Lower back coverage with endoscopically harvested pedicled greater omental flap

An alternative surgical treatment is proposed here for radionecrosis of the lower back. A 78-year-old patient was treated successfully for a nonhealing ulcer with a pedicled omental flap. The omentum was harvested endoscopically and brought out of abdominal cavity through a limited incision on lateral left side of abdominal wall. The omentum was then tunneled to the back for coverage the lower back. The combination of an endoscopic harvest of an omental flap performed by a general surgeon and wound debridement and skin grafting of the omentum by a plastic surgeon allows minimal donor-site morbidity and avoids the use of delicate microsurgical technique. Additionally, omentum is an ideal flap for the treatment of radionecrosis.     

The omental sandwich reconstruction for a full-thickness cheek defect.

We present a case in which a large full-thickness cheek defect was successfully repaired in one stage by the "omental sandwich technique." We transferred the omentum as a free flap, anastomosing the middle omental vessels with the end stumps of the gastroepiploic vessels after they had been brought to the neck through a subcutaneous tunnel. Skin grafts were applied then on both sides of the revascularized omentum.     

Immediate breast reconstruction using a laparoscopically harvested omental flap

Use of an omental flap to reconstruct the breast after cancer surgery was first reported by Kiricuta in 1963. Since then, the omentum has been widely used in cancer surgery to cover extensive thoracic defects associated with radionecrosis. In contrast, for breast reconstruction or augmentation mammaplasty, rectus abdominis and latissimus dorsi flaps have been used far more often than omental flaps. This article describes a new technique for immediate breast reconstruction using laparoscopically harvested omentum and reports the results obtained in 10 patients. Nine patients underwent immediate breast reconstruction after subcutaneous mastectomy. In the other patient, omentum was used in combination with skin grafting to cover a postmastectomy defect. Follow-up exceeded 16 months in the first patients. The results suggest that breast reconstruction using a laparoscopically harvested omental flap may be extremely dependable in terms of vascular supply (there was one case of partial necrosis, which healed with local management alone). The postoperative course of all patients was uneventful, and the use of laparoscopy reduced the hospital stay to less than 7 days. Donor-site scars were minimal. There was no residual loss of function, and there were no cases of incisional ventral hernia. Cosmetic results were satisfactory, with a soft breast that was both natural in appearance and stable in volume. However, in two patients the amount of omentum was found to be inadequate during the procedure; consequently, an implant was inserted under the omental flap. Breast reconstruction using a laparoscopically harvested omental flap is a new technique that allows autogenous reconstruction without disfigurement of the do-nor site and that results in a soft, natural-looking breast.     

Cellular basis of tissue regeneration by omentum

The omentum is a sheet-like tissue attached to the greater curvature of the stomach and contains secondary lymphoid organs called milky spots. The omentum has been used for its healing potential for over 100 years by transposing the omental pedicle to injured organs (omental transposition), but the mechanism by which omentum helps the healing process of damaged tissues is not well understood. Omental transposition promotes expansion of pancreatic islets, hepatocytes, embryonic kidney, and neurons. Omental cells (OCs) can be activated by foreign bodies in vivo. Once activated, they become a rich source for growth factors and express pluripotent stem cell markers. Moreover, OCs become engrafted in injured tissues suggesting that they might function as stem cells.Omentum consists of a variety of phenotypically and functionally distinctive cells. To understand the mechanism of tissue repair support by the omentum in more detail, we analyzed the cell subsets derived from the omentum on immune and inflammatory responses. Our data demonstrate that the omentum contains at least two groups of cells that support tissue repair, immunomodulatory myeloid derived suppressor cells and omnipotent stem cells that are indistinguishable from mesenchymal stem cells. Based on these data, we propose that the omentum is a designated organ for tissue repair and healing in response to foreign invasion and tissue damage.     

Total ear reconstruction in the devascularized temporoparietal region: II. Use of the omental free flap

Total ear reconstruction using the omental free flap technique was performed on five patients who presented with a devascularized temporoparietal region. The main indication for this technique was unavailability of the contralateral temporoparietal fascia in those requesting autogenous auricular reconstruction. There were no microvascular failures in the procedures conducted. In one case there was a partial loss of the transferred omentum, which resulted from an inadequate omental tailoring. A normal convoluted auricle was obtained after multistage debulking operations and meticulous postoperative molding. The average follow-up period was 3.4 years. Final aesthetic results were graded as satisfactory in four patients and poor in one patient.     

