Independent Blood Supply Research Articles

Three-dimensional CT angiography facilitates uniportal thoracoscopic anatomic lung resection for pulmonary sequestration: a retrospective cohort study

BackgroundPulmonary sequestration (PS) is a rare lesion with independent blood supply from an anomalous systemic artery. A timely resection is considered as the best treatment for PS. Three-dimensional computed tomography angiography (3D-CTA) has been widely utilized for precise thoracic surgery. This study aimed to investigate the role of preoperative 3D-CTA and resection simulation in uniportal video-assisted thoracoscopic surgery (VATS) anatomical lung surgery for PS.MethodsThe data of 20 consecutive PS patents undergoing anatomic lung resection between April 2011 and May 2021 in a single centre were retrospectively reviewed. These patients were divided into the 3D-CTA group (10 patients) and the control group (10 patients) according to the initial surgical planning with or without 3D-CTA. The perioperative parameters regarding safety and fluency such as the incidence of conversion to open thoracotomy, operation time, blood loss, complications and chest tube duration were analyzed.ResultsThis cohort included 12 female and 8 male patients, with a mean age of 45 years old (range 24–60 years). Nine cases demonstrated recurrent febrile, cough, or hemoptysis; whereas the other 11 patients were asymptomatic on admission. Eighteen (90.0%) intralobar and 2 extralobar PS were confirmed, whereas 18 (90.0%) lesions were located in the left thorax. The feeding vessels originated from the thoracic aorta in 16 patients (80.0%), the abdominal aorta in 3 (15.0%), and the inferior phrenic artery in 1 patient (5.0%). There was no major bleeding or 30 days mortality. The initial surgical planning included 9 uniportal and 1 two-port VATS in the 3D-CTA group, as compared with 10 two-port VATS in the control group. Thirteen lobectomies, 5 segmentectomies and 2 mass excisions were performed. However, no conversion was needed in the 3D-CTA group; whereas 6 (60.0%) conversions (4 to multiple-port and 2 to thoracotomy) occurred in the control group, indicating a significant difference (P = 0.003). In addition, the operation time in the 3D-CTA group was significantly shorter than those in the control group [(108.5 ± 24.9) min vs. (154.5 ± 39.4) min, P = 0.006]. The other surgery-related outcomes were similar between the two groups.ConclusionPreoperative 3D-CTA facilitates the safe and fluent performance of uniportal VATS anatomical lung resection for PS with shortened operation time and lessened surgical conversions.

Clinical study of Fournier’s gangrene tertiary care center government medical college, Nizamabad

Background: Fournier's gangrene (FG) is fast-spreading necrotizing gangrene that affects the perineum, perianal, and genital regions, but spares the testicles, bladder, and rectum due to their independent blood supply from the aorta. The purpose of this research is to share our experience managing 32 cases. Patients and method: Between April 2018 and May 2022, researchers from Government Medical College in Nizamabad conducted a prospective cross-sectional study of patients with FG. During the study period, all individuals diagnosed with FG and treated for it were included. Age, sex, hospital stay, premorbid conditions, mobility, mortality, laboratory examinations, and therapies performed are among the data collected from these. Results: A total of 38 patients were seen throughout the study, with four patients being eliminated due to missing data, leaving 32 patients for the final analysis. With a male to female ratio of 15:1, there were 30 (93.75%) males and 2 (6.25%) females.

