Systematic versus sentinel-lymph-node-driven axillary-lymph-node dissection in clinically node-negative patients with operable breast cancer. Results of the GF-GS01 randomized trial.

PURPOSE: Sentinel-lymph-node (SLN) resection seems to minimize systematic axillary-lymph-node dissection (sALND) side effects in operated breast cancer patients. We explored whether SLN resection achieves similar therapeutic outcomes as sALND but with fewer side effects. METHODS: A randomized, controlled, open-label trial with parallel-group design compared sALND restricted to cases with positive SLN biopsy (test arm, n = 774) versus SLN biopsy followed by sALND (control arm, n = 770). RESULTS: The five-year overall survivals in control and test arms were 96.42 and 95.64% (P = 0.2925). The estimated difference was nearly zero (precisely, - 0.79%, one-tailed 95% confidence interval (CI) limit - 2.44%). In a multivariate Cox model, the adjusted hazard ratio in the test arm was HR 0.81 (upper 95% CI limit 1.17). Advanced age (HR 1.05 per additional year, CI [1.03-1.08]), negative progesterone receptor (HR 2.17 [1.35-3.45]), SLN metastasis (HR 1.69 [1.03-2.79]), and only one SLN identification technique (HR 4.14 [1.21-14.18]) were associated with lower survival. Patients with ≥ 1 severe side effect at 1 month in control and test arms were 173/703 = 24.6% [21.5-28.0%] and 91/693 = 13.1% [10.7-15.9%] (P < 0.001). The estimated sensitivity of SLN biopsy (control arm) was 145/178 = 81.5% [74.8-86.7%]. CONCLUSIONS: Restricting ALND to cases with positive SLN biopsy does not affect the overall survival but reduces by 11.5% [7.5-15.6%] (P < 0.001) the risk of severe short-time side effects of sALND.

Breast conservative surgery for operable invasive ductal carcinoma after neoadjuvant chemotherapy or hormonal therapy- a challenge for breast surgeon: a review based on literature and experience.

UNLABELLED: Neoadjuvant chemotherapy or hormonal therapy is based on biological data and enables more patients to be treated with breast conserving surgery for locally advanced T2 and T3 without significantly increasing the rates of ipsilateral breast recurrence. Careful consideration of an optimal preoperative planning aims at accurately determining the patterns of primary tumour down staging and at the amount and location of any residual tumour in the breast, besides converting patients from mutilating surgery candidates to candidates for breast conservative procedure. The use of induction chemotherapy has the potential to improve the cosmetic results but free margins must be achieved and surgery must be planned in onco-plastic surgery. Axillary lymph node clearance is still the gold standard surgery in the treatment of the axilla. Sentinel lymph node biopsy can be done for clinically N0 patients but only in control trials. KEYWORDS: Neoadjuvant systemic therapy, breast cancer surgery.

High expression of gabarapl1 is associated with a better outcome for patients with lymph node-positive breast cancer.

BACKGROUND: This study evaluates the relation of the early oestrogen-regulated gene gabarapl1 to cellular growth and its prognostic significance in breast adenocarcinoma. METHODS: First, the relation between GABARAPL1 expression and MCF-7 growth rate was analysed. Thereafter, by performing macroarray and reverse transcriptase quantitative-polymerase chain reaction (RT-qPCR) experiments, gabarapl1 expression was quantified in several histological breast tumour types and in a retrospective cohort of 265 breast cancers. RESULTS: GABARAPL1 overexpression inhibited MCF-7 growth rate and gabarapl1 expression was downregulated in breast tumours. Gabarapl1 mRNA levels were found to be significantly lower in tumours presenting a high histological grade, with a lymph node-positive (pN+) and oestrogen and/or progesterone receptor-negative status. In univariate analysis, high gabarapl1 levels were associated with a lower risk of metastasis in all patients (hazard ratio (HR) 4.96), as well as in pN+ patients (HR 14.96). In multivariate analysis, gabarapl1 expression remained significant in all patients (HR 3.63), as well as in pN+ patients (HR 5.65). In univariate or multivariate analysis, gabarapl1 expression did not disclose any difference in metastasis risk in lymph node-negative patients. CONCLUSIONS: Our data show for the first time that the level of gabarapl1 mRNA expression in breast tumours is a good indicator of the risk of recurrence, specifically in pN+ patients.

Clinical implications of axillary sentinel lymph node 'micrometastases' in breast cancer.

