Patricia B. Cerrito

Sentinel Lymph Node Biopsy for Breast Cancer: A Suitable Alternative to Routine Axillary Dissection in Multi-Institutional Practice When Optimal Technique Is Used

PURPOSE Previous studies have demonstrated the feasibility of sentinel lymph node (SLN) biopsy for nodal staging of patients with breast cancer. However, unacceptably high false-negative rates have been reported in several studies, raising doubt about the applicability of this technique in widespread surgical practice. Controversy persists regarding the optimal technique for correctly identifying the SLN. Some investigators advocate SLN biopsy using injection of a vital blue dye, others recommend radioactive colloid, and still others recommend the use of both agents together. PATIENTS AND METHODS A total of 806 patients were enrolled by 99 surgeons. SLN biopsy was performed by single-agent (blue dye alone or radioactive colloid alone) or dual-agent injection at the discretion of the operating surgeon. All patients underwent attempted SLN biopsy followed by completion level I/II axillary lymph node dissection to determine the false-negative rate. RESULTS There was no significant difference (86% v 90%) in the SLN identification rate among patients who underwent single- versus dual-agent injection. The false-negative rates were 11.8% and 5.8% for single- versus dual-agent injection, respectively (P <.05). Dual-agent injection resulted in a greater mean number of SLNs identified per patient (2. 1 v 1.5; P <.0001). The SLN identification rate was significantly less for patients older than 50 years as compared with that of younger patients (87.6% v 92.6%; P =.03). Upper-outer quadrant tumor location was associated with an increased likelihood of a false-negative result compared with all other locations (11.2% v 3. 9%; P <.05). CONCLUSION In multi-institutional practice, SLN biopsy using dual-agent injection provides optimal sensitivity for detection of nodal metastases. The acceptable SLN identification and false-negative rates associated with the dual-agent injection technique indicate that this procedure is a suitable alternative to routine axillary dissection across a wide spectrum of surgical practice and hospital environments.

Dermal injection of radioactive colloid is superior to peritumoral injection for breast cancer sentinel lymph node biopsy: results of a multiinstitutional study.

ObjectiveTo determine the optimal radioactive colloid injection technique for sentinel lymph node (SLN) biopsy for breast cancer. Summary Background DataThe optimal radioactive colloid injection technique for breast cancer SLN biopsy has not yet been defined. Peritumoral injection of radioactive colloid has been used in most studies. Although dermal injection of radioactive colloid has been proposed, no published data exist to establish the false-negative rate associated with this technique. MethodsThe University of Louisville Breast Cancer Sentinel Lymph Node Study is a multiinstitutional study involving 229 surgeons. Patients with clinical stage T1–2, N0 breast cancer were eligible for the study. All patients underwent SLN biopsy, followed by level I/II axillary dissection. Peritumoral, subdermal, or dermal injection of radioactive colloid was performed at the discretion of the operating surgeon. Peritumoral injection of isosulfan blue dye was performed concomitantly in most patients. The SLN identification rates and false-negative rates were compared. The ratios of the transcutaneous and ex vivo radioactive SLN count to the final background count were calculated as a measure of the relative degree of radioactivity of the nodes. One-way analysis of variance and chi-square tests were used for statistical analysis. ResultsA total of 2,206 patients were enrolled. Peritumoral, subdermal, or dermal injection of radioactive colloid was performed in 1,074, 297, and 511 patients, respectively. Most of the patients (94%) who underwent radioactive colloid injection also received peritumoral blue dye injection. The SLN identification rate was improved by the use of dermal injection compared with subdermal or peritumoral injection of radioactive colloid. The false-negative rates were 9.5%, 7.8%, and 6.5% (not significant) for peritumoral, subdermal, and dermal injection techniques, respectively. The relative degree of radioactivity of the SLN was five- to sevenfold higher with the dermal injection technique compared with peritumoral injection. ConclusionsDermal injection of radioactive colloid significantly improves the SLN identification rate compared with peritumoral or subdermal injection. The false-negative rate is also minimized by the use of dermal injection. Dermal injection also is associated with SLNs that are five- to sevenfold more radioactive than with peritumoral injection, which simplifies SLN localization and may shorten the learning curve.

