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OBJECTIVE: To identify the factors that affect the disease-free survival (DFS) of rectal cancer patients. METHOD: Patients from an IRB approved rectal cancer database were reviewed (1990-2000). All patients underwent either abdominoperineal resection or low anterior resection using total mesorectal excision with curative intent. Univariate and multivariate analyses were performed to analyse the factors that influenced DFS. RESULTS: A total of 304 patients were reviewed (mean age 64, 52% male). Seventy-seven per cent of patients received neoadjuvant therapy (28.6% short-course radiation therapy (RT), 35.5% long-course RT, 12.5% chemo-RT). The radial margin was involved with tumour in 5.2% of patients (final pathology). The overall survival rate was 85.2% with a mean follow-up time of 33 +/- 26 months. The mean time to death was 34.8 +/- 26.8 months. Local recurrence (+/- distant recurrence) occurred in 4%. Anastomotic leaks occurred in 3.6% of patients. Overall pathologic stage, pathologic T stage, nodal status, the use of adjuvant chemotherapy, tumour fixation, involvement of the radial margin, the presence of mucin, and lymphatic and perineural invasion (PNI) were predictors of DFS by univariate analysis. Of note, anastomotic leaks and obstructing cancers did not influence DFS. Using multivariate analysis with backward elimination, overall pathologic stage, radial margin status, adjuvant chemotherapy, and PNI predicted the DFS. CONCLUSION: Major predictors of DFS in rectal cancer are the overall pathologic stage, adjuvant chemotherapy, radial margin status and PNI. Radial margin status may be a marker of tumour aggressiveness and should be considered in deciding on adjuvant chemotherapy.

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Scanning electron microscopes (SEMs) are the most extensively used tools for dimensional metrology and defect inspection for integrated circuit technologies with 180 nm and smaller features. Currently, almost all SEMs are designed to collect as many secondary and backscattered electrons as possible. These signals are mainly secondary electrons (SE1, SE2, and SE3) detected with various detection schemes. To facilitate the electron collection, very strong electric and magnetic fields are applied not just in the path of the primary electron beam but to the emerging electrons as well. These new systems provide strong signals, thus better signal-to-noise ratio, and thus resulting in higher throughput than older ones. On the other hand, the use of secondary electrons means that measurement results are much more prone to the detrimental effects of electron beam interactions, sample charging, and sample contamination than measurements with higher-energy backscattered electrons. The use of backscattered electrons, especially low-loss electrons (LLE), can provide better surface sensitivity, edge accuracy, and repeatability, possibly at the expense of measurement speed. This two-part study investigates the benefits and drawbacks of low-loss electron imaging to edge characterization for dimensional metrology and enhancement of fine surface features done through filtration or separation of the generated LLE signal and the use of energy-dependent signals. Part 1 reviews and illustrates the potential for accurate dimensional measurements at low accelerating voltage by LLE, and Part 2 will concentrate on the enhancement of surface features in chemical-mechanically planarized specimens with the use of a novel LLE detector.

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OBJECTIVE: To investigate the expression of interferon regulatory factors 1 and 2 (IRF-1 and IRF-2) in human breast cancer. SUMMARY BACKGROUND DATA: Interferon regulatory factors 1 and 2 are transcription factors in the interferon gamma signal transduction pathway. IRF-1 acts as the effector arm of the interferon gamma response; IRF-2 binds to the same DNA consensus sequence and opposes IRF-1 activity. Previous work in the authors' laboratory has shown the tumor suppressor activity of IRF-1 expression and the oncogenic effect of IRF-2 in human and murine tumor models, including human breast cancer cell lines. The authors' hypothesis is that this pathway is involved in human tumor development, and alterations in the expression of IRF-1 and IRF-2 may occur in breast cancer tissue compared with normal breast tissue, and between more and less differentiated breast cancers. METHODS: Formalin-fixed paraffin-embedded human archival tissue specimens were obtained from 33 patients with pure ductal carcinoma in situ (DCIS) and 49 women with invasive ductal cancer. Adjacent areas of normal breast tissue were assayed in 31 women. These specimens were stained with polyclonal IRF-1 and IRF-2 antibodies using an avidin-biotin-peroxidase complex technique after epitope retrieval. RESULTS: Most normal breast tissue showed expression of IRF-1 and no expression of IRF-2 by immunohistochemistry. High-grade DCIS or node-positive invasive ductal cancers were less likely to express the tumor suppressor IRF-1 than normal tissue. More strikingly, high-grade DCIS and invasive ductal cancers were much more likely to express the oncogenic IRF-2 protein than was normal tissue. CONCLUSIONS: Expression of IRF-1 and IRF-2 is altered in human breast cancer compared with normal adjacent tissue. The loss of IRF-1 expression is consistent with tumor suppressor loss and the development of IRF-2 expression with oncogenic activation. These data support the hypothesis that this pathway is involved in human breast oncogenesis, which warrants further investigation regarding prognostic and therapeutic implications.

