Outcome of treated anogenital intraepithelial neoplasia among human immunodeficiency virus-infected women

OBJECTIVE: To determine characteristics and clinical course of high-grade anogenital intraepithelial neoplasia (AIN) in human immunodeficiency virus (HIV)-infected women. STUDY DESIGN: HIV-positive women with biopsy-proven high-grade (II and III) vulvar (VIN), vaginal (VAIN) or perianal intraepithelial neoplasia (PAIN) were identified in the electronic databases of 2 colposcopy clinics. RESULTS: A total of 31 patients were identified from 1992 to 2007, of which 30 had a mean follow-up of 47.7 months (SD = 46.0; range, 2.6-166.2). Of the patients, 77.4% had VIN, 12.9% VAIN and 9.7% PAIN at first diagnosis. Age at diagnosis of IN was 36.2 years (SD +/- 5.2; range, 23.5-47.0). Ninety percent of patients received antiretroviral therapy at first diagnosis of IN; 65% (13 of 20) of patients with a follow-up of > 2 years required a second treatment, and 2 developed invasive vulvar cancer (10%). CONCLUSION: AIN among HIV-positive women shows a high relapse rate despite treatment modality used and a substantial invasive potential.

[HPV type 16-associated anal intraepithelial neoplasia (AIN)]

A 25-year-old woman had suffered from a perianal ulcer for approximately 1 year. Topical and systemic treatments had been unsuccessful. Employing virologic and histologic techniques, we confirmed the diagnosis of an intraepithelial neoplasia. Anal intraepithelial neoplasia (AIN) is induced by carcinogenic human papillomaviruses. It can occur anywhere in the anogenital area. Because of its frequency, AIN is a crucial differential diagnosis for lesions of the anogenital area region failing to respond to standard therapies.

Gingival labial recessions in orthodontically treated and untreated individuals: a case - control study

OBJECTIVES To evaluate the long-term development of labial gingival recessions during orthodontic treatment and retention phase. MATERIAL AND METHODS In this retrospective case-control study, the presence of gingival recession was scored (Yes or No) on plaster models of 100 orthodontic patients (cases) and 120 controls at the age of 12 (T12 ), 15 (T15 ), 18 (T18 ), and 21 (T21 ) years. In the treated group, T12 reflected the start of orthodontic treatment and T15 - the end of active treatment and the start of retention phase with bonded retainers. Independent t-tests, Fisher's exact tests and a fitted two-part "hurdle" model were used to identify the effect of orthodontic treatment/retention on recessions. RESULTS The proportion of subjects with recessions was consistently higher in cases than controls. Overall, the odds ratio for orthodontic patients as compared with controls to have recessions is 4.48 (p < 0.001; 95% CI: 2.61-7.70). CONCLUSIONS Within the limits of the present research design, orthodontic treatment and/or the retention phase may be risk factors for the development of labial gingival recessions. In orthodontically treated subjects, mandibular incisors seem to be the most vulnerable to the development of gingival recessions.

Development of labial gingival recessions in orthodontically treated patients

INTRODUCTION Our aim was to assess the prevalence of gingival recessions in patients before, immediately after, and 2 and 5 years after orthodontic treatment. METHODS Labial gingival recessions in all teeth were scored (yes or no) by 2 raters on initial, end-of-treatment, and posttreatment (2 and 5 years) plaster models of 302 orthodontic patients (38.7% male; 61.3% female) selected from a posttreatment archive. Their mean ages were 13.6 years (SD, 3.6; range, 9.5-32.7 years) at the initial assessment, 16.2 years (SD, 3.5; range, 11.7-35.1 years) at the end of treatment, 18.6 years (SD, 3.6; range, 13.7-37.2 years) at 2 years posttreatment, and 21.6 (SD, 3.5; range, 16.6-40.2 years) at 5 years posttreatment. A recession was noted (scored "yes") if the labial cementoenamel junction was exposed. All patients had a fixed retainer bonded to either the mandibular canines only (type I) or all 6 mandibular front teeth (type II). RESULTS There was a continuous increase in gingival recessions after treatment from 7% at end of treatment to 20% at 2 years posttreatment and to 38% at 5 years posttreatment. Patients less than 16 years of age at the end of treatment were less likely to develop recessions than patients more than 16 years at the end of treatment (P = 0.013). The prevalence of recessions was not associated with sex (P = 0.462) or extraction treatment (P = 0.32). The type of fixed retainer did not influence the development of recessions in the mandibular front region (P = 0.231). CONCLUSIONS The prevalence of gingival recessions steadily increases after orthodontic treatment. The recessions are more prevalent in older than in younger patients. No variable, except for age at the end of treatment, seems to be associated with the development of gingival recessions.

