Breastfeeding and risk of breast cancer: a metaanalysis of published studies.

Evidence in favour of an association of breastfeeding with a breast cancer risk reduction remains limited and inconsistent. To evaluate the relation between breastfeeding and breast cancer, a meta-analysis based on a review of the literature was carried out, using as variables ever/never breastfeeding and duration of breastfeeding. Menopausal status at the time of diagnosis of breast cancer was considered to be a potential effect modifier. Only case-control studies could be included in the final analysis. A slight but significant decreased risk of breast cancer was observed in ever breastfeeding, compared with never breastfeeding parous women, using both the fixed and random-effect models. This decrease was more pronounced in non-menopausal women at the time of diagnosis of breast cancer and in long-term breastfeeding women. Hence, breastfeeding appeared to be a protective factor but was of small magnitude compared with other known risk factors for breast cancer. Whether this result should imply a modification in the attitude of both health care providers and women towards breastfeeding, which represents one of the few identified protective factors which is under the control of the mother, and is thus (theoretically) modifiable, remains questionable.

Effects of proton beam irradiation on uveal melanomas: a comparative study of Ki-67 expression in irradiated versus non-irradiated melanomas.

AIMS: To assess the cellular proliferation using the monoclonal antibody Ki-67, in paraffin embedded uveal melanomas irradiated by proton beam, as well as in non-irradiated uveal melanomas. METHODS: 30 enucleated eyes were included for histopathological study and Ki-67 immunostaining. Patients were enucleated between 1991 and 1996 for uveal melanoma, 14 after proton beam irradiation and 16 without treatment (control group). The mean follow up period was 2.5 years after diagnosis and 1 year after enucleation. RESULTS: A significant relation was found between Ki-67 score and mitotic index (r = 0.56, p = 0.001), histological largest tumour diameter (r = 0.38, p = 0. 03), fibrosis (r = -0.35, p = 0.05), absence of tumoral pigmentation (p = 0.05), and presence of vascular thrombosis (p = 0.03). The Ki-67 score was significantly higher in the non-irradiated group (p = 0.01) and in the group of patients whose cause of enucleation was tumoral evolution (p = 0.005) compared with the group of patients enucleated after neovascular glaucoma. The Ki-67 score was very high in a case of orbital recurrence of uveal melanoma and metastatic death. 70% of metastasised tumours showed a Ki-67 score higher than the median value. CONCLUSION: Ki-67 labelling is a reliable method of estimating the proliferative activity in uveal melanomas after proton beam irradiation. The Ki-67 score is significantly correlated with prognostic variables (mitotic index and histological largest tumour diameter), and with radiation effects after proton beam irradiation.

[Treatment of soft tissue sarcomas of the extremities and the trunk by conservative surgery and postoperative irradiation. Apropos of a series of 96 patients]. / Traitement des sarcomes des parties molles des extrémités et du tronc par chirurgie conservatrice et irradiation postopératoire. A propos d'une série de 96 patients.

AIM OF STUDY: Retrospective study of a series of 96 patients presenting with soft tissues sarcoma. Homogeneous treatment between 1980-1992 with conservative surgery and post operative irradiation. PATIENTS AND METHODS: Median age of the 96 patients was 58 years. Tumor site was: upper limb 20, lower limb 46, trunk 30. In 35 cases largest diameter of the tumor was 5 cm or less (T1). All patients were M0. The most frequent pathological sub type was: malignant histiocytofibroma 28, liposarcoma 28. A gross complete surgery was performed in 89 cases. Radiotherapy was performed with cobalt or x 18 MV photons. The dose delivered was 50 Gy with a boost of 10 Gy. No adjuvant chemotherapy was given. RESULTS: Mean follow up was 68 months. Local relapse was seen in 19 patients, six were salvaged by surgery, a limb amputation rates were necessary in 4 cases. The 5 and 10 year-overall survival was 70% and 64%. There was no severe radiation toxicity requiring surgery. A good function of the limb was preserved in all cases. CONCLUSION: These results are in agreement with those of the literature and justify a conservative approach for these soft tissues sarcomas.