AIMS: The aim of this study was to determine, from a series of cases, the frequency and prognostic factors of invasion of non-sentinel lymph nodes when the axillary sentinel lymph node contains a metastasis < or =2 mm, and thereby select a population in which completion axillary dissection could be omitted. METHODS: Between July 1996 and July 2003, 62 patients, which axillary sentinel lymph node contained a metastasis < or =2 mm had an evaluation of the axillary non-sentinel lymph nodes. Eleven patients had also an evaluation of internal mammary lymph nodes. RESULTS: Eleven patients had axillary non-sentinel lymph node invasion: six by metastases < or =2 mm and five by macrometastases. When internal mammary lymph nodes were also concerned, nodal invasion apart from the axillary sentinel lymph node was seen in 14 patients. Vascular lymphatic invasion was the only factor, statistically significant, linked to non-sentinel lymph node invasion (p = 0.02). CONCLUSION: Whatever the size or method of histological detection (pN1mi or pN0(i+)), the presence of a metastasis < or =2 mm in the axillary sentinel lymph node leads us to carry out completion axillary dissection to optimize staging and loco-regional control of the disease.

[Sensitivity and specificity of two methods used to identify incident breast cancer in specialized units using claims databases]. / Sensibilité et spécificité de deux méthodes d'identification des cancers du sein incidents dans les services spécialisés à partir des données médico-administratives.

BACKGROUND: Hospital claims databases from acute care units are available nationwide and contain most patients at the beginning of their cancer. The goal is to define the ability of these databases to provide a number of incident breast cancer cases using identification methods. Two identification methods were assessed in three specialized sections of a teaching hospital. METHODS: The first method identified women who had at least one stay with a principal diagnosis of breast cancer. The second, which is more restrictive, identified women who had at least one stay with a principal diagnosis of breast cancer and a breast cancer-specific surgical treatment code. Both methods were applied to 4588 women 20 Years of age or older hospitalized in three specialized sections of the Hospices Civils de Lyon in 2000. To categorize these women in two groups, incident breast cancer cases or non-incident breast cancer cases, 150 women were randomized in each of two groups, one for incident breast cancer cases and one for non-incident breast cancer cases. Their medical records were used as references. RESULTS: Sensitivity, specificity and their credibility intervals were respectively 99.4% (84-99.9) and 91.7% (90.3-93.3) for the first method and 93.8% (76.2-98.7) and 97.3% (96.1-98) for the second. Among women wrongly identified with an incident breast cancer in 2000, 75.4% (43/57) had a breast cancer that was not incident that Year with the first method, compared to 96% (24/25) with the second. Among these women wrongly identified with an incident breast cancer, coding errors of the principal diagnosis were found for 24.6% (14/57) of patients with the first method and for 4% (1/25) with the second. Their correction led to 99.2% (86.5-99.9) sensitivity and 92.9% (91.4-94.6) specificity for the first method and to 94.2% (76.5-98.7) sensitivity and 97.3% (96.2-98.1) specificity for the second. CONCLUSIONS: The second method using cancer-specific surgical codes appeared more specific with a slight loss in sensitivity. The use of identification methods to assess the number of incident cancer cases still have to be defined.

Conformity to clinical practice guidelines, multidisciplinary management and outcome of treatment for soft tissue sarcomas.

BACKGROUND: The primary management of adult soft tissue sarcomas (STS) is characterized by heterogeneity across centers. Several studies suggest that it is improved when coordinated by specialized sarcoma centers. PATIENTS AND METHODS: This study, comparing STS patients of the Rhône-Alpes region treated within and outside the cancer network, retrospectively assesses the conformity of medical practice with 'evidence-based medicine' (EBM) reported under the clinical practice guidelines (CPGs) of the French Federation of Cancer Centers. Institutional records of 100 new STS patients seen between 1999 and 2001 in the regional comprehensive cancer center and Lyon University hospital were analyzed retrospectively (50/300 new files randomly selected in each institution). Medical decisions were checked for conformity with CPGs. RESULTS: Median age was 58 years (range 18-88) and median tumor size was 9 cm (range 1-26). The most common primary sites were extremities, viscera or trunk. The most frequent histology was leiomyosarcoma (21%) or liposarcoma (12%). Only 7% of cases were reviewed by formal multidisciplinary committee before biopsy (with 42% pre-surgery biopsies only). The first surgical resection was R0, R1 and R2 in 26, 29 and 45% of cases, respectively. Conformity to CPGs was rated 52, 81, 94 and 95% for initial surgery, radiation therapy, chemotherapy and follow-up, respectively. At multivariate analysis, pre-surgery multidisciplinary discussion, management in reference center and management within cancer network independently predicted conformity to CPGs. CONCLUSIONS: Conformity with EBM was similar to previous reports. Elaboration of treatment strategy within a formal multidisciplinary staff and treatment within a cancer network are both important prognostic factors for optimal clinical care.

