Local recurrence after ductal carcinoma in situ breast conserving treatment. Analysis of 195 cases.

PURPOSE: Ductal carcinoma in situ overall prognosis is excellent, but after breast conserving surgery, with or without radiotherapy, local recurrences can lead to locoregional or distant evolution and death. However, there are few data on optimal local recurrences treatment and long-term impact on survival. PATIENTS AND METHODS: This study included 195 women treated from 1985 to 1996 by conservative surgery (CS) or conservative surgery followed by radiotherapy (CS+RT), presenting local recurrences, with a 156-month median follow-up. RESULTS: Eighty-two out of 195 (42%) local recurrences were non-invasive (in situ) and 113 (58%) invasive. In situ local recurrence was discovered by mammography in 80.5% of the cases versus 47.5% for invasive local recurrence (P=0.0001). Salvage mastectomy was used in 53% of the cases after conservative surgery and 75% after conservative surgery followed by radiotherapy. The axillary nodal involvement rates were 11.8% and 25.8% among 17 and 62 patients with in situ and invasive local recurrences. Among 113 patients with invasive local recurrences and 82 with in situ local recurrences, 19 (16.8%) and three (3.6%) developed metastases, respectively. Among invasive local recurrences, comedocarcinoma subtype was highly predictive of subsequent metastases (32% versus 4.4%, P<0.0007). CONCLUSION: Invasive local recurrence after ductal carcinoma in situ treatment could be a dramatic event, fully changing long-term prognosis. Early mammographic local recurrence diagnosis (if possible still at non-invasive stage) seems essential to avoid or minimize metastatic risk. Mastectomy remains the safest option but, in some cases, a new conservative approach could be discussed.

Ductal carcinoma in situ of the breast in younger women: a subgroup of patients at high risk.

BACKGROUND: After breast conservative treatment (BCT), young age is a predictive factor for recurrence in patients with Ductal Carcinoma In Situ (DCIS) of the breast. The purpose of this study was to evaluate predictive factors for recurrence and outcomes in these younger women (under 40 years) treated for pure DCIS. METHODS: From 1974 to 2003, 207 cases were collected in 12 French Cancer Centers. Median age was 36.3 years and median follow-up 160 months. Seventy four (35.8%) underwent mastectomy, 67 (32.4%) lumpectomy alone and 66 (31.9%) lumpectomy plus radiotherapy. RESULTS: 37 recurrences occurred (17.8%): 14 (38%) were in situ and 23 (62%) invasive. After BCT, the overall rate of recurrence was 27% (33% in the lumpectomy plus radiotherapy group vs. 21% in the lumpectomy alone group). Comedocarcinoma subtype (p = 0.004), histological size more than 10 mm (p = 0.011), necrosis (p = 0.022) and positive margin status (p = 0.019) were statistically significant predictive factors for recurrence. The actuarial 15-year rates of local recurrence were 29%, 42% and 37% in the lumpectomy alone, lumpectomy and whole breast radiotherapy and lumpectomy + whole breast radiotherapy with additional boost groups respectively. After recurrence, the 10-year overall survival rate was 67.2%. CONCLUSION: High recurrence rates (mainly invasive) after BCT in young women with DCIS are confirmed. BCT in this subgroup of patients is possible if clear and large margins are obtained, tumor size is under 11 mm and necrosis- and/or comedocarcinoma-free.

[Ductal carcinoma in situ of the breast (DCIS). Histopathological features and treatment modalities: analysis of 1,289 cases]. / Carcinomes canalaires in situ (CCIS). Caractéristiques histopathologiques et traitement : analyse de 1 289 cas.

From March 2003 to April 2004, were prospectively collected in France 1,289 ductal carcinoma in situ (DCIS) with data on diagnosis, patient and tumour characteristics, and treatments. Median age was 56 years (range, 30-84). DCIS was diagnosed by mammography in 87.6% of patients. Mastectomy (M), conservative surgery alone (CS) and conservative surgery with radiotherapy (CS + RT) were performed in 30.5, 7.8 and 61.7% of patients, respectively. Sentinel node biopsy (SNB) and axillary dissection (AD) were performed in 21.3 and 10.4% of patients, respectively. Hormone therapy was administered to 13.4% of the patients. Nuclear grade was low in 21% of patients, intermediate in 38.5% and high in 40.5%. Excision was considered complete in 92% (CS) and 88.3% (CS + RT) of patients. Treatment modalities varied widely according to region: mastectomy rate, 20-37%; adjuvant RT, 84-96%; hormone treatment, 6-34%. Our survey on current DCIS management in France has highlighted correlations between pathological features (tumour size, margin, grade) and treatment options, with several similar variations to those observed in recent UK and US studies.

