Partial protection and abomasal cytokine expression in sheep experimentally infected with Haemonchus contortus and pre-treated with Taenia hydatigena vesicular concentrate.

The abomasal expression of IL-2, IL-4, IL-6, IL-10 and IFNγ in lambs experimentally infected with Haemonchus contortus and its relationship to protection induced by a Taenia hydatigena larvae vesicular concentrate (ThLVC) were evaluated. The lambs that were only infected with H. contortus larvae showed a worm burden greater (p<0.05) than the lambs that received ThLVC prior to infection. Moreover, the lambs that received ThLVC showed a greater (p<0.05) number of blood eosinophils than the lambs that did not receive the ThLVC. In general, the lambs that received ThLVC prior to infection had a greater amount of eosinophils and mast cells and higher in situ expression of IFNγ, IL-2, IL-4, IL-6 and IL-10 in the abomasal wall than the lambs that were infected with H. contortus only or that received ThLVC (p<0.05) only. A higher expression of IL-2 and IFNγ in the submucosa compared to the abomasal mucosa and a higher expression of IL-4 in the abomasal mucosa compared to the submucosa was observed (p<0.05). These results suggest that there is a Th1 type response in the abomasal submucosa and a Th2 type response in in the abomasal mucosa. The amount of eosinophils and mast cells and the in situ expression of IFNγ, IL-2, IL-4 and IL-6 in the abomasal walls were negatively correlated with the worm burden (p<0.05). These results suggest that ThLVC is a non-specific immune stimulator for the abomasal immune response, and it is likely that the protection observed is the result of this effect.

Preoperative concomitant radiochemotherapy in squamous cell carcinoma of the esophagus: results of a study of 56 patients.

PURPOSE: Today the prognosis for patients with esophageal carcinoma still remains quite poor. In the last few years interesting results have been obtained by associating radio- and chemotherapy with or without surgery with this type of cancer. In this work we report the results of concomitant radio- and chemotherapy in a split-course schedule preceeding surgery for the treatment of squamous cell carcinomas of the esophagus. METHODS AND MATERIALS: Fifty-six patients with squamous cell carcinomas of the esophagus were treated between April 1989 and September 1993 in the Centre Hospitalier Universitaire in Brest, France with two courses of preoperative concomitant radiochemotherapy, separated by a 2-week interval, and followed by surgery (each course 18.5 Gy in five fractions, days 1-5 with continuous infusion 5-fluorouracil (5-FU) 800 mg/m2 days 1-5 and cisplatinum 70 mg/m2 day 2). Patients who had responded well to preoperative treatment (response > 50%) received four more courses of chemotherapy alone. The two patients who were not operated and those with palliative surgery received a third course of radiochemotherapy (radiotherapy 12 Gy in five fractions, days 1-5). RESULTS: Fifty-four patients were operated on. Twenty-one showed histological complete response at surgery (37.5% of the whole group). Actuarial survival for the 56 patients was 55% at 3 years and 30% at 4 years, with a median survival of 37.4 months (40.4 months for complete responders to preoperative treatment). Toxicity of preoperative concomitant radio-chemotherapy was low (5-FU had to be stopped in one patient because of cardiac rythm disturbances and in another patient because of aplasia Grade 4 associated with infection after the first course). Postoperative mortality was 11% (six patients). CONCLUSION: This combination of preoperative radiochemotherapy followed by surgery seems to improve both response rates and survival in patients with esophageal cancer when compared with previous patients treated with surgery alone in our hospital or with results found in literature and it warrants further studies.

[Fotemustine (Muphoran) in 22 patients with relapses of high-grade cerebral gliomas]. / Fotémustine (Muphoran) chez 22 patients présentant des récidives de gliomes cérébraux de haut grade.

Fotemustine is a third-generation nitrosourea characterized by a phosphoalanine carrier group grafted onto the nitrosourea radical, which gives it a high lipophilicity and a better penetration through the cell membrane. Between September 1988 and December 1997, 22 patients with inoperable or incompletely resected recurrent high-grade gliomas of the brain were treated at the University Hospital in Brest (France). Treatment consisted of three weekly infusions of fotemustine (100 mg/m2 days 1, 8 and 15). If patients responded or were stabilized, fotemustine was continued at the same dose, but every three weeks only. Four patients responded to the treatment (18%), while 6 were stabilized (32%). Main toxicity was haematologic (leucopenia and, above all, thrombocytopenia); treatment was only interrupted in one patient for leucothrombopenia, and there was no toxic death. Medium duration of response and/or stabilisation was 6.5 months, and median survival 9.4 months in responding and/or stabilized patients, while it was only 5.0 months if tumour progressed under chemotherapy (median survival for all patients: 7.5 months). Besides, there was a difference in survival in favour of the young patients (< 50 years-median survival = 11.8 months) in comparison with patients between 50 and 60 years (median survival = 6.8 months; p = 0.0282) or elderly patients (> 60 years-median survival = 5.8 months; p = 0.0634). In our series, we did not found any difference in survival according to the initial performance status of patients before treatment. Therefore, fotemustine seems to represent an interesting well-tolerated treatment possibility in patients with inoperable recurrent malignant gliomas of the brain.

