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.

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.

[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.

[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.

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.

[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.

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.

[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.

Conservative management of rectal adenocarcinoma by radiotherapy.

PURPOSE: The aim of this study was to analyze the experience of Centre GF Leclerc for conservative and curative treatment by radiotherapy of low rectal cancer. PATIENTS AND METHODS: A total of 151 patients received radiotherapy alone for rectal adenocarcinoma with curative intent. They were clinically staged according to size (T1 < 3 cm, and T2 > 3 cm) and depth of infiltration (A=superficial, and B=impaired mobility and T3 fixed). Over the past 6 years, rectal ultrasound (US) has been used systematically, compared with computed tomographic scan and magnetic resonance imaging when needed. Intracavitary contact X ray was given to 129 patients (69%), and brachytherapy in 45 of 151. External radiotherapy was used in 34 cases (22.5%). RESULTS: Complete response was obtained in 93%. Local failures were observed in 50 cases (28%); two occurred in pelvic nodes after intracavitary X rays. Size (tumors > 3 cm) and alteration of mobility significantly influenced the rate of local failure (p=0.009 and 0.007). The addition of external radiotherapy in patients with poor prognostic factors improved the local control rate. A total of 39 patients with recurrence were amenable to salvage surgery. After salvage treatment, the local control rate was 82% with unlimited follow-up. The 5-year actuarial survival rate was 57%, with a specific survival of 66%. There was no difference in local control or survival according to differentiation of the tumors and distance between anal margin and the inferior level of the lesion. Severe late effect (grade 3) was 3.8%. The sphincter preservation was obtained in 104 of 124 cases (84%). The sphincter function was judged to normal in 102 of 104 patients (98%). CONCLUSION: Intracavitary contact X ray is the treatment of choice for clinical Stage T1A rectal tumors. External radiotherapy significantly improved the results of treatment of tumors > 3 cm. Clinical staging and transrectal ultrasound allows a safe selection of indications. Radiotherapy alone may be proposed for selected cases as an alternative to mutilating surgery for small rectal adenocarcinoma.

Preoperative radiotherapy and surgery for endometrial carcinoma: prognostic significance of the sterilization of the specimen.

INTRODUCTION: We report a retrospective study on the analysis of the operative specimen after preoperative radiotherapy for FIGO (1971) stage I or II endometrial carcinoma. METHODS AND MATERIALS: From 1976 to 1996, 221 patients were treated with external radiotherapy (XRT) and/or low-dose-rate brachytherapy (BT) followed by surgery (S). Patients with cervical involvement (89 patients) or with high-grade tumors (49 patients) received XRT and BT. Patients stage FIGO Ia (89 patients) or with low-grade tumors (57 patients) received BT alone. Surgery was performed 5 to 6 weeks after irradiation. RESULTS: The mean follow-up is 78 months (12-216). The 5-year survival was 90% for FIGO Ia, 80% for FIGO Ib, and 84% for FIGO II (p = 0.51). According to the differentiation, 5-year survival was 87% for grade 1, 84% for grade 2, 84% for grade 3 (p = 0.10). Grade 3 complications were registered in 2% (no grade 4). The tumors were sterilized in 37 patients (17%), sterilized but with dystrophic glands in 34 patients (16%), only modified and altered in 21 patients (9.5%), with viable cells in 56 patients (26%). After preoperative radiotherapy, 37/148 specimens were sterilized (25%), 14/74 after brachytherapy and surgery (19%), 23/74 after external radiotherapy-brachytherapy and surgery (31%). According to the response of the specimen, 5-year survival was 87% when the tumor was sterilized, 96% when altered glands were present, 85% when modified, and 76% if residual tumor with viable cells was identified (p = 0.043). CONCLUSION: Preoperative radiotherapy followed by surgery is a safe and effective treatment of FIGO stage I or II endometrial carcinomas. BT with two uterine tubes seems to be of interest in the contribution of the treatment of the uterus to sterilize the specimen. The analysis of this new prognostic factor remains important to select a population with worst prognosis.

Preoperative radiotherapy in stage I/II endometrial adenocarcinoma.

