Robotic surgery for gastrointestinal malignancies.

BACKGROUND: This report describes our initial experience with the use of robotic-assisted surgery for the treatment of gastrointestinal (GI) malignancies. METHODS: Between November 2004 and July 2007, 73 robotic procedures (26 female, 47 male) for GI cancer were performed and retrospectively reviewed. Procedures included 25 oesophagectomies, 11 gastrectomies and 37 rectal resections. The median body mass index (BMI) for this patient population was 26. RESULTS: The median operative times for rectal, oesophageal and gastric resections were 285, 482 and 430 min, respectively. There were three conversions. Major postoperative morbidity was 16% for rectal, 32% for oesophageal and 9% for gastric procedures. The leak rate was 11% for rectal, 16% for oesophageal and 9% for gastric anastomoses. Median length of stay was 4, 11 and 5 days, respectively. The median number of lymph nodes harvested was 13, 22, and 26 for rectal, oesophageal and gastric lymphadenectomies, respectively. At a median follow-up of 9 months, one patient developed a port site recurrence; 30 day mortality was zero. CONCLUSION: This initial experience suggests that the robotic approach is safe and feasible for a variety of radical oncological surgical procedures.

Deficiences in phenotype expression and function of dentritic cells from patients with early breast cancer.

PURPOSE: Monocytes derived from patients with early breast cancer (EBC) have shown functional deficiencies. These functional deficiencies are characterized by changes in phenotype and morphology. We have expanded these investigations to dendritic cells generated from monocytes from patients with early breast cancer. - PATIENTS AND METHODS: Peripheral blood from 36 patients with EBC and from 26 healthy age-matched women was drawn and prepared for ex vivo generation of dendritic cells (DC) by incubation with granulocyte/macrophage-colony stimulating factor (GM-CSF) and interleukin 4 (IL4). The phenotype of DC was examined by flow-cytometry. T cell - proliferation was induced with tetanus toxoid pulsed autologous dendritic cell. - RESULTS: Dendritic cells generated from monocytes from EBC-patients showed a significantly lower expression of the phenotype-associated antigens CD1a, CD83, CD80, CD86 and CD54 than the dendritic cells from healthy controls. T cell - proliferation in response to TT-pulsed autologous dendritic cells was significantly decreased when induced with dendritic cells from patients with early breast cancer, when compared to healthy controls. Morphologically, only dendritic cells from healthy women possessed prominent dendrites indicating maturity. - CONCLUSIONS: These findings indicate that dendritic cells generated from monocytes from patients with early breast cancer express an immature phenotype, exhibit immature morphology and show functional deficits when compared to the cells derived from healthy age-matched controls. Whether these findings offer a potential target for therapeutic interventions remains to be elucidated.

Breast cancer size in postmenopausal women is correlated with body mass index and androgen serum levels.

Our objective was to investigate the effects of age, weight, body mass index (BMI), sex steroid receptor status and serum parameters such as estradiol, testosterone, androstenedione, dehydroepiandrosterone sulfate (DHEAS) and leptin on the size of a malignant breast tumor. A total of 62 premenopausal (median age 44.0 years) and 151 postmenopausal (median age 59.1 years) Caucasian women undergoing lumpectomy or mastectomy for invasive breast cancer were examined. Patient parameters (age, body weight, BMI), tumor parameters (tumor size, estrogen and progesterone receptor status) and serum parameters (estradiol, testosterone, androstenedione, DHEAS and leptin) were measured. An increase of BMI and DHEAS levels was associated with larger tumors by partial correlation (rp) analysis (rp = 0.418, p = 0.008; and rp = 0.329, p = 0.041, respectively), whereas higher androstenedione levels corresponded with smaller tumors. Furthermore, BMI, androstenedione and DHEAS levels were correlated: an increase in DHEAS was associated with higher androstenedione serum concentrations (rp = 0.603, p < 0.001), but was also associated with a lower BMI (rp = -0.378, p < 0.001). BMI and androstenedione serum concentrations were also associated (rp = 0.242, p = 0.009), thus closing a circle of mutual interactions. We conclude that, although breast cancer progression is characterized by autonomous growth that has become independent of growth regulatory mechanisms, tumor size at the time of detection is influenced by a complex system of counter-regulatory feedback mechanisms that might represent the body's physiological attempt to control the size of a malignant tumor.