Surgical management of retroperitoneal sarcomas associated with external and intraoperative electron beam radiotherapy.

AIMS: To report outcomes of adults with retroperitoneal sarcoma (RS) treated by surgery, external beam radiotherapy (EBRT) and intraoperative electron beam radiotherapy (IORT). METHODS: From July 1988 to February 2001; 24 patients with primary and recurrent RS were diagnosed and treated. The median dose and energy of IORT delivered was 15 Gy/9meV. EBRT dose varies between 45-50 Gy. RESULTS: There were five primary and 19 recurrent tumours. One primary and five recurrent tumours underwent R0 resection. There were 12 liposarcomas and 19 grade I tumours; 13 patients developed local recurrence and three developed distant metastases.Twenty-two patients received IORT associated with EBRT: 11 developed recurrences. Six patients developed Neurotoxicity (4 grade II and 2 grade III). Disease free survival and overall survival at 5 years was 28 and 56% respectively. CONCLUSIONS: EBRT with IORT treatment is a promising technique for local control. Lower recurrence rates are associated with radical (R0) surgical procedures.

[Lymphatic mapping and inguinal sentinel lymph node biopsy in anal canal cancers to avoid prophylactic inguinal irradiation]. / Le marquage lymphatique et la biopsie du ganglion sentinelle inguinal dans les cancers du canal anal pour éviter l'irradiation inguinale prophylactique.

Thirty-five patients with clinically N0 cancers of the canal anal, 33 epidermoid carcinomas et 2 melanomas were histologically staged with inguinal sentinel lymph node biopsy (ISN). With the combined technique, blue dye and radiocolloid the ISN was identified in 100% of the cases. The ISN was invaded in 7 cases/33 for epidermoid tumors and 2/2 for melanomas. After 18 months of follow-up, no inguinal recurrence could be seen in ISN pN0 cases. In conclusion, ISN biopsy is a reliable procedure to stage anal canal cancers. It should prevent unnecessary prophylactic inguinal irradiation for pN0 ISN. Inguinal irradiation is only indicated in pN1 ISN.

[Local control in the management of cancer: a few thoughts]. / Le contrôle local en cancérologie: quelques réflexions.

Cancer is still considered from a physiopathological point of view as a disease of the cell. This concept is underlying the idea of cure. Treatment with curative intent should aim at eradicating all the tumoral cells. Local control is mandatory and essential in cancers localized in organ with vital function. In breast cancer a complex and controversial relationship exists between local relapse and increased risk of fatal distant metastasis. In case of organ preserving treatment, a complete local control is necessary from the start. If a too high risk of local relapse is foreseable, conservative treatment should not be recommended.

Management of inguinal lymph node metastases in patients with carcinoma of the anal canal: experience in a series of 270 patients treated in Lyon and review of the literature.

BACKGROUND: The authors performed a specific analysis of the clinical significance of inguinal lymph nodes metastases in patients with anal canal carcinoma (ACC). METHODS: A retrospective analysis was conducted of 270 patients who were treated in Lyon between 1980 and 1996 with radiotherapy with curative intent for ACC: No elective irradiation of clinically normal inguinal areas was performed. Patients with metastatic inguinal lymph nodes were treated with inguinal dissection and postoperative irradiation with a dose of 50 grays over 5 weeks. Concomitant chemoradiation, usually with a regimen of fluorouracil and cisplatinum, was given to 159 patients. RESULTS: The median follow-up for the whole series was 72 months. Synchronous inguinal metastases were observed in 10% of patients (n = 27; the rate was 16% for patients with T3--T4 lesions), and the 5-year overall survival rate was 54.4%. Metachronous inguinal metastases were seen in 19 patients (7.8%), and the 5-year overall survival rate of these patients was 41.4%. An original finding was that, when the primary tumor clearly was located on a single lateral side of the anal canal, the inguinal lymphatic metastases was always homolateral to it (36 of 36 synchronous plus metachronous tumors). CONCLUSIONS: The data from this series of patients and a review of the literature are in favor of a selective approach in the management of inguinal lymph node involvement for patients with ACC, depending on the disease stage and the location of the primary tumors.

Angiosarcoma after conservative treatment and radiation therapy for adenocarcinoma of the breast.

Radio-induced angiosarcoma of the breast after conservative therapy for invasive adenocarcinoma is a very rare tumour. Between 1996 and 2000, four cases were operated in our Department of Surgical Oncology. After a review of the literature over the same period of time, natural history and treatment of radio-induced angiosarcomas of the breast were analysed.