Between anxiety and hope: the experiences of women with vulval intraepithelial neoplasia during their illness trajectory - a qualitative approach

The vulvar intraepithelial neoplasia (VIN) is a rare chronic skin condition that may progress to an invasive carcinoma of the vulva. Major issues affecting women's health were occurring symptoms, negative influences on sexuality, uncertainty concerning the illness progression and changes in the body image. Despite this, there is little known about the lived experiences of the illness trajectory. Therefore, the aim of this study was to describe the experiences of women with VIN during the illness trajectory. In a secondary data analysis of the foregoing qualitative study we analysed eight narrative interviews with women with VIN by using thematic analysis in combination with critical hermeneutics. Central for these women during their course of illness was a sense of "Hope and Fear". This constitutive pattern reflects the fear of recurrence but also the trust in healing. The eight narratives showed women's experiences during their course of illness occurred in five phases: "there is something unknown"; "one knows, what IT is"; "IT is treated and should heal"; "IT has effects on daily life"; "meanwhile it works". Women's experiences were particularly influenced by the feeling of "embarrassment" and by "dealing with professionals". Current care seems to lack adequate support for women with VIN to manage these phases. We suggest, based on our study and the international literature, that new models of counselling and providing information need to be developed and evaluated.

Disease progression and recurrence in women treated for vulvovaginal intraepithelial neoplasia

OBJECTIVE The malignant potential of intraepithelial neoplasia of the vulva and vagina after treatment is not well defined. Our objective was to examine risk factors for recurrence and invasive disease. METHODS Four hundred sixty-four women with biopsy proven high-grade intraepithelial neoplasia of the vulva and vagina were identified in the electronic databases of four colposcopy clinics. Inclusion criteria were a follow-up of more than one year, no history of invasive cancer and no invasive cancer within the first year after initial treatment. We investigated the potential factors associated with recurrence and progression using a logistic regression analysis to estimate odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS Of the 411 eligible patients, 123 patients (29.9%) recurred later than one year after initial treatment and 24 patients (5.8%) progressed to invasive disease. According to multivariate analyses, the risk factors associated with recurrence were multifocality (OR, 3.33; 95% CI, 2.02 to 5.51), immunosuppression (OR, 2.51; 95% CI, 1.09 to 5.81), excision as initial treatment (vs. laser evaporation; OR, 1.79; 95% CI, 1.11 to 2.91) and smoking (OR, 1.61; 95% CI, 1.02 to 2.55). Risk factors for progression to invasive disease were immunosuppression (OR, 4.00; 95% CI, 1.30 to 12.25), multifocality (OR, 3.05; 95% CI, 1.25 to 7.43) and smoking (OR, 2.97; 95% CI, 1.16 to 7.60), but not treatment modality. CONCLUSION Laser evaporation combined with extensive biopsy is at least as efficacious as initial treatment of intraepithelial neoplasia with excision. Smoking is a risk factor for both recurrence and progression to invasive disease. Hence, smoking cessation should be advised and maintaining a long follow-up period due to late relapses is necessary.

A patient-reported outcome measure to identify occurrence and distress of post-surgery symptoms of WOMen with vulvAr Neoplasia (WOMAN-PRO) - a cross sectional study.

