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Background: Analysing the results of breast reconstruction is important both in terms of oncological safety and health-related quality of life (HRQoL). Immediate breast reconstruction (IBR) is thought to be prone to complications and heavy for patients with no time to adapt to having cancer. Delayed reconstruction (DR) is an option after primary surgery and oncological treatments, but requires patients to go through two recovery periods after surgery. Methods: A prospective study of 1065 breast cancer patients with repeated measurement of HRQoL with both generic (15D) and disease specific (EORTC QLQ C-30 BR23) measuring tools included 51 IBR patients and 41 DR patients. These patients' HRQoL and reconstruction methods were studied in more detail alongside with clinical data to determine HRQoL levels for patients with IBR and those with mastectomy and DR during a 24-month follow-up. Measuring points were baseline, 3, 6, 12 and 24 months. Results: Most frequent techniques used were abdominal flaps (IBR n = 16, DR n = 14), latissimus dorsi flaps (LD) (IBR n = 19, DR n = 10), implants (IBR n = 12) and fat grafting (DR n = 6). Smaller groups were excluded from group comparisons. Approximately one third of the patients encountered complications. Symptom scores did not differ between reconstruction methods. DR patients had better overall HRQoL at 12 months, but at 24 months the situation had changed in favour of IBR. Both approaches of reconstructive surgery produced good HRQoL with no significant differences between the approaches studied. [ABSTRACT FROM AUTHOR]

Background: The prognosis of breast cancer has improved significantly during the last few decades increasing the interest in health-related quality of life (HRQoL). The aim of this study was to compare the HRQoL scores produced by different instruments and to shed light on their validity in various states of breast cancer by studying the association of cancer-related symptoms with HRQoL. Material and methods: An observational, cross-sectional study of breast cancer patients treated in the Helsinki and Uusimaa Hospital District from September 2009 to April 2011. A total of 840 patients completed three HRQoL questionnaires: the EQ-5D-3L (including VAS), 15D and EORTC QLQ-30 and a questionnaire concerning sociodemographic factors. Patients were divided into five mutually exclusive groups: primary treatment (n=118), recovery (6-18 months from diagnosis) (n=150), remission (>18 months) (n=382), metastatic disease (n=176) and palliative care (n=14). The association of HRQoL with sociodemographic and clinical factors and cancer-related symptoms, screened by the EORTC QLQ- 30, was studied by multivariate modeling using stepwise linear regression analysis. Results: HRQoL scores were the best at the time closest to diagnosis and deteriorated with disease progression. The EQ-5D had a pronounced ceiling effect with 40.8% of the respondents scoring 1 (perfect health) compared to 6% for the 15D and 5.6% for VAS. In regression analyses, pain, fatigue and financial difficulties were the most important predictors of lower HRQoL. The 15D showed better discriminatory power and content validity. The EORTC QLQ-C30 functioning deteriorated in advanced states of the disease with physical, social and role functioning being the most affected. Insomnia, fatigue and pain were the most commonly reported symptoms in all groups. Conclusions: Different HRQoL instruments produce notably different HRQoL scores. The EQ-5D has a pronounced ceiling effect. Pain and fatigue are the most common symptoms associated with poor HRQoL in all disease states. [ABSTRACT FROM AUTHOR]

Background: Non-O1, non-O139 Vibrio cholerae is endemic in temperate waters. Most often encountered as the pathogen in transient gastroenteritis, it can also cause severe soft tissue infections. While normally a rare pathogen in Finland, we observed seven cases of non-O1, non-O139 V. cholerae infections in Helsinki University Hospital during the hot summer of 2018. Here we present three of these cases with fulminant V. cholerae cellulitis in detail. Methods: Patients with tissue culture positive soft tissue infections between 2017 and 2019 were identified using a local laboratory database. Patients with severe infections requiring surgical revision were included in this series. Results: Three patients with tissue culture positive non-O1, non-O139 V. cholerae cellulitis were identified. All were treated in the summer of 2018 for fulminant lower leg cellulitis. Two patients were febrile and hemodynamically unstable at presentation. One had septicaemia. Surgical revisions were done within the first week of admission, and defects covered with partial-thickness skin grafts several weeks later. Antibiotic treatment varied and continued until the wounds were healed, between one and over two months in total. [ABSTRACT FROM AUTHOR]