Complications associated with sentinel lymph node biopsy for melanoma

AbstractBackground: Sentinel lymph node (SLN) biopsy has become widely accepted as a method of staging the regional lymph nodes for patients with melanoma. Although it is often stated that SLN biopsy is a minimally invasive procedure associated with few complications, a paucity of data exists to specifically determine the morbidity associated with this procedure. This analysis was performed to evaluate the morbidity associated with SLN biopsy compared with completion lymph node dissection (CLND). Methods: Patients were enrolled in the Sunbelt Melanoma Trial, a prospective multi-institutional study of SLN biopsy for melanoma. Patients underwent SLN biopsy and were prospectively followed up for the development of complications associated with this technique. Patients who had evidence of nodal metastasis in the SLN underwent CLND. Complications associated with SLN biopsy alone were compared with those associated with SLN biopsy plus CLND. Results: A total of 2120 patients were evaluated, with a median follow-up of 16 months. Overall, 96 (4.6%) of 2120 patients developed major or minor complications associated with SLN biopsy, whereas 103 (23.2%) of 444 patients experienced complications associated with SLN biopsy plus CLND. There were no deaths associated with either procedure. Conclusions: SLN biopsy alone is associated with significantly less morbidity compared with SLN biopsy plus CLND.

Sentinel lymph node biopsy for breast cancer: impact of the number of sentinel nodes removed on the false-negative rate

BACKGROUND Numerous studies have demonstrated that sentinel lymph node (SLN) biopsy can accurately determine axillary nodal status for breast cancer, but unacceptably high false negative rates have also been reported. Attention has been focused on factors associated with improved accuracy. We have previously shown that injection of blue dye in combination with radioactive colloid reduces the false negative rate compared with injection of blue dye alone. We hypothesized that this may be from the increased ability to identify multiple sentinel nodes. The purpose of this analysis was to determine whether removal of multiple SLNs results in a lower false negative rate. STUDY DESIGN The University of Louisville Breast Cancer Sentinel Lymph Node Study is a prospective multiinstitutional study. Patients with clinical stage T1-2, N0 breast cancer were eligible for enrollment. All patients underwent SLN biopsy using blue dye alone, radioactive colloid alone, or both agents in combination, followed by completion level I and II axillary dissection. RESULTS A total of 1,436 patients were enrolled in the study from August 1997 to February 2000. SLNs were identified in 1,287 patients (90%), with an overall false negative rate of 8.3%. A single SLN was removed in 537 patients. Multiple SLNs were removed in 750 patients. The false negative rates were 14.3% and 4.3% for patients with a single sentinel node versus multiple sentinel nodes removed, respectively (p = 0.0004, chi-square). Logistic regression analysis revealed that use of blue dye injection alone was the only factor independently associated with identification of a single SLN (p<0.0001), and patient age, tumor size, tumor location, surgeons previous experience, and type of operation were not significant. CONCLUSIONS The ability to identify multiple sentinel nodes, when they exist, improves the diagnostic accuracy of SLN biopsy. Injection of radioactive colloid in combination with blue dye improves the ability to identify multiple sentinel nodes compared with the use of blue dye alone.

Role of graft flow measurement technique in anastomotic quality assessment in minimally invasive CABG

BACKGROUND Anastomotic quality is currently the critical issue in minimally invasive coronary surgery. Although little is known about its effectiveness, surgeons routinely assess grafts intraoperatively using flow probes. This study was designed to determine whether mean flow and the pattern of flow tracing in internal mammary artery grafts obtained with a transit-time flow probe are reliable indicators of anastomotic quality. METHODS Mongrel dogs (n = 14, 30 to 35 kg) underwent off-pump left, right, or left and right internal mammary artery to left anterior descending artery anastomosis (23 grafts). Moderate to severe degrees of stenosis were created at the anastomosis by an additional suture. Internal mammary artery graft flow was measured before and after the stenosis was created with the left anterior descending artery occluded. Angiography was performed at random postoperatively to validate the degree of stenosis. Mean flow and flow tracing morphology were compared under various degrees of stenosis. RESULTS There were no significant differences in mean graft flow or the morphology of the flow tracing between patent (<15%), mild (<25%), moderate (<50%), and moderately severe (<75%) stenosis. However, mean graft flow decreased (p < 0.05) with severe stenosis (>75%). CONCLUSIONS Although differences in mean graft flow and graft flow morphology were detectable in anastomoses with severe stenosis (>75%), they were indistinguishable in anastomoses with mild (<25%) to moderately severe (<75%) stenosis. Flow measurement techniques are valuable tools intraoperatively, but surgeons should exercise caution in their interpretation.

Resection of the metatarsal head for diabetic foot ulcers

BACKGROUND Diabetic foot ulceration is a worldwide health problem. Approximately 15% of the 10 million diabetic patients in the United States will develop a foot ulceration at some time in their lives. The presence of a foot ulcer in this population is extremely debilitating and dramatically increases the risk of lower extremity amputation, accounting for approximately 67,000 lost limbs each year. Additionally, the costs associated with treating foot ulcers in diabetic patients is a major expense in the overall care of this patient group. METHODS An 11-year retrospective study was conducted to evaluate 101 consecutive patients with diabetic ulcers of the forefoot who were treated using resection of the metatarsal head as the primary means of obtaining wound closure. RESULTS The results indicate that 88% of the ulcers were healed by using this technique, and relatively more rapidly than would be expected when compared with historical norms. CONCLUSIONS Resection of the metatarsal head is a safe and relatively inexpensive procedure that facilitates closure of the lesion, helps to control infection, and prevents countless and costly amputations.