From 1972 to 1993, 170 patients received preoperative radiotherapy followed, 5-6 weeks later, by total extrafascial hysterectomy with bilateral salpingo-oophorectomy without lymphadenectomy. Eighty-three patients with good prognostic factors (low grade tumour and no cervical involvement) received low dose rate utero vaginal brachytherapy alone before surgery (Group 1). Eighty-seven patients with poor prognostic factors (high grade tumors and/or cervical involvement) received external radiotherapy to 40 Gy and low dose rate brachytherapy before surgery (Group 2). A single vaginal failure was observed (0.6%). The overall pelvic failure rate was 2.3% (four patients) including two cases with pelvic recurrence and metastases. Three of the four pelvic failures occurred in Group 1. Using the 1971 FIGO clinical staging, 5-year disease-free survival was 82% in Stage Ia, 79% in Stage Ib, and 81% in Stage II (P = 0.36). Five-year disease-free survival was 86% in Grade 1, 76% in Grade 2, and 83% in Grade 3 (P = 0.20). Five-year overall survival was 83% in Stage Ia, 79% in Stage Ib, and 83% in Stage II (P = 0.78). Five-year overall survival was 88% in Grade 1, 77% in Grade 2,83% in Grade 3 (P = 0.27). Complications were recorded with the French-Italian syllabus. Grade 2 complications occurred in 12 cases (7%), Grade 3 in five cases (3%). The lack of correlation between classical risk factors (stage, grade) and disease outcome suggests that preoperative radiotherapy strategies should be preferred when such factors can be identified before surgery.

Variant translocation in Burkitt's lymphoma: 8;22 translocation in a French patient with an Epstein-Barr virus-associated tumor.

A variant translocation t(8;22)(q23;q11) has been found in tumor cells from a 19-year-old white man with an Epstein-Barr virus-associated Burkitt's lymphoma (BL). The tumor, which appeared 2 years after the patient had infectious mononucleosis, bore histopathological features characteristic of BL, although only the lymph nodes in the cervical region were involved. This case and some other recent cytogenetic observations of nonendemic BL emphasize the importance of chromosome #8 rearrangement in this B-cell-type lymphoma.

Association of t(15;17) and t(8;21) in the initial phase of an acute promyelocytic leukemia.

Two clones were observed at the initial phase of an acute myelogenous leukemia (AML): 46,XX,t(15;17) and 46,XX,t(8;21),t(15;17). Clinical, immunologic, and morphologic findings were in favor of expression of both chromosomal anomalies. Relapse occurred after 12 months of complete remission with typical acute promyelocytic leukemia (APL) syndrome when t(15;17) alone was then most predominant.

Persistence of t(4;11) in cytologically normal bone marrow treated ex vivo with Asta-Z.

The chromosomal anomaly t(4;11) is closely related to a specific type of acute leukemia: occurrence in young children, hyperleukocytosis with a particular immunologic phenotype, and poor response to therapy. Allogeneic bone marrow (BM) transplantation has been done in a few cases. We report a case in which a complete remission was obtained after intensive therapy. Because no donor was available, an autologous BM transplantation was performed after purge ex vivo of the BM collection by Asta-Z. Relapse occurred at day 45.

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.

Impact of UFT on tumoral TS and DPD levels in colorectal cancer.

This was an open lable, pilot translational clinical pharmacology study of a brief (7 day) course of UFT, 300 mg/m2/day, in combination with leucovorin, 90 mg/day, in six patients with newly diagnosed advanced colorectal cancer. The primary objectives of the study were to examine the impact of this treatment course on the UFT targets which are thymidylate synthase (TS) and dihydropyrimidine dehydrogenase (DPD). The rate of tumoral TS inhibition after the 7-day UFT treatment sequence varied from 5% up to 31%. UFT treatment induced a constant and variable decrease in tumor DPD activity ranging from 13% to 60%. UFT treatment induced a constant increase in uracil concentrations both in plasma and tumors. FT, 5-FU and the metabolite fluoro-beta-alanine (FBAL) were found in plasma and tumors at variable concentrations; the highest drug concentrations were those of FBAL in plasma. The present translational clinical study provides data related to the in vivo pharmacological effects of UFT with a description of its impact on cellular targets.