The Treatment of Multiple Coronary Occlusions by Internal Mammary Artery Implantation and Omental Graft: Report on Two Human Cases

The importance of triple coronary artery disease was evident in 125 patients undergoing internal mammary artery implantation, when some patients died from right coronary artery occlusion. This occurred even when the internal mammary artery was patent and revascularizing the left ventricle.In 1961 the free omental graft operation was developed to revascularize both right and left ventricles. In animals this operation has proved most effective in preventing death after application of Ameroid constrictors to all three coronary arteries. Arteriolar or larger-sized vessels rapidly formed between the aorta and omentum and the pericardium and omentum and the heart and omentum.Two patients with triple coronary artery disease underwent internal mammary artery implantation and free omental graft early in December 1962. Postoperative convalescence was uneventful. They have returned home and appear to be improved. Wrapping the entire heart with the free omental graft has produced little reaction, suggesting that, as in the animal, the grafts are surviving.     

Non-heparin-binding endothelial cell growth factor from bovine omentum

The graft of omental pedicle is known to be clinically effective for wound healing and revascularization of ischemic organs. We found that bovine greater omentum contained growth factor that was capable of stimulating the proliferation of bovine aortic endothelial cells. Gel filtration of the tissue extract showed at least two activity peaks corresponding to molecular weights of 96,000 and 21,000. The major Mr 21,000 growth factor was partially purified approx 120-fold from the omental extract. The purified factor was not mitogenic to BALB/c 3T3 cells and, importantly, had no affinity for immobilized heparin. This factor is thus clearly distinct from fibroblast growth factors and related mitogens. The pI of the factor was estimated to be 5.6-6.0. This factor may be involved in the potent angiogenic activity expressed by the implanted omentum. The omental fat, which was previously shown to cause neovascularization in the assay in vivo, did not promote the growth of endothelial cells in vitro.     

Apparent Reversion to Trophism of a Free Omental Graft: A Preliminary Report

In a previous paper we reported evidence which suggested that a free omental graft has trophic characteristics similar to those of the chorionic epithelium of the early embryo, through which it establishes arteriolar or larger connections with aorta, heart and pericardium within 10 days after it has been placed in contact with the denuded surfaces of each structure. The theory of omental trophism was tested by dropping pieces of omentum completely detached into the pleural and peritoneal cavities of white rats. When examined 25 or more days later a percentage of omental grafts appeared healthy and were attached to pleura, lung, heart and to various structures in the peritoneal cavity. In the pleural grafts, histological sections revealed a continuity between the omental grafts and the sub-pleural tissues. A blood-hungry free omental graft appears to seek out its own blood supply. Neither pleura nor serosa was able to repel its primitive probing for a new blood supply.     

Insufficient ability of omental milky spots to prevent peritoneal tumor outgrowth supports omentectomy in minimal residual disease

Background: The greater omentum is frequently involved in the course of gastrointestinal and ovarian tumors. Therefore, common practice in surgical treatment for especially gastric and ovarian cancer includes removal of the greater omentum. Paradoxically, many immune cells, such as macrophages that accumulate in so-called milky spots, reside within the omentum and are cytotoxic against tumor cells ex vivo. Consequently, omental macrophages might play an important role in killing tumor cells, and may hereby prevent development into local peritoneal recurrences. In the present study, we therefore evaluated the role of the omentum and the clinical relevance of omentectomy in minimal residual disease (MRD). Methods: Tumor cell dissemination patterns on the omentum in a rat model were examined using DiI-labelled CC531s tumor cells. Additionally, intra peritoneal (i.p.) tumor load was investigated in rats that underwent omentectomy or sham laparotomy followed by i.p. injection of CC531s cells on day 21, which represented MRD. Results: At 4 h post injection, tumor cells predominantly adhered on milky spots. Number of cells thereafter declined rapidly suggesting initial tumor killing functions in these specific immune aggregates. Despite initial reduction observed in milky spots, numbers of tumor cells however increased at fatty tissue stripes that border the omentum. This indicated proliferation at these locations, which corresponded to macroscopic observations of the omenta on day 21 after tumor cell injection. Omentectomy resulted in reduced intra-abdominal tumor load, which was completely attributable to the absence of the omentum, as tumor development did not differ on other sites. Even in the MRD group microscopic clusters of tumor cells located in the omentum eventually developed into macroscopic nodules.Conclusion: Since the ability of omental milky spots is, even in MRD, insufficient to prevent intra abdominal tumor outgrowth, omentectomy, which reduces tumor load, is recommended in surgical treatment of intra abdominal tumors that are prone to disseminate intraperitoneally.     

