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The immunosuppressive tumor microenvironment governed by tumor-associated macrophages (TAMs) remains a major obstacle to effective cancer immunotherapy. A novel humanized antibody bexmarilimab, targeting the scavenger receptor Clever-1 on TAMs, has shown clinical benefit in ~40% of patients with late-stage ER+ breast cancer (MATINS; NCT03733990). To increase response rates, a comprehensive understanding on how TAM phenotype and the tumor immune landscape affect bexmarilimab-induced immune activation is needed. Single-cell RNA sequencing analysis of breast tumor macrophages shows high phenotypic variation across pathological subtypes and Clever-1 mRNA (STAB1) expression on various immunosuppressive IL4I1+ and TREM2+ monocyte-derived TAMs. STAB1 expressing macrophages were located in both lymphocyte rich and excluded areas in the tumor stroma based on digital spatial profiling with GeoMx. Due to this diversity, we studied bexmarilimab mode-of-action in breast cancer patient-derived tumor explant cultures (PDEC) by RNA sequencing and cytokine profiling. Our results show that bexmarilimab induced TNFα and CXCL10 secretion in 30-40% of the treated explants. In depth analysis of the responsive PDECs revealed a lower baseline expression of interferon responsive genes in their tumor microenvironment. Correspondingly, in vitro assays with primary human macrophages showed that chronic IFNγ priming abolished bexmarilimab-induced immune activation, suggesting potential use of bexmarilimab in patients with immunologically cold breast tumors. Citation Format: Jenna H. Rannikko, Reetta Virtakoivu, Akira Takeda, Pia Boström, Ilkka Koskivuo, Petri Bono, Maija Hollmén. Analyzing susceptibility to macrophage-activating immunotherapy bexmarilimab in breast cancer by using patient-derived tumor explants [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P2-24-02.

Introduction: The aim of this study was to evaluate the rate of postoperative bleeding complications (primary outcome) and any other surgical complications (secondary outcome) in mastectomy between two surgical instruments, ultrasonic SonoSurg (R) scissors (US) and traditional electrocautery (EC). Materials and methods: In total 728 patients undergoing mastectomy in two adjacent university hospitals were retrospectively evaluated in terms of postoperative bleeding episodes, surgical site infections, skin flap necrosis, and any reoperations for 30 postoperative days. A propensity score matching was performed to acquire balanced groups. Patients consuming medications affecting hemostasis were excluded from the study. A multivariable logistic regression analysis was conducted to define the odds ratio (OR) for each complication separately. A cost analysis was performed. Results: The rate of postoperative bleeding complications was significantly lower in patients operated with US (0.3% vs 11.5%, OR 0.020, 95% CI 0.034-0.14) when compared to EC. The rate of surgical site infections (OR 0.65, 95% CI 0.35-1.23) was similar with both instruments, but there were less skin flap necroses (OR 0.35, 95% CI 0.13-0.98) in US group. For any reoperation, the OR for US was 0.13 (95% CI 0.046-0.39), mainly due to the lower number of acute bleeding complications. Even though the US instrument is more expensive than EC, the total cost of the treatment is lower in patients operated with US (3419 vs. 3475 euro). Conclusions: US seems to be associated with a lower risk of bleeding complications in mastectomy.(c) 2022 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).

Background and Objective The aim of this study was to evaluate the safety of same-day mastectomy, with or without a sentinel node biopsy (SNB) and/or axillary lymph node dissection (ALND). Methods In this retrospective study, we reviewed 913 consecutive women who underwent a simple mastectomy for breast cancer between the years 2014 and 2019 and were treated either with same-day surgery (SDS) or an overnight stay (OS) regime. We reviewed all surgical complications, any unplanned return to care (RTC) and the rehospitalization rate for 30 postoperative days. Results A total of 259 patients (28%) were treated with SDS and 654 patients (72%) with an OS regime. There was no difference in RTC (odds ratio: 0.79 [95% confidence interval: 0.53-1.18], p = 0.26) or any major complications between the groups. None of the investigated subgroups, such as patients with previous neoadjuvant therapy, diabetes, obesity (up to a body mass index of 40 kg/m(2)), the American Society of Anaesthesiologist Class of 3, or elderly patients aged 75-84 years, showed an increased complication rate when treated with the SDS regime. Conclusion A same-day simple mastectomy is safe with SNB and/or ALND. It can be performed safely for most patients with stable co-morbidities.