Feasibility of sentinel lymph node biopsy in multiple unilateral synchronous breast cancer: results of a French prospective multi-institutional study (IGASSU 0502).

BACKGROUND: To prospectively determine the feasibility of sentinel lymph node biopsy (SLNB) in preoperatively diagnosed multiple unilateral synchronous invasive breast cancers. PATIENTS AND METHODS: The Interest of Axillary Sentinel Lymph Node Biopsy in Multiple Invasive Breast Cancer (IGASSU) study was a prospective multi-institutional study with initial breast surgery, SLNB, and systematic axillary lymph node dissection (ALND). Patients eligible for the IGASSU study had an operable invasive multiple synchronous tumor (MST), defined as two or more physically separate invasive tumors in the same or different quadrant. RESULTS: From 1 March 2006 to 31 August 2007, 216 patients were prospectively included from 16 institutions. Of these patients, 211 were assessable. The SLNB-identified rate was 93.4% (197 of 211). The false-negative rate (FNR) was 13.6% (14 of 103) [95% confidence interval (CI) 7% to 20%], and the accuracy was 92.9% (183 of 197) (95% CI 89% to 96%). In a univariate analysis, tumor location (only external location versus other location) was the only clinicopathological factor influencing the FNR [22% (11%-33%) versus 7% (4%-10%)], even then median aggregate histological tumor size was smaller in external tumors [17 mm (range 12-80 mm) versus 34 mm (range 8-90 mm), P = 0.016]. CONCLUSION: With a FNR of 13.6%, we do not recommend SLNB as a routine procedure for MST, even for small tumor.

[Anaphylactic shock due to patent blue: four case report and review of literature]. / Choc anaphylactique et bleu patente: à propos de quatre cas et revue de la littérature.

OBJECTIVES: Description of four cases of anaphylactic shock with blue dye injection (bleu patenté V Guerbet 2.5%) during sentinel node biopsy for breast cancer. PATIENTS AND METHODS: Women with breast carcinoma and combined approach with radioactive tracer and blue patent injection. RESULTS: Four cases were observed, which means an incidence of 0.57%. We report one case of grade II anaphylactic reaction and three cases of grade III requiring active reanimation and adrenaline perfusion. One patient developed a pulmonary embolism during the postoperative period, but no death was observed. DISCUSSION AND CONCLUSION: We find an incidence of 1.06% of allergy but only 0.25% of anaphylactic shock (grade III). These rare but serious cases must weigh up the benefits and risks of using blue dye. We suggest using blue dye injection only in case of radioisotope detection failure. Of course, this approach must be evaluated.

Breast-conserving surgery with or without radiotherapy vs mastectomy for ductal carcinoma in situ: French Survey experience.

From March 2003 to April 2004, 77 physicians throughout France prospectively recruited 1289 ductal carcinoma in situ (DCIS) patients and collected data on diagnosis, patient and tumour characteristics, and treatments. Median age was 56 years (range, 30-84). Ductal carcinoma in situ was diagnosed by mammography in 87.6% of patients. Mastectomy, conservative surgery alone (CS) and CS with radiotherapy (CS+RT) were performed in 30.5, 7.8 and 61.7% of patients, respectively. Thus, 89% of patients treated by CS received adjuvant RT. Sentinel node biopsy (SNB) and axillary dissection (AD) were performed in 21.3 and 10.4% of patients, respectively. Hormone therapy was administered to 13.4% of the patients (80% tamoxifen). Median tumour size was 14.5 mm (6, 11 and 35 mm for CS, CS+RT and mastectomy, respectively, P<0.0001). Nuclear grade was high in 21% of patients, intermediate in 38.5% and low in 40.5%. Excision was considered complete in 92% (CS) and 88.3% (CS+RT) of patients. Oestrogen receptors were positive in 69.8% of assessed cases (31%). Treatment modalities varied widely according to region: mastectomy rate, 20-37%; adjuvant RT, 84-96%; hormone treatment, 6-34%. Our survey on current DCIS management in France has highlighted correlations between pathological features (tumour size, margin and grade) and treatment options, with several similar variations to those observed in recent UK and US studies.

A nomogram predictive of non-sentinel lymph node involvement in breast cancer patients with a sentinel lymph node micrometastasis.

