J. Gregory McKinnon

Prognosis for patients with thin cutaneous melanoma: long-term survival data from New South Wales Central Cancer Registry and the Sydney Melanoma Unit.

Estimates of long‐term survival for patients with thin (≤ 1 mm) primary cutaneous melanomas vary widely. Two separate methods were used to study the survival of patients with melanoma from New South Wales (NSW), Australia, and from the Sydney Melanoma Unit (SMU).

Outcome in 846 Cutaneous Melanoma Patients From a Single Center After a Negative Sentinel Node Biopsy

BackgroundA negative sentinel node biopsy (SNB) implies a good prognosis for melanoma patients. The purpose of this study was to determine the long-term outcome for melanoma patients with a negative SNB.MethodsSurvival and prognostic factors were analyzed for 836 SNB-negative patients. All patients with a node field recurrence were reviewed, and sentinel node (SN) tissue was reexamined.ResultsThe median tumor thickness was 1.7 mm, and 23.8% were ulcerated. The median follow-up was 42.1 months. Melanoma specific survival at 5 years was 90%, compared with 56% for SN-positive patients (P < .001). On multivariate analysis, only thickness and ulceration retained significance for disease-free and disease-specific survival. Five-year survival for patients with nonulcerated lesions was 94% vs. 78% with ulceration. Eighty-three patients (9.9%) had a recurrence. Twenty-seven patients developed recurrence in the regional node field, and in 22 of these, it was the first recurrence site. Six developed local recurrence, 17 an in-transit metastasis, and 58 distant disease. The false-negative rate was 13.2%. SN slides and tissue blocks were further examined in 18 patients with recurrence in the node field, and metastatic disease was found in 3 of them.ConclusionsThis large, single-center study confirms that patients with a negative SNB have a significantly better prognosis than those with positive SNs. In those with a negative SNB, primary tumor thickness and ulceration are independent predictors of survival. Incorrect pathologic diagnosis contributed to only a minority of the false-negative results in this study.

Pathologic review of negative sentinel lymph nodes in Melanoma patients with regional recurrence: A clinicopathologic study of 1152 patients undergoing sentinel lymph node biopsy

A sentinel lymph node (SLN) that is melanoma negative by pathologic examination implies absence of melanoma metastasis to that regional lymph node field. However, a small proportion of patients develop regional node field recurrence after a negative SLN biopsy. In this study, we reviewed the histopathology of negative SLNs from such patients to determine whether occult melanoma cells were present in the SLNs, to characterize the pathologic features of false-negative SLNs, and to provide recommendations for the histopathologic examination of these specimens. Between March 1992 and June 2001, of 1152 patients who had undergone SLN biopsy for primary melanomas at the Sydney Melanoma Unit, 976 were diagnosed with negative SLNs by initial pathologic examination (using 2 hematoxylin and eosin stained sections, and 2 immunostained sections for S-100 protein and HMB45), and follow-up was available in 957. Of these, 26 (2.7%) developed regional lymph node recurrence during a median follow-up period of 35.7 months. For 22 of them, the original slides and tissue blocks were available for reexamination. The original slides of each block were reviewed. Multiple further sections were cut from each block and stained with hematoxylin and eosin, for S-100, HMB45, and Melan A. Deposits of occult melanoma cells were detected in 7 of the 22 cases (31.8%). In 5 of the 7 cases, deposits of melanoma cells were present only in the recut sections. There were no significant differences in clinical and pathologic variables for those patients in whom occult melanoma cells were found by pathologic reexamination of their SLNs, compared with those in whom no melanoma cells were detected. The detection of melanoma cell deposits in only 7 of 22 false-negative SLNs suggests that mechanisms other than failure of histopathologic examination may contribute to the failure of the SLN biopsy technique in some patients. The failure rate for melanoma detection in SLNs by our routine pathologic examination, using the current protocol at our institution, was <1% (7 of 957 patients). Routinely performing more intensive histopathologic examination of SLNs is difficult to justify from a cost benefit perspective; we therefore recommend examining two hematoxylin and eosin stained sections and two immunostained sections (for S-100 and HMB45) routinely on SLNs from melanoma patients.

