Effects of FGFR inhibitors TKI258, BGJ398 and AZD4547 on breast cancer cells in 2D, 3D and tissue explant cultures.

PURPOSE: Fibroblast growth factor receptors (FGFR) and pathways are important players in breast cancer (BC) development. They are commonly altered, and BCs exhibiting FGFR gene amplification are currently being studied for drug development. Here, we aimed to compare the effects of three FGFR inhibitors (FGFRis), i.e., non-selective TKI258 and selective BGJ398 and AZD4547, on different BC-derived cell lines (BCCs) and primary tissues. METHODS: The human BCCs MCF-7 and MDA-MB-231(SA) (wild-type FGFR) and MFM223 (amplified FGFR1 and FGFR2) were analyzed for FGFR expression using qRT-PCR, and the effects of FGFRis on FGFR signaling by Western blotting. The effects of FGFRis on proliferation, viability, migration and invasion of BCCs were assessed in 2D cultures using live-cell imaging, and in 3D cultures using phenotypic analysis of organoids. To study radio-sensitization, FGFRi treatment was combined with irradiation. Patient-derived BC samples were treated with FGFRis in explant cultures and immunostained for Ki67 and cleaved caspase 3. RESULTS: We found that all FGFRis tested decreased the growth and viability of BC cells in 2D and 3D cultures. BGJ398 and AZD4547 were found to be potent at low concentrations in FGFR-amplified MFM233 cells, whereas higher concentrations were required in non-amplified MCF7 and MDA-MB-231(SA) cells. TKI258 inhibited the migration and invasion, whereas BGJ398 and AZD4547 only inhibited the invasion of MDA-MB-231(SA) cells. FGFRi treatment of MCF7 and MFM223 cells enhanced the inhibitory effect of radiotherapy, but this effect was not observed in MDA-MB-231(SA) cells. FGFRi-treated primary BC explants with moderate FGFR levels showed a tendency towards decreased proliferation and increased apoptosis. CONCLUSIONS: Our results indicate that, besides targeting FGFR-amplified BCs with selective FGFRis, also BCs without FGFR amplification/activation may benefit from FGFRi-treatment. Combination with other treatment modalities, such as radiotherapy, may allow the use of FGFRis at relatively low concentrations and, thereby, contribute to better BC treatment outcomes.

Ligasure impact™ might reduce blood loss, complications, and re-operation occurrence after abdominoplasty in massive-weight-loss patients: A Comparative Study.

BACKGROUND AND AIMS: The most effective dissection technique for raising the flap in abdominoplasty is still controversial, particularly in high-risk massive-weight-loss patients. LigaSure Impact™ vessel-sealing system (Medtronic, Dublin, Ireland) is an energy device commonly used among different surgical specialties to reduce morbidity and implement outcomes. The aim of this study was to investigate the effectiveness of LigaSure Impact in abdominoplasty compared with the conventional techniques, diathermia. MATERIAL AND METHODS: Patients underwent primary abdominoplasty after massive weight loss at a single center from 1 January 2008 to 31 May 2015 and were retrospectively reviewed. A total of 94 patients eligible for the study were divided into two groups on basis of the dissection technique: LigaSure Impact group (29 patients) and the conventional technique group (65 patients). Total intraoperative blood loss was the primary endpoint. Duration of the operation, perioperative complications and re-operation were recorded as secondary endpoints. RESULTS: Baseline characteristics were well balanced between the groups. Significant differences were found in intraoperative blood loss favoring LigaSure Impact group (259.6 ± 198.8 mL vs 377.9 ± 190.0 mL, p = 0.004) and blood transfusion rates (13.8% vs 35.4%, p = 0.047). In contrast, operative time was significantly longer in LigaSure Impact group (168.6 ± 121.2 vs 179.7 ± 57.6 min, p = 0.005), while a tendency to shorter hospital stay was found in LigaSure Impact group (3.6 ± 1.1 days vs 4.6 ± 3.2 days, p = 0.081). Overall complications occurrence, Clavien-Dindo grade II (24.1% vs 55.4%) and grade III (13.8% vs 30.8%) complications were significantly lower in LigaSure Impact group (respectively, p = 0.005, p = 0.007, p = 0.016). Late (>30 days) re-operation rate was significantly lower in the LigaSure Impact group (6.9% vs 27.70%, p = 0.0028). Specific wound complications showed no significant difference. CONCLUSION: LigaSure Impact vessel-sealing system may be beneficial in improving abdominoplasty outcomes in massive-weight-loss patients because it might reduce blood loss, need for transfusions, complications, and re-operations.

