Long term results of treatment of breast cancer without axillary surgery - Predicting a SOUND approach?

BACKGROUND: Traditionally axillary surgery has been used to provide staging information and until recently was thought to improve loco-regional control. However, a more minimal approach to the axilla is now being adopted. The aim of this study was to assess long term outcomes of patients with 'low-risk' breast cancers who did not undergo any axillary surgery. 'Low-risk' criteria were: postmenopausal, <20 mm grade 1 or <15 mm grade 2, LVI-ve, ER +ve. METHODS: Women with invasive breast cancer that did not undergo any axillary surgery were identified. Patients were censored when an event or death occurred or at last follow-up at breast clinic or with their General Practitioner. RESULTS: Between 05/01/1995-20/11/2006, 194 patients (199 tumours) were operated upon without axillary surgery. Median follow-up was 10.4 years. 128 patients met low-risk criteria and 71 did not (patient choice = 42, medical fitness = 29). In the 'low risk' cohort there were two axillary recurrences, with a cumulative incidence of 0.8% and 1.9% at 5 and 10 years respectively. DDFS was 99.2% (94.1-99.9%), and 97% (90.0-99%) at 5 and 10 years respectively and DFS was 96.6% (91.1-98.7%) and 91.2% (82.6-95.6%). OS was 90.3% (95% CI: 83.6-94.4) and 75.5% (95% CI: 65.9-82.8) at 5 and 10 years respectively. CONCLUSION: Axillary recurrence and DDFS in this low-risk cohort is favourable. In the modern era of breast cancer management it is possible to define a group of women in whom axillary surgery can be omitted.

Lipomodelling for the management of symptomatic peristomal contour abnormalities: a pilot and feasibility study.

AIM: Lipomodelling has been successfully used in reconstructive breast surgery but not yet in patients with permanent stomas. METHOD: A feasibility study of six patients with permanent stomas was undertaken. Patients underwent lipomodelling of the peristomal area. The number of leakages and quality of life were measured before and for 6 months after the procedure. RESULTS: All patients reported an improvement in their stoma-related quality of life and a reduction in the number of leakages experienced (mean: 2.25 leakages/24 h before lipomodelling and 0.5 leakages/24 h after lipomodelling). CONCLUSION: Lipomodelling appears to be an effective method to reduce stoma leakages caused by peristomal skin contour abnormalities.

Role of lipomodelling in improving aesthetic outcomes in patients undergoing immediate and delayed reconstructive breast surgery.

AIMS: The objective of this article is to report our findings regarding large-volume fat transfer in patients who have undergone autologous breast reconstruction with the latissimus dorsi (LD) flap and/or implant-based reconstruction with subsequent lipomodelling for symmetrisation. METHODS: We retrospectively collected data on all patients who have undergone lipomodelling from October 2008 to October 2011. Fat was harvested using a low-negative pressure syringe method and centrifuged at 3000 r.p.m. for 3 min. The purified fat was injected in 1 mL increments into multilayered microtunnels, starting from deeper layers and moving to superficial layers in the subcutaneous tissue. Patient satisfaction was assessed using validated Picker questions in a face-to-face consultation during follow-up visits, and the results were documented in the case notes. RESULTS: Thirty-one patients underwent lipomodelling following autologous breast reconstruction using the LD flap and implant-based reconstruction. Three patients in the study group had bilateral lipomodelling, and one patient required 3 lipomodelling sessions. Seven patients required 2 sessions, and 21 patients required a single session to achieve bilateral symmetry. The mean volume of fat that was harvested was 396 mL, and the mean injected volume of fat was 247 mL. Four patients (1 breast cancer recurrence, 2 patients with fat necrosis and 1 patient with oil cysts) developed postoperative complications. Twenty-nine patients (93%) were satisfied with the postoperative cosmetic outcome. CONCLUSION: Lipomodelling offers an additional tool to refine breast reconstructive surgery. This study demonstrates that large volumes of fat can be injected for sculpture optimisation and for reshaping reconstructed breasts with improved softness and a natural feel.

Prevention of postoperative seroma-related morbidity by quilting of latissimus dorsi flap donor site: a systematic review.