Sentinel lymph node biopsy (SLNB) is a critical staging tool for melanoma patients. The optimal number of lymph nodes removed in SLNB remains unclear. In this study, we retrospectively analysed and tested different criteria for selecting sentinel lymph nodes (SLNs) by radiotracer uptake and blue dye, and their impact on nodal staging. We also evaluated the association between SLN tumour burden and radiotracer uptake. The study population consisted of melanoma patients undergoing SLNB. During the operation all radioactive and blue nodes were removed and sent for histopathological analysis. The ex vivo radioactive count and presence of blue dye of each node were recorded, and these were correlated with presence and size of metastasis in each SLN. Altogether 175 patients with clinically occult metastasis presented with one or more positive, i.e. metastatic, SLNs. The mean number of lymph nodes removed was 4.5, and the mean number of positive lymph nodes was 1.5 per patient. The most radioactive or hottest node was negative in 38 patients (22%). By removing the hottest node and all nodes with radioactivity >10% of the hottest node, 97% of patients would have been staged correctly. In five patients, metastasis was found solely in a SLN with radioactivity <10% of the hottest node. Of all 267 positive nodes removed, 125 (47%) contained blue dye. Patients with a negative hottest node were associated with lower SLN tumour burden. By removing the hottest node and all nodes with radioactivity >10% of the hottest node, 97% of patients with SLN metastases are correctly staged with or without using blue dye. [ABSTRACT FROM AUTHOR]

Background: The role of preoperative imaging and the usability of different imaging modalities is highly variable and controversial in reduction mammaplasty patients. Our study describes the imaging process in a single center in regard to modality selection, age and timing, and of the association between imaging and histopathological findings in reduction mammaplasty specimens. Methods: Nine hundred eighteen women, who underwent reduction mammaplasty during 1.1.2007-31.12.2011, were retrospectively reviewed for demographics, preoperative imaging, further preoperative examinations, and pathology reports. Results: Preoperative imaging had been conducted for 89.2% ( n = 819) of the patients. In 49 (6.0%) patients, suspicious preoperative imaging led to further examinations revealing 2 high-risk lesions (atypical ductal hyperplasia (ADH), lobular carcinoma in situ (LCIS)), and 2 cancers preoperatively. Postoperatively abnormal histopathology specimens were revealed in 88 (10.4%) patients. The incidence of high-risk lesions was 5.5% ( n = 47), and the incidence of cancer was 1.2% ( n = 10). Preoperative imaging was normal (BI-RADS 1 and BI-RADS 2) in 80.8% of these patients. The sensitivity of the preoperative imaging for cancer detection was 20.0%, and the specificity was 100.0%. Conclusions: Preoperative imaging and further examinations do not sufficiently detect malignant or cancer risk-increasing findings. Therefore, histopathological analysis of reduction mammaplasty specimens seems mandatory. [ABSTRACT FROM AUTHOR]

Background: Reconstruction of the breast following mastectomy can improve patients' health-related quality of life (HRQL). We aimed to assess HRQL in women after mastectomy and breast reconstruction and to identify differences in HRQL related to the reconstruction method used. Methods: A cross-sectional study was performed on patients who had undergone breast reconstruction in Helsinki University Hospital between 08/2017 and 7/2019. The postoperative HRQL was assessed using the BREAST-Q (2.0) Reconstruction Module. The results were compared between patients with different reconstruction methods using the Kruskal–Wallis test. Results: A total of 146 patients were identified. Microvascular flaps (n = 77) were the most common method for primary breast reconstruction, followed by latissimus dorsi (LD) flaps (n = 45), fat grafting (n = 18) and implant reconstruction (n = 6). The satisfaction with breasts was high in all groups (median 61, IQR 49–71). The physical well-being of the chest was high regardless of the reconstructive method (median 100, IQR 80–100). However, women with fat grafting reported more adverse effects of radiation (median 17, IQR 14–17 vs. 18, IQR 17–18 for other groups, p = 0.02). Donor site morbidity was low, and patients reported high satisfaction with the back (median 66/100, IQR57-90) and abdomen (median 9/12, IQR 8–10), and physical well-being of the back (median 61/100, IQR 53–70) and abdomen (median 65/100, IQR 60–86). Conclusions: The patient-reported HRQL after breast reconstruction is high. Most women report being satisfied with the reconstruction, irrespective of the reconstruction method used. The reconstruction method can thus be chosen individually in cooperation between the patient and the surgeon. [ABSTRACT FROM AUTHOR]

