Meir Cohen

Clinical applications of gamma-detection probes – radioguided surgery

Abstract.Radioguided surgery (RGS) is a surgical technique that enables the surgeon to identify tissue ”marked” by a radionuclide before surgery, based on the tissue characteristics, the radioactive tracer and its carrying molecule, or the affinity of both. Thus, yet another tool has been added to the inspection and palpation traditionally used by the surgeon. Current clinical applications of radioguided surgery are: radioimmunoguided surgery (RIGS) for colon cancer, sentinel-node mapping for malignant melanoma (which has become state-of-the-art), sentinel-node mapping for breast, vulvar and penile cancer, and detection of parathyroid adenoma and bone tumour (such as osteid osteoma). Although the same gamma-detecting probe (GDP) may be used for all these applications, the carrier substance and the radionuclide differ. MoAb and peptides are used for RIGS, sulphur colloid for sentinel-node mapping, iodine-125 for RIGS, technetium-99m for sentinel node, parathyroid and bone. The mode of injection also differs, but there are some common principles of gamma-guided surgery. RIGS enables the surgeon to corroborate tumour existence, find occult metastases, and assess the margins of resection; this may result in a change on the surgical plan. Sentinel lymph-node (SLN) scintigraphy for melanoma guides the surgeon to find the involved lymph nodes for lymph-node dissection. SLN for breast cancer is being investigated with promising results. This procedure has also changed the outlook of lymph-node pathology by giving the pathologist designated tissue samples for more comprehensive examination. Gamma-guided surgery will result in more accurate and less unnecessary surgery, better pathology and, hopefully, in better patient survival.

Gamma probe-guided sentinel node biopsy--optimal timing for injection.

Aims. We initiated a Phase I feasibility study using a gamma-detecting probe (GDP) and radiolabelled colloid to localize the sentinel lymph node (SLN) in breast cancer. The aim of the study was to establish the ideal timing for injection and examine any possible exclusion criteria for this method. Methods. Thirty breast cancer patients diagnosed by fine needle aspiration (FNA) were included in this study. All were injected with 60 M Bq rhenium colloid labelled with 99m Tc (Tck-17). Scintigraphy was done 20 min, 2, 6 and 25 hours post-injection. Patients were then taken to surgery where they were injected with patent blue dye. During surgery, the SLN was located with a GDP (Neoprobe ® Model 1000). In 28 patients, the SLN was identified by scintigraphy 2 hours after injection, identical to the images seen after 24 hours. Results. In all 28 patients, the SLN was found by the GDP during surgery. In 26 patients the SLN was dyed blue. The two patients with no SLN localization had received prior radiation. Pathology disclosed SLNs with metastases in seven patients. Two patients had a negative SLN but had an axillary lymph node replaced by tumour. Conclusions. Two to 24 hours prior to surgery is suitable timing for injection. Previous radiotherapy predicts failure for this procedure. Further studies are needed to find the exact false-negative rate of this method for breast cancer.

Aerosolization of epidermal cells with fibrin glue for the epithelialization of porcine wounds with unfavorable topography

Aerosolized epidermal cell suspension was previously found to be effective for the epithelialization of full-thickness wounds. This suspension is less expensive than and requires a shorter preparation time than the currently used cultured epithelial autografts. Still, convex and irregular wounds present unfavorable conditions for homogenous dispersion of the aerosolized cell suspension. The authors hypothesized that the addition of fibrin glue to the aerosol of cells would reduce cell movement and ensure homogenous dispersion of the cells, thereby promoting wound epithelialization. The objectives of the study were to evaluate the healing of wounds with unfavorable topography after autotransplantation of an epidermal cell aerosol with and without fibrin glue. Six Yorkshire piglets were studied. An epidermal suspension was made from full-thickness groin skin. Dispase was used to separate the epidermis from the dermis, and trypsin was used to separate the epidermal cells from one another. Twenty-four hours later, full-thickness wounds with unfavorable topography were created adjacent to the vertebral column of six pigs. Twelve wounds were treated with an aerosol of epidermal cell suspension mixed with fibrin glue (study group), and 12 wounds were treated with the same suspension without the fibrin glue (control group). The percentages of total wound contraction and the epithelialized and nonepithelialized areas were evaluated 1, 2, 3, and 4 weeks after aerosolization. The histologic characteristics of the newly formed skin were examined by light microscopy using slides stained with hematoxylin and eosin. Study wounds were characterized by central epithelialization, whereas control wounds were characterized by peripheral epithelialization. Study wounds contracted at a slower rate than control wounds, but wound size was the same in both groups after 4 weeks. The addition of fibrin glue facilitated epithelialization: Study wounds showed 75.5 +/- 22.4 percent (mean +/- SD) and 94.2 +/- 8.8 percent epithelialization after 3 and 4 weeks, respectively, compared with 46.3 +/- 9.5 percent and 47.9 +/- 13.1 percent epithelialization of the control wounds at the same times. These differences between the study and control groups were statistically significant (p < 0.001, paired t test). The addition of fibrin glue to an aerosol of epidermal cells significantly enhances the epithelialization of wounds with unfavorable topography in pigs.

