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In France, 20% of breast cancers occur in women over the age of 70 and 10% in women over the age of 80. As these women are not included in screening programs, breast cancer is often diagnosed later, at the stage of a large tumor.To analyze clinical response, possibilities of conservative treatment and course of hormonal receptors in patients receiving neoadjuvant aromatase inhibitor (AI) therapy for at least 6 months.There were 75 patients, with a mean age of 75 +/- 8 years (range, 58-91 years) received AI for 6 months after the diagnosis of invasive breast cancer with positive hormonal receptors. Clinical and radiologic tumor reduction, the number of conservative treatments and the course of estrogens receptor-labeled cells were determined for each patient.All but 1 of these patients obtained clinical reduction of their tumor. Of these, 86% patients received conservative treatment. In the majority of patients, estrogen receptor (ER) level did not vary between the initial assay and analysis of the operative specimen.Aromatase inhibitors are effective as neoadjuvant therapy in ER positive elderly patients with large tumors, as is tamoxifen. Changes in hormone receptor expression during treatment do not predict clinical response. In our experience, neoadjuvant AI therapy should be administered for at least 6 months to optimize clinical response before deciding upon surgery. Discrepancy observed in the literature could be explained by the duration of the treatment.

Our objective was to study the prognostic value of stoutness in non-metastatic breast cancer, from a population of French women.We constituted a large observational cohort of patients followed since a first unilateral breast cancer without distant dissemination. Stoutness was assessed using the body mass index (BMI, in kg/m(2)) at the time of diagnosis. Patients were classified into the four main categories of BMI, defined according to the World Health Organization recommendations. The risk of prognosis events was analyzed according to the BMI categories. To this end, survival analyses were achieved.The patients having a BMI value of at least 25 kg/m(2) presented significantly higher risks of death and metastasis recurrences when they were compared to the patients having a normal value of BMI. The multivariate analyses found a modest increase of risk, about 10 to 20%, depending on the degree of fatness. It reached about 20 to 50% according to the univariate analyses. The obese patients (BMIor= 30 kg/m(2)) had an increase of 50% of the risk of second primary cancers, comparatively to the patients having a normal value of BMI. Regarding contralateral, nodal and local recurrences, the survival analyses did not achieve any significant relationship with stoutness.A poorer prognosis is observed when breast cancer patients have a value of BMI that matches at least with overweight. Contrary to the results of few recent surveys, underweight patients do not present a poorer prognosis than normal weight patients. Excess of weight represents a modifiable factor in order to improve female breast cancer prognosis.

Lipofilling is usually performed in breast surgery for treatment of aesthetics sequelae after breast conserving surgery or correction after breast reconstruction by prothesis or musculocutaneous flaps. We present a case of a patient where exclusive lipofilling breast reconstruction has been successfully performed. Aesthetic result is assessed by the patient and the surgeon as very satisfactory after one year of follow-up. This technology not much used in this present indication have important advantages in terms of tolerance or morbidness but the long-term results depend on not controlled factors such as volumetric cast iron or fatty resorption. Further studies are necessary to define the patients will be able to benefit from this technology and to assess the modalities of follow-up but also to measure evenly practicability, stability of reconstruction and its evolution in time. However, aesthetic result and contentment of the patient allow us to envisage the broadcasting of this technology of mammary reconstruction for selected patients.

Nipple and areola reconstruction is very important in the evaluation of the quality of breast reconstruction. It can be done during the primary or secondary breast reconstruction or later. We have performed the techniques of nipple reconstruction routinely since 1992. Under local anesthesia during a second operative time or general anesthesia during breast reconstruction, the local "F" and "Z" skin flaps and tattooing grant a quality result in the wound and the long-term projection. They are easily reproduced, rapid and as there is no graft the choice of the incisions grants a good tolerance. Complications are rare and it is always possible to use other techniques in case of poor result. We also present the main techniques of nipple and areola reconstruction with their advantages and limits.

Breast cancer surgery has long consisted in the sole use of mastectomy. Then, it was proved that, in terms of global survival, conservative treatments associated with radiotherapies could give the same results. But breast deformations due to classic conservative treatments led some authors to use plastic surgery procedures: breast plastic surgery. Some breast plastic surgery procedures are well-known, others have been adapted to breast cancer treatment and more particularly in case of tumor of superior and internal quadrants. After the retrospective analysis of a series of 298 cases from the Institute Curie, the aim of this survey is to find whether there is a difference between: breast plastic surgery and usual treatments like mastectomy and classic conservative treatments. For most cases, the tumors were invasive ductal carcinoma and T2N0M0 carcinoma. This survey showed, among these cases, 94.56% of global survival, 86.81% of survival without metastasis and a five-year 93.47% without local recurrence, which is comparable to the results for mastectomies and classic conservative treatments. In selected cases, the use of mammaplasty could be interesting for breast cancer surgery treatment.