Abstract 122: Surgical Angiogenesis To Nerve Allografts Improves Early Functional Recovery In A Rat Sciatic Nerve Defect Model

Purpose: It is widely accepted that functional results are poor when nerve grafts are transplanted in severely scarred tissue beds and that independent blood supply of nerve grafts could improve outcomes. Optimized processed allografts (OPA) have no vascular supply. Addition of vascularization to the OPA promotes immediate revascularization and minimizes the period of ischemia, diminishing fibrosis and central necrosis potentially enhancing functional recovery. The purpose of this study was to determine how addition of vascularization to nerve allografts would affect functional recovery. Methods: Sixty Lewis rats were divided into three groups of 20 animals each. Nerves harvested from Sprague Dawley rats were decellularized according to protocol (Hundepool et al, 2017), irradiated and stored until use as OPA. Unilateral 10 mm sciatic nerve defects were repaired with (i) OPA, (ii) OPA wrapped with a superficial inferior epigastric fascial (SIEF) flap to provide vascularization to the nerve bed, and (iii) autografts. Twelve and 16 weeks after surgery, nerve regeneration was assessed using functional, electrophysiologic, histomorphologic, and immunofluorescence analyses (N=10/time point). Ultrasound was used during the survival period to noninvasively evaluate muscle atrophy. Results: Rats in which a well-vascularized SIEF flap was provided to the nerve allograft showed significantly better isometric tetanic force (ITF) recovery at 12 weeks, compared to allograft alone. ITF recovery normalized between groups at 16 weeks. Ultrasound showed a trend toward less atrophy in SIEF rats, compared to allograft only, however, this was not significant. Electrophysiology showed superiority of autografts at both time points. Histomorphometric analysis revealed no differences between groups with regard to axon area, axon count and myelin area, however, the N-ratio was significantly inferior in allografts at 12 weeks compared the autograft and SIEF group. Using immunofluorescence, the expression of CD34, indicating vascularity, showed significantly improved levels in SIEF samples compared to allografts at 12 weeks, and highest expression at 16 weeks compared to all groups. Protein gene product 9.5 (PGP9.5), a pan-neuronal marker, did not reveal any differences between groups at 12 or 16 weeks. Conclusion: This study suggests that addition of a well-vascularized fascial flap to the nerve allograft bed increases vascularity in the nerve allograft, subsequently improving early functional recovery, comparable to autografts.

013Novel Method of Substitution for Combine Through-and-through Angle of the Mouth, Fragments of Upper and Lower Lips Defect

Through-and-through defect of soft tissues of the cheek, mouth angles, upper and lower lip originate from surgical intervention of tumors of the oral cavity involving external skin, soft tissue and oral lining. The article describes an original method of one-stage reconstruction in N. N. Blokhin National Medical and Research Center of Oncology. Russian Federation’s patent № 2489096 was granted for this method. We propose to use 3 different flaps from different anatomic areas, which have varying histological structures and independent blood supply. The first flap - muscle, is formed from the biggest part of the muscles masseter from the affected side and serves to restore the functions of the lips and cheek due to the fact that after the formation of the flap two its parts fixed to the remnants of the muscles of the upper and lower lips and part of the buccal muscle. The flap is perfusion by a. maxillaris and a. facialis. The second flap - musculocutaneous, formed from the skin of areas adjacent to the defect, nasolabial or submandibular. The flap serves to replace a skin defect, defect of the cheek, upper and lower lips. The flap is perfusion by a. facialis. The third flap - fascial, formed from the temporal fascia on the affected side. The temporal fascial flap is used to replace the defect of the mucous membrane of the cheek, upper and lower lips, in addition, the red border of the lips and the corner of the mouth. The flap is perfusion by aa. temporalis profunda et superficialis. All three flaps perfectly carry out hermetic sealing of the oral cavity, independent perfusion of each flap, even in the case of necrosis of one of the flaps, allows preservation of hermeticism. The use of three flaps with different histological structure allows to achieve a good functional and aesthetic result. Flaps perform various functions, ensuring the functional and anatomical usefulness of the resected tissues. By improving the blood suppling of flaps, we reduce time for patient’s rehabilitation and postoperative damage.