Blindness as a complication of subcutaneous nasal steroid injection.

Blindness as a result of steroid injection into areas adjacent to the eyes, namely the interior of the nose and eyelids, has been described in the otolaryngologic and ophthalmologic literature but at no time in the plastic surgery literature. We describe a case of permanent visual loss at the time of injection of a long-acting steroid to the dorsum of the nose for postrhinoplasty scarring. We suggest that before steroid injection for elective procedures, the patient be informed of all possible consequences of complications even if their occurrence is very rare.

In vitro and in vivo effects of photodynamic therapy on murine malignant melanoma

AbstractBackground: The role of photodynamic therapy (PDT) in the treatment of malignant melanoma is not well defined, nor is it known whether the dark melanoma cells absorb the light used in PDT. Methods:In vitro studies: 2×105 B16 murine melanoma cells were incubated with aluminum phthalocyanine (AlpcS4, 2.5 mg/kg) and were then subjected to photoradiation (50, 100 or 200 J/cm2). Viability was then assessed.In vivo studies: Histology: C57/B1 mice received 2×105 B16 cells subcutaneously and were randomized into study (PDT) and three control groups. AlpcS4 2.5 mg/kg was injected intraperitoneally and the mice were exposed to light (100 J/cm2). After 24 hours they were sacrificed and underwent autopsies. Survival: 40 mice were randomized into PDT (40 J/cm2) and control groups and were monitored for 50 days. Tumor growth: 40 mice were randomized into one control and three treatment groups (PDT on day 3, 6, or 12 after injection with B16 cells), and were monitored for 50 days. Temperature: Tumor temperatures before and at the end of PDT were recorded. Results:In vitro studies: PDT caused a decrease in cell viability to 15.5±0.7%, 11.5±2.1%, and 1.5±0.7% (at 50, 100, and 200 J/cm2, respectively;P<.001). A significant reduction in thymidine incorporation was noted at all energy levels.In vivo studies: Histology: PDT caused massive tumor necrosis. Survival: PDT prolonged the survival of mice (41±13.4 days) compared to controls (15.8±3.8 days,P<.001). Tumor growth: 31 days after injection with B16 cells, the tumor size was 2.6±0.3 cm in the control group and 1.6±0.2, 0.9±0.3, and 1.0±0.4 cm in the PDT groups (days 3, 6 and 12, respectively;P<.01). Temperature: PDT increased skin temperature to 42.8°C±1.3°C, 45.3°C±3.5°C, and 51.7°C±2.7°C at 40, 60, and 100 J/cm2, respectively (P<.01). Conclusions: Photodynamic therapy was found to have significant effects in experimental melanoma in mice. The role of PDT in human melanoma remains to be studied.

Squamous cell carcinoma in perineal inflammatory disease

Four patients with squamous cell carcinoma of the perineal region were diagnosed and treated during the last 4 years in our institutions. The underlying diagnoses consisted of recurrent pilonidal disease, Crohns disease, and hidradenitis suppurativa. In all patients, a pattern of a long-term inflammatory process was evident. Current concepts regarding the pathophysiology of a chronic inflammatory state and malignant transformation are reviewed. We conclude that regardless of the original pathology, all chronic inflammatory processes in the perineal region should be evaluated for malignant degeneration. A high index of suspicion may potentiate an early diagnosis, possibly improving the chance of cure.