OBJECTIVE The aim of the study was to describe the (a) symptom experience of women with vulvar intraepithelial neoplasia and vulvar cancer (vulvar neoplasia) during the first week after hospital discharge, and (b) associations between age, type of disease, stage of disease, the extent of surgical treatment and symptom experience. METHODS This cross-sectional study was conducted in eight hospitals in Germany and Switzerland (Clinical Trial ID: NCT01300663). Symptom experience after surgical treatment in women with vulvar neoplasia was measured with our newly developed WOMAN-PRO instrument. Outpatients (n=65) rated 31 items. We used descriptive statistics and regression analysis. RESULTS The average number of symptoms reported per patient was 20.2 (SD 5.77) with a range of 5 to 31 symptoms. The three most prevalent wound-related symptoms were 'swelling' (n=56), 'drainage' (n=54) and 'pain' (n=52). The three most prevalent difficulties in daily life were 'sitting' (n=63), 'wearing clothes' (n=56) and 'carrying out my daily activities' (n=51). 'Tiredness' (n=62), 'insecurity' (n=54) and 'feeling that my body has changed' (n=50) were the three most prevalent psychosocial symptoms/issues. The most distressing symptoms were 'sitting' (Mean 2.03, SD 0.88), 'open spot (e.g. opening of skin or suture)' (Mean 1.91, SD 0.93), and 'carrying out my daily activities' (Mean 1.86, SD 0.87), which were on average reported as 'quite a bit' distressing. Negative associations were found between psychosocial symptom experience and age. CONCLUSIONS WOMAN-PRO data showed a high symptom prevalence and distress, call for a comprehensive symptom assessment, and may allow identification of relevant areas in symptom management.

Hyperplasia to neoplasia sequence of duodenal and pancreatic neuroendocrine diseases and pseudohyperplasia of the PP-cells in the pancreas.

Hyperplastic changes of the neuroendocrine cell system may have the potential to evolve into neoplastic diseases. This is particularly the case in the setting of genetically determined and hereditary neuroendocrine tumor syndromes such as MEN1. The review discusses the MEN1-associated hyperplasia-neoplasia sequence in the development of gastrinomas in the duodenum and glucagon-producing tumors in the pancreas. It also presents other newly described diseases (e.g., glucagon cell adenomatosis and insulinomatosis) in which the tumors are (or most likely) also preceded by islet cell hyperplasia. Finally, the pseudohyperplasia of PP-rich islets in the pancreatic head is defined as a physiologic condition clearly differing from other hyperplastic-neoplastic neuroendocrine diseases.

Immunodeficiency and the risk of cervical intra-epithelial neoplasia 2/3 and cervical cancer: A nested case-control study in the Swiss HIV Cohort Study.

HIV-infected women are at increased risk of cervical intra-epithelial neoplasia (CIN) and invasive cervical cancer (ICC), but it has been difficult to disentangle the influences of heavy exposure to HPV infection, inadequate screening, and immunodeficiency. A case-control study including 364 CIN2/3 and 20 ICC cases matched to 1,147 controls was nested in the Swiss HIV Cohort Study (1985-2013). CIN2/3 risk was significantly associated with low CD4+ cell counts, whether measured as nadir (odds ratio (OR) per 100-cell/μL decrease=1.15, 95% CI: 1.08, 1.22), or at CIN2/3 diagnosis (1.10, 95% CI: 1.04, 1.16). An association was evident even for nadir CD4+ 200-349 versus ≥350 cells/μL (OR=1.57, 95% CI: 1.09, 2.25). After adjustment for nadir CD4+, a protective effect of >2-year cART use was seen against CIN2/3 (OR versus never cART use=0.64, 95% CI: 0.42, 0.98). Despite low study power, similar associations were seen for ICC, notably with nadir CD4+ (OR for 50 versus >350 cells/μL= 11.10, 95% CI: 1.24, 100). HPV16-L1 antibodies were significantly associated with CIN2/3, but HPV16-E6 antibodies were nearly exclusively detected in ICC. In conclusion, worsening immunodeficiency, even at only moderately decreased CD4+ cell counts (200-349 CD4+ cells/μL), is a significant risk factor for CIN2/3 and cervical cancer. This article is protected by copyright. All rights reserved.

