Post-diagnosis serum 25-hydroxyvitamin D concentrations in women treated for breast cancer participating in a lifestyle trial in Italy.

OBJECTIVE: To report cross-sectionally serum levels of 25-hydroxyvitamin D [25(OH)D] in women living in Italy within 12 months from breast cancer (BC) diagnosis. METHODS: Baseline data were obtained from 394 women diagnosed with primary BC, enrolled from 2016 to 2019 in a lifestyle trial conducted in Italy. Subjects' characteristics were compared between two 25(OH)D concentrations (hypovitaminosis D<20 and ≥20 ng/mL) with the Chi-squared test or Fisher's exact test for small-expected counts. Using multiple logistic regression-adjusted models, we estimated odds ratios (ORs) of hypovitaminosis D with 95% confidence intervals (CIs) in the total sample and in the unsupplemented subgroup. RESULTS: Hypovitaminosis D was found in 39% of all subjects, 60% in unsupplemented subjects, and 10% in supplemented subjects. Increasing ORs of hypovitaminosis D were found with increasing body mass index, 25-30, >30, and ≥35 versus <25 kg/m2 (ORs: 2.50, 4.64, and 5.81, respectively, in the total cohort and ORs: 2.68, 5.38, and 7.08 in the unsupplemented); living in the most southern Italian region (OR 2.50, 95%CI 1.22-5.13); and with hypertriglyceridemia (OR 2.46; 95%CI 1.16-5.22), chemotherapy history (OR 1.86, 95%CI 1.03-3.38), and inversely with anti-estrogenic therapy (OR 0.43, 95%CI 0.24-0.75) in the total sample. CONCLUSIONS: Hypovitaminosis D in women recently diagnosed with BC and participating in a lifestyle trial in Italy was widespread and highest with obesity, hypertriglyceridemia, and chemotherapy use. Considering that hypovitaminosis D is a risk factor for lower efficacy of bone density treatments and possibly BC mortality, our results suggest the need to promptly address and treat vitamin D deficiency.

Painful bone metastasis in elderly treated with radiation therapy: Single- or multiple-fraction regimen? A multicentre retrospective observational analysis.

BACKGROUND: Bone metastases are a frequent complication of advanced oncologic disease. Pain associated to bone metastasis is a major cause of morbidity in cancer patients, especially in elderly. AIMS: The aim of this multicentric retrospective observational study is to evaluate the efficacy of different schedules of radiation therapy in elderly patients in terms of pain relief. METHODS: 206 patients over the age of 60 were enrolled in 1 year time for a multicentre retrospective observational study. Patients were treated with palliative purposes for painful bone metastases. RESULTS: Pain intensity difference (PID) was found in 72% of patients. Reported PID was statistically significant for p < 0.01. Pain intensity measured by a point numeric rating scale was statistically significant reduced for p < 0.05 by one-fraction regimen compared to other two regimens. DISCUSSION: In recent years, numerous studies have evaluated the most appropriate regimen of fractionation in individual cases, despite this, a consensus about the best schedule is still debated. CONCLUSIONS: On our analysis, single-fractionation scheme (8 Gy) confirmed to be statistical significant effective in providing pain reduction due to bone metastases. Radiation therapy provides significant pain relief of symptomatic bone metastases, but appropriate radiotherapy scheduled is needed in order to get significant response to treatment. Multidisciplinary approach is warranted to value the balance between the therapeutic objectives and the patient quality of life.

Body weight and risk of molecular breast cancer subtypes among postmenopausal Mediterranean women.

