Intraoperative radiation therapy in surgical oncology

This is the first publication about intraoperative radiation therapy (IORT) to be written for surgeons through a collaborative effort of surgeons and radiation therapists. This article introduces the basic concepts of radiation therapy and the rationale of its use in the operating room, and presents the advantages for the surgeon and radiation therapist to work together for the benefit of our patients.     

New TNM melanoma staging system: linking biology and natural history to clinical outcomes

The American Joint Committee on Cancer (AJCC) implemented major revisions of the melanoma TNM and stage grouping criteria in the recently published 6th edition of the Staging Manual. The new staging system better reflects independent prognostic factors that are used in clinical trials and in reporting the outcomes of various melanoma treatment modalities. Major revisions include: 1) melanoma thickness and ulceration but not level of invasion to be used in the T classification, 2) the number of metastatic lymph nodes rather than their gross dimensions and the delineation of microscopic vs. macroscopic nodal metastases to be used in the N classification, 3) the site of distant metastases and the presence of elevated serum lactic dehydrogenase (LDH) to be used in the M classification, 4) an upstaging of all patients with Stage I, II, and III disease when a primary melanoma is ulcerated, 5) a merging of satellite metastases around a primary melanoma and in transit metastases into a single staging entity that is grouped into Stage III disease, and 6) a new convention for defining clinical and pathological staging so as to take into account the new staging information gained from intraoperative lymphatic mapping and sentinel node biopsy.     

Does hormonal manipulation in conjunction with permanent interstitial brachytherapy,with or without supplemental external beam irradiation,improve the biochemical outcome for men with intermediate or high‐risk prostate cancer?

OBJECTIVE

To determine whether hormonal manipulation improves the biochemical outcome for men with intermediate or high‐risk prostate cancer and undergoing permanent brachytherapy with or without supplemental external beam radiation therapy.

PATIENTS AND METHODS

From April 1995 to August 2000, 350 patients with intermediate‐risk (225 men; a Gleason score of ≥ 7 or a prostate specific antigen, PSA, level of ≥ 10 ng/mL or clinical stage ≥ T2b) or high‐risk features (125 men; two or three of a Gleason score of ≥ 7 or PSA ≥ 10 ng/mL or clinical stage ≥ T2b) underwent transperineal ultrasonography‐guided permanent brachytherapy. No patient underwent pathological lymph node staging. Of these patients, 293 received supplemental external beam radiation therapy (EBRT), 141 received hormonal manipulation, with 82 having hormonal therapy for ≤ 4 months (median 4) for cytoreduction, while 59 had neoadjuvant and adjuvant hormonal manipulation (median 8 and 12 months for intermediate‐ and high‐risk, respectively). The median patient age was 68.5 years. No patient was lost to follow‐up. The mean (sd ) and median follow‐up was 50 (18) and 49 months (calculated from the day of implantation). Biochemical disease‐free (BDF) survival was defined using a consensus definition. The clinical variables evaluated for BDF survival included risk group, Gleason score, patient age, clinical T‐stage and pretreatment PSA. Treatment variables included use of hormonal manipulation stratified into cytoreductive (≤ 4 months) vs adjuvant (> 4 months) regimens, supplemental EBRT, isotope and dosimetric variables.

RESULTS

For intermediate‐risk patients, the 6‐year actuarial BDF survival rates were 98%, 96% and 100% for hormone naïve, cytoreductive and adjuvant treatment, respectively (P = 0.693); for high‐risk patients the respective values were 79%, 94% and 92% (P = 0.046). When stratified by pretreatment PSA, hormonal manipulation improved the outcome for patients with a PSA of ≥ 10 ng/mL (P = 0.019), but not for those with < 10 ng/mL (P = 0.661). Hormonal status was not statistically significant in predicting biochemical outcome when stratified by Gleason score. The follow‐up in hormone‐naïve patients was significantly longer than that in hormonally manipulated patients, at 55 (20) vs 43 (15) months (P < 0.001). In a multivariate analysis only the Gleason score predicted failure in intermediate‐risk patients, while pretreatment PSA, the use of hormonal manipulation and Gleason score predicted the outcome in high‐risk patients (P = 0.035). For both hormone‐naïve and hormonally manipulated BDF patients, the median PSA level after implantation was < 0.1 ng/mL.

CONCLUSION

In patients treated by permanent prostate brachytherapy, hormonal manipulation improved the biochemical outcome for those at high‐risk and those with an initial PSA of ≥ 10 ng/mL, but not for those with intermediate‐risk features. The use of hormonal therapy for> 4 months conferred no additional biochemical advantage over short‐course regimens. Because the follow‐up in hormone‐naïve patients was longer than that for those receiving hormonal manipulation, additional follow‐up will be mandatory to confirm the durability of these findings.

     

Validity of the WCST-64 after traumatic brain injury

The Wisconsin Card Sorting Test-64 (WCST-64) is a recent modification of the Wisconsin Card Sorting Test (WCST) that utilizes only one deck of cards. The present study investigated the validity of the WCST-64 in a sample of 100 patients with traumatic brain injury (TBI). Mean T scores for Perseverative Responses were more than half a standard deviation lower for the WCST-64 than for the full-length version, even though the respective variables shared almost two thirds of common variance. Moreover, about a quarter of the sample had a T score discrepancy between the respective Perseverative Responses indexes that was greater than one standard deviation. The findings indicate that the WCST-64 cannot be used interchangeably with the original WCST, at least not in patients with TBI.     

Refractive errors and visual anomalies in Down syndrome

A comparatively high incidence of ocular and orbital abnormalities has been reported in persons with Down syndrome. Eighty six children (50% male, 50% female) with Down syndrome in several institutions for individuals with learning difficulties (age range 5-18 years, mean 12.5) were examined for visual impairment in order to relate the ocular impairment to the level of learning difficulty. 6% had mild, 7% moderate, 45% severe and 42% profound learning difficulty. 9% of the children had no refractive errors. A significant (P < 0.01) positive correlation was found between progressive amounts of strabismus and ocular pathology with increasing amount of learning difficulty. On the other hand no correlation was found between refractive errors and the level of learning difficulty. Due to the significant number of ocular disorders found it is recommended that all children with Down syndrome should have an eye examination during the first six months of life and annually thereafter.     

An intragenic deletion of nuclear localization signal-1 of p53 tumor suppressor gene results in loss of apoptosis in murine fibroblasts

We established mouse lines containing either full-length wild-type p53 or nuclear localization signal-I (NLS-I) deleted p53 to study the role of NLS-I in p53 translocation and function. Induction of apoptosis in response to DNA damage, a primary function of p53, was tested in these cell lines. After exposure to gamma-ionizing radiation or hydrogen peroxide, DNA ladders and labeling of nucelosomal fragments were detected in cells with wild-type p53 gene, but not in p53 null cells or NLS-I deleted cells, suggesting that the NLS-I of p53 protein is necessary for apoptosis. Analysis of p53 protein from subcellular fractions indicated that NLS-I deprived p53 remained in the cytoplasmic fraction, which may explain why NLS-I deleted p53 failed to induce apoptosis.