A case report of ectopic pancreatitis in an isolated enteric duplication cyst

BackgroundIsolated enteric duplication cyst is an intestinal duplication cyst found in a distant location from the intestinal tract and it is said to have its own blood supply. Meckel’s diverticulm is considered as an antimesenteric structure and has its own blood supply. However, there are some reported cases of Meckele’s diverticum in the mesenteric side. Ectopic pancreas may be found in both entities.Case presentationA 5-year-old girl presented with increasing abdominal pain around the umbilicus. On laboratory investigation serum pancreatic enzymes and C-reactive protein were elevated. Abdominal computed tomography (CT) revealed a normal pancreas but a cystic lesion in the mesentery of the ileum. A nodule with a marked enhancement was observed in the wall of the lesion. During the laparoscopy, the lesion was found at the root of the mesentery and was distant from the ileum. The lesion was resected suspecting an abscess. Pathologically, the wall of the lesion consisted of small bowel like tissue, and pancreatic tissue was seen beneath the mucosa. There were some post inflammatory changes in the pancreatic tissue. Retrospectively on thin slice enhanced CT, an independent blood supply was noted. Based on these findings, a diagnosis of ectopic pancreatitis in an iliac intestinal duplication cyst was made.ConclusionIsolated enteric duplication cyst in the root of ileal mesentery and mesenteric Meckel’s diverticulum have similarities. In the present case, the diagnosis of isolated enteric duplication cyst was made since it was found distant from the ileum. It is important to consider the possibility of ectopic pancreatitis when serum pancreatic enzymes are elevated even when the pancreas appears normal.

Thoracoscopy resection of a giant solitary fibrous tumor with double pedicles and double blood supply: a case report

BackgroundSolitary fibrous tumors are rare tumors derived from the pleura. A tumor generally has only one pedicle. Video-assisted thoracoscopic surgery is generally used when a tumor is small (< 10 cm), and traditional open surgery is often used when a tumor is large.Case presentationWe report a 49-year-old male patient with a space-occupying lesion in the right chest. Three-dimensional reconstruction showed that the blood supply to the tumor originated from the right lower pulmonary artery and vein. The patient was treated with minimally invasive surgery. Intraoperative exploration revealed that the tumor had two tumor pedicles, and each pedicle has an independent blood supply. The special bagging and extraction of the specimen were applied. The size of the specimen was 18 × 12 × 6 cm. Postoperative pathological examination revealed a solitary fibrous tumor.ConclusionsThe solitary fibrous tumor with double pedicles and double blood supply is very rare, and it has not been reported before. Preoperative three-dimensional reconstruction plays an important role in understanding the blood supply to the tumor and the location of the tumor pedicles. After careful and comprehensive evaluation, endoscopic surgery can also be applied to the treatment of the larger fibroma (> 10 cm). The larger specimen can be extracted from the smaller incision by the “pulling carrot” method.

Tubularized urethral reconstruction using a prevascularized capsular tissue prelaminated with buccal mucosa graft in a rabbit model.

Tubularized graft urethroplasty fails largely because of inadequate graft take. Prefabrication of buccal mucosa lined flap has theoretical indications for constructing neourethra with an independent blood supply. The efficacy of using a tissue expander capsule as an induced vascular bed to prefabricate an axial vascularized buccal mucosa-lined flap for tubularized urethral reconstruction in a rabbit model was tested. The experiments were performed in three stages. First, silicone tissue expanders were inserted into the groin to induce vascularized capsule pouch formation. Next, buccal mucosa grafts were transplanted to the newly formed capsular tissue supplied by the axial vessel for buccal mucosa-lined flap prefabrication. Then, circumferential urethral defects were created and repaired by buccal mucosa graft (Group 1), capsule flap (Group 2) and prefabricated capsule buccal mucosa composite flap (Group 3). With retrograde urethrography, no rabbits in Group 1 maintained a wide urethral caliber. In Group 2, the discontinued epithelial layer regenerated at 1 month, and the constructed neourethra narrowed even though the lumen surface formed intact urothelial cells at 3 months. In Group 3, buccal mucosa formed the lining in the neourethra and kept a wide urethral caliber for 3 months. The capsule may serve as an induced vascular bed for buccal mucosa-lined flap prefabrication. The prefabricated buccal mucosa-lined flap may serve as a neourethra flap for circumferential urethral replacement.

