Mark S. Granick

Telomeres shorten at equivalent rates in somatic tissues of adults

Telomere shortening in somatic tissues largely reflects stem cell replication. Previous human studies of telomere attrition were predominantly conducted on leukocytes. However, findings in leukocytes cannot be generalized to other tissues. Here we measure telomere length in leukocytes, skeletal muscle, skin and subcutaneous fat of 87 adults (aged 19–77 years). Telomeres are longest in muscle and shortest in leukocytes, yet are strongly correlated between tissues. Notably, the rates of telomere shortening are similar in the four tissues. We infer from these findings that differences in telomere length between proliferative (blood and skin) and minimally proliferative tissues (muscle and fat) are established during early life, and that in adulthood, stem cells of the four tissues replicate at a similar rate.

The relationship of angiogenesis to biological activity in human squamous cell carcinomas of the head and neck.

Tumor angiogenesis has recently been related to tumor growth and metastasis, which determine the clinical outcome of the patient. This study was designed to determine the relationship between angiogenesis in primary squamous cell carcinomas (SSC) of the head and neck and the development of recurrent or metastatic disease, or both. Different SCC of the head and neck were studied. Microvessels were selectively stained using a monoclonal antibody for factor VIII. Microvessel counts were performed in the tumor, in the tissues immediately adjacent, and in normal tissues of similar topographies. Microvessel counts were then correlated with clinical outcome (development of recurrent or metastatic disease, or both). Recurrent or metastatic disease, or both, developed in patients with high microvessel counts (mean, 121.25) in the tissues adjacent to the tumor 7 to 16 months after initial treatment. Those with low microvessel counts (mean, 33.75) were disease-free for 16 months to 6 years (p < 0.01). Microvessel counts inside the tumor were also higher in those in whom recurrences or metastasis, or both, developed, but were not statistically significant. In this study, angiogenesis was directly related to clinical outcome. Thus, angiogenesis may be an independent predictor of recurrent or metastatic disease, or both, which could help in the selection of patients with SCC of the head and neck for aggressive therapy.

Toward a common language: surgical wound bed preparation and debridement

Wound management encompasses a number of disciplines. As new concepts and innovative technologies develop within this exciting field, it is important to share them in spite of the divergence of clinical perspectives between the expert disciplines. One such divergence exists between surgeons and nonsurgical wound specialists. As a result, there is a need to develop a common language between these two groups. How can we develop a common language that unites surgical expertise within medical wound management? One route may be through the principles of wound bed preparation, which we believe have great potential for the communication of effective surgical techniques. Another is through sharing our concepts of surgical debridement as it is applied to different wounds by a variety of surgical disciplines. In this monograph, we try to bring these two themes together. We discuss how wound bed preparation has added to our understanding of the pathophysiology of the nonhealing wound and has provided us with some general clinical concepts. We discuss what role debridement, and then specifically surgical debridement, has to play within wound bed preparation, before analyzing the importance of surgical debridement in tissue preservation and the control of infection. We finally look at ongoing work that examines the cost of various surgical debridement techniques. We will also review a new hydrosurgery system (VERSAJET®, Smith and Nephew, Hull, UK), which we believe has an important role to play in the surgical preparation of the wound. We also expect that this paper will remind our medical colleagues about the critical role played by surgery in wound management.

Sternotomy Infections with Mycoplasma hominis

Mycoplasma hominis caused sternal wound infections with mediastinitis in three patients. One infection occurred in a nonimmunocompromised man after coronary artery bypass grafting. The wound did not heal after repeated debridement, closed irrigation of the mediastinum with povidone-iodine solution, and antimycoplasmal chemotherapy; muscle flap grafting was eventually required. Two infections occurred in recipients of heart-lung transplants after the isolation of mycoplasma from bronchial secretions. Although no Mycoplasma species were isolated after specific antimycoplasmal therapy was begun, the wounds still did not heal. Both patients died of other complications. Infection of wounds after sternotomy is another of an increasing number of infections caused by M. hominis in the normal and immunocompromised host. Familiarity with the morphologic characteristics of M. hominis on bacteriologic culture media may increase the recognition of this pathogen in atypical clinical settings.

Efficacy and cost-effectiveness of a high-powered parallel waterjet for wound debridement

Current concepts of wound healing acknowledge the essential role of wound bed preparation in achieving a wound with good healing potential. Critical to wound bed preparation is the removal of necrosis, unhealthy tissue, foreign matter, and infection. One of the accepted methods of wound bed preparation is surgery. The high‐power parallel waterjet is a new surgical device, which allows the operator to remove very precisely undesirable tissue and debris with maximal preservation of viable tissue. A retrospective study was performed to evaluate the efficacy, safety, and economic impact of using this technique of surgical debridement. Forty patients who had waterjet debridements were compared with 22 patients with matched wounds who had conventional surgical debridement. The waterjet group had significantly fewer procedures (p<0.002) than the conventional group. Based on these outcomes, the use of the new device in appropriate patients is expected to lead to cost savings of approximately

Bipedicle muscle flaps in sternal wound repair.