X-ray CT monitoring of iceball growth and thermal distribution during cryosurgery

X-ray CT is able to image the internal architecture of frozen tissue. Phantoms of distilled water, a saline-gelatin mixture, lard and a calf liver-gelatin suspension cooled by a plastic tube acting as a long liquid nitrogen cryoprobe were used to study the relationship between Hounsfield unit (HU) values and temperature. There is a signature change in HU value from unfrozen to completely frozen tissue. No discernible relation exists between temperature in a completely frozen tissue and its HU value for the temperature range achieved with commercial cryoprobes. However, such a relation does exist in the typically narrow region of phase change and it is this change in HU value that is the parameter of concern for quantitative monitoring of the freezing process. Calibration of temperature against change in HU value allows a limited set of isotherms to be generated in the phase change region for direct monitoring of iceball growth. The phase change temperature range, mid-phase change temperature and the absolute value of HU change from completely frozen to unfrozen tissue are shown to be sensitive to the medium. Modelling of the temperature distribution within the region of completely frozen phantom using the infinite cylinder solution to the Fourier heat equation allows the temperature history of the phantom to be predicted. A set of isotherms, generated using a combination of thermal modelling and calibrated HU values demonstrates the feasibility of routine x-ray CT assisted cryotherapy. Isotherm overlay will be a major aid to the cryosurgeon who adopts a fixed target temperature as the temperature below which there is a certainty of ablation of the diseased tissue.

A Sentinel Node Biopsy Does Not Increase the Incidence of In-Transit Metastasis in Patients With Primary Cutaneous Melanoma

BackgroundIt has been suggested that performing a sentinel node biopsy (SNB) in patients with cutaneous melanoma increases the incidence of in-transit metastasis (ITM).MethodsITM rates for 2018 patients with primary melanomas ≥1.0 mm thick treated at a single institution between 1991 and 2000 according to 3 protocols were compared: wide local excision (WLE) only (n = 1035), WLE plus SNB (n = 754), and WLE plus elective lymph node dissection (n = 229).ResultsThe incidence of ITM for the three protocols was 4.9%, 3.6%, and 5.7%, respectively (not significant), and as a first site of recurrent disease the incidence was 2.5%, 2.4%, and 4.4%, respectively (not significant). The subset of patients who were node positive after SNB and after elective lymph node dissection also had similar ITM rates (10.8% and 7.1%, respectively; P = .11). On multivariate analysis, primary tumor thickness and patient age predicted ITM as a first recurrence, but type of treatment did not. Patients who underwent WLE only and who had a subsequent therapeutic lymph node dissection (n = 149) had an ITM rate of 24.2%, compared with 10.8% in patients with a tumor-positive sentinel node treated with immediate dissection (n = 102; P = .03).ConclusionsPerforming an SNB in patients with melanoma treated by WLE does not increase the incidence of ITM.

False Negative Sentinel Lymph Node Biopsies in Melanoma May Result From Deficiencies in Nuclear Medicine, Surgery, or Pathology.

Objective:To investigate a cohort of melanoma patients with false negative (FN) sentinel node (SN) biopsies (SNBs) to identify the reasons for the FN result. Summary of Background Data:SNB is a highly efficient staging method in melanoma patients. However, with long-term follow-up FN SNB results of up to 25% have been reported. Methods:Seventy-four SNs from 33 patients found to have had an FN SNB were analyzed by reviewing the lymphoscintigraphy, surgical data, and histopathology, and by assessing nodal tissue using multimarker real-time quantitative reverse transcription (qRT) polymerase chain reaction, and antimony concentration measurements (as a marker of “true” SN status) using inductively coupled plasma mass spectroscopy. Results:Nine SNs (12%) from 9 patients (27%) had evidence of melanoma on histopathologic review. Twelve SNs (16%) from 10 patients (30%) were qRT(+). Four of these 12 SNs were positive on histopathology review and 8 were negative. Four patients (12%) were upstaged by qRT. Sixteen patients had their SNB histology, lymphoscintigraphy, and surgical data reviewed. Identifiable causes of the FN SNBs were not found after review of all modalities in 4 patients. SNs from all 4 patients had antimony levels indicative of an SN. Of the SNs evaluable by qRT, 1 was qRT(+) and 7 SNs from 2 patients were qRT(−). Conclusions:An FN SN can occur because of deficiencies in nuclear medicine, surgery, or pathology. qRT can detect “occult” metastatic melanoma in SNs that have been identified as negative by histopathology.

