Electrophysiological evidence that drug cues have greater salience than other affective stimuli in opiate addiction.

Previous research has demonstrated that drug cues are able to capture attentional resources in addicted populations. However, few studies have controlled for the possibility that drug users find all motivationally significant (i.e., affective) stimuli particularly salient. We examined this issue in opiate addiction, by exploring the impact of drug-related and affective stimuli on central attentional processes. Sixteen male heroin addicts (seven on opiate pharmacotherapy and nine recently detoxified subjects) and 12 matched controls were studied. Subjects were fitted with a 32-channel electrode cap and were instructed to passively view a series of neutral, affective and opiate-related images. The P300 elicited by drug-related stimuli was significantly larger than that elicited by affective and neutral stimuli in opiate users but not controls. Baseline ratings of craving were also found to predict the degree of P300 facilitation to the drug-related stimuli in the addicted group. Further, the opiate group demonstrated an absence of the typical enhancement of ERP responses to non-drug affective stimuli. These results suggest that opiate addicts demonstrate greater cortical processing of drug cues than other types of affective stimuli. Further research is required to assess whether addiction is specifically associated with reduced sensitivity to natural rewards, aversive stimuli or affective cues in general.

Attentional bias for drug cues in opiate dependence.

BACKGROUND: In a number of theories of compulsive drug use conditioned responses to stimuli associated with drug taking play a pivotal role. For example, according to incentive-sensitization theory (Robinson & Berridge, 1993), drug-related stimuli selectively capture attention, and the neural mechanisms underlying this attentional bias play a key role in the development and maintenance of drug dependence, and in relapse. However, there has been little work that assesses attentional biases in addiction. METHODS: We used a pictorial probe detection task to investigate whether there is an attentional bias to stimuli associated with drug use in opiate dependence. Stimuli presented included pairs of drug-related and matched neutral pictures. Methadone-maintained opiate addicts (N = 16) were compared with age-matched controls (N = 16). RESULTS: A mixed design analysis of variance of response times to probes revealed a significant three-way interaction of group x drug picture location x probe location. Opiate addicts had relatively faster reaction times to probes that replaced drug pictures rather than neutral pictures, consistent with the predicted attentional bias to drug-related stimuli. CONCLUSIONS: These results support the idea that an attentional bias for drug-related stimuli occurs in opiate dependence. This is consistent with the concept of a central role for such salient stimuli in compulsive drug use.

The case for completing the lymphadenectomy when positive lymph nodes are found during radical hysterectomy for cervical carcinoma.

BACKGROUND: In the present study we report on the results of a retrospective study on the effect on survival of the pelvic lymphadenectomy in a group of 294 patients with stage Ia2-IIa cervical carcinoma treated by radical hysterectomy from 1984 through 1996 at the Leiden University Medical Center. METHODS: Lymphadenectomy was called 'complete' when lymph node bearing tissue had been removed from 5 or 6 lymph node stations and 'not-complete' when this was the case in 1-4 stations. RESULTS: A radical hysterectomy was carried out in 294 patients. In 63 patients positive lymph nodes were found. Patients with positive nodes showed poorer 5 year survival: 64.5% compared to 90% in patients with negative nodes. In the univariate analysis the following factors were found to affect the presence of node metastases in a statistically significant way: age, tumor size, depth of infiltration, vaso-invasion, surgical margins, parametrial infiltration, stage and place of referral. In 63 patients with positive nodes, a complete lymphadenectomy was carried out in 23 patients, and in 40 patients the procedure was incomplete. All 63 patients were treated by adjuvant radiation therapy; those with complete lymphadenectomy had significantly less recurrences (25%) compared to those with incomplete lymphadenectomy (56%): the relative risk (RR) was 2.9 (95% ci: 1.3-6.7), p=0.012. After adjustment for other prognostic factors including tumor size, depth of infiltration and parametrial involvement, the complete lymphadenectomy showed an independent effect on disease free survival: RR= 3.2 (95% ci: 1.3-7.7), p=0.011. Prognostic factors were not significantly different for patients with complete or incomplete lymphadenectomy. CONCLUSIONS: From the results of this study, although retrospective and non randomized, it can be concluded that to complete removal of lymph nodes in combination with radical hysterectomy seems to have a beneficial effect on prognosis in case of positive nodes. The policy of aborting the procedure when lymph node metastases are found in frozen section should be questioned.

The long learning curve of gynaecological cancer surgery: an argument for centralisation.

OBJECTIVE: To study the development of surgical performance of an unchanging surgical team over 13 years. DESIGN: Prospective, observational study. SETTING: A university hospital, The Netherlands. PARTICIPANTS: Three hundred and eight women who underwent surgical treatment for early cervical cancer. INTERVENTIONS: Radical hysterectomy and pelvic lymphadenectomy between 1 January 1984 and 31 December 1996. RESULTS: The surgical procedure and indication for treatment remained unchanged during the study period. This applied also to the surgical team. The women's age increased significantly during the study years, as was the case with the number of nodes removed. The depth of infiltration by the tumour increased steadily throughout the study, but this failed to reach statistical significance. The distribution of FIGO stages, percentage of positive lymph nodes, radicality of the surgical margins and post-operative morbidity remained the same. Overall, the five year survival rate was 83%; for women with negative nodes 91%, and for women with positive nodes 53%. Survival tended to improve during the course of the study, but this was not statistically significant. Blood loss during surgery decreased consistently during the whole study period, from a mean of 1,515 mL at the beginning of the study to a mean of 1,071 mL at the end (P < 0.0001). The operating time also diminished significantly by 8 minutes per year (P < 0.0001). In 1985 the average operating time was 270 minutes, compared with 187 minutes in 1996. CONCLUSIONS: These findings indicate that it takes a long time to acquire skill in the surgical treatment of early cervical cancer. Centralisation of relatively infrequent operations for cancer should be encouraged.

