Impact of axillary surgery on outcome of clinically node positive breast cancer treated with neoadjuvant chemotherapy.

PURPOSE: Axillary Lymph Node Dissection (ALND) is recommended for breast cancer patients who present with clinically node positive disease (cN1) especially if they have residual nodal disease (ypN+) following neoadjuvant therapy (NAT). It is unknown whether axillary dissection improves outcome for these patients. METHODS: A prospectively maintained database was used to identify all patients who were diagnosed with cTis-T4N1M0 breast cancer treated with NAT. RESULTS: In our study, of 292 cN1 breast cancer patients who received NAT, we compared ALND with targeted axillary surgery (TAS) in ypN+ patients. ALND was performed in 75% of the ypN+ subgroup, while 25% underwent TAS. Axillary recurrence occurred in four ALND patients, but no recurrence was observed in the TAS group (p = 0.21). Five-year axillary recurrence-free survival was 100% for TAS and 90% for ALND (p = 0.21). Overall survival at five years was 97% for TAS and 85% for ALND (p = 0.39). Disease-free survival rates at five years were 51% for TAS and 61% for ALND (p = 0.9). Clinicopathological variables were similar between the groups, although some differences were noted. ALND patients had smaller clinical tumor size, larger pathological tumor size, more lymph nodes retrieved, larger tumor deposits, higher rates of extranodal extension, and greater prevalence of macrometastatic nodal disease. Tumor subtype and size of lymph node tumor deposit independently predicted survival. CONCLUSION: Axillary recurrence is infrequent in cN1 patients treated with NAT. Our study found that ALND did not reduce the occurrence of axillary recurrence or enhance overall survival. It is currently uncertain which patients benefit from axillary dissection.

Breast metastasis from nasopharyngeal carcinoma: A case report and review of the literature.

Although often localized at diagnosis, nasopharyngeal carcinoma (NPC) has an established potential for distant metastasis. Breast metastasis from NPC is an uncommon presentation. In the present case study, the fifth reported case of breast metastasis from NPC is presented and the use of Epstein-Barr virus testing is demonstrated for the confirmation of this diagnosis. A 49-year-old female was diagnosed with advanced NPC and developed a unilateral breast mass. The biopsy was indicative of a primary breast carcinoma. Subsequent Epstein-Barr virus testing was positive in the primary tumor and the breast mass, establishing the true diagnosis of NPC metastasis to the breast. In summary, breast metastasis from NPC is an uncommon presentation and Epstein-Barr virus testing is suitable for confirmation of the diagnosis and exclusion of primary breast cancer.

Leptomeningeal carcinomatosis in sinonasal undifferentiated carcinoma.

BACKGROUND: Sinonasal undifferentiated carcinoma (SNUC) is an uncommon neoplasm characterized by local extension and an aggressive course. Treatment often includes a combination of chemotherapy, radiation therapy, and surgery, although the optimal strategy remains unclear. Here, we present the first reported case of leptomeningeal carcinomatosis from SNUC. METHODS AND RESULTS: A 28-year-old man with rapidly progressive headaches, congestion, and exophthalmos was found to have a nasal mass. Biopsy revealed sinonasal undifferentiated carcinoma. He had a transient response to chemotherapy followed by a sustained response to concurrent chemoradiation. At the completion of radiation, he developed subtle neurologic findings and MRI revealed diffuse, bulky leptomeningeal spread. He was able to receive only a single fraction of external beam radiation to his spinal axis before his disease rapidly progressed, leading to respiratory failure and death. CONCLUSIONS: Sinonasal undifferentiated carcinoma can be associated with leptomeningeal carcinomatosis, which can lead to a fulminant clinical course.

Elucidating the mechanism of wound contraction: rapid versus sustained myosin ATPase activity in attached-delayed-released compared with free-floating fibroblast-populated collagen lattices.