[Radiotherapy of cancer of the anal canal. 15 years experience at the Lyon civil hospices and brief review of the literature]. / La radiothérapie du cancer du canal anal. Quinze ans d'expérience aux Hospices Civils de Lyon et brève revue de la littérature.

AIM: Retrospective analysis of a series of 287 anal canal carcinomas seen during a 15-year period in the Department of Radiotherapy Oncology of Hospices Civils de Lyon. MATERIAL AND METHOD: Between 1980 and 1995, 287 patients were managed in the radiotherapy department of Hospices Civils de Lyon. In 25 cases, the patients were referred for recurrence. Post or preoperative irradiation was performed in 12 and 23 cases. Palliative treatment was given to 15 cases and simple follow-up in 7 cases. Radiotherapy was given to 205 patients. In 71 cases irradiation alone and in 134 concomitant radiochemotherapy was given. RESULTS: The 5-year overall survival of the group treated by radiotherapy (205 patients) was 71.5% and the 10 year-overall survival was 60.8%. The specific survival at 5 and 10 years was 81.9% and 74.7% respectively. At 5 years the overall survival was 78% for the group treated by concomitant radiochemotherapy and 60% for the group treated by irradiation alone. CONCLUSION: Radiotherapy is the standard treatment for anal canal carcinoma. Radiochemotherapy seems to improve results in advanced cases. The best irradiation of technique has yet to be defined.

The role of radiotherapy in the conservative treatment of rectal carcinoma--the Lyon experience.

The purpose of this study was to present the Lyon experience using radiotherapy alone or with surgery, with intent to cure rectal cancer and to avoid rectal amputation. Two groups of patients were treated between 1980 and 1996: Group I with radiotherapy alone with contact x-ray for T1 N0 (101 patients) or with a combination of external beam radiation therapy (EBRT), contact x-ray and 192 iridium implant in inoperable T2-3 N0-1 patients (43 patients); Group II with preoperative EBRT either as a pilot study (158 patients) or in a randomized trial (210 patients). With contact x-ray alone it was possible to control T1 N0 in 90% of cases, and with the combined approach 70% of the inoperable patients were controlled. In Group II, anterior resection was performed in 60% to 70% of the patients. Local recurrence was seen in 11% of cases. Surgery is the basic treatment used for rectal cancer but radiotherapy is playing an increasing role in the conservative treatment of this cancer.

Treatment of anal canal carcinoma with high dose radiation therapy and concomitant fluorouracil-cisplatinum. Long-term results in 95 patients.

PURPOSE: To evaluate the long-term results of the treatment of anal canal carcinoma (ACC) with a combined concomitant radiochemotherapy (CCRT) treatment using fluorouracil (5 FU) and cisplatinum (CDDP) with a high dose of radiation therapy. PATIENTS AND METHODS: Between 1982 and 1993 a series of 95 patients were treated. Staging showed a majority of advanced squamous ACC, i.e. 6 T1, 47 T2, 28 T3, 14 T4, 53 NO, 32 N1, 6 N2 and 4 N3. Irradiation was done with high dose external beam radiation therapy (EBRT) followed by a boost with 192 Iridium implant. During EBRT all patients received one course of 5 FU continuous infusion (1 g/m2/day, days 1-4) and CDDP (25 mg/m2/day, bolus days 1-4). RESULTS: The median follow-up time was 64 months. At 5 and 8 years the overall survival was 84 and 77%, the cancer specific survival was 90 and 86% and the colostomy-free survival was 71 and 67%, respectively. The stage and the response of the tumor after EBRT were of prognostic significance. Patients with pararectal lymph nodes had an overall 5-year survival of 76% (versus 88% for non-N1). Among 78 patients who preserved their anus, the anal sphincter function was excellent or good in 72 (92%). CONCLUSION: According to these results and recent randomized trials, CCRT appears as the standard treatment of ACC. Radical surgery should be reserved for local recurrence or persisting disease after irradiation. High dose irradiation in a small volume with concomitant 5 FU-CDDP appears to give a high rate of long-term local control and survival. Careful evaluation of pararectal nodes is essential for a good staging of the disease.

Intraoperative radiation therapy combined with limited lymph node resection in gastric cancer: an alternative to extended dissection?

