A Retrospective Comparative Analysis of Latissimus Dorsi (LD) Flap Versus Thoracodorsal Artery Perforator (TDAP) Flap in Total Breast Reconstruction with Implants: A Pilot Study.

BACKGROUND: In breast surgery, an autologous flap combined with implant may reduce the risk or repair the soft-tissue defects in several cases. Traditionally, the preferred flap is the myocutaneous latissimus dorsi (LD) flap. In the perforator flap era, the evolution of LD flap is the thoracodorsal artery perforator (TDAP) flap. The aim of this study is the comparison between LD flap and TDAP flap with implants in terms of early complications and shoulder function. METHODS: We performed a retrospective cohort study in accordance with the STROBE guidelines. Between January 1 2015 and January 1 2020, 27 women underwent a unilateral total breast reconstruction with LD or TDAP flap combined with an implant at our institution. 15 women were operated with LD flap and 12 with TDAP flap. The most frequent indications for intervention were results of mastectomy and radiation-induced contracture. We evaluated several data in terms of clinical and demographical characteristics, operative and perioperative factors, and follow-up variables. We assessed shoulder function through the Disability of the Arm, Shoulder and Hand Questionnaire (DASH). RESULTS: The rate of complications was significantly lower in the TDAP group compared with the LD group (16.7% vs 60.0%, p = 0.047. Table 3). Although the small sample size limited further detailed statistical analyses, we particularly noticed no cases of donor site seroma in the TDAP group, as compared with four in the LD group. Patients in the TDAP group had an ∼11-point lower mean DASH score compared with the LD group (9.8 vs 20.5). This difference was statistically significant (p = 0.049). CONCLUSIONS: TDAP flap seems to be a reliable technique for soft-tissue coverage in total breast reconstruction with implants. In comparison with the traditional LD flap, it could be a more favorable option in terms of less complications and better quality of life.

Monoclonal antibody to fibulin-1 generated by genetic immunization.

Fibulin-1 (Fbln-1) is an extracellular matrix (ECM) and plasma glycoprotein. Considering the growing evidence indicating that Fbln-1 plays a role in cancer we sought to develop monospecific antibodies to better facilitate further studies of the function of Fbln-1 in breast cancer. Using a plasmid expression vector encoding full-length human Fbln-1D as an immunogen and CpG oligodeoxyribonucleotides as adjuvant a monoclonal antibody (MAb) against Fbln-1 was produced. This MAb, designated MEM-2 was of IgM isotype and reacted with bacterially expressed Fbln-1. Furthermore, MEM-2 reacted with Fbln-1 expressed in the ECM released by cultured human breast carcinoma SKBR-3 cells in ELISA, and also with Fbln-1 present in SKBR-3 cell extract in immunoprecipitation and Western blotting. MEM-2 also reacted with Fbln-1 in human breast carcinoma specimens. These findings illustrate the utility of genetic immunization as a means of generating monoclonal antibodies to tumor-related ECM proteins. MEM-2 represents a useful new tool for the study of Fbln-1 in breast cancer.

Axillary lymph node staging in breast cancer by 2-fluoro-2-deoxy-D-glucose-positron emission tomography: clinical evaluation and alternative management.

BACKGROUND: Surgical removal of axillary lymph node and histologic examination for metastases are used to determine whether adjuvant treatment is necessary for patients with breast cancer. Axillary lymph node dissection (ALND) is a costly procedure associated with various side effects, and 80% or more of patients with tumors of 20 mm or less are lymph node negative and might avoid ALND. In this study, we evaluated whether an alternative, noninvasive method--i.e., positron emission tomography (PET) with 2-[(18)F]fluoro-2-deoxy-D-glucose (FDG)-- could be used to determine axillary lymph node status in patients with breast cancer. METHODS: One hundred sixty-seven consecutive patients with breast cancers of 50 mm or less (range = 5-50 mm; mean = 21 mm) scheduled for complete ALND were studied preoperatively with FDG-PET, and then PET and pathology results from ALND were compared. All statistical tests were two-sided. RESULTS: The overall sensitivity, specificity, and accuracy of lymph node staging with PET were 94.4% (PET detected 68 of 72 patients with axillary involvement; 95% confidence interval [CI] = 86.0% to 98.2%), 86.3% (82 of 95 patients without axillary involvement; 95% CI = 77.8% to 91.9%), and 89.8% (150 of 167 patients with breast cancer; 95% CI = 84.2% to 93.6%), respectively. Positive- and negative-predictive values were 84.0% (68 patients with histologically positive lymph nodes of 81 patients with positive FDG-PET scan; 95% CI = 74.2% to 90.5%) and 95.3% (82 patients with histologically negative lymph nodes of 86 patients with negative FDG-PET scan; 95% CI = 88.2% to 98.5%), respectively. When PET results for axillary metastasis were analyzed by tumor size, the diagnostic accuracy was similar for all groups (86.0%-94.2%), with higher sensitivity for tumors of 21-50 mm (98.0%) and higher specificity for tumors of 10 mm or less (87.8%), and the range was 93.5%-97.3% for negative-predictive values and 54.5%-94.1% for positive-predictive values. Among the 72 patients with axillary involvement, PET detected three or fewer metastatic lymph nodes in 27 (37.5%) patients, about 80% of whom had no clinically palpable axillary lymph nodes. CONCLUSIONS: Noninvasive FDG-PET appears to be an accurate technique to predict axillary status in patients with breast cancer and thus to identify patients who might avoid ALND. These results should be confirmed in large multicenter studies.