Median sternotomy wound complication : The effect of reconstruction on lung function

The objective of the study was to evaluate the lung function of patients with median sternotomy wound complication during the early postmedian sternotomy period and to compare the long-term pulmonary effects of reconstruction using pectoralis major and rectus abdominis muscle flaps. The percentage of predicted, standardized forced vital capacity (FVC); the standardized forced expiratory volume in 1 second (FEV1), and FEV1/FVC ratios of 45 patients with a median sternotomy wound complication were evaluated before and at a mean time of 10.6 months after wound reconstruction. Both mean FVC and FEV1 increased after wound revision compared with the prereconstruction results (8.4% and 9.2% increase, respectively). Patients with painful chest wall movement had the worst (60%) mean FVC and FEV1 before reconstruction when compared with a nonpainful complication. Reconstruction with a muscle flap was followed by an increase of 8.6% and 7.3% in FEV1 and FVC, respectively, from prereconstruction results. However, long-term results indicate that these patients have a mild, restrictive impairment of their lung function tests (LFTs), with about 80% of the predicted FVC and FEV1. Among the muscle flaps, the best improvement and best longterm LFT results were after sternectomy and reconstruction with a pectoralis major muscle flap as compared with a rectus abdominis muscle flap. Sternectomy and reconstruction with a muscle flap is a well-tolerated procedure associated with improvement of lung function compared with prereconstruction values. A pectoralis major muscle flap should be the first choice for muscle flap reconstruction while a rectus abdominis muscle flap should be reserved only for patients with good LFTs before reconstruction.

Clinical-radiological evaluation of poststernotomy wound infection.

&NA; The presumption that computed tomography is the “gold standard” imaging method for diagnosing poststernotomy sternal wound infection was never validated. This study was designed to evaluate the accuracy and role of computed tomography in diagnosing the extent of infectious complications following sternotomy. A high postoperative infection recurrence rate in our earliest cases (30 percent, 1984 to 1988) motivated us to assess whether this modality enables the surgeon to choose the optimal surgical approach, which will make it possible to reduce morbidity and mortality rates. Two‐hundred three patients with poststernotomy sternal wound infections were operated upon between 1984 and 1993. All pertinent clinical and radiological data of these patients were collected retrospectively and reinterpreted by an unbiased radiologist; the radiological data were correlated both to the intraoperative clinical findings and to histological interpretation of the surgical specimens. The study group available for statistical analysis included 160 patients. Predictive statistical analysis confirmed that computed tomography is a highly reliable imaging method for identifying the different pathologies as soft tissue, sternum mediastinal infections, in sternal wound infection with overall sensitivity of 93.5 percent and specificity of 81.7 percent. New radiographic findings were identified for the distinction of costochondral infection. This complication was, and still is, a major deceptive clinical problem in these patients and the major contributor to recurrences. We propose a sternal wound infection classification system that outlines the recommended approach for each clinical‐radiological condition. Since computerized tomography was found to be a highly accurate modality, we strongly believe that the surgeon should take its pathological‐radiographic findings into serious consideration, even if there are no “clear‐cut” clinical signs for an existing or recurring infection. (Plast. Reconstr. Surg. 101: 348, 1998.)

The granulometer--a pocket scale for the assessment of wound healing.

In spite of the availability of high-tech devices for wound assessment, plastic surgeons recognize that the Color and confluence of granulation tissue are the most important indicators of open-wound healing. We developed a simple and inexpensive pocket-size scale–4he Granulometer–to facilitate a firier assessment and to standardize the documentation of wound healing. This device overcomes limitations set by conditions such as lighting or recent exposure to other wounds that could distort the examiners perception of the wound in question. In this study we examined the inter- and intraobserver variations in judgment, and the validity of the Granulometer. Our results demonstrate that skin graft viability can be predicted accurately by this eight-grade scale. Since graft survival depends on proper wound healing, we believe that the Granulometer can also be used for fine assessment of wound treatmeht. the low inter- and intraobserver variations indicate that the Granulometer measurements are both reproducible and accurate.

Single-injection gamma probe-guided sentinel lymph node detection in 40 melanomatous lymphadenectomies

The aim of the study was to evaluate single-injection gamma probe-guided sentinel lymph node (SLN) detection, applied in 40 melanomatous selective sentinel lymphadenectomies (SSLNDs). Thirty-four patients underwent preoperative lymphoscintigraphy, intraoperative SLN identification by a gamma-detecting probe and blue dye, and SLN sampling. The first 11 patients underwent formal lymphadenectomy. The following 23 patients underwent formal lymphadenectomy only when the SLN was involved with tumor. Evaluation included hematoxylin-eosin-stained slide microscopy, monoclonal antibodies to S-100 protein, and the melanoma-associated antigen HMB45. In all patients, single or multiple SLNs were identified by the gamma-detecting probe. However, only 82.5% of these specimens included blue-stained nodes. None of the non-SLN specimens were the exclusive site of metastases. Four patients had metastases in their SLN specimen without non-SLN involvement. We conclude that SSLND can be performed easily and precisely with the exclusive use of the gamma-detecting probe. A single injection is feasible, and decreases operating room contamination and patient discomfort.