PURPOSE: To describe the results of a series of 63 Western patients presenting with gastric adenocarcinoma and treated with surgery and intraoperative radiation therapy (IORT) over a 8-year period and to discuss the role of IORT when combined with limited lymph node dissection. METHODS AND MATERIALS: From 1986 to 1993, 63 patients with gastric adenocarcinoma have been operated in the department of radiation oncology of the Hospices Civils de Lyon. The stage was: I in 17, II in 11, IIIA in 9, IIIB in 20, and IV in 6. The lymph node dissection was considered to be limited in 56 patients and extended in 7. The IORT dose ranged from 12 to 23 Gy (median: 15). Thirty patients also underwent a postoperative external beam irradiation with a standard dose of 44-46 Gy. RESULTS: The postoperative mortality rate was 4.8%. The 5-year overall survival in the entire series was 47% and was 82, 55, 78, 20, and 0% in Stages I, II, IIIA, IIIB, and IV, respectively. Loco-regional relapse occurred in 15 of 63 patients and metastases in 15 of 63. CONCLUSION: In Western patients treated by gastrectomy for adenocarcinoma of the stomach, IORT combined with limited lymph node dissection may provide overall survival similar to that observed after gastrectomy with extended lymph node dissection but with less postoperative mortality.

Intraoperative radiotherapy in resected pancreatic cancer: feasibility and results.

BACKGROUND AND PURPOSE: To evaluate the impact of intraoperative radiotherapy (IORT) combined with postoperative external beam irradiation in patients with pancreatic cancer treated with curative surgical resection. MATERIALS AND METHODS: From January 1986 to April 1995 25 patients (11 male and 14 female, median age 61 years) underwent a curative resection with IORT for pancreatic adenocarcinoma. The tumour was located in the head of the pancreatic gland in 22 patients, in the body in two patients and in the tail in one patient. The pathological stage was pT1 in nine patients, pT2 in nine patients, pT3 in seven patients, pN0 in 14 patients and pN1 in 11 patients. All the patients were pM0. A pancreaticoduodenectomy was performed in 22 patients, a distal pancreatectomy was performed in two patients and a total pancreatectomy was performed in one patient. The resection was considered to be complete in 20 patients. One patient had microscopic residual disease and gross residual disease was present in four patients. IORT using electrons with a median energy of 12 MeV was performed in all the patients with doses ranging from 12 to 25 Gy. Postoperative EBRT was delivered to 20 patients (median dose 44 Gy). Concurrent chemotherapy with 5-fluorouracil was given to seven patients. RESULTS: The overall survival was 56% at 1 year, 20% at 2 years and 10% at 5 years. Nine local failures were observed. Twelve patients developed metastases without local recurrence. Twenty patients died from tumour progression and two patients died from early postoperative complications. Three patients are still alive; two patients in complete response at 17 and 94 months and one patient with hepatic metastases at 13 months. CONCLUSION: IORT after complete resection combined with postoperative external beam irradiation is feasible and well tolerated in patients with pancreatic adenocarcinoma.

Adenocarcinoma of the body and tail of the pancreas: is there room for adjuvant radiotherapy?

AIMS AND BACKGROUND: Adenocarcinoma of the body and tail of the pancreas is a rare malignancy with a poor prognosis. Few long-term survivors have been reported in the literature. The role of adjuvant treatment after curative resection has not yet been assessed. This retrospective study aims to describe the patterns of failure and the survival of 10 patients treated with resection and adjuvant radiotherapy. MATERIALS AND METHODS: From 1982 to June 1994, 10 patients with adenocarcinoma of the body and tail of the pancreas received adjuvant radiotherapy in our department. There were 4 females and 6 males, with a median age of 63 years (range, 45-77). The pT distribution was 2 pT1, 4 pT2, 4 pT3 and for pN it was 7 pN0 and 3 pN1. Four patients had stage I, 3 stage II and 3 stage III disease. All the patients underwent a resection: distal pancreatectomy in 7, partial resection of the body in 1, and total pancreatectomy in 2. Gross residual disease was present in 2 cases. Three patients received intraoperative radiotherapy up to a dose of 12-15 Gy. Postoperative radiotherapy was given in 9 patients with a dose ranging from 40 to 50 Gy (median, 45). One patient who received intraoperative radiotherapy had no postoperative radiotherapy. In 4 patients, chemotherapy with 5-fluorouracil was given during the first week of irradiation. RESULTS: Six patients experienced a local-regional relapse and 3 developed metastases. The median survival was 21 months. The 5-year overall survival was 15%. Eight patients died of progressive disease. One patient who presented with stage I disease was alive and free of disease at 24 months from diagnosis and, interestingly, one with stage III disease was alive at 111 months. No severe treatment-related complications were observed. CONCLUSIONS: As in carcinoma of the head of the pancreas, adjuvant radiotherapy should be considered as an adjuvant treatment of resected adenocarcinoma of the body and tail of the pancreas. Further evaluation is necessary to assess the role of intraoperative radiotherapy.