Breast cancer patients treated without axillary surgery: clinical implications and biologic analysis.

OBJECTIVE: To evaluate the impact of breast carcinoma (T1-2N0) surgery without axillary dissection on axillary and distant relapses, and to evaluate the usefulness of a panel of pathobiologic parameters determined from the primary tumor, independent of axillary nodal status, in planning adjuvant treatment. METHODS: In a prospective nonrandomized pilot study, 401 breast cancer patients who underwent breast surgery without axillary dissection were accrued from January 1986 to June 1994. At surgery, all patients were clinically node-negative and lacked evidence of distant metastases after clinical or radiologic examination. A precise 4-month clinical and radiologic follow-up was performed to detect axillary or distant metastases. Patients with clinical evidence of axillary nodal relapse were considered for surgery as salvage treatment. Biologic characteristics of primary carcinomas were investigated by immunohistochemistry, and four pathologic and biologic parameters (size, grading, laminin receptor, and c-erbB-2 receptor) were analyzed to determine a prognostic score. RESULTS: The 5-year follow-up of these patients revealed a low rate of nodal relapses (6.7%), particularly for T1a and T1b patients (2% and 1.7%, respectively), whereas T1c and T2 patients showed a 10% and 18% relapse rate, respectively. Surgery was a safe and feasible salvage treatment without technical problems in all 19 cases of progressive disease at the axillary level. The low rate of distant metastases in T1a and T1b groups (<6%) increased to 15% in T1c and 34% in T2 patients. Analyzing the primary tumor with respect to the panel of pathologic and biologic parameters was predictive of metastatic spread and therefore can replace nodal status information for planning adjuvant treatment. CONCLUSIONS: Middle-term follow-up shows that the rate of axillary relapse in this patient population is lower than expected, suggesting that only a minimal number of microembolic nodal metastases become clinically evident. Avoidance of axillary dissection has a negligible effect on the outcome of T1 patients, particularly in T1a and T1b tumors with no palpable nodes, because the rate of axillary node relapse is very low for both. In T1 breast carcinoma, postsurgical therapy should be considered on the basis of biologic characteristics rather than nodal involvement. The authors' prognostic score based on the primary tumor identified patients who required postsurgical treatment, providing a practical alternative to axillary status for deciding on adjuvant treatment. Conversely, in the T2 group, the high rate of salvage surgery for axillary relapses, which is expected in tumors larger than 2.5 cm or 3.0 cm, represents a limit for avoiding axillary dissection. Preoperative evaluation of axillary nodes for modification of surgical dissection in this subgroup would be more useful more than in T1 breast cancer because of the high risk. Complete dissection is feasible without technical problems if precise follow-up detects progressive axillary disease.

Fluctuation of HER2 expression in breast carcinomas during the menstrual cycle.

The hormonal milieu at time of tumor surgery seems to have a significant impact on survival in premenopausal breast cancer patients. Indeed, surgery performed during the follicular phase of the menstrual cycle was suggested to correlate with a poor prognosis. To investigate the relationship between prognosis and menstrual cycle at time of surgery, we analyzed the expression of some markers associated with tumor aggressiveness, such as the hormone receptors, HER2, p53, Bcl2, and cathepsin D in breast carcinomas obtained from 198 premenopausal women who underwent surgery during different phases of the menstrual cycle. HER2 overexpression was found to fluctuate in hormone receptor-positive tumors. In actual fact, 20% of the tumors removed during the follicular phase scored HER2-positive, versus 8% of those removed during the luteal phase. Similarly, a number of hormone receptor-positive tumor specimens, obtained from the same patients during follicular and luteal phases, were scored HER2-positive when the sample was removed during the follicular phase and HER2-negative when removed in the luteal phase. Southern blot analysis of the HER2 gene indicated that, in hormone receptor-positive cases, the overexpression of HER2 is often not associated with gene amplification. The finding that overexpression of the HER2 gene, associated with tumor aggressiveness, can fluctuate according to the hormonal milieu may explain the increased survival of patients operated during the luteal phase. It is also relevant to the selection and treatment of patients most likely to benefit from anti-HER2 antibody therapy.