Breast cancer (BC) is the most common malignant tumor in women, obesity is associated with increased BC incidence and mortality and high levels of circulating insulin may negatively impact on cancer incidence. In the present study, we investigated whether the strength of several anthropometric and metabolic parameters varies between BC molecular subtypes. Eligible cases were 991 non-metastatic BC patients recruited between January 2009 and December 2013. Anthropometric, clinical and immunohistochemical features were measured. Multivariate logistic regression models were built to assess HER2 positive BC risk, comparing (a) triple positive (TP) with luminal A, luminal B and triple negative (TN) and (b) HER2-enriched group with luminal A, luminal B and TN. We stratified patients in pre- and post-menopause: significant differences emerged for luminal A in relation to age: they were more likely to be older compared to other groups. Among postmenopausal patients, the adjusted multivariate analysis showed that high BMI and high waist circumference were inversely correlated to TP subtype when compared to luminal B (OR=0.48 and OR=0.49, respectively). Conversely, HOMA-IR was a risk factor for TP when compared to luminal A and TN (OR=2.47 and OR=3.15, respectively). Our findings suggest a potential role of higher abdominal fat in the development of specific BC molecular subtypes in postmenopausal women. Moreover, they support a potential role of insulin resistance in the development of HER2 positive BC, although this role appears to be stronger when hormone receptors are co-expressed, suggesting a difference in the etiology of these two BC subtypes.

Electrochemotherapy in the Treatment of Cutaneous Metastases from Breast Cancer: A Multicenter Cohort Analysis.

BACKGROUND: The management of breast cancer (BC) skin metastases represents a therapeutic challenge. Electrochemotherapy (ECT) combines the administration of bleomycin with temporary permeabilization induced by locally administered electric pulses. Preliminary experience with ECT in BC patients is encouraging. METHODS: A total of 125 patients with BC skin metastases who underwent ECT between 2010 and 2013 were enrolled onto a multicenter retrospective cohort study. The treatment was administered following the European Standard Operative Procedures of Electrochemotherapy. Tumor response was clinically assessed adapting the Response Evaluation Criteria in Solid Tumors, and toxicity was evaluated according to Common Terminology Criteria for Adverse Events 4.0. Cox regression analysis was used to identify predictive factors. RESULTS: Response was evaluable in 113 patients for 214 tumors (median 1 per patient, range 1-3). The overall response rate after 2 months was 90.2 %, while the complete response (CR) rate was 58.4 %. In multivariate analysis, small tumor size (P < 0.001), absence of visceral metastases (P = 0.001), estrogen receptor positivity (P = 0.016), and low Ki-67 index (P = 0.024) were significantly associated with CR. In the first 48 h, 10.4 % of patients reported severe skin pain. Dermatologic toxicity included grade 3 skin ulceration (8.0 %) and grade 2 skin hyperpigmentation (8.8 %). Tumor 1-year local progression-free survival was 86.2 % (95 % confidence interval 79.3-93.8) and 96.4 % (95 % confidence interval 91.6-100) in the subgroup of those with CR. CONCLUSIONS: In this study, small tumor size, absence of visceral metastases, estrogen receptor positivity, and low Ki-67 index were predictors of CR after ECT. Patients who experienced CR had durable local control. ECT represents a valuable skin-directed therapy for selected patients with BC.

Intraoperative radiotherapy in early breast cancer.

BACKGROUND: Intraoperative radiotherapy (IORT) constitutes a paradigm shift from the conventional 3-5 weeks of whole-breast external beam radiotherapy (EBRT). IORT enables delivery of radiation at the time of excision of the breast tumour, targeting the area at highest risk of recurrence, while minimizing excessive radiation exposure to healthy breast tissue. The rationale for IORT is based on the observation that over 90 per cent of local recurrences after breast-conserving surgery occur at or near the original operation site. METHODS: This article reviews trials of IORT delivered with different techniques and devices. RESULTS: IORT is a very attractive option for delivering radiotherapy, reducing the traditional fractionated treatment to a single fraction administered at the time of surgery. IORT has been shown to be associated with reduced toxicity and has several potential benefits over EBRT. Only two randomized clinical trials have been published to date. The TARGIT-A and ELIOT trials have demonstrated that IORT is associated with a low rate of local recurrence, although higher than that after EBRT (TARGIT-A: 3·3 versus 1·3 per cent respectively, P = 0·042; ELIOT: 4·4 versus 0·4 per cent, P < 0·001). However, the local recurrence rate for IORT fell within the predefined 2·5 per cent non-inferiority margin in TARGIT-A, and the 7·5 per cent equivalence margin in ELIOT. CONCLUSION: Longer follow-up data from existing trials, optimization of patient criteria and cost-effectiveness analyses are needed. Based on the current evidence, IORT can be offered as an alternative to EBRT to selected patients within agreed protocols, and outcomes should be monitored within national registries.