Tissue Expander Capsule as an in Vivo Bioreactor to Construct Axial Pattern Buccal Mucosa-Lined Flap for Tubularized Urethral Reconstruction: Preliminary Results in an Animal Model

Background: Tubularized buccal mucosa (BM) graft urethroplasty fail largely because of inadequate graft take and prefabrication of BM-lined flap has theoretical indications for constructing neourethra with independent blood supply. The efficacy of a prefabricated BM-lined flap for tubularized urethral reconstruction was tested. Methods: Tissue expanders were used for vascularized capsule induction. Autologous buccal mucosa graft were transplanted to the capsule pouch for evaluation. A circumferential urethral defect was created and tubed urethroplasty was performed with buccal mucosa graft (8 rabbits, group 1), capsule flap (8 rabbits, group 2) and the prefabricated capsule-buccal mucosa composite flap (8 rabbits, group 3). At 1 and 3 months after urethroplasty, retrograde urethrography and histological analyses were performed to evaluate the results of urethroplasty. Findings: The mucosa showed complete survival on the vascularized capsule and was expanded by the tissue expansion process. Under retrograde urethrography, none rabbits in group 1, 3 rabbits in group 2 and 6 in group 3 maintained a wide urethral caliber. Histologically, part of the tubed buccal mucosa graft survived in the neourethra. In group 2, discontinued epithelial layer regenerated at 1 month and the constructed neourethra narrowed even though the lumen surface formed intact urothelial cells at 3 months. In group 3, buccal mucosa formed the lining in the neourethra and kept a wide urethral caliber for 3 months. Interpretations: The capsule may serve as an in vivo bioreactor for buccal mucosa-lined flap prefabrication. The prefabricated buccal mucosa-lined flap could be used for tubularized urethral reconstruction. Funding: This study was supported by grants from the National Natural Science Foundation of China (81470911) and the Ph.D. Candidate Innovation Fund of Shanghai Jiao Tong University School of Medicine (BXJ201741). Declaration of Interest: The author declared no potential conflicts of interest with respect to the research, authorship, and publication of this article. Ethical Approval: The whole animal experimental protocol was approved by the Animal Care and Use Committee of Shanghai Jiao Tong University School of Medicine.

Surgical and Oncological Outcomes in Patients After Vascularised Flap Reconstruction for Locoregionally Advanced Penile Cancer

BackgroundTreatment of locoregionally advanced penile squamous cell carcinoma (LAPSCC) is challenging. The exact role (in terms of oncological benefit) of extensive surgery is not well established. Moreover, surgery invariably leads to large defects requiring reconstructive surgery. Rectus abdominis myocutaneous (RAM) and abdominal advancement flaps have an independent and constant blood supply, are easily harvested, and provide substantial skin coverage and soft tissue. ObjectiveTo determine the surgical and oncological outcomes in patients with LAPSCC undergoing surgical resection with RAM flaps. Design, setting, and participantsFrom 2002 to 2016, a multi-institutional database identified 15 LAPSCC patients undergoing flap reconstructions. InterventionLocal surgical resection with RAM or abdominal advancement flap reconstruction. Outcome measurements and statistical analysisPerioperative and pathologic data were collected. Postoperative complications were identified using the Clavien-Dindo classification for surgical complications. Results and limitationsFifteen patients (median age 61 yr) were treated, ten with curative intent. Thirteen patients received induction chemotherapy. Thirteen of the 15 patients (87%) experienced wound complications, including five Clavien-Dindo grade III complications. In 11/15 patients (73%), the disease recurred (median recurrence-free interval 106 d). The majority of recurrences (91%) were locoregional, and in four cases the patient also had lesions in distant organs. Ten of the 15 patients (67%) died of their disease. The overall median follow-up interval was 10.5 mo. The study was limited by its retrospective design, the absence of quality-of-life measurements, and the cohort size. ConclusionsThe results of this study show that surgical resection with reconstruction is associated with a risk of perioperative complications, including high-grade Clavien-Dindo complications. With a cure rate of 27%, surgery must be carefully considered and there is a need for alternative treatments. Lack of robust quality-of-life-data is also a serious shortcoming in the decision process for this patient category. Patient summarySurgery in locoregionally advanced penile cancer has a low cure rate. Reconstruction of defects is surgically feasible, albeit with a high risk of complications. Furthermore, decision-making lacks robust data on quality of life after surgery.