A model for the time-dependent thermal distribution within an iceball surrounding a cryoprobe

The optimal cooling parameters to maximize cell necrosis in different types of tissue have yet to be determined. However, a critical isotherm is commonly adopted by cryosurgeons as a boundary of lethality for tissue. Locating this isotherm within an iceball is problematic due to the limitations of MRI, ultrasound and CT imaging modalities. This paper describes a time-dependent two-dimensional axisymmetric model of iceball formation about a single cryoprobe and extensively compares it with experimental data. Thermal histories for several points around a CRYOprobe are predicted to high accuracy (5 degrees C maximum discrepancy). A realistic three-dimensional probe geometry is specified and cryoprobe temperature may be arbitrarily set as a function of time in the model. Three-dimensional temperature distributions within the iceball, predicted by the model at different times, are presented. Isotherm locations, as calculated with the infinite cylinder approximation, are compared with those of the model in the most appropriate region of the iceball. Infinite cylinder approximations are shown to be inaccurate when applied to this commercial probe. Adopting the infinite cylinder approximation to locate the critical isotherm is shown to lead the user to an overestimate of the volume of target tissue enclosed by this isotherm which may lead to incomplete tumour ablation.

Lymphedema After Complete Axillary Node Dissection for Melanoma: Assessment Using a New, Objective Definition

Objectives:The objectives of this study were to define appropriate criteria for assessing the presence of lymphedema, and to report the prevalence and risk factors for development of upper limb lymphedema after level I–III axillary dissection for melanoma. Summary Background Data:The lack of a consistent and reliable objective definition for lymphedema remains a significant barrier to appreciating its prevalence after axillary dissection for melanoma (or breast carcinoma). Methods:Lymphedema was assessed in 107 patients (82 male, 25 female) who had previously undergone complete level I–III axillary dissection. Of the 107 patients, 17 had also received postoperative axillary radiotherapy. Arm volume was measured using a water displacement technique. Change in volume of the arm on the side of the dissection was referenced to the volume of the other (control) arm. Volume measurements were corrected for the effect of handedness using corrections derived from a control group. Classification and regression tree (CART) analysis was used to determine a threshold fractional arm volume increase above which volume changes were considered to indicate lymphedema. Results:Based on the CART analysis results, lymphedema was defined as an increase in arm volume greater than 16% of the volume of the control arm. Using this definition, lymphedema prevalence for patients in the present study was 10% after complete level I–III axillary dissection for melanoma and 53% after additional axillary radiotherapy. Radiotherapy and wound complications were independent risk factors for the development of lymphedema. Conclusions:A suggested objective definition for arm lymphedema after axillary dissection is an arm volume increase of greater than 16% of the volume of the control arm.

Histopathologic Excision Margin Affects Local Recurrence Rate Analysis of 2681 Patients With Melanomas 2 mm Thick

Objective:Prospective trials have shown that 1-cm and 2-cm margins are safe for melanomas <1 mm thick and ≥1 mm thick, respectively. It is unknown whether narrower margins increase the risk of LR or mortality. Summary Background Data:To determine the relationship between histopathologic excision margin, local recurrence (LR) and survival for patients with melanomas ≤2 mm thick. Methods:Data were extracted from the Sydney Melanoma Unit database for all patients with cutaneous melanoma ≤2 mm thick, diagnosed up to 1996. Patients with positive excision margins or follow-up <12 months were excluded, leaving 2681 for analysis. Outcome measures were LR (recurrence <5 cm from the excision scar), in-transit recurrence, and disease-specific survival. Factors predicting LR and overall survival were tested with Cox proportional hazards analysis. Results:Median follow-up was 83.8 months. LR was identified in 55 patients (median time to recurrence, 37 months). At 120 months, the actuarial LR rate was 2.9%. Five-year survival after LR was 52.8%. In multivariate analysis, only margin of excision and tumor thickness were predictive of LR (both P = 0.003). When all patients with a margin <0.8 cm in fixed tissue (corresponding to a margin of <1 cm in vivo) were excluded from analysis, margin was no longer significant in predicting LR. Thickness, ulceration, and site were predictive of survival, but margin was not (P = 0.49). Conclusions:Histopathologic margin affects the risk of LR. However, if the in vivo margin is ≥1 cm, it no longer predicts risk of LR. Patient survival is not affected by margin.

Considerations during clinical operation of two commercially available cryomachines

Advances in the technology of cryomachines in the last 10 years have led to the development of both liquid nitrogen and argon‐based Joule‐Thompson cryomachines. Theoretical and practical evaluation of the CMS Accuprobe™ and the ENDOcare CRYOcare™ was performed as respective examples of these technologies.