[Conservative surgery for T2 > 3 cm, T3 N0 N1 M0 breast cancer after induction chemotherapy]. / La chirurgie conservatrice des cancers du sein T2 > 3 cm, T3 N0 N1 M0 après chimiothérapie d'induction.

Induction chemotherapy (IC) provides in more than 20% of cases a complete shrinkage of the tumor. This down staging is a new challenge for the surgeons for breast conservative procedure. Although, IC has become the standard of care for breast cancer T2 > 3 cm T3 N0 N1 M0. No guidelines have devoted attention to the surgical problems due to this down staging after IC. Location and size of the tumor before IC have to be studied and outlined by the surgeon himself. During surgery, the residual tumor volume and how much mammary gland must be removed are very difficult to determine. The maximum volume of mammary gland to be removed after IC around the primary site of the tumor before IC is the volume which permits a good cosmetic reconstruction of the breast. After IC, in spite of an important downstaging, an axillary clearance must be done. For N0 patients, sentinel lymph node biopsy could be performed before IC. If the sentinel node is p N0, axillary clearance could be avoided.

[Complete remission after abdominal wall metastasis from uterine cervical cancer on a laparoscopic trochar site: a case report]. / Rémission complète après métastase pariétale sur trajet de trocart de coelioscopie d'un cancer du col utérin. A propos d'un cas.

Abdominal wall metastasis to laparoscopic trochar sites after preoperative staging procedure is rare for uterine cervix cancer. Prognosis is unfavorable. We report a case of metastasis to a laparoscopic trochar site in a patient with a stage IIB cervical cancer with no nodal involvement who is alive four and a half years after radical surgery and radiotherapy.

[Pelvic and para-aortic lymphadenectomy in epithelial ovarian cancer. Report of a series of 86 cases]. / La lymphadénectomie lombo-aortique et pelvienne dans les cancers épithéliaux de l'ovaire. A propos d'une série de 86 cas.

AIM OF THE STUDY: The impact of lymphadenectomy in therapeutic strategy of ovarian carcinomas is strongly debated. The aim of this retrospective study was to report a series of 86 patients with ovarian carcinoma who underwent pelvic and paraaortic lymphadenectomy. PATIENTS AND METHOD: From 1993 to 1998, a retroperitoneal lymphadenectomy was performed in 86 patients (median age: 54 years) during the first laparotomy (n = 52) or later (n = 34) for ovarian carcinoma stade I and II (n = 33), stade III and IV (n = 53). Sixty patients underwent pelvic and paraaortic lymphadenectomy with separate study of the different groups of nodes. RESULTS: There was a lymph node involvement in 48.8% of all cases and in 36% of stade I and II carcinomas. Lymph node involvement was observed for all histological types. It was present in both pelvic and paraaortic nodes in 52.3% of the patients N+. Its incidence was 46.1% in patients before chemotherapy and 52.9% in patients after chemotherapy. It may concern all anatomical location with a 5 to 31% frequency. There was no postoperative death and a low morbidity rate (13.9%). CONCLUSIONS: Retroperitoneal lymphadenectomy is feasible; it is a contribution to the tumoral cytoreduction and to a better classification of ovarian carcinomas. According to this series and to the other reported series, an initial, complete, pelvic and paraaortic lymphadenectomy should be recommended for all cases of ovarian carcinomas but prospective randomised trials are necessary to appreciate the impact of this lymphadenectomy on survival.

[Tolerance, reliability and efficiency of inflatable breast implants after breast reconstruction. Retrospective study of 101 consecutive cases]. / Tolérance, fiabilité et efficacité des prothèses mammaires gonflables en reconstruction mammaire. Etude rétrospective de 101 cas consécutifs.

A long-term retrospective study of breast reconstruction with inflatable implants is presented. One hundred and one patients were studied, with a median follow-up of 44 months. Prosthetic implants used were round McGhan implants, model 168. Median volume was 215 mL. Twenty-two patients had contralateral symmetrisation, an average of five months after implant. The advantages of this sort of reconstruction are ease, speed and homogenously good results. Drawbacks include the appearance of prosthetic leaks (7%), waves and folds (13%), stage III and IV capsular contractures (26%), asymmetry and incorrect placement of the implant (25%). Breast reconstruction with implants alone gives good results for specific indications: immediate reconstructions, bilateral reconstructions, no history of radiotherapy, and good quality chest wall tissues.

Methodological questions in sentinel lymph node analysis in breast cancer patients.