OBJECTIVE: To systematically analyze the effectiveness of quilting of latissimus dorsi (LD) flap donor site in the prevention of seroma and related morbidities. METHODS: All published studies comparing the effectiveness of quilting versus no-quilting of LD flap donor site in the prevention of seroma and related morbidities in patients undergoing breast reconstruction were analysed systemically. RESULTS: Five comparative studies on quilting versus no-quilting encompassing 440 patients were suitable for statistical analysis. There was no heterogeneity among trials. Therefore, in the fixed-effects model, quilting was effective in terms of reducing the incidence of donor-site seroma formation, reducing the average volume of the seroma, and reducing the total volume of drained seroma. In addition, quilting did not increase the risk of postoperative complications. Combined quilting and fibrin glue was also effective in reducing the average volume of the seroma and total drained volume of the seroma. Combination of quilting and glue did not influence the incidence of seroma formation at LD flap donor site and overall operative complications. CONCLUSION: Quilting of the LD flap donor site is helpful in reducing the incidence of seroma formation, reducing seroma volume, and reducing total drained seroma volume. Combined quilting and fibrin glue further enhances its effectiveness. Quilting with or without fibrin glue may be considered an option in patients undergoing LD flap breast reconstruction to control seroma-related morbidity. However, a major multicenter randomized controlled trial is required to achieve stronger and reliable evidence before recommending it as a routine procedure.

Skin-reducing mastectomy with breast reconstruction and sub-pectoral implants.

One of the difficulties of an immediate breast reconstruction with a sub-pectoral tissue expander is fashioning the lower, medial end of the pouch because of the insertion of the fibres of the pectoral muscle into the ribs. This often requires delayed corrections to provide a good cosmetic result with fullness of the lower medial quadrant of the reconstructed breast. Skin-reducing mastectomy (SRM) is a technique that potentially resolves this cosmetic problem by creating a dermomuscular pouch with adequate volume in the lower-medial quadrant and, at the same time, provides satisfactory coverage of the silicone implant. Much of the surgical scarring lies in relatively concealed areas of the breast. The risk of complications is reduced by use of permanent expanders and achieving compatibility between the length of the skin flaps and that of the dermomuscular pouch. The indications for this technique are the same as those of a skin-sparing mastectomy. The procedure is particularly useful for women with large breasts and in cases of bilateral prophylactic mastectomy for women at increased risk of breast cancer. We report our experience with 18 skin-reducing mastectomies carried out in 10 women. One had a complication (5%) (haematoma and infection) and one had poor long-term cosmetic result (5%) (fibrosis of the lower pole of the reconstructed breast). SRM is, from an oncological perspective, a skin-sparing mastectomy (type IV) that provides a good cosmetic result by creating a dermomuscular pouch.

Axillary staging in women with small invasive breast tumours.

AIMS: To identify a group of women with small breast cancers of favourable histological grade for whom observation alone may be an acceptable approach for management of the axilla. METHODS: In a retrospective analysis the incidence of nodal metastases was examined in a group of 355 consecutive patients over 55 years of age who underwent mastectomy or breast conserving surgery. All patients had either grade I (<20 mm) or grade II (<15 mm) oestrogen receptor positive tumours without lymphovascular invasion (LVI). In a related study on 173 clinically node negative patients, the rate of axillary recurrence was assessed in patients with small (<10 mm), non-high grade (I and II), ER-positive invasive ductal carcinomas without LVI. Axillary surgery was either omitted (135 patients) or delayed (38 patients) at the time of wide local excision or mastectomy. RESULTS: The overall incidence of positive nodes in this good prognostic group of patients was 13% (95% confidence interval 9.5-16.5). When the analysis was confined to grade I (< or =20 mm) and grade II (< or =10 mm) the overall incidence of nodal metastases was 10%. Rates of axillary recurrence at a median follow up of 49 months were only 1% when axillary surgery was omitted according to patient choice/departmental policy with no cases of uncontrolled axillary recurrence. CONCLUSION: The risk:benefit ratio for detection of node positive cases in a selected group of older patients does not justify any form of axillary procedure at the time of primary surgery.

Molecular characterisation of two human cancer cell lines selected in vitro for their chemotherapeutic drug resistance to ET-743.

ET-743 (Yondelis(TM), Trabectedin) isolated from the tunicate Ecteinascidia turbinata, is being tested in phase II clinical trials in Europe and the United States of America (USA). Studies with different solid tumours have shown antitumour activity in advanced, pre-treated sarcomas as well as in drug-resistant breast and ovarian cancer. The primary mechanism of action for ET-743 has not been fully elucidated and different models have been suggested to explain its molecular mechanism of action. ET-743 binds tightly to the minor groove of DNA and previous data have suggested that ET-743 acts by interfering with RNA transcription. To further investigate the mechanism of in vitro drug resistance, we evaluated the gene expression profile in ovarian and chondrosarcoma cell lines selected for resistance to ET-743. We found 70 genes whose expression was modulated in both drug-resistant cell lines when compared with their respective parental drug-sensitive cell lines. This pattern of gene expression seems to be selective for ET-743-resistant cells, since ovarian cancer cells resistant to paclitaxel did not share the same gene expression changes. Data presented in this study reveal different molecular pathways that could be involved in the cellular mechanism of ET-743 resistance.