Since more than twenty years, methods of breast reconstruction using implants have continued to evolve in order to improve their aesthetic results. Shapes and materials of these implants have also evolved to obtain contours similar to that of the natural opposite breast. Therefore it can be considered that the use of asymmetric implants is the last step in implant technology before using made to measure implants. Asymmetric implants allow obtaining different contours in harmony to the different breast shapes according to the side, left or right, of the reconstructed breast which maximise the naturalness of the result. Such implants have an axis directed towards the exterior and lower part of the chest wall, are wider than high with a thinner part on their inner edge and a concave rear side moulding the curves of the chest wall. In our own experience, we placed more than 500 asymmetric implants. When analysing retrospectively the medical records of 156 patients, no distinctive features were observed when compared to symmetric classic implants in easiness in the surgical procedure or in complications except a slightly higher rate of seroma formation. When compared to usual implants the main benefits of asymmetric implants are: to offer a wider breadth, to slope down gently on their upper and inner sides according to their concave rear side, and therefore to better match subtle curves of a normal breast. Moreover such contours allow a distribution of the volume which fit better to the usual natural breast configuration of patients who underwent surgery for breast carcinoma. At last, such implants are easy to place and a very low rate of secondary rotation has been observed. In summary, for all these reasons, asymmetric implants, can be considered to be the class one in the choice of implants for breast reconstruction after breast surgery.

Accurate mark of macrobiopsy site, carried out borderline or malignant lesions, is very important for surgeons. We report a woman case, 68 year's old, who presents intraductal carcinoma diagnoses on macrobiopsy. On postbiopsy X-ray, we can note lipiodol used instead of clip to reaper macrobiopsy site. Our observation shows how lipiodol use is not adapted into this indication.

Large teratomas with gastric mucosa are rare. We report a case of mature cystic teratoma in an ovary of a young woman. Tumor growth was large and rapid enough to displace abdominal organs. The cyst was aspirated (removing 101 of mucinoid liquid) and excised by medial hypogastric laparotomy. The histological examination revealed differentiated gastric fundal mucosa with no other tissue involvement.

Surgical resection of liver metastases is performed increasingly frequently after chemotherapy, which can induce fatty degeneration, possibly modifying the postoperative course after hepatectomy. This study evaluated the effect of chemotherapy on postoperative liver function tests according to the use of preoperative chemotherapy or not.Thirty-two patients were operated on for isolated breast cancer hepatic metastases, after stabilization or complete response to systemic therapy. The first group included 20 patients operated on after chemotherapy (9 major and 11 minor hepatic resections). The second group included 12 patients operated on without chemotherapy (3 major and 9 minor hepatic resections).Histological examination after chemotherapy confirmed micronodular fatty degeneration in 85% of cases, versus none in the control group (P = 0.05). Fall in prothrombin time on day 1 (D1) was more marked in the chemotherapy group (58%) versus control group (74%) (P = 0.001). gamma-glutamyl transpeptidase did not rise on D7 in the chemotherapy group (1.4 x N), even after major hepatectomy (1.6 x N), in contrast with the control group, in which the mean gamma-glutamyl transpeptidase on D7 was 4.6 x N after major hepatectomy and 2 x N after minor hepatectomy (P = 0.05).Chemotherapy induces almost constant fatty degeneration of the liver. Hepatic regeneration in the postchemotherapy liver is delayed, as reflected by a later and lower elevation of gamma-glutamyl transpeptidase. The predictive risk of liver failure, reflected by prothrombin time, following minor hepatectomy on postchemotherapy liver is similar to that of major hepatectomy to healthy liver.

To report results of liver resections for breast cancer liver metastasis (BCLM) and to evaluate the rate of survival and the prognostic factors.Between 1988 and 1999, 69 patients were operated on for BCLM and 65 who had liver resection were analyzed. The selection criteria for surgery were: normal performance status and liver function test; radiological objective response to chemotherapy (and/or hormonotherapy); in cases of non-isolated BCLM, complete response of associated metastatic site (usually bone) and no brain metastases. The mean age of the 65 patients was 47 (30-70) years. BCLM was diagnosed an average of 60 (0-205) months after the initial cancer. The BCLM was more frequently solitary (n = 44). The mean diameter was 3.8 (0-12) cm. The mean number of cycles of chemotherapy before surgery was 7.5 (3-24). Liver resections included major hepatectomy (n = 31): right n = 19, extended left n = 4, left n = 8, minor hepatectomy (n = 25) and limited resection (n = 9).There was no postoperative mortality. The 18% morbidity rate included a majority of pleural effusions with two reoperations. The median follow-up was 41 months (6-100 months). The survival rate after surgery was 90% at 1 year, 71% at 3 and 46% at 4 years. Thirteen patients are alive at 4 years. The 36-month survival rate differed according to the time to onset of BCLM: 55% before versus 86% after 48 months (p = 0.01). The other studied factors were not statistically associated with survival. The recurrence rate in the remaining liver at 36 months differed according to the lymph node status of the initial breast cancer: 40% for N0-N1 versus 81% for N1b-N2 (p = 0.01) and according to the type of liver resection: 45% for minor liver resection versus 73% for major (p = 0.02).Adjuvant liver surgery should be included in multicenter treatment protocols for medically-controlled breast cancer liver metastasis.