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The goals of operative treatment of primary hyperparathyroidism are (1) cure; (2) minimal invasion; and (3) cost-effectiveness. The optimal strategy is controversial. Retrospective review of was undertaken 66 previously unoperated patients having minimal-incision, full-neck exploration by one surgeon over 29 months. A group of 51 women and 15 men had open full neck exploration under general anesthesia through a small (25-40 mm) incision using specifically selected instruments; patients remained hospitalized overnight. Preoperative sestamibi scans were obtained before referral for 17 patients: 11 had localized disease, and 6 did not (65% sensitivity). Four parathyroid glands were identified in 98% of patients; intraoperative frozen section was used selectively on a median of one gland per patient. About 76% of patients had single-gland disease, 6% had two-gland disease, and 18% had four-gland hyperplasia. One patient had four normal cervical parathyroid glands and an aortopulmonary window parathyroid adenoma resected at thoracotomy 1 week later; preoperative sestamibi scans failed to localize his disease. There were no nerve injuries and a 98% cure rate after initial cervical exploration. Excluding the cost of the sestamibi scans, there was no difference between those who had preoperative localization and those who did not; 60% of hospital costs were operating room time-related. Minimal-incision parathyroidectomy is effective for curing hyperparathyroidism and has excellent cosmetic results with negligible scar. Preoperative sestamibi scanning had no impact on cure or treatment costs. Strategies to improve cost-effectiveness must address the substantial costs of anesthesia and operating room services.

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BACKGROUND: Interferon regulatory factor (IRF)-1 and IRF-2 are nuclear transcription factors that respond to interferon-gamma. IRF-1 acts as the effector arm of the interferon-gamma response in tumor cells, whereas IRF-2 binds to the same DNA consensus sequence and opposes IRF-1 activity. This effect is intact in human and murine tumor models, including melanomas; previous work in our laboratory demonstrated the tumor-suppressing activity of IRF-1 expression in in vivo models and the opposing effect of IRF-2. The expression of IRF-1 and -2 in human solid tumors had not been previously investigated. METHODS: Formalin-fixed, paraffin-embedded, archival tissue specimens from 38 human melanomas were obtained and stained with polyclonal anti-IRF-1 and anti-IRF-2 antibodies, using an avidin-biotin-peroxidase complex technique with epitope retrieval. RESULTS: Twenty-nine specimens showed granular cytoplasmic staining with the anti-IRF-1 or anti-IRF-2 antibodies. IRF-1 staining was correlated with less advanced disease. Superficial spreading and in situ lesions exhibited more frequent IRF-1 staining, compared with nodular or metastatic disease. Only more advanced lesions showed neither IRF-1 nor IRF-2 staining. CONCLUSIONS: Immunohistochemical staining of archival tissue identified IRF-1 and -2 in human melanomas; this had not been previously demonstrated. IRF-1 staining was correlated with the morphologic characteristics of less advanced disease. Tumor-suppressing effects of IRF-1 may account for the less aggressive biologic features of IRF-1-expressing melanomas, as we would predict from the experimental data.