Weekly docetaxel versus CMF as adjuvant chemotherapy for older women with early breast cancer: final results of the randomized phase III ELDA trial.

BACKGROUND: Evidence on adjuvant chemotherapy in older women with breast cancer is poor. We tested whether weekly docetaxel is more effective than standard chemotherapy. PATIENTS AND METHODS: We carried out a multicenter, randomized phase III study. Women aged 65-79, operated for breast cancer, with average to high risk of recurrence, were allocated 1 : 1 to CMF (cyclophosphamide 600 mg/m², methotrexate 40 mg/m², fluorouracil 600 mg/m², days 1, 8) or docetaxel (35 mg/m(2) days 1, 8, 15) every 4 weeks, for four or six cycles according to hormone receptor status. Primary end point was disease-free survival (DFS). A geriatric assessment was carried out. Quality of life (QoL) was assessed with EORTC C-30 and BR-23 questionnaires. RESULTS: From July 2003 to April 2011, 302 patients were randomized and 299 (152 allocated CMF and 147 docetaxel) were eligible. After 70-month median follow-up, 109 DFS events were observed. Unadjusted hazard ratio (HR) of DFS for docetaxel versus CMF was 1.21 [95% confidence interval (CI) 0.83-1.76, P = 0.32]; DFS estimate at 5 years was 0.69 with CMF and 0.65 with docetaxel. HR of death was 1.34 (95% CI 0.80-2.22, P = 0.26). There was no interaction between treatment arms and geriatric scales measuring patients' ability or comorbidities. Hematological toxicity, mucositis and nausea were worse with CMF; allergy, fatigue, hair loss, onychopathy, dysgeusia, diarrhea, abdominal pain, neuropathy, cardiac and skin toxicity were worse with docetaxel. One death was attributed to CMF and two to docetaxel. Increasing age, impairment in instrumental daily living activities, number of comorbidities and docetaxel treatment were independently associated with severe nonhematological toxicity. QoL was worse with docetaxel for nausea-vomiting, appetite loss, diarrhea, body image, future perspective, treatment side-effects and hair loss items. CONCLUSIONS: Weekly docetaxel is not more effective than standard CMF as adjuvant treatment of older women with breast cancer and worsens QoL and toxicity. CLINICALTRIALSGOV: NCT00331097.

Bone effect of adjuvant tamoxifen, letrozole or letrozole plus zoledronic acid in early-stage breast cancer: the randomized phase 3 HOBOE study.

BACKGROUND: To measure bone mineral density (BMD) reduction produced by letrozole as compared with tamoxifen and the benefit of the addition of zoledronic acid. PATIENTS AND METHODS: A phase 3 trial comparing tamoxifen, letrozole or letrozole+zoledronic acid in patients with hormone receptor-positive early breast cancer was conducted; triptorelin was given to premenopausal patients. Two comparisons were planned: letrozole versus tamoxifen and letrozole+zoledronic acid versus letrozole. Primary end point was the difference in 1-year change of T-score at lumbar spine (LTS) measured by dual energy X-ray absorptiometry scan. RESULTS: Out of 483 patients enrolled, 459 were available for primary analyses. Median age was 50 (range 28-80). The estimated mean difference (95% confidence interval [CI]) in 1-year change of LTS was equal to -0.30 (95% CI -0.44 to -0.17) in the letrozole versus tamoxifen comparison (P<0.0001) and to +0.60 (95% CI +0.46 to +0.77) in the letrozole+zoledronic acid versus letrozole comparison (P<0.0001). Bone damage by letrozole decreased with increasing baseline body mass index in premenopausal, but not postmenopausal, patients (interaction test P=0.004 and 0.47, respectively). CONCLUSIONS: In the HOBOE (HOrmonal BOne Effects) trial, the positive effect of zoledronic acid on BMD largely counteracts damage produced by letrozole as compared with tamoxifen. Letrozole effect is lower among overweight/obese premenopausal patients.