Sentinel node detection in breast cancer can be realized with colorimetric and isotopic procedures often associated. The aim of this study was to report results obtained with blue dye injection only.From September 1998 to July 1999, blue dye injection was performed in 73 consecutive patients (mean age: 51 years, range: 36-71 years); 51/70 70% were post-menopausal and half of them were under substitute hormonal treatment; 70% of cancers were discovered through routine mammography. There were 12 bilateral cancers, six of them synchronous, and 84% of cancers were located in the external quadrants. Individualization of sentinel node was performed through blue dye injection into the tumor in case of preoperative diagnosis or in the tumoral site in case of discovery of the cancer through extemporaneous histological examination.71 out of 73 cancers were classified pT1 and 70% measured 10 mm and over. Individualization of sentinel node failed in two obese patients. Sentinel node invasion concerned one node (n = 7), two nodes (n = 1) and three nodes (n = 1). Conservative treatment was performed in 72 patients out of 73; in case of sentinel node invasion, axillary irradiation was performed without reoperation.Blue dye injection for sentinel node individualization is an accurate technique in selected patients in case of small tumors. Reoperation can be avoided and replaced by axillary irradiation in case of N+ tumors. Duration of hospitalization was 48 hours or under in 70/73 patients. Nevertheless isotopic procedure must be recommended as a routine technique in learning centers and for most surgical teams.

Sentinel lymph node (SN) biopsy is a recently developed, minimally invasive technique for staging the axilla in breast cancer. This new procedure of selective lymphadenectomy has been the subject of several studies, but there is not currently a consensus of opinion to define which is the best method of identification. At the Institut Curie since 1996, we have been using the Patent blue dye. The current series present the result of 122 patients with T1, T2, N0 or N1a breast cancer consecutively operated between december 1997 and august 1998. Sentinel nodes were identified in 107 out of 122 (87.7%) and accurately predicted axillary nodal status in 104 out of 107 (97.1%) cases. Three out of 35 node positive patients would have been missed with sentinel node biopsy alone, for a false negative rate of 8.5%. In all 3 cases, one lymph node presented with a micrometastases. In 15 cases out of 35 with metastatic axillary nodes, the only positive node was the SN (43%). The encouraging results of this study shows that it is possible to identify, in a large number of cases, the sentinel node by means of Patent blue dye only. This article detailed the technique used and reviews the literature concerning other methods of identification.

The development of radiochemotherapy associations has raised the percentage of sphincters preserved in surgery for anal cancer. These protocols have also made the surgeon's task more difficult as abdomino-perineal amputations, progressively reserved for treatment failures, cause intraoperative and postoperative problems in this type of tissue. Programmed surgery would be the ideal solution and requires a multidisciplinary approach.

The sentinel node is defined as the first-line axillary lymphatic drainage node in breast cancer. If the sentinel node can be identified, during axillary dissection for breast cancer, resection could be limited reducing subsequent morbidity. However, before modifying the standard dissection procedure, it is important to prove that the sentinel node is representative of the metastatic status of other axillary nodes.Between March and December 1996, 86 patients (mean age 58 years, range 32-82) underwent amputation (n = 20), tumorectomy with dissection (n = 56) or tumorectomy followed by secondary dissection (n = 10) for breast cancer. Ten ml of diluted patent blue was injected either into the peripheral portion of the tumor or the tumorectomy cavity. Node dissection was performed 10 to 20 minutes after injection. The blue sentinel node was identified prior to standard dissection.A mean 12 nodes were removed (range 4-21). Seventy-nine sentinel nodes were identified (91%) and in 7 cases (8%) a sentinel node could not be identified. In 7 other cases the sentinel node was a false negative, i.e. non malignant despite metastases in other dissected nodes. In all the other cases, the status of the sentinel node predicted the status of the other nodes, i.e. a non-metastatic sentinel node associated with other metastatic nodes. Finally, in 7 cases, the sentinel node was the only invaded node among the nodes dissected. During the last 3 months of the study, the sentinel node was identified in 100% of the cases and was representative of the overall dissection.Identifying the sentinel node is an alternative to standard axillary node dissection procedures. The method requires a training period and identification can be improved with radioimmunologic guidance. Patient selection within the framework of a rigorous multidisciplinary protocol is indispensable. A nationwide study is currently being conducted to validate these preliminary results.

Multiple technical and strategical improvements have modified surgical management of breast cancer. Screening mamographies are able to focus small tumors in which excision eventually after percutaneous biopsy can necessitate two surgical procedures. Reduction of axillary dissection in these small lesions can benefit from sentinel node biopsy technique. Immediate or delayed breast reconstruction reduces the mutilation of the mastectomies with their psycho-social disaster. Technically these reconstruction requires a multidisciplinary approach and psychological support. These surgical evolutions in parallel with other therapies for breast cancer developed with two major points: necessity of a good local control for cure, multidisciplinary approach which makes surgeons reals oncologists.