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We investigated the role of interferon (IFN) regulatory factor-2 (IRF-2) as an oncoprotein in vivo, opposing endogenous IFN-gamma suppression of tumor growth. Using syngeneic IFN-gamma knockout mice, we show that endogenous IFN-gamma slows growth of the mouse melanoma cell line B16-F10 in immunocompetent mice, suggesting that tumor cell resistance to IFN-gamma may lead to greater tumorigenicity. IRF-2 is a nuclear transcription factor induced by IFN-gamma that represses numerous IFN-inducible genes, including genes that regulate cell growth, in opposition to the transcriptional activator IRF-1. B16-F10 has a marked growth inhibitory response to IFN-gamma in vitro and has very little IRF-2 induction compared with other murine tumor cell lines. We engineered B16-F10 cells to stably overexpress murine IRF-2. In vitro, these transfected cells showed a marked resistance to the growth-inhibitory effect of IFN-gamma. In normal mice the IRF-2-transfected cells grew much faster than control tumors. In syngeneic IFN-gamma knockout mice, control cells grew at a rate similar to that of IRF-2-transfected cells, implicating resistance to endogenous IFN-gamma as playing the major role in enhanced growth of IRF-2-transfected tumors in intact mice. These experiments demonstrate that (1) IRF-2 enhances B16 melanoma growth and increases resistance to IFN-gamma in vitro, and (2) IRF-2 opposes the growth suppression mediated by endogenous IFN-gamma in vivo.

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BACKGROUND: Islet cell tumor (ICT) metastasis is one of the potentially lethal outcomes of multiple endocrine neoplasia type 1 (MEN 1). Management of ICT in patients with MEN 1 is controversial; some advocate resection based on biochemical evidence of progression, whereas others use tumor size to predict the risk of metastasis and the need for resection. This study correlates the size of primary ICT with the presence of metastases. METHODS: Forty-eight patients with MEN 1 with ICT, from 34 kindreds followed up in our multiple endocrine neoplasia program, were evaluated; 43 of the 48 have been explored for ICT. Metastases to the lymph nodes and liver were documented. RESULTS: Thirty-three percent of patients with pancreatic tumors less than 1 cm in greatest diameter had metastatic disease at surgery and in follow-up, whereas 34.8% of patients with tumors greater than 2 cm in diameter had metastases to lymph nodes or liver. The 2 patients with liver metastases each had primary tumors greater than 2 cm. Follow-up revealed subsequent metastasis in 1 patient. CONCLUSIONS: The size of primary tumors in MEN 1 does not correlate with metastatic potential. This is not a good criterion for exploration. Continued follow-up of these patients will be necessary to define the effect of operation on the course of ICT in MEN 1.

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The production of cytokines has been associated with the biology of tooth movement in animal populations. The purpose of this study was to measure tumor necrosis factor-alpha (TNF) directly in the human gingival sulcus before and after the application of an orthodontic force. To recover TNF from the sulcus, paramagnetic beads, coated with monoclonal antibodies for TNF, were introduced into the gingival sulcus of 50 teeth undergoing orthodontic tooth movement (by two force systems) in 20 patients. Retrieval was performed by a permanent magnetic device designed to fit the periodontal sulcus. The samples were taken before force application (controls), and at a fixed time after force application. The amount of immunoabsorbed TNF was quantified with an immunochemical assay. There was a greater than twofold increase in TNF recoverable from the gingival sulcus after application of orthodontic forces (mean of 12.9 ng vs 30.5 ng). A Student's t test for paired samples demonstrated statistical significance at p < 0.01. We conclude that the quantity of paradental TNF, found in human gingival sulcus, is elevated during tooth movement. The source may be from the adjacent gingiva, but more likely the compressed periodontal ligament and the resorbing bone adjacent to the root surface.