Background: The goal of the present study was to evaluate the impact of delayed autologous breast reconstruction on disease relapse in breast cancer patients treated with mastectomy. Material and methods: The study was based on 503 consecutive patients younger than 70 years of age who underwent mastectomy between January 2000 and December 2003. Overall, 391 (78 %) received mastectomy alone and 112 (22 %) underwent a delayed breast reconstruction. The median time from mastectomy to delayed breast reconstruction was 34 months. The median duration of follow-up was 102 months. Results: There were no locoregional recurrences (LRR) in patients who underwent delayed reconstruction (0.0 %); 21 LRR developed in patients treated with mastectomy only (5.4 %), P = 0.011. Distant metastases occurred less frequently in the reconstruction group (12.5 %) than in the patients who underwent mastectomy alone (21.5 %); P = 0.0343. The 8-year breast cancer specific survival in the reconstruction group was 98.2 and 85.7 % for the mastectomy only group, P = 0.000. Conclusions: Delayed autologous breast reconstruction does not appear to adversely influence disease progression when compared to patients treated with mastectomy only. [ABSTRACT FROM AUTHOR]

Background: Cancer stem cells/initiating cells (CSC/CIC), are thought to exist as a small population in malignant tissues. They are resistant to conventional cancer treatments and possibly underlie post-treatment relapse. The CIC population can be targeted with capsid modified oncolytic adenoviruses. Methodology/Principal Findings: We studied the mechanisms of innate immunity to oncolytic adenovirus Ad5/3-Delta24 in conventional treatment resistant non-CIC breast cancer cells, breast cancer CD44+/CD24-/low CIC population and normal breast tissue CD44+/CD24-/low stem cells. We compared virus recognition by pattern recognition receptors for adenovirus, Toll-like receptors (TLR) 2 and 9 and virus induced type I interferon (IFN) response regulation in these cell types. We show TLR mediated virus recognition in these non-immune cell types. Normal tissue stem cells have intact type I IFN signaling. Furthermore, TLR9 and TLR2 reside constantly in recognition sites, implying constant activation. In contrast, breast cancer CD44+/CD24-/low CIC have dysregulated innate immune responses featuring dysfunctional virus recognition caused by impaired trafficking of TLR9 and cofactor MyD88 and the absence of TLR2, having a deleterious impact on TLR pattern recognition receptor signaling. Furthermore, the CIC have increased inhibitory signaling via the suppressor of cytokine signaling/Tyro3/Axl/Mer receptor tyrosine kinase (SOCS/TAM) pathway. These defects in contribute to dysfunctional induction of type I IFN response in CIC and therefore permissivity to oncolytic adenovirus. Conclusions/Significance: CICs may underlie the incurable nature of relapsed or metastatic cancers and are therefore an important target regarding diagnostic and prognostic aspects as well as treatment of the disease. This study addresses the mechanisms of innate infection immunity in stem cells deepening the understanding of stem cell biology and may benefit not only virotherapy but also immunotherapy in general. [ABSTRACT FROM AUTHOR]

Abstract: Background: Oncoplastic breast surgery refers to a wide range of techniques with a parallel goal of safely removing all malignant breast tissue while achieving the best possible esthetic outcome. We report the results of our oncoplastic breast operations from 2005 to 2007. Methods: Ninety selected breast cancer patients were treated with a variety of oncoplastic operations. The patients were prospectively monitored. Radiotherapy and systemic adjuvant treatment were given according to national guidelines. Results: Fifteen patients had an immediate surgical complication, of which 8 required a reoperation. Eleven patients had an inadequate surgical margin and required a completion mastectomy. During a median follow-up of 26 months no local or regional recurrences were noticed. Three patients developed distant metastases. Conclusions: Oncoplastic breast surgery offers tools for breast conservation in patients otherwise destined for mastectomy or poor esthetic outcome. Despite the high proportion of patients in this series with large-volume ductal carcinoma in situ (DCIS) or extensive intraductal component, the use of oncoplastic techniques achieved negative margins with acceptable cosmetic results in the majority (84%) of patients. [ABSTRACT FROM AUTHOR]