PURPOSE: Predictive factors of non-sentinel lymph node (NSN) involvement at axillary lymph node dissection (ALND) have been studied in the case of sentinel node (SN) involvement, with validation of a nomogram. This nomogram is not accurate for SN micrometastasis. The purpose of our study was to determine a nomogram for predicting the likelihood of NSN involvement in breast cancer patients with a SN micrometastasis. METHODS: We collated 909 observations of SN micrometastases with additional ALND. Characteristics of the patients, tumours and SN were analysed. RESULTS: Involvement of SN was diagnosed 490 times (53.9%) with standard staining (HES) and 419 times solely on immunohistochemical analysis (IHC) (46.1%). NSN invasion was observed in 114 patients (12.5%), whereas 62.3% (71) had only one NSN involved and 37.7% (43) two or more NSN involved. In multivariate analysis, significant predictive factors were: tumour size (pT stage < or = 10 mm or >11 and < or = 20 or >20 mm [odds ratio (OR) 2.1 and 3.43], micrometastases detected by HES or IHC [OR 1.64], presence or absence of lymphovascular invasion (LVI) [OR 1.76], tumour histological type mixed or not [OR 2.64]. The rate and probability of NSN involvement with the model are given for 24 groups, with a representation by a nomogram. CONCLUSION: One group, corresponding to 10.1% of the patients, was associated with a risk of NSN involvement of less than 5%, and five groups, corresponding to 29.8% of the patients, were associated with a risk < or = 10%. Omission of ALND could be proposed with minimal risk for a low probability of NSN involvement.

SOR guidelines for concomitant chemoradiotherapy for patients with uterine cervical cancers: evidence update bulletin 2004.

BACKGROUND: In 1993 the French National Federation of Cancer Centres (FNCLCC) initiated the Standards, Options and Recommendations (SOR) project. This is a collaboration between the FNCLCC, the 20 French cancer centres, and specialists from French public universities, general hospitals and private clinics, and some specialists learned societies. The main objective is to develop clinical practice guidelines to improve the quality of health care and the outcome of cancer patients. MATERIALS AND METHODS: The SORs are developed using a methodology based on a literature review and critical appraisal by a multidisciplinary group of experts, with feedback from specialists in cancer care delivery. RESULTS: In 1999, the initial SORs for the management of women with cervical cancer were published. At that time the use of chemoradiotherapy was considered as an option. Since this original publication, five randomised trials comparing chemoradiotherapy with radiotherapy have been published, as well as a systematic review and two other clinical practice guidelines. In the light of this additional evidence, it was decided to update the guidelines on chemoradiotherapy in women with cervical cancer. CONCLUSION: After selection, critical analysis and integration of new evidence, chemoradiotherapy has become a standard for women with cervical cancer.

Clinical experience with 99mTc-MIBI scintimammography in patients with breast microcalcifications.

The aim of this study was to evaluate whether 99mTc-MIBI scintimammography can improve the diagnostic value of mammography for the differentiation of benign and malignant breast microcalcifications. In 41 women presenting 45 clusters of microcalcifications, a 99mTc-MIBI scintimammography was performed before open biopsy. There were 24 malignant lesions (53%). The sensitivity (SE) and specificity (SP) of 99mTc-MIBI scintimammography were 58.3% and 81%, and the positive and negative predictive values (PPV, NPV) were 78% and 63%, respectively. SE and PPV increased for lesions over 10 mm and for the younger patients (under 50 years). No correlation was found between true positive uptake and breast cancer invasiveness: 69% (9/13) for invasive lesions and 45% (5/11) for noninvasive lesions (P = 0.48). 99mTc-MIBI scintimammography was more often positive in high grade than in low- or intermediate-grade ductal carcinoma in situ (P = 0.03). The results were analysed according to the morphologic aspect of the microcalcifications. 99mTc-MIBI scintimammography could not be used for routine evaluation of all the microcalcifications detected by mammography.

[Surgical treatment for endometrial adenocarcinoma: first approaches. Review of the literature]. / Traitement chirurgical des adénocarcinomes de l'endomètre: voies d'abord. Revue de la littérature.

Three surgical approaches have been described for the treatment of women presenting an endometrial cancer. The aim of this study was to appreciate the current criteria that would offer guidelines for this choice. We reviewed the data available in the literature (search Medline). Only laparotomy and laparoscopy permit the carrying out of all the routine surgical staging according to the FIGO's criteria (classification 1988). Only one randomised study compares the results obtained by laparotomy and laparoscopy. Laparoscopy patients had significantly less morbidity. Overall survival did not differ in both groups with a limited follow-up. The other not randomised studies show that laparoscopy is usually proposed to patients having a lower IMC and presenting limited stages. No randomized study had compared laparotomy with the only vaginal surgery. The latter is generally proposed for patients having an associated comorbidity and presenting limited stages. In such cases, no difference in survival is highlighted. Obesity does not represent an absolute contra indication for any way. It makes the surgery generally more complex. A suspicious ovarian lesion, a large uterus are, currently, an indication for laparotomy. Laparoscopy can be accepted only if the uterine volume is lower than 500 g and without deep myometrial infiltration. Laparotomy surgery is the standard. The main indication of vaginal surgery is to permit treatment to high operatory risk patients. Laparoscopy is an option for the early stages. It is not recommended if an ovarian lesion or a deep uterine parietal infiltration are suspected. Whatever the route used, the surgeon must be trained.