[Adjuvant radiotherapy after radical prostatectomy. Apropos of a series of 73 patients in Lyons (France)]. / La radiothérapie adjuvante après prostatectomie radicale. A propos d'une série lyonnaise de 73 patients.

PURPOSE: Descriptive analysis of adjuvant radiation therapy after radical prostatectomy. MATERIALS AND METHODS: From 1986 to 1993, 73 patients (median age, 64.5 years; Gleason score > or = 7 : 36 pts; T1:22; T2:40; T3:11) were included into the study. On the operative specimen, the cancer grades were pT2:5 (involvement of the apex), pT3:67, pT4:1, pN1-2:8. Radiation therapy was performed after a mean resting period of 112 days. The target volume was the prostatic area. The technique used was a four-field box with an 18 MV-X photon beam. The dose was 50 Gy/20 fractions/5 weeks. No hormonal treatment was administered, except for 5 patients for a short duration. RESULTS: The median follow up was 46 months. One anastomotic local failure was salvaged by trans-urethral resection, three distant metastatic failures. Out of 72 patients with a PSA < 3 ng/mL at the end of radiotherapy, 13 showed an isolated elevation. The 5-year overall survival rate was 93%. The event-free survival was 72% after 5 years. Pathological differentiation and Gleason score were significantly correlated with the survival. There was no complication related to radiotherapy. CONCLUSION: Elective adjuvant radiation therapy for pT3 prostate adenocarcinoma after radical prostatectomy provides a good local control with minimal morbidity.

Stereotactic radiosurgery for arteriovenous malformations of the brain using a standard linear accelerator: the Lyon experience.

Radiosurgery (RS) was initiated in Lyon in October 1989. The technique was adapted from that described by Lutz and Saunders in Boston (BRW stereotactic frame). Irradiation is delivered with 18-MV photons produced by a LINAC. From December 1989 to December 1992, 41 patients with arteriovenous malformations were treated by RS; the median age was 33 years. The largest lesion diameter was 11.2-38.5 mm. Fifteen to 20 Gy were delivered on the 70% isodose line. Angiography was performed at 2 years post-treatment in 32 patients demonstrating an overall complete thrombosis rate of 81.3%. This incidence was significantly correlated with the Spetzler and Martin grade before RS (P = 0.0055). Two patients (4.9%) experienced haemorrhage after radiosurgical treatment and one died from an intracerebral-intraventricular haemorrhage. Four patients (9.7%) experienced permanent radiation-induced neurological complications.

Endocavitary irradiation for early rectal carcinomas T1 (T2). A series of 101 patients treated with the Papillon's technique.