Purpose Surgical site infection (SSI) after axillary lymph node dissection (ALND) for breast cancer increases morbidity and delays the onset of adjuvant treatment. Only a few studies have investigated the feasibility of wound exudate analysis in SSI prediction. This study assessed changes in cytokine levels in postsurgical wound exudate after ALND and examined their predictive value for the early diagnosis of SSI. Methods An observational prospective pilot study was conducted in 47 patients with breast cancer undergoing ALND. Wound exudate samples were collected on the first and sixth postoperative days (POD). Interleukin (IL)-1α, IL-1β, IL-4, IL-10, IL-13, tumor necrosis factor alpha (TNF-α), transforming growth factor beta1 (TGF-β1) and vascular endothelial growth factor (VEGF) C and D levels were measured by immunoassay. Patients were followed to detect SSI. Results SSI was diagnosed in 8/47 (17.0%) patients. Four SSI patients were hospitalized and treated with intravenous antibiotics. The concentration of TGF-β1 in wound exudate was significantly lower on POD#1 in the SSI group compared to the no SSI group (p=0.008). The receiving operator characteristics (ROC) curve for TGF-β1 showed an area under curve of 0.773 (p=0.0149) indicating good diagnostic potential. On POD#6, the concentration of TGF-β1 remained significantly lower (p=0.043) and the concentrations of IL-10 (p=0.000) and IL-1β (0.004) significantly higher in the SSI group compared to the no SSI group. Conclusion To our knowledge, this is the first study suggesting a predictive role of wound exudate TGF-β1 levels for SSI. Our results suggest that the risk for SSI can be detected already on POD#1 and that the assessment of TGF-β1 levels in the wound exudate after ALND can provide a usefull method for the early detection of SSI. The key findings of this pilot study warrant verification in a larger patient population.

Introduction: Skin-sparing mastectomy (SSM) with immediate breast reconstruction is the ideal treatment for interested and suitable patients with extensive ductal carcinoma in situ (DCIS). There is no guideline to indicate on how large DCIS the procedure can be performed safely. The primary target of this study was to define the oncological safety of SSM in extensive pure DCIS. The secondary target was to find predictive factors for DCIS upstaging to invasive disease.Materials and methods: A total of 71 consecutive patients with extensive pure DCIS and undergoing SSM with immediate latissimus dorsi (LD) breast reconstruction were retrospectively evaluated. Results: The median size of DCIS lesion in preoperative imaging was 60 mm, the median weight of mastectomy specimen was 350 g, and the median resection margin (RM) was 2.0 mm. A total of 20 patients (28%) had an RM less than 0.5 mm and nine patients (13%) had ink positive margins. Six patients having positive RM underwent reoperation. A total of 29 patients (41%) presented invasive cancer foci in final histopathological assessment and nine patients (13%) had an axillary metastasis. Adjuvant therapy was given to 23 patients presenting invasive cancer. There were no local recurrences or distant metastases (0%, 95% confidence interval 0-0.051) during the mean follow-up of 71 mo. None of the factors evaluated predicted upstaging to invasive disease.Conclusions: SSM with immediate breast reconstruction in patients with extensive DCIS is oncologically safe even when the margins are close or positive. Additional invasive foci and solitary axillary lymph node metastases are frequent but do not worsen the outcome. (c) 2022 The Author(s). Published by Elsevier Inc. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).

Background and objective: The reported rate of surgical site infections (SSIs) in breast cancer surgery varies widely in previous literature. The use of antibiotic prophylaxis is controversial but recommended by several guidelines. The aim of this study was to evaluate the efficacy of routine antibiotic prophylaxis in patients with breast cancer undergoing mastectomy. Methods: In this retrospective single-institution study, we reviewed 1413 consecutive female breast cancer patients who underwent mastectomy and/or axillary lymph node surgery between years 2012 and 2019. Prophylactic antibiotics for all patients undergoing mastectomy was introduced in our hospital in 2016 and before that the prophylaxis was prescribed individually on surgeons’ preference. All patient records for 30 postoperative days were evaluated in detail and all SSIs were recorded. The rate of SSIs was compared between patients who received antibiotic prophylaxis and those who did not. A multivariate logistic regression model was used to define the odds ratio (OR) for the efficacy of antibiotic prophylaxis. Results: A total of 335 patients underwent mastectomy without antibiotic prophylaxis and 1078 with prophylaxis. The rate of SSIs was 6.9% in patients who received prophylaxis and 6.3% in patients without prophylaxis ( p = 0.70). The rate of SSIs was similar before and after the introduction of regular antibiotic prophylaxis and there was no difference in any of the patient subgroups investigated. In multivariable logistic regression analysis, the OR for antibiotic prophylaxis was 1.04 (95% CI: 0.62–1.73, p = 0.88). Conclusions: Routine use of antibiotic prophylaxis did not reduce the rate of SSIs in mastectomy. Unselective antibiotic prophylaxis for all patients does not seem mandatory in mastectomy.