Wound contraction closes open wounds by the generation of contractile forces within granulation tissue. We investigated the mechanism of wound contraction using the in vitro fibroblast-populated collagen lattice (FPCL) contraction model. The contraction of the free-floating (FF)-FPCL is through rapid myosin ATPase activity, while the contraction of the attached-delayed-released (ADR)-FPCL is through sustained myosin ATPase activity. All FPCLs were cast identically and the contraction of FF-FPCLs was recorded daily for 4 days and the contraction of ADR-FPCLs was recorded 1 hour after release on day 4. At day, 4 cell numbers were determined and cells undergoing apoptosis were identified and counted. Differences in sustained and rapid myosin ATPase activity were shown by added inosine triphosphate-induced cell contraction in permeabilized fibroblast monolayer preparations. At 2 days, the FF-FPCLs were mostly contracted, while an ADR-FPCL completed contraction 1 hour after release at day 4. Contracted myofibroblasts, identified by alpha-smooth muscle actin-stained stress fibers, were identified in contracted ADR-FPCL, whereas elongated fibroblasts were identified in contracted FF-FPCLs. Vanadate inhibited both inosine triphosphate-induced cell contraction and ADR-FPCL contraction, but neither inhibited ATP-induced cell contraction or FF-FPCL contraction. Genistein inhibited FF-FPCL contraction, but not ADR-FPCL contraction. Advancing tyrosine phosphorylation in fibroblasts promotes rapid myosin ATPase activity, while advancing tyrosine dephosphorylation in myofibroblasts promotes sustained myosin ATPase. The ADR-FPCL had a reduced cell count and a greater proportion of cells had entered apoptosis compared with FF-FPCL. These experiments show that FF-FPCL contraction is through elongated fibroblasts and rapid myosin ATPase, requiring tyrosine phosphorylation. In contrast, the mechanism for ADR-FPCL contraction is through cell contraction by sustained myosin ATPase, involving tyrosine dephosphorylation.

Gap junction communications influence upon fibroblast synthesis of Type I collagen and fibronectin.

In rats polyvinyl alcohol sponge subcutaneous implants treated with gap junctional intercellular communications (GJIC) uncouplers showed reduced deposition of connective tissue. Do uncouplers inhibit the synthesis and deposition of a new connective tissue by fibroblasts? Confluent human dermal fibroblasts in serum-free medium received either endosulfan or oleamide, GJIC uncouplers. Collected media were subjected to Dot Blot analysis for native Type I collagen and fibronectin. Uncoupler-treated fibroblasts released less Type I collagen, while there was no change in fibronectin release. Collagen synthesis was restored to normal, when the uncouplers were removed, showing that these uncouplers were reversible and not toxic to cells. Northern blot analysis revealed procollagen alpha1 (I) mRNA was minimally affected by endosulfan. Oleamide-treated 17-day chick embryo calvaria explants were incubated with Type I collagen antibody, frozen, cryosectioned, and then subjected to rhodamine (Rh) tagged anti-mouse-IgG antibody, to detect newly deposited Type I collagen. Fluorescent antibody-collagen complexes were localized on the periphery of cells in control calvaria, but absent around cells in oleamide-treated calvaria. GJIC optimize collagen synthesis but not fibronectin synthesis. The lack of connective tissue deposited in granulation tissues treated with uncouplers appears related to the inhibition of collagen synthesis. These findings suggest that altering GJIC might control collagen deposition in scarring.

Living with achondroplasia: quality of life evaluation following cervico-medullary decompression.

Achondroplasia is the most common of the heritable skeletal dysplasias. Cervico-medullary compression is a frequently encountered and potentially lethal neurological complication. Cervico-medullary decompression (CMD) at the foramen magnum is often employed to relieve the pressure on the emerging cervical cord. Given the inherent risks associated with major surgery, there has been a substantial debate regarding the best criteria for CMD. Our objectives for this study are to explore the quality of life of patients who had undergone CMD, and to assess whether surgery is associated with mortality and increased long-term morbidity. A Medical Outcome Study 36-item Short Form General Health Survey designed to evaluate eight general health concepts as well as achondroplasia-related issues, was administered to patients assessed in the neurosurgery department in Johns Hopkins Hospital between 1977 and 1998. One hundred and sixty-seven patients were eligible for inclusion. Forty-three could not be contacted, and two refused consent. One hundred and twenty-two patients were assessed. Fifty-six (46%) individuals had CMD and 66 (54%) did not. There was 1 case of mortality in the CMD group and 12 cases in the non-CMD group. In the non-CMD group, all deaths, as far as we know, were unrelated to cervico-medullary compression. In this cohort of surviving patients (n = 109), the quality of life of the 55 (50.5%) who had undergone CMD is comparable to that of the 54 (49.5%) who did not have surgery, controlled for age and sex. CMD is indicated for patients with achondroplasia with significant symptomatic foramen magnum compression. It can be life saving. It can abolish profound central apnea that may cause sudden death and alleviate neurological complications associated with damage of the significantly compressed spinal cord. With regards to long-term outcome evaluation, the quality of life of individuals with achondroplasia who had CMD is similar to those age- and sex-matched patients who did not have this surgery. Moreover, CMD, with all its inherent surgical risks, does not appear to be associated with higher mortality or increased long-term morbidity.