PURPOSE: This work is a retrospective analysis of a series of patients treated with endocavitary irradiation stressing the role of transrectal ultrasound (TRUS), which has been used routinely in the staging since 1987. METHODS AND MATERIALS: Between 1977 and 1993, 101 patients with infiltrating adenocarcinomas were treated. Clinical staging was 65 T1 N0 and 36 T2 N0. TRUS used in 36 patients showed: 22 UT1 N0, 10 UT2 N0, and 3 UT2 N1. Contact x-ray was delivered with a 50 kV radiotherapy unit. The median dose was 92 Gy (60-125) in five fractions, 55 days. In 28 patients a boost was given with 192Ir implant delivering a median dose of 25 Gy/21 h. RESULTS: Complete response was observed in all patients at the completion of treatment. Loco-regional failures were seen in 14 patients (local in 7 patients, nodal pararectal in 6 patients, and local + nodal in 1 patient). A curative salvage treatment was attempted in 13 patients and resulted in an ultimate pelvic control rate of 99 patients. Rectal preservation was possible in 92 patients. Overall and specific 5-year survival was 83.3% and 94.4%. No serious complication was observed. TRUS was more sensitive than digital rectal examination to detect involvement of pararectal metastatic nodes (N1). No loco- regional relapse was observed out of 22 UT1 N0. CONCLUSION: Endocavitary irradiation can cure early adenocarcinoma of the rectum without complication. TRUS appears as a significant improvement in the selection of patients amenable to this treatment. If restricted to UT1 N0 tumors, endocavitary irradiation should control locally more than 90% of these patients. Any UN1 is a contraindication for endocavitary irradiation alone.

Combined curative radiation therapy alone in (T1) T2-3 rectal adenocarcinoma: a pilot study of 29 patients.

AIM: Analysis of a pilot study including 29 consecutive patients with high surgical risk or refusal of colostomy treated with radiation therapy alone with curative intent. PATIENTS: Between 1986 and 1992, 29 patients were treated for infiltrating adenocarcinoma of the rectum. Median age was 72 years. Transrectal ultrasound staging was used in 24 patients (T1, 2; T2, 14; T3, 13; N0, 23; N1, 6). In 20 patients the lower border of the tumor was at 5 cm or less from the anal verge and in 19 patients the diameter exceeded 3 cm. CEA was elevated in seven cases. TREATMENT: Contact X-ray (50 kV) was given first (70 Gy/3 fractions). External beam radiation therapy used a three-field technique in the prone position. Accelerated schedule (39 Gy/13 fractions/17 days) with a concomitant boost "field within the field' (4 Gy/4 fractions). Six weeks later an iridium-192 implant was performed in 21 (20 Gy/22 h). RESULTS: Median follow-up time was 46 months. Overall and specific survival at 5 years was 68% (SE = 0.09) and 76% (SE = 0.08). Local control was obtained in 21/29 patients (72%). There was one grade 2 rectal bleeding and five grade 2 rectal necroses. The overall tolerance was good in these frail patients. DISCUSSION: For T2. T3 or T1 > 3 cm diameter rectal adenocarcinoma, where contact X-ray alone is not recommended, a combined treatment with radiation therapy alone is able to give good local control with acceptable toxicity. This treatment should be restricted to inoperable patients.

[Occupational exposure and malignant hemopathies: a case-control study in Lyon (France)]. / Expositions professionnelles et hémopathies malignes: une enquête cas-témoins réalisée à Lyon (France).

A hospital based case-control study was carried out in Lyon with the aim of assessing the association between haematologic malignancies and occupational exposures to 320 compounds. Job histories were obtained by questionnaire for 118 cases (52 non Hodgkin lymphomas, 48 acute myeloid leukemia, 18 others leukaemias), and 118 controls with diseases other than cancer from the same general hospital; controls were matched for sex, age and nationality. Systematic coding of exposures based on a blind analysis of job histories, was done by a team of experts in chemistry and occupational health. Mantel-Haenszel analysis was performed. Significantly elevated odds-ratio were observed for non Hodgkin lymphomas and exposure to mineral oils (14.86; 2.76-80.0), excavation dusts (3.91; 0.94-15.95), alkali compounds (2.90; 1.09-7.68), inks (2.47; 1.09-5.17). For inks, a dose-response relation was observed. Elevated odds-ratios appeared for acute myeloid leukaemias and arsenic compounds (3.02; 0.90-10.13) and lead compounds (3.70; 1.09-13.44). When regarding industrial activities, two of them are more frequently found: food industries (14 cases/5 controls), public works (12 cases/0 control). When regarding jobs, winding (6 cases/0 control), glass workers (8 cases/1 control) and warehousemen (10 cases and 4 controls) are more often seen among cases.

Curative endocavitary irradiation of small rectal cancers and preoperative radiotherapy in T2 T3 (T4) rectal cancer. A brief overview of the Lyon experience.