Defective antigen presentation resulting from impaired expression of costimulatory molecules in breast cancer.

Previous experiments from our laboratory have shown that immune mechanisms aiming at the destruction of tumour cells including the recognition of target cells and their elimination via the expression of intercellular adhesion molecule-1 (ICAM-1; CD54), the production of tumour necrosis factor-alpha (TNF-alpha) by monocytes and appropriate function of lymphocyte subpopulations were defective in breast cancer. Previous observations were extended to assess expression levels and regulatory mechanisms of costimulatory molecules CD54, CD80 and CD86 on monocytes derived from patients with early breast cancer (EBC). In addition, antigen presentation by antigen-presenting cells (APC) was analyzed within this context. We report that monocytes derived from patients with EBC exhibited significantly decreased expression levels of CD54 (p = 0.0002), CD80 (p = 0.009) and CD 86 (p = 0.002) compared with monocytes derived from healthy females. Simultaneously, lipopolysaccharide (LPS)-induced TNF-alpha production of monocytes was found to be defective in patients with EBC. Finally, T-cell proliferation in response to tetanus toxoid (TT) was significantly decreased in patients with EBC compared with healthy control females (p < 0.0001). Furthermore, T-cell proliferation in response to TT-pulsed APC derived from healthy controls was significantly inhibited in the presence of anti-CD54 and/or anti-CD80 antibodies in a dose-dependent manner, thus corroborating the necessity of the presence of CD54 and CD80 as costimulatory molecules in the present setting. We conclude that monocytes derived from patients with EBC showed a simultaneous defect of expression of CD54 and its regulation via TNF-alpha, CD80 and CD86 as well as T-cell proliferation following exposure to TT-pulsed APC. Based upon these findings, it is speculated that defects in costimulatory molecule expression might contribute to tolerance of the immune system towards the presence of malignant cells in patients with EBC.

Identification of women with early breast cancer by analysis of p43-positive lymphocytes.

Regular screening mammographies and increasing knowledge of high-risk groups have resulted in an improvement in the rate of detection of smaller malignant lesions. However, uncertain minimal mammographic features frequently require further costly and often uncomfortable investigation, including repeat radiological controls or surgical procedures, before cancerous lesions can be identified. Placental isoferritin (p43), a protein with immunosuppressive effects, has been detected on the surface of lymphocytes taken from peripheral blood in patients with breast cancer. In this study we evaluated the sensitivity and specificity of the expression of p43-positive lymphocytes as a marker in early stage breast cancer and also investigated its expression on T-cell subpopulations. The presence of p43-positive lymphocytes was investigated using the monoclonal antibody CM-H-9 and flow cytometry in 76 women with controversial, non-palpable mammographic findings who were undergoing surgical biopsy. Patients with early breast cancer (n = 48) had significantly higher p43-positive cell values (median 3.83%, range 0.98-19.4) than patients with benign lumps (n = 28, median 1.43%, range 0.17-3.7) or controls (n = 22, median 1.3%, range 0.4-1.87) (P < 0.0001). At a cut-off level of 2% p43-positive cells a sensitivity of 91.7% and a specificity of 89.3% for detection of breast cancer could be reached. While the median ratio of total CD4+/CD8+ cells was 2.6, a ratio of 1.3 was found for the p43-positive subpopulation (P < 0.001), thus indicating a significant link between p43 and CD8+ cells. The determination of p43-positive lymphocytes in peripheral blood could serve as an additional diagnostic tool in patients with controversial mammographic findings and could also reduce the need for cost-intensive and often uncomfortable management of these patients.

Inhibitory effects of a novel marine terpenoid on sensitive and multidrug resistant KB cell lines.

Mechanisms of growth inhibition by the novel marine compound dehydrothyrsiferol (DHT) were investigated in a sensitive and an MDR+ human epidermoid cancer cell line. DHT was found to circumvent multidrug resistance mediated by P-glycoprotein. Cell cycle analysis revealed an accumulation in S-phase. The anchorage independent clonogenic growth in soft agar was not significantly reduced at IC50 concentrations. Reduced cell growth caused by induction of apoptotic or necrotic cell death could not be verified. Therefore, cell proliferation during an incubation period of five days was measured and found to be significantly reduced. We conclude that growth inhibition by dehydrothyrsiferol in KB cancer cells is not mediated by apoptosis but by growth retardation; the reasons for this are worth being investigated in detail.