Limitations of size as a criterion in the evaluation of adrenal tumors.

BACKGROUND: Size has been considered to be the single best predictor of malignancy in adrenal neoplasms that have been identified incidentally. However, small adrenal cortical cancers have been reported from multiple centers. METHODS: We retrospectively evaluated the value of tumor size and other clinical parameters in the prediction of the presence of adrenal malignancy. RESULTS: The records of 117 patients who underwent evaluation for tumors of the adrenal gland were reviewed. The median tumor size of the adrenal cortical carcinomas (n = 38 carcinomas) was 9.2 cm (range, 1.7-30 cm); 5 cancers (13.5%) were smaller than 5.0 cm. The median overall size of the benign tumors, excluding pheochromocytomas, was 4.0 cm (n = 38 carcinomas); 10 benign tumors (26%) were larger than 5.0 cm. The imaging features of 4 of 5 small adrenal cancers predicted malignancy; the remaining patients had hormonally functioning tumors. The imaging features of 7 of 10 large benign adrenal tumors predicted benign histologic features, including 5 of 5 myelolipomas. CONCLUSIONS: Although size remains a good predictor of the histologic features and clinical behavior of adrenal neoplasms, both small adrenal cortical cancers and large benign tumors occur with measurable frequency. High-quality imaging studies may be helpful in the identification of relatively small adrenal cancers and of characteristic benign lesions that may be selectively followed.

The detection of telomerase activity in patients with adenocarcinoma of the pancreas by fine needle aspiration.

Telomerase activation in differentiated cells is associated with cell immortalization. Detection of telomerase expression in cancer provides a potential biomarker to be evaluated in the diagnosis and prognosis of cancer patients. Analysis of telomerase activity in biopsy specimens may serve as a useful marker for the diagnosis of pancreatic adenocarcinoma. This study was conducted to determine if telomerase could be detected in fine needle aspirates from patients with pancreatic carcinoma. The telomeric repeat amplification protocol (TRAP) assay was used to determine telomerase activity from pancreatic cancer cell lines, paired tumor/normal human pancreatic tissues and specimens obtained at the time of diagnostic fine-needle aspiration (FNA) biopsies. In this report, we demonstrate that: i) telomerase activity is present in pathologically confirmed pancreatic cancer specimens, but absent in matched adjacent areas of normal pancreatic tissues; ii) telomerase activity is present in FNA samples obtained at the time of CT-guided FNA of pancreatic adenocarcinomas; and iii) this activity can be detected in material normally discarded during FNA slide preparation. Activation of telomerase can be identified in FNA specimens obtained at the time of routine cytologic diagnosis. These findings may be useful for further diagnostic or therapeutic investigations of telomerase activity in pancreatic carcinoma.

Significance and management of local recurrences and limited metastatic disease in the abdomen.

The management of patients with synchronous or metachronous metastatic carcinoma, sarcoma, or melanoma in the abdomen requires a knowledge of the natural history of the disease and of the available treatment options. Patients with advanced malignant disease may be of marginal performance status yet may require large surgical procedures or combined modality therapy; the most challenging therapeutic decisions involve such patients. The authors highlight the role of surgery in selected patients with metastatic or recurrent malignancy as it is practiced at The University of Texas M. D. Anderson Cancer Center.

Management of skin trauma.

The majority of skin trauma incidents cause minor injury that can be treated effectively in the outpatient setting. A new approach to the closure of skin lacerations using tissue adhesive is presented and the current management of abrasions, blisters, burns, skin tears, and subungual hematomas are reviewed. An overview of wound dressings is provided to assist in obtaining the optimal wound-healing environment.

Up-regulation of the proapoptotic mediators Bax and Bak after adenovirus-mediated p53 gene transfer in lung cancer cells.