Preoperative Magnetic Resonance Imaging in Patients With Stage I Invasive Ductal Breast Cancer: A Prospective Randomized Study.

BACKGROUND AND AIMS: Preoperative magnetic resonance imaging has become an important complementary imaging technique in patients with breast cancer, providing additional information for preoperative local staging. Magnetic resonance imaging is recommended selectively in lobular breast cancer and in patients with dense breast tissue in the case when mammography and ultrasound fail to fully evaluate the lesion, but the routine use of magnetic resonance imaging in all patients with invasive ductal carcinoma is controversial. The purpose of this randomized study was to investigate the diagnostic value of preoperative magnetic resonance imaging and its impact on short-term surgical outcome in newly diagnosed unifocal stage I invasive ductal carcinoma. MATERIAL AND METHODS: A total of 100 patients were randomized to either receive preoperative breast magnetic resonance imaging or to be scheduled directly to operation without magnetic resonance imaging on a 1:1 basis. There were 50 patients in both study arms. RESULTS: In 14 patients (28%), breast magnetic resonance imaging detected an additional finding and seven of them were found to be malignant. Six additional cancer foci were found in the ipsilateral breast and one in the contralateral breast. Magnetic resonance imaging findings caused a change in planned surgical management in 10 patients (20%). Mastectomy was performed in six patients (12%) in the magnetic resonance imaging group and in two patients (4%) in the control group ( p = 0.140). The breast reoperation rate was 14% in the magnetic resonance imaging group and 24% in the control group ( p = 0.202). The mean interval between referral and first surgical procedure was 34 days in the magnetic resonance imaging group and 21 days in the control group ( p < 0.001). CONCLUSION: Preoperative magnetic resonance imaging may be beneficial for some patients with early-stage invasive ductal carcinoma, but its routine use is not recommended without specific indications.

Improved Survival in Male Melanoma Patients in the Era of Sentinel Node Biopsy.

BACKGROUND AND AIMS: Sentinel node biopsy is a standard method for nodal staging in patients with clinically localized cutaneous melanoma, but the survival advantage of sentinel node biopsy remains unsolved. The aim of this case-control study was to investigate the survival benefit of sentinel node biopsy. MATERIALS AND METHODS: A total of 305 prospective melanoma patients undergoing sentinel node biopsy were compared with 616 retrospective control patients with clinically localized melanoma whom have not undergone sentinel node biopsy. Survival differences were calculated with the median follow-up time of 71 months in sentinel node biopsy patients and 74 months in control patients. Analyses were calculated overall and separately in males and females. RESULTS: Overall, there were no differences in relapse-free survival or cancer-specific survival between sentinel node biopsy patients and control patients. Male sentinel node biopsy patients had significantly higher relapse-free survival ( P = 0.021) and cancer-specific survival ( P = 0.024) than control patients. In females, no differences were found. Cancer-specific survival rates at 5 years were 87.8% in sentinel node biopsy patients and 85.2% in controls overall with 88.3% in male sentinel node biopsy patients and 80.6% in male controls and 87.3% in female sentinel node biopsy patients and 89.8% in female controls. CONCLUSION: Sentinel node biopsy did not improve survival in melanoma patients overall. While females had no differences in survival, males had significantly improved relapse-free survival and cancer-specific survival following sentinel node biopsy.