Impact of the diagnostic methods on the therapeutic strategies.

Over the last 25 years the diagnostic approaches and therapeutic strategies of breast cancer have dramatically changed. The relationship between diagnosis and therapy has gradually become more complex due to the ever more sophisticated diagnostic tools (mammographic screening, digital mammography, magnetic resonance, SPECT scan and FDG-PET), which have improved resolution limits and accuracy, and also due to the different therapeutic planning applied to breast cancer in these years (conservative surgery, neo-adjuvant chemotherapy, axillary dissection or not). Thus, in this paper, we have briefly analyzed the many open questions in breast cancer management and the clinical challenges of present diagnostic tools in relation to pre-, peri- and postoperative phases, and to therapeutic strategies in general. The main goal of mammographic screening is to detect early invasive cancers and to treat them at the first useful moment. However, at which age should one begin screening, and what is the impact on overall survival, the cost-effectiveness, and, most of all, the best operative approach to suspect lesions? Can digital mammography give a better quality of imaging with respect to conventional mammography? Does unexpected multicentricity and/or multifocality, which is sometimes showed by magnetic resonance, have any clinical relevance? Is this technique really better than traditional methods for the identification of local recurrence? Is scintimammography able to improve the low diagnostic accuracy of mammography on non-palpable breast lesions? Moreover, at present, the need for axillary dissection and its therapeutic and staging value is deeply debated: however, clinical detection of axillary metastases is not a reliable diagnostic tool and there are no conventional radiologic techniques to be used: recently nuclear medicine imaging has provided various approaches, such as SPECT scan with different tracers, FDG-PET, or lymphoscintigraphy with gamma probe sentinel biopsy: there are not only methodologic but also phylosophic differences in using these techniques. Neo-adjuvant chemotherapy has allowed a dramatic reduction of primary breast cancer with a replanning of the surgical approach to large breast tumours but, at the same time, has posed new questions such as the adequacy of diagnostic pre- and perioperative revaluation. Finally, does postoperative follow-up take advantage of intensive diagnostic programs and are there therapeutic margins which would improve survival of patients with metastatic disease? This paper is an attempt to analyze the answers given in the literature. Nevertheless, at present, this matter is globally in progress and a scientific debate will provide, in the near future, a new promising scenario for breast cancer management.

Axillary dissection can be avoided in selected breast cancer patients: analysis of 401 cases.

The role of axillary dissection in early breast cancer remains controversial because of its uncertain value with respect to disease free and overall survival. 401 breast cancer patients underwent breast surgery without axillary dissection from January 1986 to June 1994. 323 (81%) patients were postmenopausal whereas 78 (19%) were premenopausal status, the mean age was 62.9 years. 216 out of 401 patients (53.6%) had a pathological tumour < or = 1 cm, 133 (33.6%) were between 1 and 2 cm, whereas 38 (9.5%) had a tumour size > 2 cm. Breast conservative surgery was performed in 383 patients (95.6%), 257 patients (64.1%) received radiotherapy to the operated breast. In elderly patients adjuvant hormonotherapy was preferred considering the hormonal receptorial status. Accurate follow-up showed that 25 patients underwent delayed full axillary dissection, and pathological metastases were determined in 19 cases, so that the total rate of axillary relapses, histologically confirmed, was 4.7%. We conclude that axillary surgery can be avoided in selected breast cancer patients.

Total rectal resection, mesorectum excision, and coloendoanal anastomosis: a therapeutic option for the treatment of low rectal cancer.

BACKGROUND: There is recent and sporadic evidence indicating that patients with very low rectal cancer may be treated via a sphincter-saving procedure, obviating the need for abdominoperineal resection and definitive colostomy. This study confirms these findings. METHODS: From March 1990 to October 1994, 79 patients affected with primary low rectal cancers were submitted for total rectal resection, mesorectum excision, and coloendoanal anastomosis. All lesions were located within 8 cm of the anal verge (within 6 cm in 64 cases). RESULTS: Eight patients relapsed at the pelvic level, and one patient only at the paraanastomotic site. Postoperative morbidity attributable to the procedure was low. A perfect continence was documented in 66% of cases after colostomy closure, and many patients (63%) had one or two bowel movements a day. Sixty-two patients of this series are alive, 49 without actual evidence of disease. Follow-up ranged from 2 to 56 months (median 23). CONCLUSIONS: The clinical and pathological data derived from this study suggest that radical mesorectum excision more than a large clearance margin of resection remains the most important factor in reducing the incidence of local relapse after low rectal cancer surgery and that total rectal resection and coloendoanal anastomosis is a suitable and safe option to traditional, demolitive surgical techniques.