Rifle impulse noise affects middle-ear compliance in soldiers wearing protective earplugs.

OBJECTIVE: We tested middle-ear functioning in humans following intense exposure to noise. Noise generated by small caliber firearms was thought to have no effect on the middle-ear. DESIGN: A cross-over design. We measured middle-ear impedance, acoustic reflex, distortion product otoacoustic emissions (DPOAEs), and transient evoked otoacoustic emissions (TEOAEs) before and after practice rounds performed twice per day. STUDY SAMPLE: Fifty-nine soldiers equipped with earplugs undergoing regular training for a special mission. The mean noise exposure (LAeq8h) was estimated to be 106 ±1 dB SPL. RESULTS: Impedancemetry revealed a significant increase in the compliance and gradient of the tympano-ossicular chain after impulse noise exposure in the right and left ears. Acoustic reflex reactivity did not show a significant change. DPOAEs and TEOAEs were slightly decreased at 2 kHz, and showed a marked asymmetry in disfavor of the left ear. In soldiers with initial high reactivity of acoustic reflex, increased compliance was associated with a significant decrease in left TEOAEs at 1.5 and 2 kHz. CONCLUSION: Our results suggest that the use of small-caliber firearms, even while wearing earplugs, affects middle-ear function and may play a role in the early stage of auditory fatigue encompassing tinnitus.

[Not Available].

PURPOSE OF THE STUDY: To evaluate the efficacy of fractionated stereotactic reirradiation with CyberKnife (CK) performed in 6 patients with high grade gliomas treated in Luxembourg with local recurrence (LR). PATIENTS AND METHODS: Between 04.2014 and 06.2016, 6 patients with multiform grade IV gliomas LR were reirradiated with CK (protocol CNER re-RT CFB 1), as reirradiation. The mean time between primary radiotherapy and local recurrence (LR) is 14.1 months [4 - 38]. CK is performed with a dose of 36 Gy in 6 fractions (5 cases) and 30 Gy in 3 fractions (1 case) Results : LR after CK (progression free survival) is 3.4 months [2 - 7] (5 cases assessment). Mean survival after CK is 12 months [3 - 22] (3 cases assessment). Mean survival after initial diagnosis is 37 months [17 - 58] (3 cases assessment). No toxicity is noticed (4 cases assessment). Time to first progression after primary treatment is a strong predictor for survival. Fractionated stereotactic reirradiation with CK is well tolerated and effective (survival) in patients with LR high grade gliomas. In accordance with these results, the CFB Conseil Scientifique recommends a new paradigm for MRI follow-up high grade gliomas. After first line treatment, an MRI has to be performed every 3 months, to identify LR earlier, and to offer the patients a way of salvage with CK option, in order to increase his chances of better survival.

[Radiotherapy after prostatectomy: experiences in Luxembourg from 2005 to 2006]. / Radiothérapie après prostatectomie: expérience au Luxembourg de 2005 a 2006.

Radical prostatectomy is a therapeutic option for the treatment of localized prostate cancer (T1 and T2). The prognostic factors which define risks of recurrence after prostatectomy are: capsular invasion, invasion of resection margins, seminal vesicle invasion. Two randomized trials show that adjuvant radiotherapy improves local control and biochemical recurrence-free survival. Between 2005 and 2006, 12 patients of Centre François Baclesse have been irradiated on theprostatic loge. Immediate post-operative radiotherapy was preferably used. Late toxicity (grade 1) occurred only in one patient (1 case out of 8). Based on the literature, immediate postoperative irradiation is preferentially proposed in case of unfavourable factors, or possibly used secondly, in case of biological recurrence (in early situation i.e. PSA < 0.5).

[Localized prostatic cancer: treatment exclusive by radiotherapy guided by imagery, experiences in Luxembourg in 2005 and 2006]. / Cancer localisé de la prostate: traitement par radiothérapie exclusive guideée par l'imagerie, expérience au Luxembourg en 2005 et 2006.

Exclusive radiotherapy is one of therapeutic standard in the curative treatment of localized prostate cancer. Results are equivalent when compared with other treatment regimens (radical prostatectomy or curietherapy) in localized forms. However, the patients risks profiles to predict noxious effects are different. Between 2005 and 2006, 27 patients have been treated with intensity modulated radiation therapy and image-guided radiotherapy (IGRT), after implantation of gold markers to target prostate localization during daily radiotherapy seances. The total dose of radiation delivered in prostate is 74 Gy with respect to the maximal dose defined to the rectum and to the bladder. Late toxicity was limited to grade 2 (rectitis and cystitis). These symptoms were temporary. One patient out of 20 patients with one-year follow-up experienced biological recurrence with metastasis progression. New radiotherapy technologies have allowed to reduce the incidence of the toxicity especially late rectal toxicity (2.2% in 2006) within a limited time period (one-year minimum).

