Intra-abdominal pressure increases peri-operatively in patients undergoing deep inferior epigastric perforator flap reconstruction: A prospective study linking high intra-abdominal pressure to non-fatal lung embolism within one patient.

BACKGROUND: The deep inferior epigastric perforator (DIEP) flap is the gold standard for autologous breast reconstruction. The procedure and peri-operative period are associated with the risk of severe post-operative complications, like venous thromboembolic events (VTE) and lung embolism. Whether the intra-abdominal pressure (IAP) increases after the closure of the abdominal defect, thereby potentially affecting the venous backflow and the risk of VTE, is currently not known. AIM: The primary aim is to test if the closure of the abdominal donor site increases the IAP in women undergoing secondary DIEP flap breast reconstruction. MATERIALS AND METHOD: By using a Unometer, we measured the intravesical pressure as a surrogate marker for the IAP, at baseline, immediately after, and 24 h after abdominal skin closure, for 13 patients. RESULTS: The mean IAP increased from 6.1 mmHg (95% CI 4.6-7.7) at baseline to 9.0 mmHg (95% CI 8.0-10.0) immediately after skin closure [mean diff. 2.9 (95% CI 1.0-4.8) (p = 0.007)] and further up to 11.7 mmHg (95% CI 9.0-14.5) 24 h after closure [mean diff. 5.3 (95% CI 1.4-9.1) (p = 0.012)]. We found that IAP varies among the patients, regardless of the tightness of abdominal closure or rectus plication (n = 3). Immediately after closure, none of the isolated patients showed abnormal levels of IAP (>12 mmHg), while eight out of 12 isolated patients (67%) showed IAP levels above the normal range after 24 h. One patient developed a non-fatal lung embolism. CONCLUSION: The mean IAP increases significantly over the post-operative period after DIEP flap reconstruction, although abnormal IAP values are only seen 24 h after the closure of the skin.

Innate immune cell infiltration in melanoma metastases affects survival and is associated with BRAFV600E mutation status.

Little is known about the infiltrative pattern of innate immune cells in primary melanoma compared with their paired metastases and in BRAF-mutated tumors. Therefore, our aim was to characterize the inflammatory microenvironment in primary ulcerated and nonulcerated melanomas and paired metastases, to investigate the relation between inflammation and BRAF mutation in primary melanoma and paired metastases, and to evaluate the effect of the analyzed biomarkers on melanoma-specific survival. A total of 385 primary tumors and 96 paired metastases were stained with immunohistochemistry for BRAF, CD163+ macrophages, CD123+ plasmacytoid dendritic cells, CD66b+ neutrophils, and E-cadherin and estimated using objective computer-assisted image analysis. BRAF was semiquantitatively scored as either present or absent. In metastases of nonulcerated melanomas, we observed higher neutrophil (P=0.02) and macrophage (P=0.01) numbers. In the metastases of ulcerated melanomas, we found a higher number of macrophages (P<0.0001). Increase in the neutrophil numbers in the metastases was associated with poor patient survival after first relapse (hazard ratio=1.19, 95% confidence interval: 1.03-1.38, P=0.02). BRAF-positive primary tumors (P=0.02) and metastases (P=0.01) exhibited increased plasmacytoid dendritic cell numbers compared with BRAF-negative tumors. Lastly, primary melanomas in men had higher neutrophil numbers than women (P≤0.0001), and men had worse melanoma-specific survival (hazard ratio=1.52, 95% confidence interval: 1.04-2.21, P=0.03). Our data show that melanoma metastases are densely infiltrated with neutrophils, which affects survival. Our results also highlight the importance of recognizing the presence of inflammatory cells in the metastases as a prognostic marker, and that they may potentially be used to improve the precision of immunotherapy and BRAF targeted therapy.

Consumption of the epidermis: a suggested precursor of ulceration associated with increased proliferation of melanoma cells.

It has recently been demonstrated that the extent of ulceration and the presence of epidermal involvement that theoretically precede ulceration (consumption of epidermis, COE) or seen subsequent to inflammation (reactive epidermal hyperplasia or re-epithelialization) allowed better prognostic stratification of ulcerated melanoma. Understanding why these histopathologic markers have prognostic potential is important, not least because accurate consensual assessment of ulceration lies at the root of proper staging and clinical management. The authors therefore performed immunohistochemical analyses of tumor cell proliferation (Melan-A/Ki67) and infiltration of inflammatory cells (CD66b neutrophils and CD163 macrophages) to better understand the biology of the epidermal changes described. Tumors with a COE configuration showed 37% (95% CI: 4-54, P = 0.0046) increased tumor cell proliferation compared with tumors of normal epidermal configuration. COE is therefore suggested a precursor of ulceration associated with increased proliferation of melanoma cells. There was no observed correlation between COE and an increased inflammatory response (CD163 macrophages or CD66b neutrophils), which supports that the proliferation drive is noninflammatory. In contrast, the presence of re-epithelialization and/or reactive epidermal hyperplasia demonstrated an 18% (95% CI: 6-53, P = 0.0021) increased density of neutrophils compared with tumor with no evidence of these possibly prolonged late-stage or resolved ulcerations. These results further support the relevance of including these epidermal changes into the definition of ulceration and to define ulceration of a primary melanoma as loss of epidermis with evidence of a host response (infiltration of neutrophils or fibrin deposition) and thinning, effacement, or reactive hyperplasia of the surrounding epidermis.