The ability of cancer cells to metastasize might depend on their reduced dependency on the originating tissue. To test this hypothesis, 10 human colorectal carcinomas (CRC) were implanted either onto nude mouse caecum wall (orthotopic site), or into the subcutaneous tissue (ectopic site), and their growth in these sites compared. Prognostic factors were studied: Astler-Coller modified Dukes's stage, loss of chromosome 17p and/or 18q, and their TP53 gene. Early stage CRC [B2 (n = 3) and C1 (n = 1)] were found to grow 1.7 to 3.6 times (p0.05, p0.008 respectively) more rapidly in the caecum than in subcutaneous tissue. Metastatic stage CRC [C1 (n = 1), C2 (n = 2) or D (n = 3)] grew similarly in both sites, and more slowly than those of the first group. No relationship was found between growth rates, TP53 mutations or karyotypes. Growth rate of non metastatic cancers was slowed down by implantation in a foreign tissue whereas growth of metastatic tumours was similar in both sites, indicating that they do not recognize or need tissue growth factors.

Gastric cancer remains a serious health problem 5 years survival remains low and early diagnosis anecdotical in France. Gastrectomy is the only curative treatment and the extent of surgery depends upon the tumor location. The extent of the node dissection is under discussion, Japanese surgeons recommend extensive dissection and publish better results in term of survival than Europeans groups. Two randomized prospectives trials comparing limited and extensive dissection have not shown any difference but an increased morbidity in the group with extensive dissection. Adjuvant treatments radiation or chemotherapy should be given therapeutic trials because they have not been proved as efficient.

Instability of microsatellites is a hallmark of the DNA replication error phenotype (RER+) due to the inactivation of mismatch repair genes. In humans, microsatellite instability has first been described in colorectal tumors developing in either hereditary nonpolyposis colorectal cancer or sporadic patients. Colorectal tumorigenesis in RER+ and RER- tumors is probably due to distinct mechanisms, and RER+ tumors have a better prognosis than RER- tumors. The study of the RER status of a tumor may thus be important in the future to determine biological prognosis factors and investigate therapeutical strategies. The RER status of 134 primary tumors and 26 cell lines derived from colorectal cancers was established by PCR amplification and analysis of a minimum of 32 microsatellite loci. This characterization allowed us to unambiguously classify 35 primary tumors and 7 cell lines as RER+. Typing of a single poly(A) tract, BAT-26, was sufficient to confirm the RER status of 159 of these 160 tumors and cell lines. Moreover, in DNA from unaffected individuals, normal tissues of a subset of the RER+ patients, and all RER- tumors or cell lines, BAT-26 was quasi-monomorphic, showing only minor size variations. BAT-26 alleles showing shortening from 4 to 15 bp were observed in all but 1 of the RER+ tumors and cell lines. The size difference between the range of normal large alleles and unstable small alleles was sufficient to be detected by electrophoresis on conventional polyacrylamide gels stained with ethidium bromide. We thus propose a simple, low-cost, and rapid method to screen for the RER status of colorectal cancer primary tumors and cell lines, even in the absence of matching normal DNA and, in most cases, without the need for radioactivity. This method could easily be set up in routine laboratories.

Surgery for hepatic metastases from breast cancer remains anecdotal and controversial. This retrospective series of 21 patients analyses survival after hepatic resection. These patients presented with isolated metachronous metastases, controlled by systemic treatment; surgery was considered to be an adjuvant treatment. There was no surgical mortality. The TNM stage of the initial breast cancer, the time to onset of metastases and the number of hepatic metastases did not influence survival. The 5-year survival, after diagnosis of metastatic disease, was 60%; clearly better than the expected survival. Eleven patients are currently alive without recurrence. Six patients developed a recurrence in the remaining liver after a mean interval of 12 months, including 4 patients who died after a mean interval of 49 months. These results suggest that a subgroup of patients with hepatic metastases from breast cancer may benefit from surgical resection. This surgery must be proposed in patients with isolated disease progression controlled by systemic treatment. In our experience, adjuvant surgery of hepatic metastases from breast cancer is followed by an uneventful postoperative course, improves survival and, in 50% of cases, allows discontinuation of chemotherapy, improving the patient's quality of life.

Recurrent allelic losses on chromosome 22q have been reported in colorectal cancer, distal to the NF2 gene, suggesting that another tumor suppressor gene might be involved. We report here the typing of 256 sporadic colorectal tumors and 18 colonic cancer cell lines using a set of chromosome 22 polymorphisms, ranging from 20 to 45. A panel of somatic cell hybrids, that allows to distinguish 11 bins in the 22q13 region, was used to localize 19 of the 45 selected markers and the putative tumor suppressor gene BZRP. Allelic-loss was observed in 43% of tumors. The minimal region of deletion that could be determined, telomeric to locus D22S270, refines significantly the position of the gene. The localization of the BZRP gene in this region led to a systematic screening for somatic point mutation. Direct sequencing of its coding sequence in 36 tumors hemizygous for chromosome 22 allowed the identification of three polymorphisms but failed to detect somatic mutation.