Postoperative pelvic radiotherapy with or without elective irradiation of para-aortic nodes and liver in rectal cancer patients. A controlled clinical trial of the EORTC Radiotherapy Group.

OBJECTIVE: The purpose of this randomized multicenter study was to assess the impact on disease free and overall survival of low dose irradiation to para-aortic nodes and liver in patients with a locally advanced resected rectal cancer receiving a 50 Gy postoperative pelvic radiotherapy. PATIENTS AND METHODS: Main inclusion criteria were: a curative resection for a histologically proved carcinoma of the rectum, Gunderson-Sosin stages B2-B3, C1-C3, age <70 years. The patients were randomized between pelvic irradiation (Lim-XRT): 50 Gy in 25 fractions over 5 weeks and extended irradiation (Ext-XRT): same scheme/doses in the pelvis and extended fields on para-aortic nodes and liver, delivering 25 Gy in 19 fractions over 25 days. From 1983 to 1992, 484 patients were enrolled by 18 EORTC institutions and 29 patients were ineligible. The end-points were local and distant relapses, toxicity and survival. RESULTS: Compliance to treatment: 87.2% in Lim-XRT arm and 71.8% in Ext-XRT arm. Moderate acute hematological and hepatic toxicities were significantly increased in Ext-XRT arm. Among 325 patients at risk, 44 suffered a severe intestinal complication requiring surgery in 29. The 5- and 10-year estimates of disease free survival were respectively 42 and 31% in Lim-XRT arm and 47 and 31% in Ext-XRT arm (ns). The corresponding figures for overall survival were respectively 45 and 40% in Lim-XRT arm and 48 and 37% in Ext-arm (ns). The 10 years estimate of intra-pelvic failures was approximately 30% in both arms. Patients in Ext-arm appeared to have a slight shorter interval free of liver metastases (P=0.047). CONCLUSION: Low dose irradiation to the para-aortic nodes and liver did not improve survival for patients with resected adenocarcinoma of the rectum.

The glutathione-related detoxification system is increased in human breast cancer in correlation with clinical and histopathological features.

PURPOSE: The glutathione detoxification pathway includes glutathione S-transferase (GST) and peroxidase (GPX) isoenzymes as well as glutathione reductase (GSSR). Though well established from cultured cancer cell lines, its involvement in resistance is still unclear in the tumours. This study aimed to describe the parameters that influence the glutathione contents and associated activities in breast cancer. METHODS: The components of the glutathione pathway were measured in the tumours from 41 women with primary breast cancer in comparison with those in the matched tumour-free samples. Appropriate statistical studies (regression analysis, Wilcoxon signed rank test) explored the influence of clinical and prognostic factors. RESULTS: Reduced and total glutathione contents were largely increased (P < 0.0001) and all related activities were significantly enhanced in the tumours. Interindividual variations were described, probably due to various parameters (age, menopause, axillary lymph node status, S and G2 + M cell fractions, ER, cathepsin-D and c-ErbB-2 expressions) that influence particular components of the glutathione pathway, especially the glutathione levels. CONCLUSIONS: The breast tumours improved their redox status and detoxification capacities depending on various parameters of significance for cell proliferation and aggressiveness, which supports the involvement of the glutathione pathway in malignant cell resistance to oxidative stress and apoptosis.

Gemcitabine and protracted 5-FU for advanced pancreatic cancer. A phase II study.

BACKGROUND/AIMS: Although chemotherapy in advanced pancreatic cancer procures dismal results, both 5-fluorouracil and gemcitabine have shown a modest activity. We report a phase II study of gemcitabine combined with protracted 5-fluorouracil. METHODOLOGY: Gemcitabine was given at 1000 mg/m2/week intravenously, in combination with concomitant 5-fluorouracil 200 mg/m2/day as a protracted venous infusion, both 3 out of 4 weeks in patients with locally advanced or metastatic pancreatic adenocarcinoma. Twenty-nine patients were enrolled, among whom 27 were metastatic. Response rate, overall and progression-free survival were endpoints, as well as tolerance and clinical benefit. RESULTS: We observed 3 (10%) partial responses, and 12 (42%) stabilizations within which the median disease control was 5.6 months. The median progression-free and overall survivals were 2.8 and 4 months, respectively. A clinical benefit was observed in 39% of patients. Myelosuppression was the main toxicity, but no grade 4 was observed. Other toxicities were mild. CONCLUSIONS: This combination chemotherapy was well tolerated in advanced pancreatic cancer patients.

The glutathione-related detoxification pathway in the human breast: a highly coordinated system disrupted in the tumour tissues.

