The star approach, a surgical approach for skin sparing mastectomy and central lumpectomies.

When preservation of the nipple-areolar complex (NAC) is not possible in oncologic breast surgery, the traditional approaches are either a horizontal incision centered on the NAC resulting in visible scars and breast distortion, or a round block with risk of healing difficulties. To address these concerns, the authors propose a star approach technique for skin sparing mastectomies and lumpectomies of central breast tumors. During the oncologic surgery, the NAC is removed with four cutaneous extensions, which can be closed as a cross-shaped scar. The scarring is similar in size to the original NAC diameter and can easily be covered by the NAC reconstruction. This technique offers good exposure during surgery, a good aesthetic result with limited scarring, no breast deformity, correction of breast sagging, and high-quality healing.

Muscle sparing latissimus dorsi flap for reconstruction of a large chemo-necrosis of the chest wall: A case report.

BACKGROUND: Extravasation of chemotherapeutic agents is a common complication in cancer centers. In severe cases involving large tissue necrosis, surgery may be needed to resect necrotic tissues and to cover the exposed areas. CLINICAL CASE DESCRIPTION: A 71 years old women was referred to our unit two month after extravasation of epirubicin from an implanted port-a-cath with a large chemonecrosis of the anterior chest wall. She presented an evolutive tissue necrosis extending from the upper anterior thoracic region to the right breast. Surgical debridements and negative wound pressure therapy were necessary in order to obtain clean areas. The final chest wall defect was covered using a Muscle Sparing Latissimus Dorsi pedicled flap. This surgical management have permitted a satisfying wound healing and functional recovery without any complication. CONCLUSION: Chemotherapeutics' extravasations can be a severe complication of oncologic treatment and have to be discussed between oncologists and plastic surgeons to find the most effective and suitable solution with consideration of the specificities of cancer therapy. In chest wall skin defect, the use of muscle sparing latissimus dorsi pedicled flap is a robust solution with low morbidity of the donor site.

Optimal biological dose: a systematic review in cancer phase I clinical trials.

BACKGROUND: Classical phase 1 dose-finding designs based on a single toxicity endpoint to assess the maximum tolerated dose were initially developed in the context of cytotoxic drugs. With the emergence of molecular targeted agents and immunotherapies, the concept of optimal biological dose (OBD) was subsequently introduced to account for efficacy in addition to toxicity. The objective was therefore to provide an overview of published phase 1 cancer clinical trials relying on the concept of OBD. METHODS: We performed a systematic review through a computerized search of the MEDLINE database to identify early phase cancer clinical trials that relied on OBD. Relevant publications were selected based on a two-step process by two independent readers. Relevant information (phase, type of therapeutic agents, objectives, endpoints and dose-finding design) were collected. RESULTS: We retrieved 37 articles. OBD was clearly mentioned as a trial objective (primary or secondary) for 22 articles and was traditionally defined as the smallest dose maximizing an efficacy criterion such as biological target: biological response, immune cells count for immunotherapies, or biological cell count for targeted therapies. Most trials considered a binary toxicity endpoint defined in terms of the proportion of patients who experienced a dose-limiting toxicity. Only two articles relied on an adaptive dose escalation design. CONCLUSIONS: In practice, OBD should be a primary objective for the assessment of the recommended phase 2 dose (RP2D) for a targeted therapy or immunotherapy phase I cancer trial. Dose escalation designs have to be adapted accordingly to account for both efficacy and toxicity.

GUIP1: a R package for dose escalation strategies in phase I cancer clinical trials.