[Carbon dioxide pneumoperitoneum and peritoneal carcinosis: review]. / Coelioscopie au CO2 et carcinose péritonéale: revue de la littérature.

OBJECTIVE: The aim of this work was to demonstration the relations between CO(2) laparotomy and peritoneal carcinosis. The first part of this review presents published observations of disseminated peritoneal carcinosis after laparoscopy with CO(2) insufflation. The second part deals with the possible effects of CO(2) laparoscopy on the mechanism of carcinosis. MATERIAL AND METHODS: We made a Medline search for cases of peritoneal dissemination after CO(2) laparoscopy. We present here the published results as well as data from comparative studies conducted in humans and animals on the effects of each step of CO(2) laparoscopy on carcinogenesis and the progress of carcinosis. RESULTS: Most of the published cases on peritoneal dissemination after CO(2) laparoscopy concerned management of ovarian carcinomas where malignancy was not diagnosed before the operation and not treated immediately with laparotomy. The significance of peritoneal dissemination appears to be related to the delay between laparoscopy and laparotomy. No comparative study in humans has been published. For animal studies, it has been difficult to design valid animal modes. Those we present show that laparoscopy has no negative influence on tumor growth but that it may affect peritoneal dissemination. Laparoscopy can participate in diffusion of tumor cells either due to repeated manipulation with contaminated instruments or because of the insufflation itself. These cells can be seeded on traumatized areas of the peritoneum or parietal wall or on the port tracts. The recent work by Volz has proven the effect of CO(2) which can cause a change in the ultra-structure of the peritoneum. This may facilitate peritoneal seeding of the malignant cells. No other study has shown any evidence of increased intraperitoneal tumor growth. Only primary results of post-laparoscopy liver metastasis have diverged. Laparoscopy does not seem to have a negative effect on general immunity, but possible changes in intraperitoneal immunity remain to be elucidated. CONCLUSION: Observations concerning peritoneal dissemination are found in cases where CO(2) insufflation was used for laparoscopy, but no studies have proven certain risk greater for laparoscopy than for laparotomy. Maximum precautions must be taken during the management of suspicious ovarian lesions.

Experimental assessment of tumor growth and dissemination of a microscopic peritoneal carcinomatosis after CO2 peritoneal insufflation or laparotomy.

BACKGROUND: Based on clinical observations and previous animal studies, laparoscopic surgery for malignant disease is regarded as controversial. We used a rat model to measure and compare the tumor growth, proliferation, and dissemination of a microscopic peritoneal carcinomatosis after CO(2) intraperitoneal insufflation or laparotomy. METHODS: Peritoneal carcinomatosis was induced in three groups of 27 BD IX rats each with intraperitoneal injections of 106 DHD/K12 cells, an aneuploid tumor cell line. At 48 h after tumor cell injection, the animals were randomly divided into three groups to undergo different types of intervention. All animals were anesthetized for 20 min (Halothane). The control group had no surgical intervention (group C), group I had CO(2) insufflation (7 mmHg),and group L had a midline laparotomy (5-cm). Neither bowel manipulation nor any other traumatic action was performed. Two weeks later, the rats were killed and the incidence, type, and dissemination of carcinomatosis were evaluated. We also measured the tumor's weight. Malignant omentum was sampled for flow cytometry analysis (DNA ploidy, S-phase fraction). RESULTS: The incidence of carcinomatosis did not differ among the groups. The mean score of macroscopic characteristics of the carcinomatosis was 2.8 +/- 1.9 in group L, 2.9 +/- 1.9 in group I, and 3 +/- 1.9 in group C (NS). The location of the implants did not differ, except for parietal peritoneum location, which was more frequent in group L (p < 0.01). The tumor weight was 4.96 g +/- 3.2 in group L, 5.55 g +/- 3.2 in group C, and 5.75 g +/- 3.4 in group I (NS). The percentage of aneuploid cells and S-phase fraction did not differ statistically among the groups. CONCLUSION: These results indicate that CO(2) insufflation does not cause more effects than laparotomy when tumors cells are present before the beginning of the surgery. Further studies are needed to determine the influence of other steps in laparoscopic surgery on tumor growth and dissemination.