Overexpression of wild-type p53 in cancer cells by adenovirus-mediated p53 gene transfer can result in the induction of apoptosis. To identify the potential mediators of this p53-induced apoptosis, we examined apoptotic protein levels in human lung cancer cells after Adp53 gene transfer. We observed up-regulation of Bax and Bak protein levels 18-36 h after transduction with Adp53 in H1299, H358, and H322 lung cancer cells. Contrary to expected observations, no changes in Bcl-2 and Bcl-X(L) protein levels were observed. Morphological cell changes and terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling staining showed evidence of apoptosis in all cell lines 48 h after transduction with Adp53. These results indicate that the induction of apoptosis by adenovirus-mediated p53 transfer may be mediated by the induction of proapoptotic mechanisms rather than suppression of antiapoptotic mechanisms.

Prognostic factors in resectable pancreatic cancer: p53 and bcl-2.

The p53 tumor suppressor gene and the Bcl-2 proto-oncogene regulate cell cycle progression and apoptosis. We evaluated the expression of these molecular markers with standard pathologic prognostic variables in patients who received multimodality therapy for resectable adenocarcinoma of the pancreas to study the effect of p53 and Bcl-2 on survival duration. Immunohistochemical staining of archival material was performed to determine levels of expression of p53 and Bcl-2 proteins in 70 patients with adenocarcinoma of pancreatic origin. All patients underwent a potentially curative pancreaticoduodenectomy and standardized pathologic analysis of resected specimens. Potential pathologic and molecular prognostic variables were assessed for their effect on survival duration. Nuclear staining for p53 was observed in 33 (47%) of 70 specimens. Immunostaining for Bcl-2 was observed in 23 specimens (33%). A trend toward improved survival duration was seen in patients whose tumors stained positive for either p53 or Bcl-2. Negative staining for both markers predicted short survival (P = 0.01). By univariate and multivariate analyses, no single pathologic factor was associated with survival duration. Immunohistochemical staging using both p53 and Bcl-2 significantly predicted survival duration by univariate and multivariate analysis; patients whose tumors stained positively for p53 and/or overexpressed Bcl-2 had a significantly longer survival than those whose tumors stained negative for both proteins.

Factors limiting adenovirus-mediated gene transfer into human lung and pancreatic cancer cell lines.

Adenoviral vectors are a widely used means of gene transfer. However, transgene expression after adenoviral administration varies among different carcinoma cell lines. We hypothesized that this variation is attributable, in part, to the presence of cell surface molecules involved in adenoviral infection. To test this, we first assessed adenovirus-mediated transgene expression in four human lung carcinoma cell lines and four human pancreatic carcinoma cell lines in terms of luciferase activities and found it to vary from 4.8 x 10(4) to 6.1 x 10(7) relative light units/microg of protein. Then, to determine whether the molecules involved in the entry of adenovirus into host cells were responsible for this variation, we evaluated the expression of alpha(v)beta5, alpha(v), beta3, alpha5, and beta1 integrins and that of coxsackievirus and adenovirus receptor (CAR) in these cell lines. Statistical analysis revealed that the levels of beta3 were associated with the levels of transgene expression. Blocking analysis showed that adenovirus-mediated gene transfer could be blocked by antibodies against these six molecules but not by the antibodies against alpha2 or alpha3 integrins, thus suggesting that the integrins alphavbeta5, alpha(v), beta3, alpha5, and beta1 and CAR molecules could limit adenovirus-mediated gene transfer when their levels fell below a certain threshold. Furthermore, cells expressing low levels of beta3 and resistant to conventional adenoviral vectors were susceptible to a vector containing the heparin-binding domain in its fiber, thus suggesting that redirecting vectors to receptors other than CAR may bypass the integrin pathway. These findings may have implications for improving the efficiency of adenovirus-mediated gene transfer and developing novel adenoviral vectors.

Intraoperative radiofrequency ablation or cryoablation for hepatic malignancies.