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In this report on the therapeutic results in patients with moderate and severe endometriosis treated by operative laser laparoscopy, we also present a comparative analysis of cost and duration of hospitalization and of convalescence in comparable patients treated by laparoscopy versus laparotomy. Sixty patients treated by the same surgeon with operative laser laparoscopy were followed for a period of at least one year to calculate cumulative pregnancy rates, monthly fecundity rates, and monthly probability of pregnancy. The mean duration of hospitalization and incapacitation as well as physician and hospital costs incurred by the laparoscopy treated patients were compared with those incurred by 60 patients with similar degrees of endometriosis but treated by microsurgery at laparotomy. In the laparoscopy group, 36 patients had stage III and 24, stage IV endometriosis. Monthly fecundity rates (6.7%), monthly probability of pregnancy (12.6%) and cumulative pregnancy rates (70.5%) did not differ between patients with stage III and IV disease. The total number of hospital days required by the 60 laparoscopy patients was 72 versus 258 for the laparotomy patients (P less than .001). The total number of days' incapacitation for laparoscopy patients was 216 versus 1,284 for the laparotomy group (P less than .001). The total cost of medical care was $223,260 for the laparoscopy group and $424,500 for the laparotomy group (P less than .001). Our results validate the therapeutic efficacy of operative laparoscopy in the treatment of moderate and severe endometriosis and confirm the substantial economic and social benefits of laparoscopy surgery over laparotomy.

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This paper reports the findings of a nonparticipant observational study of a "gang" of late-adolescent, middle-class youths in a Southern California beach community over an 11-year period. The significance of family background, interpersonal relationships in the home, and socialization processes were explored in relation to such factors as the use of drugs, sexual experiences, and other "deviant" behavior. The author also interviewed and interacted with other youths in the community of the same age range and similar socioeconomic background who were not members of the "gang." Case narration is supplemented by demographic data. The "gang" approximated Lewis Yablonsky's description of a "near-group." The youths were from above-average economic background, but 21 of the 23 "members" were from broken homes, frequently with multiple divorces and remarriages. The youths expressed attitudes of disgust with adult society and doubted the concern of their parents, particularly fathers and stepfathers, for their well-being. The youths sought out both "mother-figures" on whom they could be dependent for financial support as well as "father-figures" who would teach them to become independent. These "gang members" had erratic school and employment patterns. The types of drugs used by "nongang" youths, who had more stable family backgrounds, did not differ appreciably from those used by the "gang." The former group was distinguished in their use of drugs and alcohol by lower frequency and less tendency to use drugs in order to reduce anxiety or to facilitate their relations with the opposite sex.

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In a longitudinal study, the researcher utilized both nonparticipant observational data and quantified interview data to analyze the correspondence between attitudes of the "youth subculture" theories and overt behavioral patterns. The data were collected in an upper-middle-class, predominantly white, Southern California beach community. An initial cohort of 23 males was followed from 1971 through 1981. A separate sample of males, aged 14 to 21, was observed from the summer of 1975 through December, 1981. All subjects were interviewed at the close of the project. The interview schedule included items regarding drug use, sexual activity, employment, and school patterns as well as attitudes reflective of pleasure-seeking and deferred gratification. Subjects are classified according to degree of drug use and analyzed according to several other variables. It is found that the older cohort, analyzed qualitatively, fit the theoretical implications of the model involved both as to attitudes and behavior. However, with the end of the Vietnam War and an increased influence of the "Jesus Movement," this group did become slightly more conservative in attitudes regarding politics and religion. The heavier drug users in the later sample are similar in behavior patterns to the older cohort. However, the more recent group of heavy users express extremely conservative views regarding morality, religion and politics. Specific attitudinal measures indicate no relationship between degree of drug use and youth subculture attitudes. The attitudes measured regarding pursuit of pleasure and immediate gratification did not appear to be consistent with actual overt behavior.

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The development of a "nonparticipant observer" role in research on youthful drug use is described. The role proved valuable in gathering the kinds of information considered necessary by Becker (1955) and others for building theories of deviant behavior. The researcher had some access to the group prior to the project, and various interventionist actions on behalf of the youth helped increase the level of acceptance. The resulting rapport and confidence enhanced the research role, making possible penetration of the protective "fronts" of the deviant subjects. While dual functions of researcher and interventionist complemented each other, they presented personal role conflicts that had to be resolved. By assuming the role of nonparticipant in the deviant behavior itself, the researcher could avoid many moral, legal and ethical dilemmas without betraying either his own values or his objectivity. The author believes it is incumbent upon such a researcher to describe the uniqueness of his role so that his objective findings may be properly appraised in light of his subjective involvement.

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