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.

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.

Metaplastic breast carcinoma (MBC) is a rare subtype of invasive breast cancer and has poor prognosis. In general, cancers are heterogeneous cellular masses comprised of different cell types and their extracellular matrix (ECM). However, little is known about the composition of the ECM and its constituents in MBC. Decorin is a ubiquitous ECM macromolecule known of its oncosuppressive activity. As such, it provides an intriguing molecule in the development of novel therapeutics for different malignancies such as MBC. In this study, decorin immunoreactivity and the effect of adenoviral decorin cDNA (Ad-DCN) transduction were examined in MBC. Multiple immunohistochemical stainings were used to characterize a massive breast tumour derived from an old woman. Furthermore, three-dimensional (3D) explant cultures derived from the tumour were transduced with Ad-DCN to study the effect of the transduction on the explants. The MBC tumour was shown to be completely negative for decorin immunoreactivity demonstrating that the malignant cells were not able to synthesize decorin. Ad-DCN transduction resulted in a markedly altered cytological phenotype of MBC explants by decreasing the amount of atypical cells and by inhibiting cell proliferation. The results of this study support approaches to develop new, decorin-based adjuvant therapies for MBC. Electronic supplementary material The online version of this article (doi:10.1007/s12307-017-0195-8) contains supplementary material, which is available to authorized users.

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 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.

Background and Aims. Vascular malformations are a vast group of congenital malformations that are present at birth. These malformations can cause pain, pressure, and cosmetic annoyance as well as downturn growth and development in a child in the case of high flow. Sclerotherapy has become an important tool in the treatment of vascular malformations. However, little is known about the success rate of sclerotherapy. Material and Methods. In this study, the efficiency of sclerotherapy in the treatment of vascular anomalies was investigated retrospectively in 63 patients treated in Turku University Hospital between 2003 and 2013. Results. Out of the 63 patients investigated, 83% (53) had venous malformations (VMs) and 9% (5) were defined as having arteriovenous malformations (AVMs). Patients with a VM were operated on, in 14% (8) out of all VM cases. Hence 86% (45) of patients with a VM received adequate help to their symptoms solely from sclerotherapy. The duration of treatment for the 14% of the VM patients that needed a surgical procedure was prolonged by 7–9 months, that is, by 41%. Conclusions. Sclerotherapy is an effective method in the treatment of VMs with a satisfactory clinical response in patients symptoms in 84% of cases.

To achieve symmetry in unilateral free flap breast reconstruction often requires a contralateral procedure. There is no evidence in the literature to support the benefit of immediate contralateral breast symmetrisation concomitant to breast reconstruction. We hypothesized that performing a simultaneous contralateral balancing operation at the time as the initial reconstruction might provide immediate symmetry and minimize the frequency of secondary procedures. Thus, we performed a comparative study on this issue. A comparative retrospective study was conducted on 78 consecutive patients who underwent unilateral breast reconstruction surgery with latissimus dorsi (LD) flap and contralateral breast symmetrisation from January 2014 to June 2016 at Turku University Hospital. Exclusion criteria included other breast reconstruction techniques and no contralateral symmetrisation at follow-up. The patients were divided according to the timing of contralateral breast balancing operation into an immediate versus a delayed group. Postoperative complications, outcomes, and re-operations were compared. Baseline characteristics were well balanced between the groups except for comorbidity, which was significantly higher in the immediate group. Mastectomy weights (735.6 vs. 390.7 g, p = 0.015), contralateral breast reduction weights (268.3 vs. 105.8 g, p = 0.014), and implant size (218.9 vs. 138.9 g, p = 0.001) were significantly larger in the immediate group. No significant differences in any kind of complications were detected. Similarly, the rates of re-operations were similar among the groups (24.0 vs. 43.3%, p = 0.134). Performing immediate symmetrisation at the time of breast reconstruction is safe and feasible in autologous LD breast reconstructions, where 76% did not require a second operation for symmetry. There were no differences in the rate of any re-operation and, therefore, performance of simultaneous contralateral reduction is a reasonable option.