BACKGROUND: The majority of patients with primary or metastatic malignancies confined to the liver are not candidates for resection because of tumor size, location, multifocality, or inadequate functional hepatic reserve. Cryoablation has become a common treatment in select groups of these patients with unresectable liver tumors. However, hepatic cryoablation is associated with significant morbidity. Radiofrequency ablation (RFA) is a technique that destroys liver tumors in situ by localized application of heat to produce coagulative necrosis. In this study, we compared the complication and early local recurrence rates in patients with unresectable malignant liver tumors treated with either cryoablation or RFA. PATIENTS AND METHODS: Patients with hepatic malignancies were entered into two consecutive prospective, nonrandomized trials. The liver tumors were treated intraoperatively with cryoablation or RFA; intraoperative ultrasonography was used to guide placement of cryoprobes or RFA needles. All patients were followed up postoperatively to assess complications, treatment response, and local recurrence of malignant disease. RESULTS: Cryoablation was performed on 88 tumors in 54 patients, and RFA was used to treat 138 tumors in 92 patients. Treatment-related complications, including 1 postoperative death, occurred in 22 of the 54 patients treated with cryoablation (40.7% complication rate). In contrast, there were no treatment-related deaths and only 3 complications after RFA (3.3% complication rate, P<0.001). With a median follow-up of 15 months in both patient groups, tumor has recurred in 3 of 138 lesions treated with RFA (2.2%), versus 12 of 88 tumors treated with cryoablation (13.6%, P<0.01). CONCLUSIONS: RFA is a safe, well-tolerated treatment for patients with unresectable hepatic malignancies. This study indicates that (1) complications occur much less frequently following RFA of liver tumors compared with cryoablation of liver tumors, and (2) early local tumor recurrence is infrequent following RFA.

Gene therapy and pancreatic cancer.

Adenocarcinoma of the pancreas is associated with a short survival due to frequent delays in diagnosis and the lack of effective systemic therapies. Advances in understanding the molecular basis of pancreatic cancer have allowed identification of molecular targets which are amenable to therapeutic intervention. Such targets include p53, K-ras, p16, and DPC-4. Gene therapy involves the transfer of genetic constructs which alter the neoplastic potential of the cancer cell. Vectors used in gene transfer include viral and non-viral methods. Presently, gene therapy of pancreatic cancer is limited to pre-clinical studies using in vitro and in vivo models. However, the initial results from these pre-clinical studies have been encouraging and will form the basis for clinical studies of gene transfer in patients with pancreatic cancer.

Detection of telomerase activity in breast masses by fine-needle aspiration.

BACKGROUND: Telomerase is an RNA-dependent DNA polymerase that compensates for the telomere shortening that occurs in its absence. Reactivation of telomerase is thought to be an important step in cellular immortalization, and recent studies have indicated that telomerase activity is often detected in primary human malignancies. The clinical implications of telomerase activity in human tumors are currently under investigation. METHODS: Eighty-nine samples (46 FNAs and 43 gross tissue biopsies) from 44 patients with breast masses were analyzed prospectively for the presence of telomerase activity by a modification of the telomere repeat amplification protocol (TRAP). All samples were obtained directly from the excised mass at the time of specimen removal in the operating room. RESULTS: Telomerase activity was detected in 17 of 19 (90%) FNA samples and 15 of 18 (83%) invasive breast cancer tissue biopsies. Telomerase was also detected in 9 of 16 (56%) FNAs and 8 of 15 (53%) tissue biopsies from 16 fibroadenomas. Other benign proliferative lesions (n = 5) did not have detectable telomerase activity in either FNA or tissue specimens. FNA-TRAP results correlated with the gross tissue specimen TRAP results in 95% of all cases. CONCLUSION: The FNA-TRAP assay for telomerase detection is a highly sensitive and accurate method for the detection of telomerase activity in breast masses. Future application of these techniques should facilitate evaluation of telomerase as a tumor marker in the clinical management of breast and other solid malignancies.

Abdominal aortic aneurysms and malignant neoplasia: double jeopardy.