A Novel Classification of Parathyroid Glands and Their Preservation in Thyroidectomy

Introduction: Hypoparathyroidism is the most frequent complication after thyroidectomy and is caused by inadvertent gland injury, removal, or devascularization. To preserve the parathyroid effectively, we recorded the parathyroid glands based on their anatomic characteristics.1–2 To avoid hypoparathyroidism, the parathyroid glands should be identified and preserved in situ.3 In a few unusual circumstances, devascularized glands that cannot be preserved should be transplanted during surgery.4 However, various locations and blood vessels make the preservation of parathyroid glands difficult. Materials and Methods: Parathyroid glands were classified into three types, considering their blood supply and location.5 Type A: The unattached type, that is, the secure or thymus type—the parathyroid glands are located outside the thyroid gland and have an independent blood supply. They are mostly safe unless patients undergo central compartment neck dissection. Type B: The half-attached type B1. The parathyroid glands are located on the surface of the thyroid gland and have a clear blood supply. These vessels are independent of the thyroid gland, and it is easy to preserve the blood vessels of the parathyroid gland during thyroidectomy. B2. The parathyroid glands are situated on the surface of the thyroid. The blood supply of the parathyroid gland is partially from the thyroid gland or its communicating branches. When separated from the thyroid gland, the parathyroid glands change in color from light red to dark red, for which, decompression should be performed by making an incision. B3. The parathyroid glands are located on the surface of the thyroid and are often found on the lateral thyroid lobe, which is far from the tracheal axis. The blood supply is partially from the vessels supplying the thyroid gland, and these vessels are hard to preserve. However, there is an opportunity to try to preserve them as type B2. If the separation is ineffective, these glands will be considered type C and need to be transplanted. Type C: The completely attached type—the parathyroid glands are embedded within the thyroid and receive their blood supply directly from the thyroid gland. Therefore, it is difficult to preserve them in situ during total thyroidectomy. Results: All of parathyroid glands were confirmed histologically by frozen sections. Conclusions: Parathyroid glands can be classified into three types based on their locations and blood supply. The difficulty of preserving each type of parathyroid gland differed. Surgeons should use different surgical techniques to treat each type. Acknowledgments: This work was supported from the key program of health and family planning commission of Hubei province (Grant No. WJ2015MA003) and the young thyroid doctors' research projects supported by International Medical Foundation of China in 2015 (Grant No. 2016026). No competing financial interests exist. Runtime of video: 3 mins 39 secs

The impact of angiogenic and adipogenic microenvironment on adipose tissue regeneration in tissue engineering chamber