Summary Lymphatic vessels form a critical component in the regulation of human health and disease. While their functional significance is increasingly being recognized, the comprehensive heterogeneity of lymphatics remains uncharacterized. Here, we report the profiling of 33,000 lymphatic endothelial cells (LECs) in human lymph nodes (LNs) by single-cell RNA sequencing. Unbiased clustering revealed six major types of human LECs. LECs lining the subcapsular sinus (SCS) of LNs abundantly expressed neutrophil chemoattractants, whereas LECs lining the medullary sinus (MS) expressed a C-type lectin CD209. Binding of a carbohydrate Lewis X (CD15) to CD209 mediated neutrophil binding to the MS. The neutrophil-selective homing by MS LECs may retain neutrophils in the LN medulla and allow lymph-borne pathogens to clear, preventing their spread through LNs in humans. Our study provides a comprehensive characterization of LEC heterogeneity and unveils a previously undefined role for medullary LECs in human immunity.

Background Immune checkpoint and serine/threonine-protein kinase inhibitors have become a standard of care for advanced cutaneous melanoma, but dacarbazine-based chemotherapies are occasionally used. This study assessed the long-term efficacy of chemoimmunotherapy (bleomycin, vincristine, lomustine and dacarbazine with/without subcutaneous interferon-alpha: BOLD-INF-α) as real-world data in patients with metastatic melanoma not eligible for clinical trials. Patients and methods Medical data of 146 patients with stage IV melanoma who had received BOLD/BOLD-INFα regimen during 1991-2010 were analyzed. Results The median overall survival was 8.9 months (95% confidence intervaI=7.5-10.4 months). The 1-year survival rate was 36%, 2-year 18%, and 5-year 13%. The 5-year survival rates in the M1a, M1b and M1c subgroups were 28%, 10% and 6%, respectively. Overall, 7% (n=11) of the patients were alive at the end of the follow-up. Conclusion Our study showed similar overall survival among patients with stage IV cutaneous melanoma treated with BOLD/BOLD-INFα as noted previously with chemotherapy.

BACKGROUND Optimum excision margins used in the removal of intermediate thickness melanomas remain unclear. OBJECTIVE This study's aim was to compare the clinical outcomes of 1-cm margins with 2-cm margins in patients with a tumor thickness of 1.1- to 4.0-mm. MATERIALS AND METHODS This was a retrospective study, which was based on a matched-pairs design. Equal patient cohorts were constructed in terms of gender, age, Breslow thickness, and the anatomic location of the primary lesion. There were 80 patients whom underwent an excision with a 1-cm margin and 80 patients with a 2-cm margin. Follow-up data were analyzed by the Kaplan-Meier method and a Cox regression model. RESULTS After a median follow-up time of 41 months, there were no differences in relapse-free survival or melanoma-specific survival between study groups. The wound was closed directly in 62 patients (78%) in the 1-cm group and in 36 patients (45%) in the 2-cm group (p < .001). CONCLUSION A 1-cm excision margin may be sufficient in melanomas of 1.1 to 2.0 mm in Breslow thickness based on these findings of low recurrence. With thicker tumors (2.1-4.0 mm), this recommendation cannot be given due to inherent study limitations.