Gingival labial recessions and the post-treatment proclination of mandibular incisors

INTRODUCTION A prerequisite for development of gingival recession is the presence of alveolar bone dehiscence. Proclination of mandibular incisors can result in thinning of the alveolus and dehiscence formation. OBJECTIVE To assess an association between proclination of mandibular incisor and development of gingival recession. METHODS One hundred and seventeen subjects who met the following inclusion criteria were selected: 1. age 11-14 years at start of orthodontic treatment (TS), 2. bonded retainer placed immediately after treatment (T0), 3. dental casts and lateral cephalograms available pre-treatment (TS), post-treatment (T0), and 5 years post-treatment (T5), and 4. post-treatment (T0) lower incisor inclination (Inc_Incl) <95° or >100.5°. Two groups were formed: non-proclined (N = 57; mean Inc_Incl = 90.8°) and proclined (N = 60; mean Inc_Incl = 105.2°). Clinical crown heights of mandibular incisors and the presence of gingival recession sites in this region were assessed on plaster models. Fisher's exact tests, t-tests, and regression models were computed for analysis of inter-group differences. RESULTS The mean increase of clinical crown heights (from T0 to T5) of mandibular incisors ranged from 0.75 to 0.83mm in the non-proclined and proclined groups, respectively (P = 0.273). At T5, gingival recession sites were present in 12.3% and 11.7% patients from the non-proclined and proclined groups, respectively. The difference was also not significant (P = 0.851). CONCLUSIONS The proclination of mandibular incisors did not increase a risk of development of gingival recession during five-year observation in comparison non-proclined teeth.

Cigarette smoking and cervical intraepithelial neoplasia among colposcopy patients

Epidemiologic and biochemical evidence suggest that smoking is an independent risk factor for cervical neoplasia; however, only two studies have adjusted by the potential confounding effect of human papillomavirus (HPV). To determine the association between self-reported current cigarette smoking and cervical intraepithelial neoplasia (CIN), we conducted a case-control study that controlled for HPV infection and other reported risk factors. The medical records of all new patients referred to the University of Texas M. D. Anderson Cancer Center (UTMDACC) Colposcopy Clinic were reviewed. The study population (n = 564) consisted of all white, black, and Hispanic non-pregnant women who were residents of Texas, and had no history of treatment for cervical neoplasia. Cases (n = 313) included women diagnosed at the UTMDACC with CIN; while controls (n = 251) included those patients diagnosed at the colposcopy clinic as non-CIN (negative 47%, inflammation or atypia 25%, and koilocytosis 27%). Diagnosis was based on a colposcopically directed biopsy in 95% of the subjects, and all subjects were tested for HPV by dot blot hybridization. The crude odds ratio for cigarette smoking and CIN was 1.37 (95% CI 0.97-1.95); however, after adjusting for HPV, age, education, race, number of sexual partners, and age at first sexual intercourse, the odds ratio decreased to 0.91 (95% CI 0.61-1.41). A higher crude odds ratio was observed with CIN 3 (OR = 1.75, 95% CI 1.08-2.83), but this effect also disappeared after adjustment (OR = 1.06, 95% CI 0.57-1.96). Similar results were observed when controlling only for HPV: OR = 1.11 (95% CI 0.77-1.59) for CIN combined and 1.25 (95% CI 0.76-2.08) for CIN 3. These findings suggest that cigarette smoking is not an independent risk factor for CIN in this population, and that HPV may be an important confounding factor for this association. ^

RB-mediated suppression of spontaneous multiple neuroendocrine neoplasia and lung metastases in Rb+/− mice

Alterations in pathways mediated by retinoblastoma susceptibility gene (RB) product are among the most common in human cancer. Mice with a single copy of the Rb gene are shown to develop a syndrome of multiple neuroendocrine neoplasia. The earliest Rb-deficient atypical cells were identified in the intermediate and anterior lobes of the pituitary, the thyroid and parathyroid glands, and the adrenal medulla within the first 3 months of postnatal development. These cells form gross tumors with various degrees of malignancy by postnatal day 350. By age of 380 days, 84% of Rb+/− mice exhibited lung metastases from C-cell thyroid carcinomas. Expression of a human RB transgene in the Rb+/− mice suppressed carcinogenesis in all tissues studied. Of particular clinical relevance, the frequency of lung metastases also was reduced to 12% in Rb+/− mice by repeated i.v. administration of lipid-entrapped, polycation-condensed RB complementary DNA. Thus, in spite of long latency periods during which secondary alterations can accumulate, the initial loss of Rb function remains essential for tumor progression in multiple types of neuroendocrine cells. Restoration of RB function in humans may prove an effective general approach to the treatment of RB-deficient disseminated tumors.