Whole body PET/CT in the follow-up of asymptomatic patients with stage IIB-IIIB cutaneous melanoma.

BACKGROUND: Whole body positron emission tomography (PET)/computed tomography (CT) is a sensitive imaging technique in patients with metastatic melanoma, but its role in the follow-up of asymptomatic high-risk patients is unclear. The aim was to study the role of PET/CT as a routine surveillance imaging tool in asymptomatic high-risk patients at the early stage of follow-up combined with a sufficient follow-up over several years. MATERIAL AND METHODS: A total of 110 asymptomatic patients with clinically local American Joint Committee on Cancer (AJCC) stage IIB-IIIB melanoma underwent routine whole body PET/CT scanning after a mean interval of seven months after initial surgery. Clinical data were retrospectively analyzed after a median follow-up time of 4.6 years. RESULTS: Recurrent melanoma was detected in 45 patients (41%) and 36 (33%) died of melanoma. In 11 asymptomatic patients (10%) occult disease was detected with a single PET/CT. In seven of these patients (64%), positive PET/CT finding had major influence in treatment decisions. Four patients underwent surgical metastasectomy and two of them remained disease-free. In 34 patients (31%) PET/CT revealed no disease, but recurrence was detected at a median time of 19 months after negative PET/CT scan. In 50 patients (45%) PET/CT finding was true negative. In 15 patients (14%) scan was false positive leading to additional management or repetitive imagings. CONCLUSION: A single PET/CT could detect 24% of all recurrences in asymptomatic melanoma patients at the early stage of follow-up, but an earlier detection of occult metastases did not improve survival.

Sentinel lymph node biopsy and survival in elderly patients with cutaneous melanoma.

BACKGROUND: Sentinel lymph node biopsy (SNB) is a widely adopted staging procedure in patients with cutaneous melanoma. The benefits of SNB have not been evaluated thoroughly in older age groups. METHODS: This was a two-centre retrospective observational study of patients with melanoma aged at least 70 years undergoing SNB. RESULTS: A total of 423 patients were included. SNB was successful in 405 patients (95·7 per cent), of whom 88 (21·7 per cent) had sentinel node metastasis. During a median follow-up of 2·5 years, recurrence developed in 80 patients (18·9 per cent). Nodal recurrence developed in eight sentinel node-negative patients, giving a false-negative rate of 8·3 per cent, a sensitivity of 91·7 per cent and an overall diagnostic accuracy of 98·0 per cent. A total of 46 patients (10·9 per cent) died from melanoma and 42 (9·9 per cent) from other causes. At 5 years, the relapse-free survival rate was 80·0 per cent in sentinel node-negative patients and 39 per cent in node-positive patients; cancer-specific survival rates were 88·6 per cent and 46 per cent respectively (P < 0·001). In multivariable analysis, sentinel node metastasis (P < 0·001), a Breslow thickness of at least 2·0 mm (P = 0·007) and presence of ulceration (P = 0·012) were independent prognostic factors for cancer-specific survival. CONCLUSION: SNB is a feasible and accurate technique for detecting nodal metastases in older patients with melanoma. Sentinel node status is the most important predictor of cancer-specific outcome in the elderly.

Leiomyoma of the bladder. Case report.

A 33-year-old woman was incidentally noted to have a benign bladder leiomyoma on pelvic ultrasonography during pregnancy. This was resected and she made an uneventful recovery. Leiomyomas of the bladder are rare and usually asymptomatic; the treatment is excision.

Traumatic luxation of the heart.

A case of luxation of the heart resulting from blunt thoracic trauma is presented. Pericardial defect with herniation of the heart was discovered preoperatively and successfully repaired with a pleural patch. Special attention is drawn in the report to the preoperative diagnosis of this life-threatening condition.