Extramammary Paget's disease (EMPD) is a rare malignant neoplasm of apocrine gland bearing skin characterized by intraepidermal proliferation of adenocarcinoma cells. Tumor growth depends on the ability of tumor cells to migrate by proteolysis and on angiogenesis. The matrix metalloproteinase (MMP) enzymes have been implicated in both of these processes in other types of skin cancer. The expression of MMP-1, MMP-2, MMP-3, MMP-7, MMP-9, MMP-13, and MMP-19 was analyzed by immuno- histochemistry and/or in situ hybridization in 27 EMPD and five mammary PD (MMPD) specimens. The distribution of laminin-5 (LN-5) and tenascin-C, two extracellular matrix proteins associated with tumor invasion, was studied by immunohistochemistry. MMP-7 (matrilysin-1) and MMP-19 were the most frequently expressed MMPs in Paget's cells. Overexpression of MMP-2, MMP-9, or MMP-13, which is seen in many cancers, was not evident in EMPD. LN-5 and tenascin-C positivity did not correlate with the level of invasion. MMP-7, MMP-13, and MMP-19 were detected abundantly in MMPD, while MMP-9 was absent. MMP expression did not generally associate with the level of invasion of EMPD. In three samples positive for MMP-7 and four samples positive for MMP-19, an underlying carcinoma was detected, suggesting the importance of these two MMPs as predictors of secondary EMPD or the putative origin of Paget's cells from the dermal adenocarcinoma cells of apocrine duct origin. Kuivanen T, Tanskanen M, Jahkola T, Impola U, Asko-Seljavaara S, Saarialho-Kere U. Matrilysin-1 (MMP-7) and MMP-19 are expressed by Paget's cells in extramammary Paget's disease. [ABSTRACT FROM AUTHOR]

Epilysin (MMP-28) is the newest member of the matrix metalloproteinase enzyme family. Several members of this enzyme family have been associated with various aspects of wound repair and cancer invasion. The aim of this study was to characterize in different types of wounds, skin cancers, and keratinocyte cultures factors that contribute to epilysin expression in vivo , as well as how and where it is induced in relation to other matrix metalloproteinases. Our results indicate that epilysin is produced by the mitotic Ki-67-positive keratinocytes distal from the wound edge in both acute and chronic wounds and that it does not generally colocalize with collagenase-1, stromelysin-2, or 92 kDa gelatinase in migrating keratinocytes. An injury of epidermis was needed for epilysin induction as it was upregulated in ulcerated pyogenic granulomas and in suction blisters but was not detected in intact acanthotic or normal skin. Unlike many other matrix metalloproteinases, epilysin was not detected in the invading cancer cell nests of sclerosing basal or squamous cell cancers of various grades. When primary keratinocytes were stimulated with tumor necrosis factor α, upregulation of epilysin mRNA was evident within 24–48 h as measured by quantitative reverse transcription polymerase chain reaction. In primary keratinocyte, HaCaT, and A431 carcinoma cell cultures none of the 10 other growth factors or extracellular matrices studied were able to upregulate epilysin expression. Our results suggest that epilysin expression is tightly spatially and temporally regulated during wound repair. Although the in vivo substrates of epilysin are not known at present, its expression pattern suggests that it may be needed to restructure the basement membrane or to degrade adhesive proteins between keratinocytes to supply new cells for the migrating front. [ABSTRACT FROM AUTHOR]

In the article, the authors present their study on the long-term prognostic value of sentinel lymph node (SLN) tumor burden in the survival of melanoma patients with clinically negative regional lymph nodes. Topics include the recommended early completion lymph node dissection (CLND) for metastatic SLN patients to remove non-sentinel lymph nodes (NSN) and the prognostic value in disease-free survival (DFS) and melanoma-specific survival (MSS).