The aim of this study was the analysis of 414 patients treated by endocavitary irradiation for small T1 (T2) infiltrating adenocarcinomas between 1951-93 and of 337 patients treated by preoperative radiotherapy for T2 T3 (T4) rectal cancer, between 1978-92. Endocavitary irradiation was delivered with Papillon's technique using the PHILLIPS RT-50 machine. Preoperative external beam radiotherapy was given to the posterior pelvis only with an accelerated schedule of 39 Gy in 13 fractions over 18 days. Endocavitary irradiation with the use of intra-rectal ultrasound for patient selection resulted in a local control rate of 91% with no complication even in the medically inoperable patients. Preoperative external beam radiotherapy followed by radical resection resulted in a 90% pelvic control rate. Sphincter-sparing surgery was possible in 60% of patients with low or middle rectal lesions.

Bladder cancer and occupational exposures.

OBJECTIVES: A hospital-based case-referent study was carried out in Lyon with the purpose of generating hypotheses about the role of occupational exposures to 320 compounds in bladder carcinogenesis. METHODS: Job histories were obtained by questionnaire for 116 cases and 232 reference patients with diseases other than cancer (one referent from the same hospital ward and one from another ward of the same hospital per case); the referents were matched for gender, hospital, age, and nationality. Systematic coding of exposures, with a blind analysis of job histories, was carried out by a team of experts in chemistry and occupational health. RESULTS: Significantly elevated odds ratios were observed for exposure to pyrolysis and combustion products [odds ratio (OR) 2.3, 95% confidence interval (95% CI) 1.0-4.0] when the general referents were used and for cutting fluids (OR 2.6, 95% CI 1.2-5.4) when tobacco consumption was adjusted for. The latter was highest among the category consisting of blue-collar and unskilled workers, supervisors, and agricultural workers (OR 4.6 95% CI 2.0-10.6), while the odds ratio for the other category was 0.8 (95% CI 0.3-2.7). An elevated odds ratio for exposure to inks was observed for the women (OR 14.0, 95% CI 1.8-106.5) on the basis of 14 exposed cases, but confounding factors could have been responsible for this result. Odds ratios for several other exposures (rubber: OR 5.7, nitrates: OR 8.2, coke dust: OR 3.5, meat additives: OR 3.8) were also elevated, but not significantly so when based on a small number of exposed cases. CONCLUSION: The observations of this investigation should be tested in future studies, in particular since exposures to agents such as cutting fluids or pyrolysis products are ubiquitous in industrial settings and may present an important public health hazard.

[Value of plasma progesterone (rapid assay) during ovarian stimulation for in vitro fertilization using LHRH agonists and hMG]. / Intérêt de l'étude de la progestérone plasmatique (dosage rapide) au cours de la stimulation ovarienne pour fécondation in vitro utilisant les agonistes de LHRH et les hMG.

We have studied all the cycles (= 276) induced for in vitro fertilization using a LHRH agonist and the hMG (113 short protocols, 163 long protocols) from 01.90 to 07.90 to know the plasmatic profiles of the estradiol (E2), of the LH and specially of the progesterone (P) between J-7 and the day of the hCG (= J0). We observe in the short protocol an elevation (effect flare up) and afterwards a fall concomitant of the P and of the LH up to J-5, J-6 (effect of pituitary down regulation), in the short and long protocols a progressive elevation of J-3 up to J0 of the P parallel to E2, so that the LH remain stable or decrease. The LH of J0 is higher in short protocol than in long protocol (10.14 +/- 2.9 versus 4.72 +/- 1.3 Ul/l, p < 0.00001). We found the same progressive elevation of the P of J-3 up to J0 in pregnant and not pregnant patients. The surveillance of the P coupled to the E2 and to the follicular ultrasonography could help in the choice of the day of the hCG and avoid a post-maturity of oocyte. The consequences of the elevation of P In the morning of J0 have been study for P levels < 1 ng/ml (73 cases) and P > or = 1 ng/ml (203 cases) and afterwards for progressive elevation of P levels (1.5-2-2.5-3 ng/ml).(ABSTRACT TRUNCATED AT 250 WORDS)