[Standards, options, and recommendations for the radiotherapy of patients with endometrial cancer. FNCLCC (National Federation of Cancer Campaign Centers) and CRLCC (Regional Cancer Campaign Centers)]. / Standards, Options et Recommandations pour la radiothérapie des patientes atteintes de cancer de l'endomètre.

OBJECTIVES: To develop clinical practice guidelines according to the definitions of the Standards, Options and Recommendations project for the radiotherapy of carcinoma of the endometrium. METHODS: Data were identified by searching Medline and personal reference lists of members of the expert groups. Once the guidelines were defined, the document was submitted for review to independent reviewers, and to the medical committees of the 20 French Cancer Centres. RESULTS: The main recommendations for the radiotherapy of carcinoma of the endometrium are: 1) For grade 1 and 2 stage IA tumours, follow-up alone is standard as additional treatment. For grade 1 and 2 stage IB tumours, vaginal brachytherapy or follow-up alone are options. For grade 3, stage IB tumours and stage IC disease, there are two treatment options: external pelvic radiotherapy with a brachytherapy boost or vaginal brachytherapy. 2) Treatment for stage II disease can be preoperative when stage II disease has been suggested by a positive endometrial curettage. Postoperative vaginal brachytherapy is given for stage IIA tumours if the penetration of the myometrium is less than 50% or if the tumour is grade 1 or 2. In the case of deep penetration, or higher grade disease, or for stage IIB external radiotherapy with brachytherapy boosting must be undertaken routinely. 3) After surgery, for stage IIIA disease, either external pelvic radiotherapy or abdomino-pelvic radiotherapy is indicated, along with medical treatment in certain patients. For stage IIIB tumours, postoperative external radiotherapy with brachytherapy (if possible) should be undertaken. For stage IIIC tumours, standard treatment is external (pelvic or pelvic and para-aortic) radiotherapy followed or not by a brachytherapy boost. In case of extrauterine sites involved abdomino-pelvic irradiation is recommended. 4) Standard treatment for inoperable stage I and II disease is external radiotherapy and brachytherapy. For patients with inoperable stage III or IV disease, treatment is often symptomatic, combining external radiotherapy and medical treatment.

[Standards, Options and Recommendations for the surgical management of carcinoma of the endometrium]. / Standards, Options et Recommandations pour la prise en charge chirurgicale des patientes atteintes de cancer de l'endomètre.

CONTEXT: The "Standards, Options and Recommendations" (SOR) project, started in 1993, is a collaboration between the Federation of the French Cancer Centres (FNCLCC), the 20 French Cancer Centres and specialists from French Public Universities, General Hospitals and Private Clinics. The main objective is the development of clinical practice guidelines to improve the quality of health care and outcome for cancer patients. The methodology is based on literature review and critical appraisal by a multidisciplinary group of experts, with feedback from specialists in cancer care delivery. OBJECTIVES: To develop clinical practice guidelines according to the definitions of the Standards, Options and Recommendations project for the surgical management of carcinoma of the endometrium. METHODS: Data were identified by searching Medline and personal reference lists of members of the expert groups. Once the guidelines were defined, the document was submitted for review to independent reviewers, and to the medical committees of the 20 French Cancer Centres. RESULTS: The main recommendations for the surgical management of carcinoma of the endometrium are: 1) where-ever possible, surgery is the primary treatment of both localised and advanced disease; 2) surgery is performed according to the stage of the cancer and the status of the patient; 3) surgery for stages I and II disease entails total abdominal hysterectomy and bilateral salpingo-oophorectomy. A modified radical hysterectomy is undertaken in cases of macroscopic cervical involvement. An omenectomy is recommended for serous papillary types. Pelvic lymphadenectomy for the purposes of precise staging is undertaken if the patient is of good performance status and without bad pronostic factors. Para-aortic lymphadenectomy can be undertaken to determine involvement of para-aortic nodes; 4) surgery for stages III and IV: radical surgery must be undertaken if at all possible with additional treatment as indicated. In the case of advanced disease, debulking surgery is indicated.

[Is ambulatory surgery suitable for cancer patients?]. / La chirurgie ambulatoire est-elle adaptée aux patients cancéreux?

The aim of this inquiry was to question 50 patients before a traditional hospitalization in a regional center, in order to know their opinion about one-day surgery. Among 44 answers from 41 women and 3 men, 29 were against, 11 favourable and 4 without opinion. After their hospitalization, only 4 changed their mind. The main reasons, in case of unfavourable answer, were lack of security and fear of pain. Psychologic aid in traditional hospitalization is frequently cited (34%). This has to be taken into account in ambulatory cases.