Preoperative weekly cisplatin, epirubicin, and paclitaxel (PET) improves prognosis in locally advanced breast cancer patients: an update of the Southern Italy Cooperative Oncology Group (SICOG) randomised trial 9908.

BACKGROUND: The present article reports the updated survival outcome of the 200 patients enrolled in the Southern Italy Cooperative Oncology Group 9908 trial, which compared 12 weekly cycles of cisplatin-epirubicin-paclitaxel (PET) with 4 triweekly (once every 3 weeks) cycles of epirubicin-paclitaxel (ET) in patients with locally advanced breast cancer (LABC). METHODS: The effects of treatment, pathologically documented response (pathological response), pre- and post-treatment biomarkers on relapse-free survival (RFS), distant metastasis-free survival (DMFS), and overall survival (OS) are analysed. RESULTS: At a median follow-up of 74 (range 48-105 months) months, the 5-year RFS, DMFS, and OS were 64 % versus 53% (P = 0.11), 73% versus 55% (P = 0.04), and 82% versus 69% (P = 0.07) in PET and ET, respectively. At multivariate analysis, after adjusting treatment effect for pretreatment biomarkers, PET independently predicted better DMFS (P = 0.018) and OS (P = 0.03), whereas the impact on RFS was of borderline significance (0.057). PET treatment was significantly better than ET treatment only in high-grade or highly proliferating tumours. The better outcome in PET arm was the results of both the higher rate of patients with optimal pathological response and the lower rate of patients with biologically aggressive residual tumour. CONCLUSIONS: The PET weekly regimen significantly improves both DMFS and OS in LABC patients, compared with the triweekly ET combination. The therapeutic advantage is limited to patients with highly aggressive tumours.

Preoperative weekly cisplatin-epirubicin-paclitaxel with G-CSF support in triple-negative large operable breast cancer.

BACKGROUND: Findings from our previously published phase II study showed a high pathologic complete remission (pCR) rate in patients with triple-negative large operable breast cancer after the administration of eight cisplatin-epirubicin-paclitaxel (PET) weekly cycles. The safety and efficacy data of the initial population were updated, with inclusion of additional experience with the same therapy. METHODS: Patients with triple-negative large operable breast cancer (T2-T3 N0-1; T > 3 cm) received eight preoperative weekly cycles of cisplatin 30 mg/m2, epirubicin 50 mg/m2, paclitaxel (Taxol) 120 mg/m2, with granulocyte colony-stimulating factor (5 microg/kg days 3-5) support. RESULTS: Overall 74 consecutive patients (T2/T3 = 35/39; N0/N+ = 26/48) were treated, from May 1999 to May 2008. At pathological assessment, 46 women (62%; 95% confidence interval 50-73) showed pCR in both breast and axilla. At a 41-month median follow-up (range 3-119), 13 events (nine distant metastases) had occurred, 5-year projected disease-free survival (DFS) and distant disease-free survival being 76% and 84%, respectively. Five-year DFS was 90% and 56% in pCRs and non-pCRs, respectively. Severe neutropenia and anemia occurred in 23 (31%) and eight (10.8%) patients, respectively. Severe non-hematological toxicity was recorded in <20% of patients. Peripheral neuropathy was quite frequent but never severe. CONCLUSIONS: Eight weekly PET cycles are a highly effective primary treatment in women with triple-negative large operable breast cancer. This approach results in a very promising long-term DFS in this poor prognosis population. This triplet regimen is worthy of evaluation in phase III trials.

Additional role of colour Doppler ultrasound imaging in intracystic breast tumours.