It is feasible to graft human colon cancer tissue into immuno-deficient nude mice, in order to maintain these tumors in vivo. Analysis of the properties tumors under such conditions might increase our knowledge of their biological characteristics. Xenografts are usually implanted into subcutaneous tissue, a site easily accessible for both graft procedure and observation of tumor growth. However these subcutaneous tumors are usually non-invasive and fail to metastasize. To override these limitations we, as others, have tried to improve the tumor xenograft model by transplanting tumors into their original location, designated as the orthotopic site. Transplanted into the cecum of nude mice, human colon cancers were frequently locally invasive and developed liver metastases. These transplantations may be done by injection of colon cancer cell suspensions into the cecal wall. Alternatively, orthotopic implantations of histologically intact tissue were performed and the thus-obtained tumors were more metastatic than tumors obtained after tumor cell injections. The chemosensibility of tumors xenografted into their orthotopic site was different from that of their subcutaneously implanted counterpart. This, added to the enhancement of invasive and metastatic properties, leads us to conclude that colon cancer xenografted into the caecum might be more representative of the clinical situation. We have reviewed the literature and report on the possibilities and limitations different models of colon cancer in vivo.

The treatment of recurrent non lactational breast abscesses is difficult. They occur with no apparent cause in young smoking patients. Twenty-two patients, mean age 40 years range 27-68, were treated over a period of 18 months by wide surgical excision with secondary spontaneous healing. No patient received post-operative antibiotics. Complete healing was obtained in 3-6 weeks. There were two recurrences with a follow up of 6-24 months. One patient developed a controlateral abscess which was treated by the same technique. No cosmetic defect was observed after complete healing. The duration of healing is upsetting for these young women, but the discomfort and pain induced by recurrent abscesses encourages them to accept this technique if properly and expertly counselled. The role of tabacco smoking seems to be the only cause of these recurring abscesses. All the patients (22/22) were heavy smokers.

Because of a family history of breast cancer, a 51-year-old patient underwent bilateral subcutaneous mammectomy in 1988. In February 1994 she presented with a nodule in the supramedial quadrant on the left. Needle biopsy suggested galactophoric adenocarcinoma which was confirmed histologically. A 1.5 cm tumour was removed together with a 3 cm reliquat of glandular tissue. Twelve axillary nodes were dissected and were found to be free of neoplastic infiltration. Hormone receptors were positive. Post-operative radiotherapy was performed. The outcome is unchanged at 6 months. Bilateral subcutaneous mammectomy can be proposed as a preventive measure in patients at risk, but as demonstrated by this case, exeresis is usually incomplete. The level of protection actually achieved is thus questionable. Clinicians should be aware of the risk of breast cancer developing after such elective operations since early screening programmes and the development of genetic methods based on the search for BRCA1 and BRCA2 genes will undoubtedly increase the number of patients requesting preventive measures.

The diagnosis of cancer can interfere with a patient's sexual relationship. It has an important impact on his "quality of life". The organ site of the cancer may be the primary cause of sexual dysfunction. Treatment modalities increase such dysfunction. The way the patient lives his disease with his family, the treatment he receives and the spectrum of death wielded by the word cancer lead to a multifactorial dysfunction which is often difficult to analyse. Although each individual member of the therapeutic team usually concentrates on one technical aspect of the disease, but prevention and treatment of sexual dysfunction has other requirements. One must listen to the patient, help coordinate the interaction between the patient's family, his personal physician and the oncology team. Coordinated efforts are difficult to achieve and not always sufficient.

WAF1/CIP1, a gene up-regulated by p53 encodes an inhibitor of cyclin-dependent kinases. Induction of WAF1/CIP1 in cells with intact p53 is believed to be instrumental in cell cycle arrest and apoptosis caused by DNA damage. In a model system, WAF1/CIP1 has been shown to have tumor suppressive activity. It is not known however whether WAF1/CIP1 is mutated in human primary tumors. Cells from colorectal cancer have been shown to acquire a series of genetic alterations, including frequent p53 mutations. Thus colorectal tumors, particularly those without identified p53 mutations, are good candidate to search for putative WAF1/CIP1 mutations. DNA extracted from 45 tumors, (including 28 tumors for which p53 mutations had previously been searched for and not found) were PCR amplified for exon 2 of WAF1/CIP1. A search for point mutations was performed in each amplified product using a denaturing gradient gel electrophoresis (DGGE) technique which enables the efficient screening of codons 9 to 139 (i.e. 80% of the WAF1/CIP1 coding sequence). Two different DNA variants were identified and shown to be present in constitutional DNAs of the corresponding patients. The first variant, a C to A transversion at codon 31, changes a serine for an arginine and was detected in eight tumors (18% of the cases). The second variant, detected in a single case (2%) is a silent A to T transversion at the third base of codon 91. DNA extracted from 70 unrelated members from the Centre d'Etude du Polymorphisme Humain (CEPH) was screened for these polymorphisms. The ser/arg polymorphism of codon 31 was detected in seven cases (10%) thus suggesting that it is not associated with a marked colorectal cancer predisposition. The polymorphism on codon 91 was not detected. Two additional variants (arginine to histidine at position 67 and threonine to methionine at position 80) were observed once each in the CEPH family members. Somatic mutation of the WAF1/CIP1 gene was not observed, indicating that, unless there are hot spots for mutations outside the screened region, this gene is not a frequent site of point mutation in colorectal cancer.