By observing the adipogenic and angiogenic microenvironment impact on the morphology of newly generated tissue for exploring the key factors which inducing mature adipose tissue regeneration in tissue engineering model. 24 healthy 6 months' New Zealand rabbits were picked and put into four groups according to different microenvironment. Every group has 6 rabbits and divided as follows: no axial-blood supply fat flap(0 ml), granular fat only(0.6 ml), axial blood vessel only (0.05 ml), axial vascularized fat flap ((0.6 ml). We separated or combined adipogenic and angiogenic environment within these groups. After 8 weeks, samples were harvested for histologic observation including macroscopic observation, volume analysis and HE testing. In granular fat group, its volume decreased by (0.25 ± 0.10) ml after 8 weeks as the shortage of blood supply and finally it could be enveloped. In axial blood vessel group, its volume increased by (0. 37 ± 0. 04) ml after 8 weeks with fibrous tissue formation as shortage of adipogenic microenvironment. The no axial-blood supply fat flap group grew into(0.12 ± 0.03) ml, which can' t support large volume adipose tissue formation because of lacking independent blood supply. Only axial vascularized fat flap model could generate mature adipose tissue in large volume(3.45 ± 0.48) ml. The number of new capillary in every group was different after 8 weeks. By counting the numbers in every single view, no axial-blood supply fat flap group 15 ± 3.5)and granular fat only group(5 ± 2.5)had a significant difference with axial vascularized fat flap group 22 ± 5) respectively. Only both adipogenic or angiogenic microenvironment exist could induce mature adipose tissue in large volume in tissue engineering chamber model.

Rapid In Vitro Derivation of Endothelium Directly From Human Cancer Cells

The development of an independent blood supply by a tumor is essential for maintaining growth beyond a certain limited size and for providing a portal for metastatic dissemination. Host-derived endothelial cells (ECs) residing in and compromising the tumor vasculature originate via distinct processes known as sprouting angiogenesis and vasculogenesis. More recently ECs originating directly from the tumor cells themselves have been described although the basis for this phenomenon remains poorly understood. Here we describe in vitro conditions that allow lung and ovarian cancer cells to undergo a rapid and efficient transition into ECs that are indistinguishable from those obtained in vivo. A variety of methods were used to establish that the acquired phenotypes and behaviors of these tumor-derived ECs (TDECs) closely resemble those of authentic ECs. Xenografts arising from co-inoculated in vitro-derived TDECs and tumor cells were also more highly vascularized than control tumors; moreover, their blood vessels were on average larger and frequently contained admixtures of host-derived ECs and TDECs derived from the initial inoculum. These results demonstrate that cancer cells can be manipulated under well-defined in vitro conditions to initiate a tumor cell-to-EC transition that is largely cell-autonomous, highly efficient and closely mimics the in vivo process. These studies provide a suitable means by which to identify and perhaps modify the earliest steps in TDEC generation.

Free flap survival after arterial ligation

During the last two decades the development of microvascular free-tissue transfer has provided a standard of care for reconstructing head and neck defects. Success rates vary from 94–99% and are dependent on the patency of vessels within the vascular pedicle.1,2 There have been reports of flaps surviving following division of the vascular pedicle. It is not known how long the flow in the pedicle must persist for the flap to survive and to develop an independent blood supply. The range found was from as little as three days up to three weeks.3,4 We present a case involving a free radial forearm flap for reconstruction of a buccal mucosa defect, with the flap surviving despite the loss of its arterial pedicle on the 12th postoperative day.

Anatomical and clinical substantiation of the long head of triceps transposition to restore active forearm flexion in patients with arthrogryposis

Purpose: to investigate anatomic features of the long head of triceps brachii in relation to its using as a pedicle flap for restoration of active forearm flexion in patients with arthrogryposis. Material and methods. Anatomical studies were performed on 15 fresh frozen human upper limbs from 9 cadavers. Arteries were perfused with radiopaque masses and following preparation, sectional roentgenography, morphometry of anatomical structures were carried. 29 patients with the lack of active elbow flexion aged from 8 months to 15 years were examined (clinical, neurological and physiological studies) and treated in Turner Scientific and Research Institute for Children's Orthopedics from 2008 to 2012. Results and conclusion. Anatomical studies demonstrated the possibility of transposition of the long head of triceps to forearm flexors position. The long head of triceps can be simply separated from the other two heads, it has independent innervation and blood supply, its vascular pedicle is easily identified, and length of extraorgan vessels and nerves is sufficient to transfer the muscle as a pedicle flap. Clinical study has shown the principal possibility and effectiveness of restoration of active forearm flexion in patients with arthrogryposis using the long head of triceps brachii.