1,900 per patient.

Inhibition of breast cancer progression by an antibody to a thrombospondin-1 receptor

&NA; Infection following median sternotomy is a devastating and potentially life‐threatening complication. The use of muscle flaps has become widely accepted as a mainstay in the treatment of these problems. We have previously described our successful use of a bipedicle muscle flap for reconstruction of sternal defects in 16 patients. In this paper, we describe follow‐up in those patients as well as an evaluation of this procedure in an additional 26 patients. All records of those patients who had sternal reconstruction using the bipedicle pectoralis major‐rectus abdominis flap were reviewed. Factors analyzed included the type of cardiac surgery, associated conditions, complications of surgery, and outcome. There were 42 patients in this group from 1989 to 1996. There were a variety of cardiac procedures represented. Associated conditions included diabetes, chronic hypertension, prolonged postcardiotomy hypotension, prior radiation therapy, pulmonary failure, and steroid use. There were no deaths in this series. There was one flap failure, one persistent infection, one pneumothorax, and one hernia in this series. Three patients developed hematomas after surgery. The most common complication was a skin slough, which occurred in nine patients. This technique provides a large flap that can fill the entire mediastinum. The dissection is rapid, and the complication rate compares favorably to that of other methods. (Plast. Reconstr. Surg. 101: 356, 1998.)

Reconstruction of musculoskeletal defects following oncologic resection in 76 patients.

BACKGROUND Thrombospondin-1 (TSP-1) is a matrix-bound adhesive glycoprotein. Breast carcinoma cells exhibit increased expression of a novel TSP-1 receptor. We evaluated the role of this receptor in breast cancer adhesion and progression. METHODS Adhesion assays were performed to evaluate MDA-MB-231 breast cancer cell adhesion to TSP-1 in vitro in the presence of either nonimmune immunoglobulin G(IgG) or anti-TSP-1 receptor IgG. Receptor-mediated tumor cell progression was evaluated in athymic nude mice. Mice were inoculated with MDA-MB-231 breast cancer cells and randomized to treatment with intraperitoneal injections of saline solution, nonspecific IgG antibody, or an anti-TSP-1 receptor antibody every other day for 20 days. Mice were killed at 21 days. The peritoneal cavity was examined grossly for primary tumor implantation. The liver and lungs were examined histologically for micrometastases. RESULTS MDA-MB-231 breast cancer cells adhered to TSP-1 in vitro. This adhesion was inhibited to 10% of control by anti-TSP-1 receptor antibody (p < 0.005). Anti-TSP-1 receptor antibody inhibited in vivo breast cancer progression. Mice treated with control IgG antibody or saline solution alone exhibited extensive intraperitoneal seeding. Only one mouse treated with the anti-TSP-1 receptor antibody exhibited any intraperitoneal tumor seeding (p < 0.01). CONCLUSIONS These data suggest that TSP-1 and its receptor play an important role in breast cancer progression.

Surgical Skin-marking Techniques

Between 1990 and 2002, 76 patients underwent 102 muscle flap reconstructions for extremity sarcomas. The patients had radical resection with immediate reconstruction. Reconstructions were performed by the Musculoskeletal Oncology and Plastic Surgery services. The mean age of our patients was 39.1 years. Patients were studied for a mean of 25.4 months. There were 79 pedicle flaps and 23 free flaps. Complications occurred in 23.7% of patients, including wound necroses, seromas, postoperative bleeding, postoperative infections, and flap loss. Five patients required a secondary flap procedure. The overall flap survival rate was 98%. Three patients had local recurrences. Sixteen patients (21.1%) have died of their disease. Five patients are alive with metastases. In 54 patients, Musculoskeletal Tumor Society (MSTS) functional evaluation scores averaged 27.1 (range, 12–30). In this large series of patients, we have demonstrated that, although minor complications are common, functional limbs can be salvaged following oncologic resection from the extremities.

Outcome assessment of an in-hospital cross-functional wound care team.

Surgical skin-marking inks and dyes are in everyday use for designing and planning incisions in plastic and reconstructive surgery. We have traced the historical development of surgical skin-marking techniques from ancient times to the present. The biochemical characteristics of the commonly used marking agents are discussed. A three-part experiment utilizing a pig model was carried out to test the tissue inflammatory response to the various dyes and inks when used intradermally as tattoos, the persistence of such tattoos, and the ease of skin erasure for each of eight stains. Methylene blue and gentian violet are recommended as the best all-purpose marking agents. The use of proprietary inks is discouraged.