BACKGROUND: The main objective of phase I cancer clinical trials is to identify the maximum tolerated dose, usually defined as the highest dose associated with an acceptable level of severe toxicity during the first cycle of treatment. Several dose-escalation designs based on mathematical modeling of the dose-toxicity relationship have been developed. The main ones are: the continual reassessment method (CRM), the escalation with overdose control (EWOC) method and, for late-onset and cumulative toxicities, the time-to-event continual reassessment method (TITE-CRM) and the time-to-event escalation with overdose control (TITE-EWOC) methods. The objective of this work was to perform a user-friendly R package that combines the latter model-guided adaptive designs. RESULTS: GUIP1 is an R Graphical User Interface for dose escalation strategies in Phase 1 cancer clinical trials. It implements the CRM (based on Bayesian or maximum likelihood estimation), EWOC and TITE-CRM methods using the dfcrm and bcrm R packages, while the TITE-EWOC method has been specifically developed. The program is built using the TCL/TK programming language, which can be compiled via R software libraries (tcltk, tkrplot, tcltk2). GUIP1 offers the possibility of simulating and/or conducting and managing phase I clinical trials in real-time using file management options with automatic backup of study and/or simulation results. CONCLUSIONS: GUIP1 is implemented using the software R, which is widely used by statisticians in oncology. This package simplifies the use of the main model-based dose escalation methods and is designed to be fairly simple for beginners in R. Furthermore, it offers multiple possibilities such as a full traceability of the study. By including multiple innovative adaptive methods in a free and user-friendly program, we hope that GUIP1 will promote and facilitate their use in designing future phase I cancer clinical trials.

Impact of sentinel node biopsy on long-term quality of life in breast cancer patients.

BACKGROUND: The aim of this study was to assess long-term quality of life (QoL) over a period of 6 years in women with breast cancer (BC) who underwent sentinel lymph node biopsy (SLNB), axillary lymph node dissection (ALND), or SLNB followed by ALND. METHODS: The European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC-QLQ)-C30 and the EORTC-QLQ-BR-23 questionnaires were used to assess QoL before surgery, just after surgery, 6, 12 and 72 months later. The longitudinal effect of surgical modalities on QoL was assessed with a mixed model analysis of variance for repeated measurements. RESULTS: Five hundred and eighteen BC patients were initially included. The median follow-up was 6 years. During the follow-up, 61 patients died. None of the patients of the SLNB group developed lymphedema during follow-up and the relapse rate was similar in the different groups (P=0.62). Before surgery, global health status (P=0.52) and arm symptoms (BRAS) (P=0.99) QoL scores were similar whatever the surgical procedure. The BRAS score (P=0.0001) was better in the SLNB group 72 months after surgery. Moreover, during follow-up, patients treated with SLNB had lower arm symptoms scores than ALND patients and there was no difference for arm symptoms between patients treated with ALND and those treated with SLNB followed by complementary ALND. CONCLUSION: Long-term follow-up showed that SLNB was associated with less morbidity than ALND.

Neoadjuvant therapy for breast cancer has no benefits on overall survival or on the mastectomy rate in routine clinical practice. A population-based study with a median follow-up of 11 years using propensity score matching.

BACKGROUND: Even though neoadjuvant chemotherapy has shown no benefits on overall survival (OS), it is being widely used in the treatment of breast cancer. This is based on the assumption that it may diminish the mastectomy rate and therefore be clinically relevant for patients. Our objective was to assess the impact of neoadjuvant chemotherapy on OS and on the rate of mastectomy in patients with non-metastatic primary operable breast carcinoma in routine practice. METHODS: The Cote d'Or district breast cancer registry was used to analyse the OS and mastectomy rate in patients with invasive primary operable unilateral breast cancer diagnosed between 1982 and 2006. We performed Cox proportional hazard ratio (HR) analyses for OS and multivariate logistic regression for the mastectomy rate for the overall population. Different matching methods based on the propensity score were used as sensitivity analyses to ensure that corrections for selection bias were adequate. RESULTS: We analysed 1578 patients, among whom 174 had received neoadjuvant chemotherapy. Median follow-up was 11.1 years. There was no difference between the two treatment groups for OS (HR=1.08 (95% confidence interval (CI): 0.77-1.51 for neoadjuvant chemotherapy)). The mastectomy rate was higher among patients treated with neoadjuvant chemotherapy (odds ratio 1.54 (95%CI: 1.03-2.31)). Sensitivity analyses confirmed these results: for OS, there was no difference between the two populations precisely matched using propensity scores (HR 1.08; 95%CI: 0.671-1.65). CONCLUSION: Despite long term follow-up, neoadjuvant chemotherapy provided no benefit for either OS or the mastectomy rate in our population.

[Metastatic tumor implantation from a primary cancer of the base of the tongue at the site of placement of a central venous portacath]. / Métastase d'une tumeur de la base de langue sur un système d'accès veineux central totalement implantable.

Central venous catheter placement with an implanted port (portacath) is used to provide long-term venous access. We report a case of metastatic implantation at a port site from a primary cancer of the base of the tongue. Insertion of portacaths must be performed using full sterile precautions to avoid spread of tumor cells; in no case should the port site incisions be in contact with the surgical field in which the tumor resection was performed.