PURPOSE: Cystic breast lesions with a nonsimple appearance, either complicated or complex, pose unique diagnostic difficulties, in part owing to their potentially malignant nature. Current ultrasound classification systems are based on morphostructural aspects only. The objective of this paper is to highlight the adjunctive role of Doppler techniques. MATERIALS AND METHODS: Over a 1-year period, we prospectively evaluated 45 women with atypical breast cysts of type IV, V or VI according to the Chang classification. Forty patients were symptomatic, whereas the cyst was discovered as an incidental finding in five cases. Our assessment included morphostructural, angioarchitectural and flowmetric aspects. RESULTS: Twenty-three nontumoural lesions were managed conservatively. All 19 type-IV cysts and all four type-V cysts according to the Chang classification showed absence of signal flow at colour Doppler imaging. Among the 22 tumoural lesions, there were eight papillomas, one atypical ductal hyperplasia and 13 carcinomas. The eight papillomas showed single (four cases) or multiple (four cases) mural projections. The atypical ductal hyperplasia showed a single parietal nodule. Among the 13 carcinomas, patterns included mural projections in 11 cases, eccentric cystic wall thickening in one and coarse intracystic septa in one. Cystic content appeared clear in six papillomas and in the case of atypical ductal hyperplasia, whereas it exhibited fine echoes in two papillomas. Among the carcinomas, cystic content showed coarse echoes in two cases and fine echoes in 11. Intralesional calcifications were seen in three carcinomas. Posterior enhancement was present in all carcinomas, whereas none showed posterior shadowing. In three carcinomas, some small solid satellite nodules were evident. Colour Doppler imaging showed lack of flow in four papillomas and subtle flow in the remaining four papillomas and in the atypical ductal hyperplasia. All 13 carcinomas showed diffuse vascularity, with multiple sparse vessels and multiple vascular poles. The resistive index, measurable in 4/8 papillomas, was 0.43 on average. Spectral analysis was measured in all carcinoma cases, yielding a mean resistive index of 0.71. CONCLUSIONS: Intracystic breast tumours exhibit distinctive morphostructural and colour Doppler features that allow effective differentiation from nontumoural cysts. Frequently, a presumptive differentiation between papillomas and carcinomas can be achieved. Absence of flow signals represents an additional criterion for complicated/complex cysts, allowing conservative management. Vascularity indicates the need for excision or biopsy of the solid projections, even in cases with negative cytology.

A 2-month cisplatin-epirubicin-paclitaxel (PET) weekly combination as primary systemic therapy for large operable breast cancer: a phase II study.

PURPOSE: The present study aimed to define the antitumor activity of eight cisplatin-epirubicin-paclitaxel (PET) weekly cycles with granulocyte colony-stimulating factor (G-CSF) support in patients with large operable breast cancer. METHODS: Operable breast cancer (T2-3 N0-1; T >3 cm) patients received eight preoperative weekly cycles of cisplatin 30 mg/m2, epirubicin 50 mg/m2 and paclitaxel 120 mg/m2, with G-CSF (5 microg/kg, days 3-5) support. RESULTS: Sixty-three patients (T2/T3=30/33; N0/N+=8/55) were enrolled. Thirty-one clinical complete (49%) and 30 partial (48%) responses were recorded, giving a 97% response rate (95% confidence interval 89% to 100%). Breast-sparing surgery was performed in 32/63 (51%) patients. At pathological assessment, 28 patients (45%) showed absence of invasive residual disease in breast and 34 (55%) had negative axilla. In 20 women (32%) both breast and axilla were found to be disease-free. At a 23-month median follow-up (range 4-63), only eight relapses and two deaths had occurred, with the 4-year projected relapse-free and overall survival being 59% and 95%, respectively. Grade 3-4 neutropenia and anemia occurred in 24% and 5% of patients, respectively. Emesis, diarrhea and mucositis were the main non-hematological toxicities; however, only nine (14%) patients experienced one or more episodes of severe non-hematological toxicity. Peripheral neuropathy was frequent, but never severe. CONCLUSIONS: A 2-month weekly treatment with PET represents a well tolerated and highly effective approach in large operable breast cancer patients. In spite of the short duration of chemotherapy, one-third of patients achieved a complete eradication of the tumor in both breast and axilla.