Simultaneous PML/RARalpha and AML1/ETO expression with t(15;17) at onset and relapse with only t(8;21) in an acute promyelocytic leukemia patient.

We report a patient with acute promyelocytic leukemia with the common translocation (15;17) and PML-RARAalpha fusion gene. In relapse, blasts showed typical FAB M2 morphologic features, and the karyotype was 45,X, -Y,t(8;21). A reexamination of the leukemic cells at diagnosis revealed that an AML1-ETO fusion gene was also present at that time without cytogenetic evidence of t(8;21). In relapse, only t(8;21) was detected. Two different clones were identified by cytogenetic standard techniques. The association of two common translocations supervening in the same time in the same cells could not be established.

Monitoring strength training: neuromuscular and hormonal profile.

PURPOSE: This study investigated changes induced by a single heavy resistance training session on neuromuscular and endocrine systems in trained athletes, using the same exercises for training and testing. METHODS: Five different groups volunteered: track and field male sprinters (MS, N = 6), track and field female sprinters (FS, N = 6), body builders (BB, N = 6), and weight lifters performing low-repetition exercise (WLL, N = 4) and high-repetition exercise (WLH, N = 4). In training, the work performed during half and full squat exercise was monitored for mechanical power output as well as EMG analysis on leg extensor muscles of the subjects belonging to the MS, FS, and BB groups. Just before and immediately after the training session, venous blood samples were obtained for RIA determination of testosterone (T), cortisol (C), lutropin (LH), human prolactin (PRL), and follitropin (FSH) in FS and MS. In the other three groups (BB, WLH, and WLL), the hormonal profile was limited to T and human growth hormone (hGH) only. RESULTS: After training the power developed in full squat demonstrated a statistically significant decrease (P < 0.01) in MS and no changes in FS. The EMG activity remained constant during the training session. Consequently, the EMG/Power ratio increased in both MS and FS, although only in MS a statistical significance was noted (P < 0.05). In MS immediately after the session the levels of C, T, and LH were significantly lower (P < 0.05). No changes were found in FS. In both groups and in BB significant negative correlation was found between changes in T level and EMG/Power ratio in half squat performance. CONCLUSIONS: It is likely that adequate T level may compensate the effect of fatigue in FT fibers by ensuring a better neuromuscular efficiency.

Duplication of band 12q24 in acute myeloblastic leukemia.

Cytogenetic studies of two patients with acute myeloblastic leukemia, classified as M1 and M2, showed a partial duplication of the distal part of the long arm of chromosome 12 (12q24) as the sole detectable chromosome abnormality. High white blood cell count was common to the two leukemic children. Fluorescence in situ hybridization analysis with the use of a whole-chromosome 12 painting probe and a telomeric probe confirmed the apparent absence of any translocation. The genes involved in the duplication could not be ascertained, but several candidate genes such as growth-factor receptors or genes encoding transcription factors localized to 12q22-q24 should be investigated in the molecular analysis of these duplications.

Is trisomy 4 a secondary chromosomal abnormality in acute myeloblastic leukemia?

Cytogenetic studies were carried out in a patient with acute monocytic leukemia (AML-M5) at diagnosis and in relapse. While no chromosome abnormality was detected initially, isolated trisomy 4 was found in relapse. The primary or secondary nature of trisomy 4 as the sole abnormality in AML is discussed.

Seasonal fluctuations of selected physiological characteristics of elite alpine skiers.

The effects of heavy resistance training and jumping exercise were examined during the 1989-1990 season in 12 international level alpine skiers. The athletes were tested before, during, immediately after training and during the period off training (June, July, October 1989, April 1990). Their mechanical behaviour was investigated using firstly squat jumps performed without (SJ) or with low extra loads (20 kg, SJ20kg) and high extra loads (equivalent to body mass on the shoulders, SJbm) and secondly 15-30 s continuous jumping. These tests allowed the assessment of explosive dynamic strength production (SJ and SJ20kg), slow dynamic strength (SJbm) and maximal mechanical power (continuous jumping). The training adopted resulted in specific changes in neuromuscular performance; in fact all the variables studied showed a significant improvement (P < 0.01) from the beginning compared to the end of training. The range of improvement was between 55.4% (SJbm) and 12.5% (average power during 15-s continuous jumping). The enhancement of SJ had become significant by July. Surprisingly, even when no strength or jumping training was performed during the competition period (November-April), no deterioration in the neuromuscular performance was observed, there being no significant difference between the test values obtained in October 1989 and April 1990. It was concluded that the demanding competition programme of alpine skiers may provide a training stimulus adequate to maintain the neuromuscular improvement induced by training throughout the competition season.