BACKGROUND: The sentinel lymph node (SLN) procedure has been proposed to women with breast cancer with clinically negative axillary lymph nodes, in order to avoid conventional axillary lymph node dissection and its associated side-effects. Methodological aspects of the validation of the SLN procedure are questioned here. MATERIALS AND METHODS: The results of relevant published studies are reviewed, with emphasis on pathological techniques. The ability of the SLN procedure to diagnose lymph node metastases, the extent to which axillary lymph node dissection contributes to treatment, apart from identification of the stage, and the effect of a modified staging procedure on treatment strategies are analyzed. RESULTS AND CONCLUSION: Both the sensitivity and the negative predictive value of the SLN procedure are overestimated if the probability of missing lymph node metastases is not taken into account, even when a complete axillary dissection is performed as a control. The SLN strategy and its effects on staging and treatment cannot be evaluated by comparison with conventional axillary lymph node dissection in a one-arm study but require carefully designed randomized trials.

[Lymph node mapping and axillary sentinel lymph node biopsy in 243 invasive breast cancers with no palpable nodes. The south Lyon hospital center experience]. / Le marquage lymphatique et la biopsie du ganglion sentinelle axillaire dans 243 cancers invasifs du sein sans ganglion palpable. Expérience du centre hospitalier Lyon-Sud.

STUDY AIM: To evaluate the effect of intraoperative lymph node mapping and sentinel lymph node dissection (SLND) on the axillary staging of patients with N0 breast carcinoma. Two techniques were used: blue dye alone (Evans Blue and Patent Blue) and combined technique (blue dye and isotope). METHODS: The incidence of axillary node metastasis in axillary lymph node dissection (ALND) and SLND was compared prospectively. Multiple sections of each SLN were examined by HPS staining and immunohistochemical techniques. Two sections of each non sentinel node in ALND specimens were examined by routine HPS staining. RESULTS: 243 patients underwent ALND after SLN biopsy. The SLN detection rate was 225/243 cases (92.59%): 89.94% with blue dye alone and 100% with the combined technique. The false-negative rate was less than 2%. CONCLUSION: SN biopsy is an accurate staging technique for N0 breast cancer. SLN biopsy with multiple sections and immunohistochemical staining of the SLN can identify significantly more patients with lymph node metastases than ALND with routine HPS staining.

Tagging sentinel lymph nodes: a study of 100 patients with breast cancer.

The aim of this study was to evaluate in breast cancer patients the feasibility of sentinel lymph node (SLN) identification and the sensitivity of this technique to detect node metastases. Between January and July 1997, SLNs were tracked with Evans Blue dye in 100 patients with breast cancer who then underwent complete level I/II axillary lymph node dissection (ALND). All SLNs were examined by haematoxylin-phloxin-saffron (HPS) staining and immunohistochemistry (IHC) of multiple sections. The findings for the SLNs were compared with results on ANLD. Axillary SLNs were identified in 83 patients (detection rate = 83%; 95% confidence interval (CI) 74-90%). Axillary SLNs were detected in 58/83 cases (70%) at level I only, and in 69/83 (83%) at levels including level I. Histologically positive axillary SLNs were found in 45% (37/83) of patients, including 2 patients with malignancy (micro-metastases) detected by IHC only. The sensitivity of axillary SLN to detect axillary lymph nodes metastases was 37/39 = 95% (95% CI 83-99%). SLNs of the internal mammary chain (IMC) were dissected for 33 tumours of the median or inner quadrants and detected in 26/33 = 79% of cases (95% CI 61-91%). In our experience, the overall sensitivity of SLN identification as a predictor of node (axillary or IMC) metastases was 41/43 = 95% (95% CI 84-99%), confirming the usefulness of the procedure.

Primary squamous cell carcinoma in a patient with vaginal agenesis.

BACKGROUND: The development of a carcinoma in a neovagina constructed in patients with congenital vaginal agenesis is rare. CASE: To our knowledge, this is the first report of a squamous cell carcinoma developing in a neovagina that had been constructed by a simple cleavage technique without tissue transplantation. The latency period between reconstruction and tumor diagnosis was 20 years, during which the patient regularly used a prosthesis. The most important observation during this time was the repeated formation of granulation tissue and chronic inflammatory pseudopolyps in the neovagina, which were removed by cauterization. Despite pre- and intraoperative irradiation and radical surgery followed by chemotherapy, the prognosis is poor. CONCLUSION: Patients with neovaginas, whatever the construction technique, need to be followed up regularly, as mechanical irritation from a prosthesis can add to other cancer risk factors, such as viral infection. Furthermore, the absence of transplanted tissue does not seem to protect from the risk.