-radiation.

The best pre-operative chemo-radiation regimen has still to be defined for patients with rectal cancer. We retrospectively performed a study comprised of 26 patients with T3/4 adenocarcinoma of the rectum. Eleven patients received concurrent protracted venous 5-FU infusion (PVI), 11 had bolus, 1 had 4-day infusions, and 3 did not receive concurrent chemotherapy. All patients underwent surgical resection. Different variables were analyzed in relation to pathologic complete response (pCR) and survival. The use of PVI is associated with a higher pCR rate (45.5% vs. 6.7%, p = 0.054) and a trend towards less proportion of death (p =0.091), but no difference in overall survival (p = 0.439). Patients in the PVI group received a higher total 5-FU dose during radiation (p < 0.001) and had a longer delay between radiation and surgery (p = 0.002). Further study with a larger patient population is needed to confirm our observation.

Adult↗

Epidoxorubicin and paclitaxel as primary chemotherapy for T > 3 cm and T4 breast cancer patients.

UNLABELLED: The Anthracyclines/Taxanes combination is often used in adjuvant and advanced breast cancer. PURPOSE: To evaluate the toxicity and pathological response of sequential epidoxorubicin/paclitaxel combination as primary chemotherapy for T > 3 cm and T4 breast cancer patients. PATIENTS AND METHODS: Forty-eight patients with T2 > 3 cm, T3 and T4 breast tumours were treated with Epidoxorubicin (90 mg/m2, i.v.) on day one and paclitaxel (200 mg/m2 over 3 hours) on day 2 every 21 days for four courses. After the fourth cycle the patients underwent modified radical mastectomy or quadrantectomy plus axillary lymph node dissection followed by six courses of intravenous CMF regimen (days 1 and 8, every 4 weeks). Radiotherapy was given to patients undergoing conservative surgery or with T4 cancers. Tamoxifen was administered in ER or PgR positive patients. RESULTS: Out of the 48 patients enrolled into this trial, 43 were evaluable for toxicity and pathological response. Primary chemotherapy with epidoxorubicin and paclitaxel was well tolerated: no heart toxicity was observed during primary chemotherapy and follow-up. Primary toxicity consisted of myalgia, grade 1 neuropathy and grade 3 alopecia. Disappearance of invasive tumours in the breast with node negative was observed in 11.6% of patients: pathological partial response was shown in 56% of patients. On the whole major pathological response was achieved in 67% of our series: in the remaining 33% we found a stable disease or a size reduction less than 50%. No progressive disease was observed. Conservative surgery was performed in 64.5% of T2 and T3 tumours. CONCLUSION: These preliminary data showed that the epidoxorubicin/paclitaxel combination was safe and effective as primary chemotherapy for patients with T > 3 cm and T4 breast cancer patients.

Antineoplastic Combined Chemotherapy Protocols↗

Cellular immune response and pathology in schistosomiasis.

In the present review, some aspects of the cellular response following the murine Schistosoma mansoni infection are described. Due to the peculiar route used by the schistosome to infect its definitive host, the skin appears as a critical site in which the initial events of the host/parasite relationship occur and where the immune response is initiated. Moreover, the induction and the modulation of the granuloma formation, which represent the main aspect of the pathology of this parasitic disease, is under the control of several cellular populations n which CD4 and CD8 T cells play a key role. The cytokines produced in response to the parasite, such as IL7 in the skin and IFN gamma in the liver, seem to influence the further development of immunity against Schistosoma mansoni.

Animals↗