Different profiles of allelic losses in cervical carcinoma cases in Surinam and The Netherlands.

BACKGROUND: Cervical carcinoma is the second most common malignancy among women worldwide. The highest incidence rates are observed in developing countries. The increased susceptibility to cervical carcinoma in high incidence populations may result from several factors including human papillomavirus exposure and both inherited and acquired genetic traits. Using comparative molecular analysis of cervical carcinomas from Surinam, a high incidence area, and the Netherlands, a low incidence area, distinct molecular genetic profiles were studied in two populations with contrasting risk for the disease. METHODS: In the two populations, the authors compared allelic loss as a marker for the involvement of putative tumor suppressor genes in 40 and 67 carcinoma specimens from Surinam and the Netherlands, respectively. Loss of heterozygosity (LOH) analysis was performed using polymorphic microsatellite markers at sites of known tumor suppressor genes (17p [p53], 13q [Rb, BRCA2], 16q [E-cadherin], and 17q [BRCA1]) and at chromosomes 3p, 6p, 6q, and 11q, which frequently are lost in cervical carcinoma. RESULTS: Remarkable differences in LOH were found between both populations. The most prominent observation was the extremely high frequency of LOH, up to 72%, in the region of the major histocompatibility complex on chromosome 6p in specimens from Surinam. In the group of specimens from the Netherlands, only 45% of LOH was observed at this locus. In addition, LOH was detected significantly more frequently at 6q and 13q in the cases from Surinam whereas LOH was found more frequently at 17p in cases from the Netherlands. CONCLUSIONS: The results of the current study show that heterogeneity exists in tumor-associated somatic genetic alterations between these two populations that may be indicative of the existence of multiple genetic pathways in cervical tumorigenesis.

Cervical carcinoma: do fast SE and fat suppression techniques improve MR tumor staging at 0.5 T?

PURPOSE: Our goal was to compare fast SE (FSE) with T2-weighted conventional SE (CSE) MRI of cervical carcinoma and to evaluate the potential advantage of fat suppression technique. METHODS: We compared the tissue contrasts between cervical carcinoma and the surrounding tissues in 24 patients. The following MR sequences were obtained at 0.5 T: T1-weighted CSE (450/20 ms), T2-weighted CSE (2,500/45, 90), and T2-weighted FSE (4,800/120), the latter with and without fat suppression using fat-selective prepulses. RESULTS: T2-weighted FSE MRI provided significantly better contrasts between tumor and normal cervical stroma (p < 0.001) and between tumor and rectum wall (p < 0.05) than T2-weighted CSE MRI. T1-weighted SE MRI gave the highest tissue contrast between tumor and parametrial tissue (p < 0.001). Fat suppression did not further improve tissue contrasts. CONCLUSION: MR staging of cervical carcinoma is best done with the combination of T1-weighted SE and T2-weighted FSE images, without additional fat suppression.

Cervical carcinoma in Surinam. Incidence and staging of cervical carcinoma between 1989 and 1994.

BACKGROUND: Epidemiologic data show a high incidence of cervical cancer throughout the world and a high mortality, particularly in developing countries. The aim of this study was to describe the incidence and stages of cervical carcinoma in Surinam. Results were compared with data from The Netherlands (used as representative of western European countries) because of a medical and patient exchange program. METHODS: Data for Surinamese patients analyzed in this study were based on the files from the Department of Pathology at the University of Surinam from 1989 through 1994. Cumulative and incidence rates standardized to the World Standard Population were calculated and compared with rates in other South American countries and in The Netherlands. Age distribution and stage of disease (according to the International Federation of Gynecology and Obstetrics) among Surinamese and Dutch women were compared. Furthermore, differences in incidence rates among the multiple ethnicities of the Surinamese population were evaluated. RESULTS: Age standardized incidence rates for Surinam and The Netherlands were 26.7 and 6.2 per 100,000 women, respectively. The cumulative rate up to age 74 years was 2.9 in Surinam versus 0.6 in The Netherlands. Incidence in Surinam rose sharply with age. More than 40% of the Surinamese women presented with Stage IIB disease or higher compared with 12% in The Netherlands. In Surinam, low stage of disease was highest in the youngest group (48%), whereas only 18% of women 65 years or older presented with Stage I disease. Incidence rates in Surinam varied by ethnic group. Amerindians and Javanese were more likely to develop cervical cancer than were other ethnicities. CONCLUSIONS: Cervical carcinoma in Surinam was characterized by high incidence rates and relatively advanced stage of disease at presentation. Moreover, incidence was not equally distributed among the different ethnic groups. This may reflect a greater exposure to risk factors and differential access to diagnostic and treatment services.