An Operation Designed to Promote the Growth of New Coronary Arteries,Using a Detached Omental Graft: A Preliminary Report

The human greater omentum exhibits a marked affinity for inflamed surfaces, to which it supplies numerous blood vessels. To achieve myocardial revascularization by omental graft the root of the aorta, the epicardium over both ventricles and the serosal layer of the pericardium were removed in 17 animals. A piece of greater omentum was removed from the abdomen, unfolded and wrapped around the entire heart, and fixed by interrupted sutures to the base of the aorta. Myocardial ischemia was created at the time of operation by ameroid constriction of coronary arteries. Vessels, arteriolar or larger, were found to grow from the root of the aorta, the myocardium and the pericardium into the detached free omental graft, which apparently acted as a conveyer for new vessels, including new coronary arteries, to reach the myocardium.     

Clinical Relevance of Increased Endothelial and Mesothelial Expression of Proangiogenic Proteases and VEGFA in the Omentum of Patients with Metastatic Ovarian High-Grade Serous Carcinoma

Epithelial ovarian cancer (EOC) metastasis to the omentum requires implantation and angiogenesis. We propose that prometastatic changes in the omental endothelium (for angiogenesis) and mesothelium (for implantation) are critical. We investigated the expression of angiogenic proteases [cathepsin D (CD), cathepsin L (CL), and matrix metalloproteinase 2 (MMP2) and MMP9] and vascular endothelial growth factor A (VEGFA) in the mesothelium and endothelium of omentum from patients with EOC with omental metastases and control patients with benign ovarian tumors. Endothelial expression of CL, VEGFA, and MMP9 and mesothelial expression of VEGFA, MMP9, and CD were significantly increased in patients with metastasized EOC. High expression of MMP9 and VEGFA in endothelium and mesothelium and CD in mesothelium was positively associated with poor disease-specific survival (DSS). High MMP9 expression in either endothelium or mesothelium and presence of ascites prospectively showed the greatest risk of shorter DSS [hazard ratio (HR)= 6.16, 95% confidence interval (CI) = 1.76-21.6, P = .0045; HR = 11.42, 95% CI = 2.59-50.35, P = .0013; and HR = 6.35, 95% CI = 2.01-20.1, P = .002, respectively]. High endothelial MMP9 expression and ascites were independent predictors of reduced DSS and overall survival, together resulting in worst patient prognosis. Our data show that omental metastasis of EOC is associated with increased proangiogenic protein expression in the omental endothelium and mesothelium.     

Cathepsin D non-proteolytically induces proliferation and migration in human omental microvascular endothelial cells via activation of the ERK1/2 and PI3K/AKT pathways

Epithelial ovarian cancer (EOC) frequently metastasises to the omentum, a process that requires pro-angiogenic activation of human omental microvascular endothelial cells (HOMECs) by tumour-secreted factors. We have previously shown that ovarian cancer cells secrete a range of factors that induce pro-angiogenic responses e.g. migration, in HOMECs including the lysosomal protease cathepsin D (CathD). However, the cellular mechanism by which CathD induces these cellular responses is not understood. The aim of this study was to further examine the pro-angiogenic effects of CathD in HOMECs i.e. proliferation and migration, to investigate whether these effects are dependent on CathD catalytic activity and to delineate the intracellular signalling kinases activated by CathD. We report, for the first time, that CathD significantly increases HOMEC proliferation and migration via a non-proteolytic mechanism resulting in activation of ERK1/2 and AKT. These data suggest that EOC cancer secreted CathD acts as an extracellular ligand and may play an important pro-angiogenic, and thus pro-metastatic, role by activating the omental microvasculature during EOC metastasis to the omentum.     

Free omental tissue transfer for extremity coverage and revascularization

Microvascular transfer of the omentum has several unique advantages for the reconstruction and revascularization of extremity wounds. The omentum provides well-vascularized, malleable tissue for reconstruction of extensive soft-tissue defects and has a long vascular pedicle (35 to 40 cm) with sizable vessels, which reduces some of the potential technical challenges of microsurgery. It can also be used for flow-through revascularization of ischemic distal extremities. The unique properties of the omentum make it an ideal tissue for the reconstruction of difficult extremity defects, allowing simultaneous reconstruction and revascularization. Experience with six free omental tissue transfers for upper-extremity and lower-extremity reconstruction is described. Three of the cases involved distal anastomoses to take advantage of the flow-through characteristics of the flap, providing distal arterial augmentation. All flaps accomplished the reconstructive goals of wound coverage and extremity revascularization. The omentum is a valuable, often overlooked tissue for the treatment of difficult extremity wounds.     