A multicenter cohort study to compare quality of life in breast cancer patients according to sentinel lymph node biopsy or axillary lymph node dissection.

BACKGROUND: This prospective multicenter study assessed and compared the impact of different surgical procedures on quality of life (QoL) in breast cancer patients. PATIENTS AND METHODS: The EORTC QLQ-C30 and the EORTC QLQ-BR-23 questionnaires were used to assess global health status (GHS), arm (BRAS) and breast (BRBS) symptom scales, before surgery, just after surgery and 6 and 12 months later. The Kruskal-Wallis test with the Bonferroni correction was used to compare scores. A mixed model analysis of variance for repeated measurements was then applied to assess the longitudinal effect of surgical modalities on QoL. RESULTS: Before surgery, GHS (P = 0.7807) and BRAS (P = 0.7688) QoL scores were similar whatever the surgical procedure: sentinel node biopsy (SLNB), axillary node dissection (ALND) or SLNB + ALND. As compared with other surgical groups, GHS 75.91 [standard deviation (SD) = 17.44, P = 0.041] and BRAS 11.39 (SD = 15.36, P < 0.0001) were better in the SLNB group 12 months after surgery. Whatever the type of surgery, GHS decreased after surgery (P < 0.0001), but increased 6 months later (P = 0.0016). BRAS symptoms increased just after surgery (P = 0.0329) and until 6 months (P < 0.0001) before decreasing (P < 0.0001). CONCLUSIONS: SLNB improved GHS and BRAS QoL in breast cancer patients. However, surgeons must be cautious, SLNB with ALND results in a poorer QoL.

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.

[Immediate patent blue-induced hypersensitivity during sentinel node detection: The value of cutaneous tests]. / Hypersensibilité immédiate après injection de bleu patenté lors du repérage du ganglion sentinelle : intérêt des tests cutanés.

BACKGROUND: Patent blue is a blue dye commonly used for sentinel node detection in the management of melanoma and breast cancer. Immediate hypersensitivity reactions to patent blue such as blue urticaria, bronchospasm or anaphylactic shock are not rare, being seen in 0.8 to 2.8% of patent blue-treated patients. PATIENTS AND METHODS: We report three cases of anaphylactic shock and two cases of urticaria developed after injection of patent blue in the context of sentinel node detection in breast cancer patients. Immediately after surgery, two patients developed generalized urticaria followed by circulatory collapse requiring resuscitation. The third patient presented massive anaphylactic shock without cutaneous or respiratory signs. Blue urticaria without haemodynamic disturbance was seen in the latter two patients. Prick tests using patent blue were positive for the three patients with positive intradermal reactions (1/10,000 dilution) in all patients. DISCUSSION: These observations underline the severity of patent blue-induced shocks with delayed onset, since they are often observed at the end of surgery. While the mode of sensitization is poorly understood, food and textile dyes are thought to play a role. Skin prick tests provide a simple and reliable method of diagnosing these events. There is a real risk of late anaphylactic shock during sentinel node detection using patent blue and discussion is needed concerning alternative methods of sentinel node detection.

[Intrathoracic localisation of desmoid tumours: a familial case of isolated desmoid tumours and current published data]. / Localisation intrathoracique des tumeurs desmoïdes: à propos d'un cas familial de tumeurs desmoïdes isolées et revue de la littérature.

We present the case of large desmoid tumor of the anterior chest wall with pleural involvement, which persistently progressed despite hormonotherapy, chemotherapy and surgery. After many years of therapeutic failures, given the tumor size and its hemodynamic repercussions, the patient was presumed to be incurable and only supportive measures were given. One year later, the desmoid tumor had completely disappeared. Even though wide surgical excision is an essential element in the treatment of desmoid tumors, spontaneous regression may occur in very advanced disease.

Malignant extraovarian endometriosis: a review.