The use of tissue sealants has increased among different surgical specialities. Face-lift and rhytidoplasty may cause several complications such as haematoma, ecchymosis, oedema, seroma, skin necrosis, wound dehiscence and wound infection. However, administration of tissue sealants may prevent the occurrence of some complications. We performed a meta-analysis of studies that compared tissue sealant use with controls to evaluate the outcomes. A systematic literature search was performed. The primary outcome was the incidence of haematoma. Secondary outcomes were wound drainage amount, oedema, ecchymosis, seroma, skin necrosis and hypertrophic scarring. Thirteen studies involving 2434 patients were retrieved and included in the present analysis. A statistically significantly decrease in post-operative haematoma [risk ratio (RR), 0.37; 95% CI, 0.18-0.74; p = 0.005] and wound drainage (MD, -16.90, 95% CI = -25.71, -8.08, p 0.001) was observed with tissue sealant use. A significant decrease in oedema was detected (RR, 0.30; 95% CI, 0.11-0.85, p = 0.02) but not in ecchymosis, seroma, skin necrosis, and hypertrophic scarring with tissue sealant use. The use of tissue sealants prevents post-operative haematomas and reduces wound drainage. Previous studies have shown a similar trend, but the power of this meta-analysis could verify this perception.III.

Background. The infl uence of pregnancy on survival in melanoma has been a controversial issue. Objective. In this retrospective study we investigated whether pregnancy (overall or temporally melanoma-related) has any effect on melanoma progression or patient outcome. Methods. Patient data were collected from Turku University Hospital records concerning all women in fertile age (15 ‐ 45 years) and diagnosed with melanoma between January 1, 1990 and December 31, 2009. We collected data on melanoma characteristics, treatment, pregnancies and patient outcomes. Results. Of the 334 patients, 248 (74%) had been pregnant in some point during their life while 55 (17%) were nulliparous. The history of pregnancies could not be verifi ed in 31 women (9%). Progression of melanoma to advanced stage was found in 58 (17%) of these women. Altogether, 35 women (14%) with at least one pregnancy had disease progression in contrast to 14 women (26%) with no pregnancies (p 0.049). Women with at least one pregnancy had a 94% probability to survive from melanoma compared to nulliparous women of whom only 83% survived (p 0.041). In Multivariate (COX) analysis pregnancy was a favourable factor for disease-specifi c survival (DSS) (HR 3.75; 95% CI 1.24 ‐ 11.34; p 0.019) when adjusted for age (HR 1.064; 95% CI 1.00 ‐ 1.13; p 0.50), localisation and stage (p 0.040), and Breslow (HR 1.32; 95% CI 1.10 ‐ 1.58; p 0.002). However, when ulceration of the primary tumour was included in the multivariate model, Breslow remained as the only independent predictor of DSS (HR 1.58; 95% CI 1.34 ‐ 1.86; p 0.0001) and pregnancy was dropped from the stepwise backward model in the step preceding the last one (p 0.081). Conclusion. Pregnancy is not a risk factor for disease recurrence or progression in melanoma patients, but instead can exert some favourable infl uence on prognosis.

There are no identified biomarkers that could predict response to antiangiogenic or traditional chemoimmunotherapy in metastatic melanoma. We hypothesized that soluble angiogenic factor receptors might help us to identify patients responsive to treatment. A series of 48 patients with stage IV melanoma participating in two phase II clinical trials were included. The trials included treatment with carboplatin, vinorelbine, and subcutaneous interleukin-2 (n=22) or treatment with bevacizumab, dacarbazine, and low-dose interferon-α2a (n=26).Serum samples were prospectively collected and soluble vascular endothelial growth factor receptor 1 (s-VEGFR-1) and 2 (s-VEGFR-2) were measured before starting the trial treatment and during response evaluation.There was a trend toward longer overall survival among patients with higher-than-median serum VEGFR-1 levels (21.3 months) compared with 12.3 months in patients with low pretreatment s-VEGFR-1 levels (P=0.146). Pretreatment s-VEGFR-2 levels did not correlate to survival. Serum VEGFR-2 levels decreased during therapy in 44% of the patients and increased in 56% of the patients. VEGFR-2 increased in 78% (14 of 18) of the patients who progressed during therapy (P=0.017). VEGFR-2 decrease was associated with clinical benefit in 65% of the patients (11 of 17) and with progression in only four patients (P=0.016).High pretreatment levels of s-VEGFR-1 are associated with improved prognosis among patients with metastatic melanoma independently on therapy, whereas increased VEGFR-2 levels during therapy are associated with disease progression. These markers might be useful in selecting patients responsive to antiangiogenic therapy.

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.