Low morbidity of bronchoplastic procedures after chemotherapy for lung cancer.

OBJECTIVE: To evaluate if induction chemotherapy, with or without irradiation, represents an additional risk factor for early and late morbidity and perioperative mortality in bronchoplastic procedures for lung cancers. METHODS: From January 1998 to January 2001, 27 patients underwent a bronchial sleeve resection after induction treatment at the European Institute of Oncology in Milan. They represent 7% of lung cancer resections (387) and 27% of those performed after neoadjuvant treatment (100 cases). Histology was: 17 epidermoid carcinoma, 8 adenocarcinoma and 2 SCLC. Twenty-four patients (89%) received a preoperative cisplatin based polichemotherapy, and three cases (11%) a chemo-radiation therapy. A right sleeve lobectomy or bilobectomy was undertaken in 21 patients (78%) and a left lobectomy in 6 (22%). A resection of tracheal carina was associated in three cases and a vascular resection in 10 (five vena cava and five pulmonary artery). Twelve patients (44%) received adjuvant mediastinal irradiation. Perioperative morbidity of the study group (group 1) was compared with that of patients submitted to sleeve resection without neoadjuvant treatment (group 2), or standard pneumonectomy after induction treatment (group 3). RESULTS: There were no postoperative deaths. A major perioperative complication occurred in two patients (7%) of group 1, one patient of group 2 (3.5%), and four in group 3 (17%). Among patients of the study group, no anastomotic dehiscence or pleural empyema were observed. Only one late anastomotic stricture occurred after postoperative radiation treatment. No significant difference in early and late complication rate was found between the three groups of patients. High rate of complete resection was achieved (93%) in patients of the study group and extent of nodal dissection was similar between sleeve resections and pneumonectomy patients. CONCLUSIONS: Preoperative chemotherapy or combination of chemo-radio therapy is not associated with an additional risk of anastomotic complications in bronco and angioplastic procedures. Parenchyma sparing resection is a valid option for selected patients with locally advanced lung cancer after induction treatment. A longer follow up is necessary to evaluate efficacy of the procedure in term of survival and local control.

Life-threatening giant mediastinal goiter: a surgical challenge.

Mediastinal goiter is a well known benign disease, usually resectable through a cervical approach with minimal morbidity and mortality. Only occasionally a median sternotomy or a lateral thoracotomy may be required. The present case is worthy of presentation because of the exceptional dimension of the disease and the surgical challenge that it presented. In a 72-year-old woman a large intrathoracic goiter of the right thorax caused a severe dyspnoea due to an important contralateral mediastinal shift with compression of the lung, superior vena cava system and trachea. At surgical exploration, through a cervico-sternotomic approach, the mediastinal structures dislocation and the strong adherences between the anomalous neovascularized capsula of the mass and the surrounding structures, complicated the surgical dissection. An accidental lesion of the innominate artery required its reimplantation on the ascending aorta. An immense mass, was finally removed and pathological examination revealed a rare case of neovascularized, pseudosarcomatoid capsula among a benign hyperplastic proliferation. In spite of its benign nature, a giant goiter caused a life-threatening compression of the respiratory tract and lung parenchyma in this patient. The dimension of the lesions, the mediastinal anatomy alterations and the severe intraoperative haemorrhage represented major technical difficulties during surgical resection.

Immediate breast reconstruction with the transverse rectus abdominis musculocutaneous flap after skin-sparing mastectomy.