The prognosis of colorectal cancer has been based essentially on pathological data for many years. The analysis of genetic anomalies has led to fundamental progress and clinical advances. Genetic anomalies are routinely studied. 1--Flowcytometry evaluates the quantity of DNA in the nucleus during the cell cycle. 2--Cytogentics is the study of karyotype anomalies by loss or gain of chromosome material and structural changes. 3--Molecular biology gives a means of recognizing chromosome losses and especially to study oncogenic or antioncogenic mutations. These analyses allow: 1--an evaluation of their value as a prognosis factor and thus their use for indicating adjuvant medical and/or surgical treatments. 2--an understanding of cancerogenic processes. 3--the development of future therapeutic techniques based on a better understanding of the mechanisms involved. 4--familial counselling in high risk families and an examination of responsible or favouring genes in certain familial cancers. Research into familial forms has recently led led to the demonstration of genetic alterations located on chromosomes 1 and 2. These anomalies called RER correspond to alterations found on tumors. Studying these alterations will allow better prediction of high risk subjects in cancer families without polyposis.

Progress in detecting genetic anomalies with proven prognostic value in colorectal cancers offers a means of selecting adjuvant therapy with the best probability of success. Several methods are currently used. With flow cytometry, a significant correlation between primary tumour ploidy and hepatic metastasis has been demonstrated. Caryotypes of tumour cells provides a means of exposing segmental or total chromosome loss and subsequent classification leads to a better understanding of tumour heterogeneity. New techniques in molecular biology are used to describe mutations. Monoclonal antibodies can then be developed against the epitopes involved. Based on these different methods clinicians and fundamentalists can analyse treatment results with more precision and thus adopt the most effective treatment protocol.

A 35-year-old woman with a histologically proven T2 N0 M0 adenocarcinoma of the breast was given 4 cycles of neodjuvant chemotherapy then underwent tumourectomy followed by irradiation. Lymph nodes were free from invasion. A 7 cm ovarian cyst developed during follow-up and after a 2 month regimen of lynestrenol, coelioscopy with peritoneal lavage was performed. The pathology diagnosis was papillary cystadenocarcinoma requiring laparotomy which revealed invasion of both ovaries, neoplasic granulations and involvements of the epiloon. Exceresis of the trocar tract also showed tumoural invasion. Pathology examination favoured metastatic extension of the breast cancer. A 6-month chemotherapy was programmed before a second look. This case illustrates the risk of neoplastic dissemination after puncture or rupture of a cyst misdiagnosed as benign. In patients with a history of breast cancer, the risk of discovering a primary malignant ovarian cancer at coelioscopy is 9%. Metastases are found in 15-30% of the cases compared with 0.4 to 1.8% in unselected subjects. Prevention of operative dissemination relies on cystectomy without opening the cyst. This may require transforming the coelioscopy into a laparotomy which should not be considered as an operative failure but as a necessary method of preventing dissemination and clinical aggravation. Careful history taking, a rigorous coelioscopy technique and extension to laparotomy in cases with suspected diffusion should reduce the number of dramatic situations where the malignant process had not been suspected in the precoelioscopic diagnosis.

The xenograft of human cancers into athymic nude mice makes it possible to obtain abundant tumour material and deepen biological characterization. Usually, the tumours are grafted into the subcutaneous tissue whose environment is indeed different from that of original colon cancer.In order to transplant tumours into an orthotopic environment, intra-caecal implantation of colon cancers was performed. A tumour fragment (30 mm3) was deposited at the surface of serous membrane of the caecum, previously scrapped, fixed with a thread and recovered with biologic glue. Six different types of colon tumour, previously adapted to transplantation in nude mice, were similarly grafted.Twenty to forty days after transplantation, tumour takes were observed with a similar rate by the subcutaneous or intra-caecal graft (93% of 115 and 96.8% of 154 transplantations, respectively). Tumour growth varied between the tumours implanted into the two sites. Moreover, only the tumours intracaecally transplanted developed nodal and liver metastases. Histological examination revealed the invasion of the muscle layer, submucosal tissue and mucosal membrane by tumour cells and the mixture of normal glands and neoplastic glands.This technique of orthotopic implantation of colon cancer samples will contribute to obtain an experimental model for colon cancer research.