Glutathione and the associated enzymes, glutathione S-transferases, peroxidases, and reductase, have been implicated in cancer chemoresistance. This pathway was investigated in paired cancerous and peritumoral breast samples from 41 women. The tumours exhibited a higher redox status as deduced from increased transferase, peroxidase, and reductase activities and from higher total and reduced glutathione contents. Several components were strongly correlated in peritumoral tissues, suggesting a highly co-ordinated glutathione pathway that appeared disrupted in breast tumours with only a few correlations left. Therefore, resistance could spontaneously result from deregulated variations in the glutathione pathway, which might be relevant to the malignant disease progression.

Outpatient treatment with subcutaneous interleukin-2 and interferon alfa administration in combination with fluorouracil in patients with metastatic renal cell carcinoma: results of a sequential nonrandomized phase II study. Subcutaneous Administration Propeukin Program Cooperative Group.

PURPOSE: We report the results of the Subcutaneous Administration Propeukin Program (SCAPP) II trial of an outpatient treatment in renal cell carcinoma using interleukin-2 (IL-2) and interferon alfa-2a (IFN-alpha) administered subcutaneously in combination with fluorouracil (5-FU). The objective of this multicenter trial was to confirm that the combination of IL-2, IFN-alpha, and 5-FU leads to a response rate greater than 20%. PATIENTS AND METHODS: Patients with metastatic renal cell carcinoma were included in this study. During the induction phase of the treatment, which lasted 10 weeks, IL-2 and IFN-alpha were administered subcutaneously three times a week for 8 weeks at doses of 18 MIU and 9 MIU, respectively. During these 8 weeks, every Monday, 5-FU was administered at a dose of 750 mg by intravenous infusion over 30 minutes. After evaluation, responding patients or patients with stable disease (SD) were given maintenance treatment, until disease progression (PD) or the appearance of unacceptable toxicity. Each maintenance cycle consisted of a 2-week treatment followed by a three-week rest period. During treatment, IL-2 and IFN-alpha were administered subcutaneously three times a week at doses of 18 MIU and 9 MIU, respectively. Every Monday, 5-FU was administered at a dose of 750 mg by intravenous infusion over 30 minutes. RESULTS: This trial was closed when the sixth sequential analysis showed the lack of benefit from this combination. At the end of the induction period, of 62 patients, 12 (19%; 95% confidence interval [CI], 10% to 31%) reached an objective response, including one complete response (CR), 16 presented with SD, and 27 showed PD. Twenty-seven patients (43%) developed severe toxicity that required reduction of the planned doses (13 patients), delayed treatment (eight patients), or treatment termination (six patients). Seventeen patients were given maintenance treatment. One- and 2-year survival rates were estimated at 55% and 33%, respectively. The 2-year survival rate was 15% in 11 patients who presented with three poor-prognosis factors and 41% in 51 patients who initially presented with no, one, or two poor-prognosis factors (P = .04). CONCLUSION: As in other recently published studies that used 5-FU, IL-2, and IFN-alpha, the multicenter SCAPP II trial in patients with metastatic renal cell carcinoma generated severe toxicity. This sequential trial failed to confirm the favorable results previously obtained by Atzpodien and Sella with this combination of three drugs. Its efficacy, assessed on the response and survival rates, is near to the results observed in programs that used IL-2 alone given subcutaneously.

[Subcutaneous administration of interleukin-2 in ambulatory treatment of patients with metastatic renal cancer. Three-year results of the SCAPP I program]. / Traitement ambulatoire par interleukine 2 administrée par voie sous-cutanée chez des patients porteurs d'un cancer du rein métastatique. Résultats à 3 ans du programme SCAPP i.

We report a french experience of subcutaneous administration of interleukin-2 in treatment of patients with metastatic renal cell carcinoma. Thirty-nine patients with metastatic renal cell carcinoma were included in the study. During the 10-week induction period, interleukin-2 was administrated subcutaneously 5 days a week for 8 weeks. The weekly dosage were 90 MIU during weeks 1 and 6; 63 MIU during weeks 2 to 4 and 7 to 9. After evaluation, responders and patients with stable disease received maintenance treatment which was discontinued upon the appearance of disease progression or unacceptable toxicity. During the maintenance period, interleukin-2 was administered 5 days a week for 4 weeks followed by a 2-week rest period. The weekly dosages were 90 MIU in week 1 and 63 MIU in weeks 2 to 4. After completion of induction treatment, 7 of 39 evaluable patients (18%) had objective responses with 1 complete response. A diminution of dose or interruption of treatment occurred with 7 patients because severe toxicity. Other systemic side effects in the remaining patients were acceptable. Seventeen patients received maintenance treatment. The median follow-up of all the patients included was 21 months. The 1, 2 and 3 years survivals were 64%, 33% and 22% respectively. This multicentric trial confirms the efficacity of subcutaneously-administered interleukin-2 in patients with metastatic renal cell carcinoma in terms of both response rate and survival. Unfortunately, increasing total doses of administrated interleukin-2 does not seem to increase efficacity according to response rate, but is more toxic.