Immediate breast reconstruction with the transverse rectus abdominis musculocutaneous (TRAM) flap after skin-sparing mastectomy is becoming an increasingly performed procedure in patients with ductal carcinoma in situ, early invasive breast cancer, and prophylactic mastectomy. Through a periareolar approach, it is possible to remove the breast parenchyma along with the nipple areola complex, preserving almost all the original skin envelope and the inframmamary fold. The TRAM flap is used to recreate the volume and shape of the original breast. This technique has higher quality and easier reconstruction. The major disadvantages, extensive scar and donor site skin color mismatch, are reduced to a minimum level because the former is limited at the natural border of the nipple areola and the latter can be effectively concealed with proper nipple reconstruction. Thirty-one patients with a mean age of 39 years (range, 26-50 years) who had undergone unilateral or bilateral mastectomy for early breast cancer and immediate breast reconstruction with the pedicled TRAM flap were retrospectively reviewed. Requirements for the skin-sparing mastectomy technique include suitability of donor site tissue for autologous tissue, early breast cancer or ductal carcinoma in situ, and adequate size and shape matching of the contralateral breast. There was no observed local recur- rence during the follow-up period (mean, 20 months; range, 11-30 months). Complications at the recipient site include mastectomy skin flap partial necrosis in 2 patients and cellulitis of the transferred flap in 1 patient. No total or partial flap necrosis was observed. One patient developed abdominal bulging 1 month after the operation, during the administration of chemotherapy. All reconstruction was considered very satisfactory from an aesthetic perspective by the surgeon and the patient. The nicer aesthetic result with oncological safety is achieved with immediate breast reconstruction with the TRAM flap after skin-sparing mastectomy. The risk of local recurrence is not higher compared with more radical surgical techniques.

Identification of a new subset of cells exhibiting dendritic phenotypes in patients affected by breast proliferative disorders.

We report that a subset of circulating cells reacting with a monoclonal antibody raised against a protein marker is significantly increased in the peripheral blood of women carrying benign or malignant breast diseases, particularly in patients under 55 years of age with ductal mammary carcinomas. These cells were statistically (confidence level of 99%) less represented in a control population including healthy women or women carrying carcinomas of origin other than breast. Double staining analysis showed that they harbor markers of dendritic cells and exhibit endo- cytic activity, as determined by their ability to internalize FITC-dextran particles. Their dendritic morphology was further demonstrated by electron microscopy of sorted antibody-positive cells. However, expression of surface molecules, such as CD34 and CD14, usually not present in differentiated populations of dendritic cells was also observed. Adherent cells of patients with breast ductal carcinoma including mostly cells of this new subset were efficient stimulators of mixed lymphocyte reaction, attaining maximal stimulatory activity attained after TNFalpha treatment. In conclusion, we have shown that a subset of cells characterized by a phenotype suggestive of a yet undescribed stage of maturation of the dendritic cell lineage is accumulated in the blood of patients affected by breast proliferative disorders.

Intra-abdominal hypertension and abdominal compartment syndrome in burn patients.

BACKGROUND: Intra-abdominal hypertension (IAH) and abdominal compartment syndrome (ACS) are known to occur in patients after major abdominal surgery. The incidence of IAH and ACS in the burn population is not known. METHODS: We prospectively recorded the intra-abdominal pressures of major burn patients admitted to our burn center from February 1999 to September 1999. A bladder pressure greater than 25 mm Hg was diagnosed as IAH. ACS was diagnosed when pulmonary compliance decreased in association with persistent IAH and was treated with abdominal decompression. RESULTS: Ten patients were placed on the protocol; of these, seven developed IAH. Five responded to conservative treatment. Two patients with 80% body surface area burns developed ACS and required decompression. CONCLUSIONS: IAH occurs commonly in major burn patients, and ACS is seen regularly in patients with more than 70% body surface area burns. We recommend bladder pressure measurements after infusion of more than 0.25 L/kg during the acute resuscitation phase and for peak inspiratory pressures greater than 40 cm H2O. Whereas ACS warrants surgical decompression of the abdominal cavity, IAH usually responds to conservative therapy.

Circulating antibodies against the breast tumor marker GCDFP-15/gp17 in mammary carcinoma patients and in patients carrying benign breast conditions.