AIMS: Malignant transformation in extra-ovarian endometriosis is a rare but known complication. This distinct pathological entity is reviewed with a specific focus on aetiology and treatment. METHODS: Studies were identified by searching the English language literature in the MEDLINE database and by an extensive review of bibliographies from articles found through that search. FINDINGS: Up to 1% of women with endometriosis will develop endometriosis-associated neoplasm. Almost a quarter of the reported cases of malignancy in endometriosis have involved extra-ovarian tissues. In many cases, hormonal factors may play a role in its pathogenesis. Estrogen monotherapy in obese patients significantly increase the risk of malignant extra-gonadal endometrial transformation. Genetic anomalies have also been reported such as loss of heterozygosity on chromosome 5q. For patients with disease confined to the site of origin, a 82-100% 5-year survival has been noted for endometrioid cell type; disseminated intraperitoneal disease, however, has a very poor associated prognosis, with a 0-12% 5-year survival overall. CONCLUSIONS: Women with endometriosis-associated cancers most likely represent a different class of patients than traditional ovarian cancer patients and may require different therapeutic options.

[Management of ureteral injuries]. / Prise en charge des lésions urétérales iatrogènes.

Ureteral injury is a rare but potential serious complication that can occur during a variety of general surgical procedures. Knowledge of the course of the ureter is the first step toward preventing ureteral injuries. While some injuries are noticed intraoperatively, most are missed and present later with pain, sepsis, urinary drainage or renal loss. The choice of treatment is based on the location, type and extend of ureteral injury. For injuries recognized during open surgery, when involving the distal 5 cm of the ureter, an antireflux ureterocystostomy such as the Politano-Leadbetter procedure or a vesicopsoas hitch can be performed. For the middle ureter, an ureteroureterostomy is satisfactory and for the proximal ureter, most injuries can be managed by transureteroureterostomy. In complex situations intestinal interposition, autotransplantation or even nephrectomy can be considered. The majority of patients with delayed diagnosed ureteral injuries should be managed by an initial endo-urologic approach.

The role of surgery and treatment trends in uterine sarcoma.

AIMS: To report a series of uterine sarcomas treated in one institution. METHODS: We report 72 cases of uterine sarcomas treated in a single institution, comparing the periods 1966-1989 and 1990-2001. The parameters studied were histological type, tumour stage and treatment. The control of pelvic, local and/or metastatic disease were also studied. RESULTS: The histological types consisted in 34 leiomyosarcomas, 25 mixte mullerian tumours, 12 endometrial stromal sarcoma and one angiosarcoma. The median age at diagnosis was 60.5 years. The presenting symptoms were genital bleeding, pelvic or abdominal pain. The proportion, of stage I was lower in 1966-1989 than in 1990-2002. During the 1966-1989 period, surgery was systematically used. The percentage of second-line surgery (post-radiotherapy or -chemotherapy) rose from 2.2% in 1966-1989 to 19.2% in 1990-2002. Radiotherapy was administered in 55.5% of cases. There was no difference between the two periods. Chemotherapy was administered in 37.5% of cases with also no difference between the two periods. The overall 2-year survival was 54.6% and the 5-year survival 36.1%. The median survival was 32.3 months (3 days-25 years). The overall 5-year survival by stage was 47.5% for stage I, 60.6% for stage II and 15.0% for stages III and IV. The median duration of pelvic disease control was 19.2 months. The 5-year pelvic disease control by FIGO stage was 66.6% for stage I, 62.5% for stage II and 18% for the more advanced stages. CONCLUSION: Surgery remains the reference treatment. Local and regional disease control, as adjuvant therapies do not seem to decrease the risk of metastatic spread or increase survival.

[Evolution of therapeutic practices and survival of ovarian cancer in Bourgandi between 1982-1996: a registry-based study]. / Evolution des pratiques thérapeutiques et survie du cancer de l'ovaire dans le département de la Côte d'Or de 1982 à 1966: données du Registre des cancers gynécologiques de Côte d'Or.

OBJECTIVE: The aim of this study is to describe the evolution of therapeutic practices and the evolution of survival between 1982 and 1996 in a population of ovarian carcinomas. All the patients were registered in the "Registre des Cancers Gynécologiques de Côte-d'Or-France". POPULATION AND METHODS: During this period, 546 cases of ovarian cancers were registered. Data about FIGO staging at the diagnosis, histologic type, initial surgical procedures and survival were studied. RESULTS: During this period, 61.7% of the patients had a complete resection of their tumor. The frequency of complete removal increased significantly during the period of this study. Complete removal moved from 56%, between 1982 and 1984, up to 75%, between 1993 and 1996. Complete removal was possible in 98.1% of the FIGO stage 1 cases while it was possible in only 18.3% of the stage IV. 76.9% of the patients younger than 50 years old had a complete removal while only 29% of the women older than 80 years old had a complete removal. Fifty percent of stage I received chemotherapy as long as 85% of patients younger than 50 years old. After 1993, only 2.6% of them had radiotherapy. The global survival rate at 5 years was 35.4%. CONCLUSIONS: Surgery is the major procedure to obtain a complete remission of ovarian cancer. The efficacy of current chemotherapies may modify the initial management of these tumors, particularly in modifying the chronology of the different therapeutic sequences.