Prefabricated Neck Expanded Skin Flap with the Superficial Temporal Vessels for Facial Resurfacing

The achievement of a normal-appearing face after surgical resurfacing remains an elusive goal. This is due in part to insufficient color matching, restoration of contours, and the persistence of visible scars. Flap prefabrication is a staged procedure that provides an independent axial blood supply to local expanded tissues. We describe a new reconstructive alternative with superior reconstructive surgical options for facial resurfacing that better matches damaged or discarded facial tissues. A superficial temporal fascial flap was harvested as the vascular supply of the prefabricated neck flap and located in a subcutaneous neck pocket over a tissue expander. After a 5-month period for expansion and maturation, the prefabricated skin flap was raised, islanded, and rotated to resurface the facial defect. Four patients with hemifacial postburn contracture and two patients affected by hemifacial vascular malformations aged 17 to 42 years (mean 29 years) were successfully treated with no major complication after a mean period of 15 months. Prefabricated neck-expanded skin flap demonstrated an excellent color and texture match with facial skin that surrounded the repair sites, and optimal aesthetic results were obtained. Importantly, facial expression was completely maintained due to thinness and pliability of the rotated skin.

Differential development of the distal and proximal femoral epiphysis and physis in mice

Many pathologic conditions of hip development result from aberrant vascularity with subsequent effects on physeal resorption and epiphyseal fusion. To elucidate the mechanisms of these developmental disorders, researchers have mainly focused on larger mammals as they have been well characterized and are known to provide a model similar to humans in which a secondary ossification center is formed through an independent blood supply followed by physeal resorption. Murine models of hip development, however, have never been characterized as it was previously assumed that all physes in rodents never resorb and therefore not suitable as a model of the human condition. The purpose of this study was to determine if murine hip development was comparable to humans as laboratory mice provide an ideal model in which genetic knockouts are readily available with a short developmental time span. Here we show for the first time the unique developmental patterns of the murine hip in which a secondary ossification center never develops. Instead, the epiphysis undergoes a prolonged phase of mineralization through chondrocyte, not osteoblast, dependent mechanisms. After skeletal growth, transphyseal vessels develop from the metaphysis resulting in resorption of the physis, ossification of the mineralized cartilage of the epiphysis, and epiphyseal fusion. Although the development of the murine hip is markedly different from that in humans, we believe that these findings have direct implications for studying the vascularity of developing bone, particularly during physeal resorption, chondrocyte-mediated mineralization and more importantly, developmental diseases of the human physis and epiphysis.

In Vivo Evolution of Tumor-Derived Endothelial Cells

The growth of a malignant tumor beyond a certain, limited size requires that it first develop an independent blood supply. In addition to providing metabolic support, this neovasculature also allows tumor cells to access the systemic circulation, thus facilitating metastatic dissemination. The neovasculature may originate either from normal blood vessels in close physical proximity to the tumor and/or from the recruitment of bone marrow-derived endothelial cell (EC) precursors. Recent studies have shown that human tumor vasculature ECs may also arise directly from tumor cells themselves and that the two populations have highly similar or identical karyotypes. We now show that, during the course of serial in vivo passage, these tumor-derived ECs (TDECs) progressively acquire more pronounced EC-like properties. These include higher-level expression of EC-specific genes and proteins, a greater capacity for EC-like behavior in vitro, and a markedly enhanced propensity to incorporate into the tumor vasculature. In addition, both vessel density and size are significantly increased in neoplasms derived from mixtures of tumor cells and serially passaged TDECs. A comparison of early- and late-passage TDECs using whole-genome single nucleotide polymorphism profiling showed the latter cells to have apparently evolved by a process of clonal expansion of a population with a distinct pattern of interstitial chromosomal gains and losses affecting a relatively small number of genes. The majority of these have established roles in vascular development, tumor suppression or epithelial-mesenchymal transition. These studies provide direct evidence that TDECs have a strong evolutionary capacity as a result of their inherent genomic instability. Consequently such cells might be capable of escaping anti-angiogenic cancer therapies by generating resistant populations.