Mutations of the p53 tumour-suppressor gene are considered to be rare in human colorectal adenomas, a premalignant state of the digestive tract. We have analysed a series of 32 exophytic tumours of the colon and rectum for the presence of p53 protein. In 26 of the 28 pure adenomas, the presence of significant levels of p53 proteins was established by a sensitive two-point enzyme-linked immunosorbent assay. The detectability of p53 protein was frequently limited to PAb 1801, recognizing an N-terminal epitope. Immunoblotting of the fractions captured by the monoclonal antibodies revealed that PAb 421 reacted exclusively with a 53-kDa species, whereas an additional 48-kDa band was detected after incubation with PAb 1801. In the adenomas, the mutant conformation-specific PAb 240 was always negative and no mutations were detected on exons 5-8 in three large and highly dysplastic lesions, selected for their high p53 protein content. The remaining four of the 32 tumours presented foci of cancer. Three of these were shown to contain 'mutant' PAb 240-reactive p53, and gene mutations were identified in two by denaturing gradient gel electrophoresis and sequencing of the amplified products. Intense p53 nuclear immunohistochemical staining was associated with the malignant areas. We conclude that a novel mechanism affecting the regulation of p53 protein could occur in colorectal adenomas.

Healing of the perineal wound after abdominoperineal amputation is a difficult technical problem for surgeons to resolve. The majority of current therapeutic protocols include pre- or post-operative radiotherapy, and most study results show a reduction in perineal relapses when compared with a control group, but at the price of delayed healing of the perineal wound. This delayed healing reaction varies with the radiation dose. The use of epiploplasty shortens the healing period, but when performed after pre-operative radiotherapy it can predispose to the development of a perineal hernia. Four cases of this complication are described. No standard procedure for treatment of these hernias exists, and although it is possible to use the uterus to fill the perineal cavity, the most effective method appears to be a double perineal and abdominal pathway using a plate.

Axillary dissection in early breast cancer remains controversial because of its substantial side-effects and because its value with respect to recurrence or survival has not been unequivocally proven. Between 1982 and 1987, 658 patients were included in a prospective randomised comparison of lumpectomy alone with lumpectomy plus axillary dissection. All patients had a unilateral breast tumour not exceeding 3 cm in diameter and lymph-node involvement or metastases. Radiation therapy was given to both groups. The two groups of patients were similar with respect to mean age, TNM stage, and presence of hormonal receptors. Median follow-up was 54 months. 5-year survival of the patients was 94.2% (95% Cl: 92.1-96.4). There was a significant advantage in survival in the axillary dissection group (p = 0.014). Recurrence of tumour in the breast was similar in the two groups but visceral metastases, supraclavicular metastases, and lymph-node recurrences were less frequent in the axillary dissection group. Survival was related to the age of the patients (p = 0.005), the presence of positive nodes (p = 0.006), the histological grading (p less than 0.0001), and the presence of hormonal receptors (progesterone p = 0.0008, oestrogen p less than 0.0001). Treatment-adjusted relative risk was 2.4 (95% Cl: 1.3-4.2). The findings show that axillary dissection is justified for treatment of small breast cancers, although whether the better survival is due to axillary clearance itself or to adjuvant treatment for lymph-node involvement is unclear.

Mutations on the TP53 tumor suppressor gene and allele loss on chromosome 17p, where this gene has been located, are among the most frequent alterations yet identified in human malignancies. The p53 protein is highly conserved through evolution and expressed in most normal tissues. Wild-type p53 has been shown to control normal cell proliferation possibly through transcriptional regulation. The wild-type TP53 gene can suppress cell transformation and neoplastic cell growth. In contrast, mutant TP53 has lost the tumor suppressing ability and, in most cases, has gained a transformation promoting ability. Many different TP53 mutations have common conformational and functional consequences on the p53 protein. However, all the TP53 mutants are not necessarily equivalent in terms of biological activity: some mutations confer a strong transforming ability, while others lead to truncated products with probably no biological function. Some mutants may exhibit a dominant behavior over wild-type TP53, others may be recessive. Point mutations of TP53 tend to occur on evolutionary conserved positions. However, the TP53 mutational spectrum differs among cancer types, and this fact may reflect different exogenous mutagens and endogenous factors contributing to human carcinogenesis. In defined types of malignancies, the tumors with TP53 alteration or tumors with allele loss on 17p are associated with more aggressive phenotypes than those without these alterations. For these malignancies, the monitoring of TP53 alteration should now be included in therapeutic trials. Germ line mutations on TP53 may also occur. Individuals with constitutional TP53 mutation have a predisposition to a wide variety of neoplasms. Further characterization of this predisposition will enable the definition of the best follow-up for these at-risk patients.