Sentinel node biopsy (SNB) is a novel staging technique in cutaneous melanoma, but it is more challenging in the head and neck (HN) than in the trunk and extremities. The aim of this study was to investigate the utility of SNB in patients with clinical stage I-II HN cutaneous melanoma, with emphasis on disease outcome.Twenty five patients with HN melanoma of1.0 mm in Breslow depth underwent SNB and were compared to 121 historic HN melanoma patients, who had either undergone routine prophylactic neck dissection or had been observed without any invasive nodal staging.Sixteen percent of the SNB patients were sentinel-positive and there have been no false-negative cases. In the Kaplan-Meier analysis, there were no significant differences between the study groups in melanoma-specific overall survival. Among the entire cohort, melanoma-specific overall survival rate was 67.1% at 5 years and 61.9% at 10 years. Predictive factors for worsen survival were nodal micrometastases, male sex, scalp location, thick primary lesion and ulceration.SNB is a reliable and mini-invasive approach for the nodal staging of HN cutaneous melanoma. Traditional neck dissection is recommended only for therapeutic purposes in clinically node-positive or sentinel-positive patients.

Background Sentinel lymph node biopsy (SLNB) is the most precise method for staging invasive cutaneous melanoma, but its therapeutic effect has been difficult to assess, and SLNB is not routinely used in all melanoma treatment centers.

Sentinel lymph node biopsy (SLNB) has been widely accepted as a precise tool to stage melanoma. In thin T1 melanomas (≤1 mm), the indication of SLNB is controversial since the risk of nodal metastasis is low. The aim of this study was to assess if SLNB detects occult nodal metastases among patients with thin melanomas. SLNB was performed prospectively in 135 patients with invasive melanoma in any depth category, including 56 T1 melanomas. Nodal metastases were detected in 18% by SLNB, and there were three sentinel-positive thin melanomas, constituting 5% of the T1 cases. Histopathologically, there were no factors of the primary tumors that would have predicted these metastases. SLNB is a precise method to detect clinically silent nodal metastases in thin invasive melanoma. Certain histopathologic features of a thin primary lesion may correlate with the predictive probability of the sentinel node status. We were unable to identify these predictors, but the conclusions from this study are limited by the small sample size. Advanced melanoma is a lethal disease, and accurate staging is essential also in the T1 group. For stage III patients with occult nodal metastases, metastasectomy is a better option for cure than observation.

Progressive hemifacial atrophy (PHA) is characterized by slow and progressive atrophy usually of one side of the face. PHA affects primarily the subcutaneous fat and muscle tissues, but may involve the bone. The cause is unknown. The treatment is symptomatic and directed at augmentation of the deficient soft-tissue volume. The reconstructive procedures may combine fat grafts, dermis fat grafts, pedicle flaps, bone grafts, microvascular free flaps, and alloplastic implants. We report a patient with of PHA whose condition was treated with a free latissimus dorsi (LD) perforator flap. The LD perforator flap was suitable for the large defect of the patient. It could easily be tailored and thinned to follow the facial contour. Minor revisions were needed for esthetic reasons. There was neither significant downward gravitation nor wasting of the flap. 23 months later, the natural appearance of the face was maintained. © 2007 Wiley-Liss, Inc. Microsurgery, 2007.

The use of an infusion pain pump with local wound catheters has increased among different surgical specialities. Autologous breast reconstruction with deep inferior epigastric perforator (DIEP) and transverse rectus abdominis myocutaneous (TRAM) flaps may cause severe abdominal donor site morbidity, and infusion devices delivering local anaesthetic are suggested to improve postoperative analgesia. This study performed a meta-analysis comparing pain pump use vs control to evaluate this issue. A systematic literature search was performed. Primary outcome was the amount of opioid use. Secondary outcomes were the amount of antiemetic drugs and the length of hospital stay. Five studies involving 248 patients were retrieved and included in the present analysis. A significantly decreased use of opioids was observed after using pain pump vs control (MD = -15.13, 95% CI = -24.20, -6.06, p = 0.001). Although not statistically significant, the pooled results showed a trend toward reduction of antiemetic medicament use (MD = -0.71, 95% CI = -2.14, 0.72, p = 0.33) and hospital stay time (MD = -0.53, 95% CI = -1.18, 0.11, p = 0.10). The use of local anaesthetic pain catheters for abdominal donor sites in microsurgical breast reconstruction might be associated with a decreased use of narcotics and antiemetic medicaments and shorter hospital stay. Further studies are needed to validate this promising treatment modality.