[Split-course concomitant radiochemotherapy plus surgery vs. surgery alone in squamous cell carcinoma of the esophagus. A non-randomized retrospective study of 184 patients]. / Radiochimiothérapie concomitante en split-course plus chirurgie contre chirurgie seule pour les carcinomes épidermoïdes de l'oesophage. Etude rétrospective non randomisée de 184 patients.

From April 1989 to October 1995, 184 patients with squamous cell carcinomas of the esophagus were treated either with surgery alone (112 patients) or with preoperative concomitant radiochemotherapy (72 patients) (2 courses of 18.5 Gy in 5 fractions, days 1-5 with continuous infusion 5-fluorouracil (5-FU) days 1-5 and cisplatinum day 2, separated by a 2-week interval) followed by surgery, and by 4 more courses of chemotherapy alone for good responders. Twenty-seven of these last 72 patients showed histological complete response at surgery (37.5%). There was no statistically significant difference in overall survival between the 2 groups although there were much more T1 patients (small tumors < or = 5 cm in the previous TNM classifications) and less T3 patients (evidence of spread beyond the esophagus) in the surgery alone group, and nevertheless, median survival was better in the combined treatment group (33.6 months versus 21.8 months). However, considering tumor size, there was a statistically significant difference in median survival in favor of the combined treatment group for all T2 patients (> 5 cm without evidence of spread beyond the esophagus in the previous TNM classification) (48.6 months versus 13.8 months), both for T2N0 and T2N1 patients, but also for T1N1 patients (< or = 5 cm with nodal involvement). For the few T3 patients (evidence of spread beyond the esophagus in the previous TNM classification), there was no statistically significant difference between the 2 groups, but the survival curves seemed to show some advantage in favor of the combined treatment group for T3N1 patients. The sex of the patients and the third of the esophagus involved by the tumor did not seem to be of any influence on survival. On the other hand, patients 70-year-old and older showed a poorer survival than other patients. Finally, significantly less patients died with loco-regional recurrences in the preoperatory radiochemotherapy group (32% versus 48%) than in the group treated by surgery alone.

[Multicenter prospective study of cardiac accidents during treatments with 5-FU]. / Etude prospective multicentrique des accidents cardiaques survenus au cours de traitements comportant du 5-FU.

In a prospective, multicenter study, we evaluated the incidence of adverse cardiac effects in 1097 patients receiving 5-FU as a short i.v. perfusion or as a continuous perfusion over 3 to 5 days. There were 29 cardiac events (incidence 1.6%; 4.5% in patients with a history of cardiovascular disease, 1.1% in the remainder). Adverse effects were more frequent in the patients with advanced WHO (WHO = OMS) stage (2 or 3) primary tumors of the upper respiratory or digestive tract, or of the gastrointestinal tract, when 5-FU was given as a continuous perfusion. They also appeared to be more frequent in patients with a history of cardiovascular disease, and mainly occurred during the second or third day of the first course of treatment. Retreatment of eight patients with 5-FU led to the recurrence of symptoms in five. The outcome of these adverse cardiac effects was generally favorable, but 11.5% of the patients died.

[Gastroduodenal metastases: an unusual manifestation of lung cancer. Study of two cases and review ot the literature]. / Métastases gastroduodénales: un mode de révélation exceptionnel du cancer du poumon. Etude de deux cas et revue de la littérature.

INTRODUCTION: Diagnosis of gastroduodenal metastases is rare. Primary tumors are essentially melanomas and breast cancer, and exceptionally lung cancer. EXEGESIS: We report two patients who have a diagnosis of gastroduodenal metastases as initial manifestation of lung cancer. In one case, the patient died 3 weeks after the diagnosis. In the other case, chemotherapy was performed and complete response was obtained for the gastric metastasis. After a few months, node recurrence was diagnosed and the patient died 8 months after the diagnosis. CONCLUSION: We review the endoscopic and non-endoscopic literature and discuss the different histological types and therapeutic strategies concerning these unusual manifestations of lung cancer.

[Immune evaluation in oncologic surgery]. / Le bilan immunitaire en chirurgie carcinologique.

Immunity-linked cells include the lymphocytes and phagocytes. The former can be counted by the rosette techniques or by monoclonal antibodies, while for the latter their function is determined mainly. Good correction has been demonstrated, for example, between the number of so-called E active rosettes and both tumor extension and patient survival. The surgical act itself exaggerates the satellite anomalies of the cancer, but in any case it is followed by immunotherapy which justifies a second application of immunologic techniques.