The antiangiogenic agent ZD4190 prevents tumour outgrowth in a model of minimal residual carcinoma in deep tissues

Background:Tumour cells may persist at the operative site after seemingly adequate surgery. Radiotherapy is often given in an attempt to prevent repopulation, but this modality cannot be relied upon to prevent locoregional recurrence. An alternative strategy is to take advantage of the requirement of tumour cells to develop an independent blood supply and block this process to prevent recurrence.Methods:In this study, we evaluate the effect of the angiogenesis inhibitor, ZD4190, using a rodent model of residual carcinoma in deep tissues, mimicking the clinical scenario where low numbers of malignant cells persist at the operative site.Results:The tumour burden that could be eliminated was dependent on the site where the cells were implanted. Immediate treatment with ZD4190 prevented outgrowth of up to 2.5 × 105 cells in the rectus muscle and 1 × 105 in the gastrocnemius, whereas control animals developed large tumours. When more than 2.5 × 106 cells were implanted into the rectus or 1 × 106 into the gastrocnemius and treatment was maintained for 3 weeks, the carcinomas that developed in ZD4190-treated animals showed a reduced microvessel density and increased necrosis when compared with the vehicle-treated controls, but an infiltrative growth pattern was common.Conclusion:These findings suggest that antiangiogenic agents have a role to play in preventing outgrowth of residual carcinoma and are likely to be most effective when the tumour burden is minimal.

Role of the CXCR4/CXCL12 signaling axis in breast cancer metastasis to the brain

Breast cancer is the most common malignancy and second leading cause of cancer death in women. Ninety percent of mortality in breast cancer is often associated with metastatic progression or relapse in patients. Critical stages in the development of aggressive breast cancer include the growth of primary tumors and their ability to spread to foreign organs and form metastases, as well as the establishment of an independent blood supply within the new tumors. Hence, it is imperative to characterize the key molecules that regulate the metastasis of human breast cancer cells. The expression of CXCR4/CXCL12 in breast tumors has been correlated with a poor prognosis, increased metastasis, resistance to conventional therapeutic agents and a poor outcome in the pathogenesis of breast cancer. However, effective anti-CXCR4 therapy remains a challenge. Here, we will review the putative involvement of the CXCR4/CXCL12 signaling axis in breast cancer metastasis to the brain. Characterization of signaling events important for breast cancer cell growth and their metastasis to the brain should provide insights into breast cancer therapies and improved, successful treatments for breast cancer.

The Combined Use of a Pedicled Superficial Inferior Epigastric Artery Flap and a Groin Flap for Reconstruction of a Dorsal and Volar Hand Blast Injury

A hand blast injury case causing a large through-and-through composite tissue loss is presented. This injury resulted in a dorsal and a palmar hand defect with segmental bone loss. Soft tissue coverage of both dorsal and palmar wounds was achieved by two separate pedicle flaps with pedicles closely arising from the femoral artery: a superficial inferior epigastric artery (SIEA) flap and a groin flap. Simultaneously, a large iliac corticocancellous bone graft was harvested from the same incision to be used for the wrist fusion procedure. This approach uses two separate pedicled flaps with robust independent blood supply to cover simultaneously a dorsal and a volar hand wound. A large through-and-through hand defect can be reconstructed readily with this approach, and it is associated with much less perioperative morbidity compared to free composite tissue transfer options. The dissection of both the groin flap and the SIEA flap is straightforward and can be easily performed by a single surgeon. The combined use of these two flaps allows stable coverage of sizable dorsal and palmar wounds of the hand.