Adipocytes promote ovarian cancer metastasis and provide energy for rapid tumor growth

Intra-abdominal tumors, such as ovarian cancer, have a clear predilection for metastasis to the omentum, an organ primarily composed of adipocytes. Currently, it is unclear why tumor cells preferentially home to and proliferate in the omentum, yet omental metastases typically represent the largest tumor in the abdominal cavities of women with ovarian cancer. We show here that primary human omental adipocytes promote homing, migration and invasion of ovarian cancer cells, and that adipokines including interleukin-8 (IL-8) mediate these activities. Adipocyte-ovarian cancer cell coculture led to the direct transfer of lipids from adipocytes to ovarian cancer cells and promoted in vitro and in vivo tumor growth. Furthermore, coculture induced lipolysis in adipocytes and β-oxidation in cancer cells, suggesting adipocytes act as an energy source for the cancer cells. A protein array identified upregulation of fatty acid-binding protein 4 (FABP4, also known as aP2) in omental metastases as compared to primary ovarian tumors, and FABP4 expression was detected in ovarian cancer cells at the adipocyte-tumor cell interface. FABP4 deficiency substantially impaired metastatic tumor growth in mice, indicating that FABP4 has a key role in ovarian cancer metastasis. These data indicate adipocytes provide fatty acids for rapid tumor growth, identifying lipid metabolism and transport as new targets for the treatment of cancers where adipocytes are a major component of the microenvironment.     

Macrophage depletion in the rat after intraperitoneal administration of liposome-encapsulated clodronate: Depletion kinetics and accelerated repopulation of peritoneal and omental macrophages by administration of freund's adjuvant

The purpose of this study was to develop a method for the depletion of macrophages from the peritoneal cavity and the omentum of the rat. Rats received two intraperitoneal injections (at days 0 and 3) with liposome-encapsulated clodronate (dichloromethylene bisphosphonate: Cl₂MBP-liposomes). This treatment resulted in complete elimination of mature tissue macrophages (ED2-positive macrophages) from the peritoneal cavity and the omentum within 2 days. The elimination included the strongly ED2-positive spindle-shaped cells of the omental membrane. Repopulation of the omental ED2-positive macrophages was not seen within the next 23 days. Whereas ED2-positive macrophages were completely depleted, few ED1-positive cells remained and repopulation of ED1-positive cells was faster. The treatment further depleted macrophages from the spleen, especially from the red pulp, parathymic lymph nodes and liver. Freund's incomplete adjuvant administered one day after the last injection of Cl₂MBP-liposomes considerably accelerated repopulation in the omentum. The protocol described might be used to investigate the contribution of mature tissue macrophages to the induction of immune responses, drug metabolism and the elimination of intestinal tumours.     

In Vivo and Ex Vivo Approaches to Study Ovarian Cancer Metastatic Colonization of Milky Spot Structures in Peritoneal Adipose

High-grade serous ovarian cancer (HGSC), the cause of widespread peritoneal metastases, continues to have an extremely poor prognosis; fewer than 30% of women are alive 5 years after diagnosis. The omentum is a preferred site of HGSC metastasis formation. Despite the clinical importance of this microenvironment, the contribution of omental adipose tissue to ovarian cancer progression remains understudied. Omental adipose is unusual in that it contains structures known as milky spots, which are comprised of B, T, and NK cells, macrophages, and progenitor cells surrounding dense nests of vasculature. Milky spots play a key role in the physiologic functions of the omentum, which are required for peritoneal homeostasis. We have shown that milky spots also promote ovarian cancer metastatic colonization of peritoneal adipose, a key step in the development of peritoneal metastases. Here we describe the approaches we developed to evaluate and quantify milky spots in peritoneal adipose and study their functional contribution to ovarian cancer cell metastatic colonization of omental tissues both in vivo and ex vivo. These approaches are generalizable to additional mouse models and cell lines, thus enabling the study of ovarian cancer metastasis formation from initial localization of cells to milky spot structures to the development of widespread peritoneal metastases.     