There are many genetic abnormalities in colorectal cancers, and they can schematically be studied according to 3 approaches. 1. The quantitative abnormalities of the DNA content of the nucleus and the cell cycle are studied with flow cytometry. 2. Karyotypic abnormalities relating to the loss and/or gain of chromosomes or structural abnormalities are studied by cytogenetics. 3. Oncogene or anti-oncogene mutations carried out by these chromosomal segments are studied by molecular biology. When compared to the clinical data, some of these abnormalities have a prognostic value. They allow an insight into the fundamental mechanisms of colorectal carcinogenesis. Finally, they may allow predicting and assessing the efficacy of some adjunctive therapies, especially that of medication.

The authors report on a case of radiation-induced malignant Triton tumor eg malignant schwannoma with rhabdomyoblastic differentiation). The tumor was situated in the brachial plexus of a patient who had received irradiation therapy 20 years previously for breast carcinoma. Pathological and immunohistological features have been described: coexpression of PS100, vimentin and desmin indicate a common neuroectodermic origin. A review of the literature has been presented in order to evaluate the diagnostic and prognostic characteristics of this unusual tumor and its relationship to neurofibromatosis.

Evidence is accumulating that the p53 anti-oncogene is a key gene in the genesis of carcinoma in human colon and rectum. Although mutations of the p53 gene have been shown to be frequent, the protein was present in only approximately 50 percent of specimens examined. However only one monoclonal antibody recognizing an epitope present on wild-type p53 had been used. We studied the p53 expression in a series of 16 colorectal carcinoma specimens using 3 different monoclonal antibodies (pAb 421, 1801, 240). Specific immunofluorescent staining was quantified by dual parameter (DNA/p53) flow cytometry. Two different types of preparations were compared in order to verify the conservation of the antigen. Nuclear suspensions prepared from frozen tumor fragments were shown to produce results equivalent to those of whole cell preparations originating from fresh surgical specimens. The p53 protein was detected in 9 of the 16 cancers with pAb 421 and 240 monoclonal antibodies (8 of which were also positive for pAb 1801 antibody). Four additional tumors were considered positive for pAb 240 antibody alone. Overall, 13/16 cancer specimens were shown to present immunoreactivity for pAb 240 antibody. Topography of staining was investigated by immunohistochemistry with peroxidase methods. Eight cases were informative, 6 of which presented nuclear staining compatible with the cytometry results. There was one discordant case i.e. pAb 240 antibody being positive on cytometry and entirely negative on immunohistochemistry. This small series allowed us to show that 81 percent of tumor samples stained with monoclonal antibody pAb 240, considered to be specific to mutated protein, and that some tumors express a p53 protein which is not detected with terminal sequence-specific antibodies.

In 1986 and 1987, 224 patients were operated on for microcalcification without palpable lesions of the breast. Classical orthogonal (perpendicular grid) localisation was performed in 123 patients: external cutaneous localisation of the nipple was performed in 78 patients and hook localisation in 25 patients. Primary excision without the need for re-excision was possible respectively in 88% and 94% with external and hook localisation and in 83% after orthogonal localisation. The mean volume of the operation specimen was lower after hook (38.3 cm3) than after cutaneous or orthogonal localisation (54.6 cm3). 43% of the patients had a malignant lesion and even when the cluster of microcalcifications was single 50% of the margins were positive. Pre-operative localisation of occult breast lesions has simplified the surgical technique of excision. Nevertheless the pre-operative diagnosis of malignancy should be improved on in order to perform a procedure both diagnostic and therapeutic in the same operation.

Pre- or postoperative radiation therapy reduces the incidence of local recurrence after surgical treatment of rectal carcinoma. Factors related to local recurrence were analyzed retrospectively by uni- and multivariate analysis. One hundred and fifty-five patients (mean age: 65 years) were operated on with curative intent between 1967 and 1984. Ninety-four patients (46 patients having abdominoperineal resections (APR), and 48 having anterior resections) did not receive radiation therapy. Sixty-one patients had preoperative radiation therapy followed by APR in 59 cases. Univariate analysis showed that the risk of local recurrence increased significantly with male sex (p less than 0.006), positive lymph nodes (p less than 0.01), vascular invasion (p less than 0.02), and Astler-Coller classification (p less than 0.05). Tumor located at less than 5 cm from the anal verge was significantly related to recurrence only in patients not receiving radiation therapy (p less than 0.02). Multivariate analysis including therapeutic modalities showed that local recurrence was significantly related with male sex (p less than 0.02), positive lymph nodes (p less than 0.01), and distance to anal verge (p less than 0.01). The beneficial role of radiation therapy appeared only for tumors located 5 cm or less from the anal verge. Prognostic scores were established using these variables and the effect of irradiation was evaluated according to these scores. Radiation therapy significatively reduced the risk of local recurrence in low-risk patients, i.e., female with low-lying tumor and with negative lymph nodes (p less than 0.03).(ABSTRACT TRUNCATED AT 250 WORDS)