• We present a case of Clostridium septicum gas gangrene in a healthy individual. • Our patient presented with severe septic shock and myonecrosis. • Patient's state improved when the origin of infection in the intestine was removed. • Despite extensive myonecrosis, no limb amputations had to be performed. [ABSTRACT FROM AUTHOR]

Wound healing involves highly controlled events including reepithelialization, neoangiogenesis, and reformation of the stromal compartment. Matrix metalloproteinases (MMPs) are a family of neutral zinc-dependent endopeptidases known to be essential for the wound-healing process. MMP-8 (collagenase-2) is a neutrophil-derived highly effective type I collagenase, recently indicated to be important for acute wound healing. MMP-26 is a more recent and less well-studied member of the MMP family. Our aim was to study the expression of MMP-8 and MMP-26 in human cutaneous wound repair and chronic wounds using histological methods and cell culture. MMP-8 expression was associated with epithelial cells, neutrophils, and other inflammatory cells in chronic human wounds. MMP-26 was prominently expressed in the extracellular compartment of most chronic wounds in close vicinity to the basement membrane area. MMP-26 was also expressed in acute day 1 wounds with declining expression thereafter. In vitro wound experiments showed that both MMP-8 and MMP-26 were expressed by migrating human mucosal keratinocytes. Inhibiting MMP-26 resulted in aberrant keratinocyte migration and proliferation. We conclude that MMP-8 and MMP-26 are differentially expressed in acute and chronic wounds. [ABSTRACT FROM AUTHOR]

Expression of tenascin-C (Tn-C) has been shown to correlate with invasion and metastasis in Merkel cell carcinoma (MCC). Cytokeratin-20 (CK-20) is used in differential diagnostics of the primary tumour. The aim of this study was to demonstrate the expression of Tn-C in MCC lymph node metastases. Immunohistochemical staining was performed for five metastatic lymph nodes using a monoclonal antibody against Tn-C and CK-20 . All five metastatic lymph nodes expressed Tn-C. The expression concentrated around the vascular structures, invasion borders and fibrotic septae. One of the metastatic lymph nodes was strongly positive for CK-20 while the others showed a focal or negative pattern. The normal lymphoid tissue was negative for Tn-C. Tn-C detected metastatic MCC tissue within the lymph nodes undisputedly. There was a clear distinction between the metastatic and normal lymphatic tissue. Furthermore, invasion to the surrounding tissue was easily demonstrated. Contrary to previous studies, CK-20 expression seemed to fluctuate. [ABSTRACT FROM AUTHOR]

Summary Stromelysin-2 is a matrix metalloproteinase that degrades in vitro several protein components relevant to wound repair such as collagens III and IV, gelatin, nidogen, laminin-1, proteoglycans, and elastin. Furthermore, it can activate other matrix metalloproteinases, such as collagenase-1 (matrix metalloproteinase-1) and collagenase-2 (matrix metalloproteinase-8), as well as 92 kDa gelatinase. The aim of this study was to determine in a large variety of wounds (normally healing dermal and mucosal wounds, suction blisters, ex vivo cultures, diabetic, decubitus, rheumatic, and venous ulcers) and keratinocyte cultures, which factors contribute to stromelysin-2 expression and how it is induced in relation to other matrix metalloproteinases. Our results show that stromelysin-2 mRNA and protein are upregulated later (at 3 d) than matrix metalloproteinase-1 in normally healing wounds and ex vivo explants, in which stromelysin-2 is invariably expressed by keratinocytes migrating over dermal matrix. The number of keratinocytes expressing stromelysin-2 was greatest in chronic inflamed diabetic and venous ulcers compared with rheumatoid and decubitus ulcers, six of which had no signal. In keratinocyte cultures, tumor necrosis factor-α, epidermal growth factor, and transforming growth factor-β1 induced stromelysin-2 expression as measured by quantitative reverse transcriptase–polymerase chain reaction, whereas different matrices did not upregulate the mRNA. Immunostaining demonstrated stromal transforming growth factor-β1 in contact with the stromelysin-2-positive keratinocytes. Our results suggest that stromelysin-2 expression is important for the normal repair process and is upregulated by cytokines rather than cell–matrix interactions. Stromelysin-2 is most likely to participate in the remodeling of the newly formed basement membrane, and is not overexpressed in retarded wound healing. [ABSTRACT FROM AUTHOR]