Subcutaneous recombinant interleukin-2 (rIL-2) in out-patients with metastatic renal cell carcinoma. Results of a multicenter SCAPP1 trial.

BACKGROUND: This multicenter phase II trial was conducted in order to evaluate the efficacy and toxicity of the subcutaneous route of administration of rIL-2 in the treatment of patients with metastatic renal cell carcinoma and to check whether an increased cumulative dose of rIL-2 increases efficacy. PATIENTS AND METHODS: Thirty-nine patients with metastatic renal cell carcinoma were included in this study. During the induction period, rIL-2 was administered subcutaneously 5 days a week for 8 weeks. The weekly dosages were 90 MIU during weeks 1 and 6;63 MIU during weeks 2 to 4 and 7 to 9. After evaluation, responders and patients with stable disease received maintenance treatment which was discontinued upon the appearance of disease progression or unacceptable toxicity. During the maintenance period, rIL-2 was administered 5 days a week for 4 weeks followed by a 2-week rest period. The weekly dosages were 90 MIU in week 1 and 63 MIU in weeks 2 to 4. RESULTS: After completion of induction treatment, 7 of 39 evaluable patients (18%) had objective responses (95% CI: 9% to 37%) with one complete response. Treatment was interrupted or reduced due to toxicity for seven patients: Neuropsychiatric symptoms (3 patients), joint pain (1 patient), major asthenia and anorexia (1 patient), stroke (1 patient), and septicemia (1 patient). Other systemic side effects in the remaining patients were acceptable. Seventeen patients received maintenance treatment. In none of the patients did the response status improve during this maintenance period. The median follow-up of all of the patients included was 19 months. The one- and two-year survivals were 65% and 33%, respectively, ad the median duration of response was 11 months (5 to 16+). CONCLUSIONS: This multicentric study confirms the efficacy of subcutaneously-administered rIL-2 in patients with metastatic renal cell carcinoma in terms of both response rate and survival. The role of a maintenance therapy needs further evaluation.

[Initial locoregional chemotherapy in recurrent and locoregional advanced or inoperable stages of pelvic uterine and anorectal cancers]. / Chimiothérapie locorégionale initiale dans les récidives et les formes locorégionales avancées ou inopérables des cancers pelviens utérins et anorectaux.

The authors report their 12 years of experience of intra arterial chemotherapy in pelvic recurrences and inoperable advanced stages of uterine carcinoma, rectal cancer and anal cancer. In squamous cell cancers the drug associations were mitomycin C, bleomycin, fluorouracil and folinic acid and cisplatin. In adenocarcinoma the same protocol contained no bleomycin. Drugs were infused for a 48 hours period in continuous infusion. The dosages were the same than in the intravenous regimens. Twenty patients with pelvic recurrences were included in this retrospective study: six were uterine cancers, fourteen were colo rectal cancers and two had advanced stage uterine cancer. Pain decreased in 10/14 patients with ano-rectal cancer pre sacral recurrence. Partial response was observed in 12 patients. Complete secondary surgical resection was possible in 4/14 rectal cancers and 6/6 uterine cancer recurrences. Chemotherapy induced a pathological complete response in 4/6 uterine cervix carcinoma recurrences. These observations led to perform pelvic intra arterial chemotherapy as first line treatment of locally-advanced inoperable pelvic tumors: 11 uterine cancers and five ano-rectal cancers. The objective were: tumor reduction before radiotherapy or surgery, tumor sterilization, decrease tumor volume for better radiation dosimetry, increase the chance of organ-preservation. The observation of tumor reduction in this small number of patients does not allow to draw definite conclusions. However the introduction of intra arterial pelvic chemotherapy as first line treatment of inoperable pelvic cancer warrants further studies.

[Therapeutic results in a series of 73 cases of nasopharyngeal carcinoma]. / Résultats thérapeutiques d'une série de 73 cas de carcinome naso-pharyngé.

From 1975 to 1982, 73 cases of nasopharyngeal carcinoma were treated in Strasbourg (Centre Paul Strauss) and Metz (CHR Bon Secours). 34.1% of the patients were of maghrebine origin, the others were europeans. Two histological types were studied: undifferentiated carcinomas of UCNT type, spinocellulars carcinomas of CS type. 60.3% of the patients had T3 and T4 stages, and only 27.4% of the patients had no pathological nodal. As to treatment, radiotherapy is the best choice, because of the deep situation and the frequent involvement of nodals in the nasopharyngeal carcinoma. Taking into account the level of radiation doses, complications remain acceptable. The rate of overall failure is 51.3% at 3 years. The prognostic factors are essentially linked with sex, age, tumor site, site, histological type, T stage of UICC classification and TNM of the same classification, N stage of HO classification, and evaluation of treatment response realised at 4 months. The crude overall survival rate is 52% for patients of the serie.