Sera samples from 111 women, including 73 breast cancer patients and 38 patients with benign diseases of the breast, were examined. These were compared with samples from healthy women or from patients carrying tumors of origin other than breast as controls. This was done to determine whether antibodies against GCDFP-15/gp17, a protein of gross cystic disease fluid also secreted by mammary apocrine tumor cells, could be found. We observed that 2.6% of mammary disease patients affected by benign conditions and 5.5% of patients carrying malignant mammary gland tumors expressed statistically significant amounts of antibodies against GCDFP-15/gp17 (p < 0.01). The highest circulating anti-GCDFP-15/gp17 antibody levels occurred in patients with highly malignant ductal or lobular carcinoma of the breast and in patients with dysplasia. No correlation was found between the presence of circulating antibodies and the size of the tumor or the age of the patients. A bimodal correlation with the percent of invaded lymph nodes was observed instead. IgM and IgG isotypes were detected among the circulating anti-GCDFP-15/gp17 antibodies, suggesting the involvement of a T-cell-mediated immunoresponse. Our findings raise the possibility that the anti-GCDFP-15/gp17 immune response may be useful as a tool for investigating some aspects of the mechanisms of breast disease progression and that GCDFP-15/gp17 may be explored as an antigen for anti-tumor vaccination. Int. J. Cancer (Pred. Oncol.) 84:568-572, 1999.

Abdominal compartment syndrome in patients with burns.

Abdominal compartment syndrome (ACS) is a well-recognized perioperative complication that occurs in patients who undergo intra-abdominal operations and who require extensive fluid resuscitation. The classic presentation of this syndrome includes high peak airway pressures; oliguria, despite adequate filling pressures; and intra-abdominal pressures of more than 25 mm Hg. A decompressive laparotomy performed at the bedside can alleviate ACS. If left untreated, sustained intra-abdominal hypertension is often fatal. In the literature, ACS has been described in pediatric patients with burns but not in adult patients with burns. This article describes 3 adults who sustained burns of more than 70% of their body surface areas, who required more than 20 L of crystalloid resuscitation, and who developed ACS during their resuscitation after the burn injury. The mortality rate among these patients was 100%, which confirms the grave consequences of this syndrome. In our institution, intra-abdominal pressure is now routinely measured as part of the burn resuscitation process in an attempt to diagnose and treat this syndrome earlier and more efficaciously. It is recommended that the possibility of ACS be considered when diagnosing any patient with burns who develops high airway pressures, oliguria, or both.

Endothelin-1, interleukin-6, and interleukin-8 levels increase in patients with burns.

Endothelin is produced by injured or ischemic endothelium and causes monocyte production of interleukins-6 and 8 in vitro. Endothelin levels increase in patients with burn injuries, and we asked whether interleukin-6 and 8 levels increased in patients with burn injuries concurrently with endothelin. Fourteen patients with more than 20% body surface area burns were resuscitated to maintain urine output of 0.5 to 1.0 ml/kg/hr. Blood was drawn on admission and at 12, 24, and 48 hours. Endothelin was measured by radioimmunoassay, interleukins-6 and 8 were measured by enzyme-linked immunosorbent assay. Endothelin levels increased to 6.1 +/- 2.3 fmol on admission, 5.7 +/- 2.1 at 12 hours, 6.9 +/- 2.7 at 24 hours, and 6.4 +/- 2.7 at 48 hours (vs 0.5 in healthy controls). Interleukin-6 increased to 243 +/- 220 pg/ml on admission, 276 +/- 198 at 12 hours, 400 +/- 282 at 24 hours, and 379 +/- 274 at 48 hours (vs less than 50 in healthy controls). Interleukin-8 increased to 504 +/- 309 pg/ml on admission, 483 +/- 263 at 12 hours, 575 +/- 306 at 24 hours, and 698 +/- 667 at 48 hours (vs less than 50 in controls). Endothelin-1 and interleukin-6 and 8 levels increase in patients with burn injuries. Endothelin-mediated activation of monocytes that cause cytokine production may have clinical relevance in patients with burn injuries.