Massive weight loss after bariatric surgery leads to excess skin with functional and aesthetic impairments. The aim of this study was to evaluate the prevalence of excess skin after bariatric surgery and identify any relationship with pre- and postoperative characteristics. A total of 360 patients who had undergone bariatric surgery procedures were asked to complete a questionnaire designed by the surgical team at least 1 year after surgery. This questionnaire was planned to estimate any impairment due to redundant skin, which was graded according to a visual analogue scale (VAS, 0--0). Mean (standard deviation, SD) age of 110 males and 250 females was 51.2 (10.8) years. Mean preoperative body mass index (BMI) was 45.7 (6.4) kg m(-2) and mean postoperative BMI at follow-up was 33.6 (6.0) kg m(-2). After a mean follow-up of 56.1 (43.6) months, the mean weight loss was 35.2 (18.8) kg. Most patients (92.8%) reported problems with redundant skin, especially on the abdomen, upper arms and rear/buttocks, which impaired daily physical activity in half of them. Excess skin was associated with female gender (β=-13.56, 95% confidence interval (CI) -16.81 to -10.32, p0.0001), weight loss (β=0.21, 95% CI 0.12-0.29, p0.0001) and ΔBMI (β=0.21, 95% CI 0.12-0.29, p0.0001) at multivariate analysis. Patients with a ΔBMI20 kg m(-2) showed a significantly surplus skin discomfort compared to ΔBMI≤5 and 5ΔBMI≤10 (p0.001). Patients with a weight loss50 kg showed a significantly redundant skin discomfort compared to weight loss20 kg (p0.001). Weight loss after bariatric surgery reduces the medical risks of obesity but psychosocial and functional problems often remain due to the surplus skin. Our data suggest that a ΔBMI≤10 kg m(-2) and weight loss20 kg, not BMI alone, might be taken into consideration as cut-off values for developing score systems with the intention to apply evidence-based indications for the surgical management of post-bariatric impairments.

Serological markers of malignant melanoma have failed to provide prognostic significance in patients who are tumour-free after surgery. Immune response regulation is important regarding progression and therapeutic interventions of malignant melanoma. Matrix metalloproteinase (MMP)-8 is one of the collagenases involved in the regulation of tissue remodelling and immune response, being incompletely studied in melanoma as yet. We assessed whether serum MMP-8 is of prognostic value in malignant melanoma. We studied serum samples of 117 patients, of which 63 were stage I, 13 stage II, 12 stage III and 29 stage IV. The mean serum MMP-8 levels (47.5 ng/ml) did not significantly correlate with patient or tumour characteristics, that is, patient sex, age, tumour Clark's or Breslow's classification, sentinel lymph node status or to survival. Importantly, high serum MMP-8 levels were significantly related to presence of vascular invasion (P=0.001) in primary tumour, tumour ulceration (P=0.003) and tumour bleeding (P=0.033). Tendency to increased serum MMP-8 levels in patients with coronary heart disease or type II diabetes mellitus was detected. These data imply that high serum MMP-8 level is associated with earlier recognized histopathology markers of melanoma progression. Results also suggest that elevated serum MMP-8 might be related to haematogenous spreading of melanoma through vascular invasion.

The aim of this study was to determine the clinical impact of whole body positron emission tomography (FDG PET) to detect clinically silent metastases in the follow-up of patients with high risk melanoma. FDG PET was performed to 30 asymptomatic melanoma patients (AJCC stage IIB-IIIC) 7-24 months after the primary surgery and sentinel node biopsy. FDG PET was able to detect six of seven recurrences, constituting 20% of all study patients. One patient presented with a negative FDG PET finding at the very first scanning, but was positive later in a repeated scan after manifestation of palpable mass in the axilla. The positive PET finding had an impact on treatment decisions in every case: three patients underwent surgical resection and four patients received chemotherapy or interferon. The mean follow-up time was 27 months (range, 12-48 months) and during that time the other 23 patients with true negative FDG PET were disease-free. One of the seven recurrences was in remission after surgical metastasectomy. In conclusion, whole body FDG PET is a valuable follow-up tool in high risk melanoma to diagnose recurrences and to select the patients, who are suitable for surgical metastasectomy.

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.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.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.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.