[Pyoderma gangrenosum and breast cancer: a new case]. / Pyoderma gangrenosum et cancer du sein: un nouveau cas.

We report here a new case of pyoderma gangrenosum (PG) associated with a breast cancer in a 39-year-old woman. We only found in literature three other reports of this rare entity which seems usually to be associated with monoclonal gammopathy, gastro-intestinal diseases such as Crohn's disease, chronic ulcerative colitis, leukemias or rheumatologic diseases. A commun hapten between of tumor and skin may explain the origin of this inflammatory lesion. In our case, PG could be a paraneoplastic syndrome.

[Experimental study of the effect of cobalt irradiation on the rabbit lung]. / Etude expérimentale de l'effet du rayonnement du cobalt 60 sur le poumon de lapin

Rabbit lungs were irradiated with a unique dose of 3,150 rads of CO60. The time related study (from the end of irradiation to 28 days after-wards) of the ultrastructural changes in the alveolo-capillary membrane, shows that the early lesions involve first of all the endothelium, then the epithelium and the surfactant, interstitial involvement being the latest. The course of the lesions is maximal on the 7th day, while interstitial involvement appears and is amplified in the three following weeks, whereas cellular involvement completely regresses. Qualitative study of phospholipids from the pulmonary washing fluid of the irradiated lung shows early changes in the composition of surfactant (fall in lecithins and appearance of substances with similar structure) then a return to a practically normal composition around the 21st day. The nature of this early change in surfactant is debated: is it a change in surfactant secreted and/or an early change in the process of synthesis of surfactant?

[Influence of the localization on the prognostic value of E, E-active and autologous rosettes in lung, esophagus and otorhinolaryngologic cancer]. / Influence de la localisation sur la valeur pronostique des rosettes E, E-actives et autologues au cours des cancers du poumon, de l'oesophage et ORL.

E, E-active and autologous-rosette-forming-lymphocytes (E, Eact-, auto-RFC) were studied in 66 patients with lung cancer (2 stage I, 17 stage II, 20 stage III, 27 stage IV), 42 patients with head and neck cancer (14 stage III, 28 stage IV) and 22 patients with esophagus cancer (11 stage II, 6 stage III, 5 stage IV). Compared to controls, E-RFC were found to be depressed in each of the three different localizations (p less than 0.001), Eact-RFC were found to be depressed in head and neck as well as esophagus cancer (p less than 0,05 and p less than 0,01 respectively) and auto-RFC were found to be depressed in lung and esophagus cancer (p less than 0,01). Mean survival times of patients with RFC over and under 1 SD below the average value were compared. Significant differences were demonstrated in E-RFC and auto-RFC for head and neck cancer and in Eact-RFC for lung cancer.

First-line high-dose sequential chemotherapy with rG-CSF and repeated blood stem cell transplantation in untreated inflammatory breast cancer: toxicity and response (PEGASE 02 trial).

Despite the generalization of induction chemotherapy and a better outcome for chemosensitive diseases, the prognosis of inflammatory breast cancer (IBC) is still poor. In this work, we evaluate response and toxicity of high-dose sequential chemotherapy with repeated blood stem cell (BSC) transplantation administered as initial treatment in 100 women with non-metastatic IBC. Ninety-five patients (five patients were evaluated as non-eligible) of median age 46 years (range 26-56) received four cycles of chemotherapy associating: cyclophosphamide (C) 6 g m(-2) - doxorubicin (D) 75 mg m(-2) cycle 1, C: 3 g m(-2) - D: 75 mg m(-2) cycle 2, C: 3 g m(-2) - D: 75 mg m(-2) - 5 FU 2500 mg m(-2) cycle 3 and 4. BSC were collected after cycle 1 or 2 and reinfused after cycle 3 and 4. rG-CSF was administered after the four cycles. Mastectomy and radiotherapy were planned after chemotherapy completion. Pathological response was considered as the first end point of this trial. A total of 366 cycles of chemotherapy were administered. Eighty-seven patients completed the four cycles and relative dose intensity was respectively 0.97 (range 0.4-1.04) and 0.96 (range 0.25-1.05) for C and D. Main toxicity was haematological with febrile neutropenia ranging from 26% to 51% of cycles; one death occurred during aplasia. Clinical response rate was 90% +/- 6%. Eighty-six patients underwent mastectomy in a median of 3.5 months (range 3-9) after the first cycle of chemotherapy; pathological complete response rate in breast was 32% +/- 10%. All patients were eligible to receive additional radiotherapy. High-dose chemotherapy with repeated BSC transplantation is feasible with acceptable toxicity in IBC. Pathological response rate is encouraging but has to be confirmed by final outcome.