In Vivo and In Vitro Photodynamic Studies with Benzochlorin Iminium Salts Delivered by a Lipid Emulsion

Benzochlorin iminium salts (Bis) are hydrophobic photosensitizers based on an octaethylbenzochlorin nucleus that absorb in the near‐IR region of the visible spectrum. In these studies the photodynamic activities of the zinc, copper and metal‐free BI derivatives were compared in vivo in C3H‐HeJ mice bearing a mammary adenocarcinoma tumor line. In vitro studies were also performed with the radiation‐induced fibrosarcoma tumor line. An argon‐pumped Ti‐sapphire laser tuned to deliver light between 710 and 800 nm or an Oriel arc‐lamp filtered to deliver broadband light above 590 nm were used as light source. A lipid emulsion was used as the delivery system for sensitizers in all studies. A pronounced solvent dependence was observed for the Q band for each of all iminium salts examined. As an example, the metal‐free (BI) derivative had an absorption maximum at 798 nm in dichloromethane and at 727 nm in serum. The action spectra showed a greater PDT response at blue‐shifted wavelengths for each of the three iminium salts both in vivo and in vitro. Among the three derivatives, the zinc analog (ZnBI) produced the greatest tumor regression at the low drug/light dose of 0.7 (μ mole/kg and 200 J/cm2. These results indicate that iminium salts have characteristics that may make them promising third‐generation photosensitizers.

Nonparametric estimation of joint discrete-continuous probability densities with applications

Abstract This investigation considers nonparametric estimation of the joint probability density function of a random vector ( X , Y ) where X is discrete and Y is continuous. Using both the kernel density estimation (for the continuous co-ordinate) and a discrete analog (for the discrete co-ordinate), we define a class of ‘kernel’ type joint estimates. Basic properties of this estimate are studied. In addition, applications of the results to non-parametric regression when the regressor is a discrete random variable as well as to the case of mixed regressors, and to a discrete version of ‘index coefficient’ (cf. Powell et al., 1989, Econometrica , 57, 1403–1430) are presented. Optimal choices of the smoothing parameters are also discussed.

Neural network pattern recognition analysis of graft flow characteristics improves intra-operative anastomotic error detection in minimally invasive CABG

OBJECTIVE The intra-operative assessment of the quality of anastomosis in minimally invasive coronary artery bypass surgery (CABG) is critical. Recent investigations demonstrated that flow probes used intra-operatively to assess anastomotic errors may give the surgeon a false sense of confidence as only severely stenotic anastomoses (>90%) could be reliably detected. We developed a neural network system using graft flow data and assessed its potential to improve anastomotic error detection. METHODS Mammary to LAD grafts (n = 46) were constructed in mongrel dogs off-pump. Continuous beat-to-beat graft flow was recorded using transit-time flow probes. Various degrees of anastomotic stenoses (0-100%) were created by an additional suture. The degree of anastomotic stenosis was confirmed by postoperative angiography. A learning vector quantization neural network was created using heart rate, mean aortic pressure, mean systolic, maximum systolic, minimum systolic, mean diastolic, maximum diastolic, minimum diastolic, and mean graft flows. In addition, a spectral analysis of the flow waveforms was performed and the magnitude and phase of the first five harmonics were used to further develop the neural network. RESULTS The neural network pattern recognition system was 94% accurate in detecting any stenosis >50%. To validate the model, a testing set was used with 20% of the data values, and the accuracy remained at 100% above chance alone. CONCLUSION Pattern recognition of transit-time flow probe tracings using neural network systems can detect anastomotic errors significantly better than the surgeons visual assessment, thereby improving the clinical outcome of minimally invasive CABG.

Goodness of fit tests based on the L2-norm of multivariate probability density functions

Using the well known kernel method of estimation for multivariate probability densities due to Rosenblatt (1956), Parzen (1962) and Cacoullos (1966), testing the goodness of fit in the one sample, two sample, and testing symmetry cases are discussed. Test statistics presented here are based on the L2-norms . The estimates presented here for δ i i=l,2, 3 are modifications on those discussed by Bickel and Rosenblatt (1973), Rosenblatt (1975) and Hall (1984), and are asymptotically normal under the null and also under the alternatives with conditions much simpler than assumed in literature.