[Malignant tumours arising in extraovarian endometriosis: three case reports and review of the literature]. / Endométriose extraovarienne dégénérée: à propos trois cas et revue de la littérature.

In its extraovarian form, co-existence of carcinoma and endometriosis is a sufficient argument used in favour of the malignant transformation of endometric lesions. Estrogen as well as the loss of 5q chromosome heterozygosity are considerate as initiators of that type of carcinogenesis. Endometrioid histological type is the most frequent and is revealed usually by abdominal pain. The incidence of carcinoma arising in endometriosis is about 0.8% and 5-year survival rate of pelvic endometrioid form is about a 100% after surgery and radiotherapy.

[Conservative surgery in breast cancer: combination skin incision for a better cosmetic result]. / Traitement conservateur du cancer du sein: proposition d'une incision cutanée combinée pour un meilleur résultat esthétique.

The authors report a surgical procedure for lumpectomy combining both areolar and radial skin incision for cancer localized in the inferior, or at the junction of the superior and inferior part of the breast. The skin incision have an "amphore-like" appearance. It allows an easy mammoplasty with all cancerologic securities.

[Metastatic renal cell carcinoma to the thyroid gland: report of seven cases and review of the literature]. / Les métastases intrathyroïdiennes du cancer du rein à cellules claires: présentation de sept cas et revue de la littérature.

PURPOSE: The aim of this study was to retrospectively report clinical manifestations, type of treatment, survival rate of thyroid metastases from renal carcinoma. PATIENTS AND METHODS: Seven patients were retrospectively collected from files of different Burgundy's hospitals. All renal and thyroid gland specimens were controlled by the anatomopathologist. RESULTS: Tumors occurred in four women and three men (mean age: 66 years). Symptoms were generally a solitary mass. The metastatic tumor to the thyroid gland was the initial presentation of renal carcinoma in one case. In the other cases, patients had documented previous evidence of renal carcinoma as remotely 8.1 years before the thyroid metastases. Thyroglobulin immunohistochemistry was always negative in the foci of metastatic renal carcinoma. All patients had surgical resection of there metastasis. The majority of patients died with disseminated malignancies (mean: 38.1 months after there thyroid resection). Three patients are still alive, one after a complementary pancreatic resection for a secondary pancreatic metastasis and one other with cervical and mediastinal lymph node recurrence. CONCLUSIONS: Surgical treatment of the metastatic disease is suggested, as this may prolonged patient survival.

Concurrent lymphoma and metastatic breast carcinoma in the axillary, confounding sentinel lymph-node biopsy.

We describe the case of a female patient who presented with the concurrence of two tumors, breast cancer and low grade lymphoma, in different nodes but in the same axillary lymphatic site. The sentinel node biopsy procedure for the detection of carcinoma cells in two well-identified sentinel nodes which had been colonised by lymphoplasmocytic cells was negative. Tumor collision lead to a mistake in the appropriate staging of the breast tumor by sentinel lymph-node biopsy. We believe that sentinel lymph-node biopsy should be avoided in cases of lymphoma.

[Histological and cytopathological cancer specimens: good practice in operating room]. / Prélèvements anatomopathologiques en cancérologie : règles de bonnes pratiques au bloc opératoire.

Concerning good practice for the management of histological cancer specimen, the main recommendations concern: (1) the quality of transmission in information between professionals; (2) the necessity of fresh, unfractionated, oriented surgical samples; (3) the importance of an appropriate storage condition for samples collected for extemporaneous examination, freezing or cell culture; (4) the quality of the deep freezer at temperatures of -80 degrees C or liquid nitrogen for frozen samples storage; (5) the importance of fixing tissues shortly after sample collection in buffered Formal solution in order to prevent cell lysis.