Genome-wide study to detect single nucleotide polymorphisms associated with visceral and subcutaneous fat deposition in Holstein dairy cows

Excessive abdominal fat might be associated with more severe metabolic disorders in Holstein cows. Our hypothesis was that there are genetic differences between cows with low and high abdominal fat deposition and a normal cover of subcutaneous adipose tissue. The objective of this study was to assess the genetic basis for variation in visceral adiposity in US Holstein cows. The study included adult Holstein cows sampled from a slaughterhouse (Green Bay, WI, USA) during September 2016. Only animals with a body condition score between 2.75 and 3.25 were considered. The extent of omental fat at the level of the insertion of the lesser omentum over the pylorus area was assessed. A group of 100 Holstein cows with an omental fold <5 mm in thickness and minimum fat deposition throughout the entire omentum, and the second group of 100 cows with an omental fold ⩾20 mm in thickness and with a marked fat deposition observed throughout the entire omentum were sampled. A small piece of muscle from the neck was collected from each cow into a sterile container for DNA extraction. Samples were submitted to a commercial laboratory for interrogation of genome-wide genomic variation using the Illumina BovineHD Beadchip. Genome-Wide association analysis was performed to test potential associations between fat deposition and genomic variation. A univariate mixed linear model analysis was performed using genome-wide efficient mixed model association to identify single nucleotide polymorphisms (SNPs) significantly associated with variation in a visceral fat deposition. The chip heritability was 0.686 and the estimated additive genetic and residual variance components were 0.427 and 0.074, respectively. In total, 11 SNPs defining four quantitative trait locus (QTL) regions were found to be significantly associated with visceral fat deposition (P<0.00001). Among them, two of the QTL were detected with four and five significantly associated SNPs, respectively; whereas, the QTLs detected on BTA12 and BTA19 were each detected with only one significantly associated SNP. No enriched gene ontology terms were found within the gene networks harboring these genes when supplied to DAVID using either theBos taurus or human gene ontology databases. We conclude that excessive omental fat in Holstein cows with similar body condition scores is not caused by a single Mendelian locus and that the trait appears to be at least moderately heritable; consequently, selection to reduce excessive omental fat is potentially possible, but would require the generation of predicted transmitting abilities from larger and random samples of Holstein cattle.     

A rapid and simple method for visualizing milky spots in large fixed tissue samples of the human greater omentum

ABSTRACT

Milky spots are unique lymphoid structures in the greater omentum that participate in both immune homeostasis of the peritoneal cavity and formation of omental metastases. We developed a rapid and simple staining method to enable macro- or stereomicroscopic identification of these miniscule structures in large samples of fixed human greater omentum. By immersing approximately 6 × 4 cm samples of omental tissue in hematoxylin, these samples could be evaluated quickly for the presence of milky spots. We used an alum hematoxylin variant containing 1 g hematoxylin, 50 g aluminium ammonium sulfate, 0.2 g sodium iodide, 1 g citric acid and 50 g chloral hydrate. This staining method enabled us to determine the number, location, dimensions and topographical relation of milky spots to other structures. Our method also facilitates isolation of milky spots for further investigation. Hematoxylin imparts a blue color to the milky spots, which remains in place during further processing for paraffin embedding. This enabled easy recognition of milky spots during transfer through various solutions and permitted selection of relevant paraffin slides prior to additional staining.     

Combined Internal Mammary Artery Implantation and Free Omental Graft Operation: A Highly Effective Revascularization Procedure: (A Study of 17 Cases)

One hundred and forty patients with coronary artery disease treated by internal mammary artery implantation were followed up from six months to 13 years. The mortality rate was 3%; improvement was obtained in 70%. Occlusive disease of all three major coronary arteries, however, requires more blood than can be supplied by the implant procedure, and the free omental graft operation was developed for the management of selected patients with this condition. Normally in animals triple coronary artery ameroid constriction results in 100% mortality. When the free omental graft operation, with or without internal mammary artery implantation, was performed, 80% of such animals survived. The free omental graft forms capillary anastomoses in three days and arteriolar vessels in eight days, which leave the base of the aorta, enter the omentum, thence to the myocardium. A combined internal mammary artery implantation and free omental graft operation was performed in 17 patients with triple coronary artery disease as shown by cine coronary arteriography. There was no operative mortality, and 12 of the patients are free of pain and have returned to work.     

Stromal cells cultured from omentum express pluripotent markers,produce high amounts of VEGF,and engraft to injured sites

When rat omentum becomes activated by intraperitoneal injection of inert polydextran particles, these particles are rapidly surrounded by cells that express markers of adult stem cells (SDF–1α, CXCR4, WT–1) and of embryonic pluripotent cells (Oct–4, Nanog, SSEA–1). We have cultured such cells, because they may offer a convenient source of adult stem cells, and have found that they retain stem cell markers and produce high levels of vascular endothelial growth factor for up to ten passages. After systemic or local injection of these cultured cells into rats with acute injury of various organs, the cells specifically engraft at the injured sites. Thus, our experiments show that omental stromal cells can be cultured from activated omentum, and that these cells exhibit stem cell properties enabling them to be used for repair and possibly for the regeneration of damaged tissues.