BACKGROUND: This study was performed to determine whether there is a significant association between abdominal aortic aneurysms (AAAs) and malignancy and to determine the impact of malignancy on late survival in patients with AAA. METHODS: We studied 126 men undergoing AAA repair and compared them with 99 men undergoing aortofemoral bypass (AFB) for occlusive disease and with 100 men undergoing herniorrhaphy during the same period. RESULTS: Fifty-one (40%) patients with AAA, 23 (23%) patients undergoing AFB, and 21 (21%) patients undergoing herniorrhaphy were diagnosed with cancer (p = 0.002). By life table analysis the proportion of subjects remaining cancer free at 5 years was 0.60 +/- 0.05 for AAA, 0.83 +/- 0.04 for AFB, and 0.81 +/- 0.04 for herniorrhaphy (p = 0.004). Multivariate analysis selected four independent risk factors for cancer: presence of AAA (p = 0.003, odds ratio 1.4, confidence interval [CI] 1.2 to 1.7), age (p = 0.001, odds ratio per year 1.1, CI 1.0 to 1.1), smoking (p = 0.04, odds ratio 1.5, CI 1.0 to 2.2), and hypertension (p = 0.04, odds ratio 0.73, CI 0.5 to 1.0). Cancer deaths accounted for 32% of late deaths in patients with AAA, which was not different compared with 26% of late deaths in patients undergoing AFB and 36% of late deaths in patients undergoing herniorrhaphy. Five-year cancer-free survival was 0.44 +/- 0.05 for patients with AAA, 0.64 +/- 0.05 for patients undergoing AFB, and 0.70 +/- 0.05 for patients undergoing herniorrhaphy (p < 0.001, AAA versus herniorrhaphy only). CONCLUSIONS: Cancer is more prevalent in men with AAA than in men undergoing AFB or herniorrhaphy. The presence of AAA appears to be an independent risk factor for cancer. Despite the higher cancer prevalence in patients with AAA, cardiovascular disease accounted for the largest number of late deaths in this series, minimizing differences in cancer-free survival between patients with AAA and patients undergoing AFB.

Exnuptial conception in New Zealand.

PIP: A survey was conducted in Auckland, New Zealand to obtain some information about exnuptial conception. The study subjects came from 2 main sources: antenatal clinics at the teaching obstetric hospital; and a hostel/hospital catering to unmarried mothers only. The clinic group was comprised of all unmarried primagravida attending over a 3 month period--Group 1 (n=92). Toward the end of this 3-month period it was decided to obtain contrast groups by interviewing all married primigravidae under the age of 23. About half of those interviewed in the married group had participated in "shotgun" weddings--Group 3 (n=22). Those who successfully avoided pregnancy before marriage formed Group 4 (n=23). The hostel group--Group 2 (n=22)--was necessarily somewhat different. The authorities allowed only volunteers to be interviewed, and the sample turned out to be ethnically and educationally advantaged over the clinic group. The hostel group was analyzed separately at all times. The data concerning conception was in the main retrospective and is subject to an unknown reminiscence error. Although not statistically significant, the study suggested that females who continue unmarried throughout their pregnancy are younger than those who marry because of the pregnancy (pregnant/married), and this latter group in turn are younger than those who manage to avoid pregnancy until after marriage (married/pregnant). If one excludes the highly selected hostel population, there was little difference across groups except that Catholics in general appear to be least successful in avoiding extranuptial conceptions, particularly those leading to "shotgun" weddings. The 3 clinic groups did not differ markedly in educational attainment or socioeconomic status as judged by the women's father's occupation so that advantaged status did not appear to protect against exnuptial preg nancy. Most had had some sex education, and mother and school were the primary sources of the information. Only 4 women, all in the single group, seemed not to have known clearly that unprotected sexual intercourse is the cause of pregnancy. Although over 1/3 of the women or their partners had used contraceptive methods at some time, mostly oral contraception and the condom, only 15-20% were using a method at the time of conception and unreliable methods dominated with the pill failures being due mostly to failure to take it regularly. At a conscious level at least, the prospect of pregnancy was simply not considered as a risk in the 2 extranuptially confined groups; the 2 married groups had better realization of the possibility of pregnancy.^ieng