Cervical carcinogenesis and contraception

Cytologic evaluation of cervical smears has been carried out in 3,374 women who used different modes of contraception (Lippes loop, copper T200, copper T220, copper devices containing higher copper content than the copper T200, Cu T380 Ag, levonorgestrel IUD, injections of noresthisterone oenanthate, and subdermal implants of levonorgestrel) under the Contraceptive Testing Programme of Indian Council of Medical Research for periods ranging from 6 months to 15 yr. While no case of severe dysplasia or malignancy was noticed with any type of contraceptive, 113 dysplastic smears (99 mild and 14 moderate) were encountered on follow-up, giving an incidence of 3.3%, which was statistically insignificant compared with the pretreatment incidence of 1.4% (47 of 3,374). The highest incidence of dysplasia was seen with devices containing a high copper content (9.2%), followed by CuT200 (6.1%) and levonorgestrel implants (4.2%), and was lowest with Lippes loop (1.8%), injection of noresthisterone oenanthate (1.7%), and CuT380 Ag (1.5%), but statistics higher than the pretreatment incidence of 1.4% were seen only with CuT200 and devices containing high copper content. Retrogression of dysplasia was seen in 85 of the 94 posttreatment dysplasia cases and in all 47 pretreatment dysplasia cases, whereas in the remaining nine posttreatment cases of dysplasia the lesion persisted for 6-12 mo, necessitating discontinuation of contraception. The accumulated follow-up data indicate that the CuT380 Ag device is a promising IUD for the future in view of its low incidence of dysplasia determined during its use up to 5 yr. However, more prolonged follow-up in larger numbers of subjects is required to confirm its innocuosness on long-term retention.     

The present status and problems with diagnosis and management of dysplasia/colitic cancer in ulcerative colitis

Patients with long-standing UC (ulcerative colitis) have an increased risk of colorectal cancer. Colonoscopic surveillance for UC patients is generally accepted to reduce mortality due to colitic cancer. However, the diagnosis and management of dysplasia remain controversial. The literature about the present status of and problems with diagnosis and management of dysplasia/colitic cancer was reviewed. The problems that arise are: (1) the surveillance program is different in each guideline; (2) the biopsy number that the guidelines propose for surveillance is too large to observe, and there is no adequate evidence of benefit from this number; (3) direct evidence to prove the efficacy of the present surveillance methods is not shown; (4) significant variability is thought to exist between diagnosticians in the diagnosis of low-grade dysplasia (LGD) and indefinite dysplasia (IND); (5) a consensus has not been reached about the management of flat LGD; (6) there is disagreement about the definition of dysplasia-associated lesions (DALM), and there are cases where the differentiation of DALM, adenoma-like mass (ALM)/adenoma-like dysplasia (ALD), sporadic adenoma and even inflammatory polyps is difficult.     

The role of arthrography in the management of dysplasia epiphysealis hemimelica

Dysplasia epiphysealis hemimelica can be diagnesed on plain radiographs of the affected areas. However, double contrast arthrography in three new cases provided additional information. The cartilaginous portions of the lesion at the articular surface of the bone were precisely demonstrated, aiding the orthopedic surgeon in deciding which patients should have surgery and planning the extent of operation necessary.     

Imiquimod for treatment of vulvar and vaginal intraepithelial neoplasia.

We searched PubMed, Scopus, Web of Science, LILACS, EMBASE, and Cochrane Library databases to assess the effectiveness and safety of 5% imiquimod cream in the treatment of vulvar and vaginal intraepithelial neoplasia. From the results of the 17 relevant articles identified (1 reported on a randomized controlled trial, 10 reported on case series, and 6 were case reports), 26% to 100% of patients had complete regression, 0% to 60% had partial regression, and 0% to 37% experienced recurrence. The most common adverse events were local burning and soreness, but not severe enough for patients to discontinue treatment. From these reports imiquimod treatment leads to complete response in a considerable percentage of patients, and those who experience partial response will require less extensive excision. Treating vulvar and vaginal intraepithelial neoplasia with 5% imiquimod cream therefore appears to be promising.     

胃粘膜上皮异型增生分型的组织病理学研究

本文指出,在对胃粘膜上皮异型增生进行分级时,应首先考虑其类型的不同。因为不同类型的异型增生,不但其组织发生不同,甚至其性质亦异。作者将152例胃粘膜上皮异型增生分为三个类型:腺瘤型异型增生多为隆起样病灶,异型增生发生在粘膜浅层,为肿瘤性质的病变;隐窝型异型增生起始于肠化生腺管部隐窝水平,是一种非肿瘤性质的病变。文内对这两型异型增生的组织发生进行了探讨;再生型异型增生虽然多是一过性可逆性病变,但也有少数呈现较重度者,并有发生癌变的病例。本文也对目前文献中所使用的有关名称进行了对证,以期有一个国际上通用的合理名称。     

Using a combination of cytochrome P450 1B1 and β-catenin for early diagnosis and prevention of colorectal cancer

Background: Although fecal occult blood test and invasive endoscopic examination are common used to detect colorectal adenomas and cancers, non-invasive and specific biomarkers are still under investigation. The objective is to evaluate the biomarker CYP1B1 alone or in combination with aryl hydrocarbon receptor (AhR), nuclear β-catenin, p53 or bcl-2 for early diagnosis and prevention of colorectal cancer. Methods: These biomarkers were analyzed semi-quantified across 231 colonic tissues including 97 adenocarcinomas, 85 adenomas and 49 non-neoplastic colons using immunohistochemistry. In order to differentiate non-neoplastic colons from colorectal neoplasms (adenoma and carcinoma), the values for CYP1B1, AhR, nuclear β-catenin, p53 and bcl-2 expressions were subjected to discrimination analysis, then the cross-validation, sensitivity and specificity of these models were calculated. Results: Expressions of CYP1B1, p53, nuclear β-catenin and bcl-2 were significantly associated with colorectal carcinogenesis (p < 0.01 for the trend test). The overexpression rates for CYP1B1, p53, nuclear β-catenin and bcl-2 were significantly higher in the adenoma and carcinoma groups than in the non-neoplastic colon group (p < 0.05). The discrimination models showed that a combination of two biomarkers was better than a single biomarker, and provided specificity ranging from 39% to 100% and sensitivity ranging from 43% to 82% for colorectal carcinoma. Conclusions: The increase in expression of CYP1B1 occurred not only in colorectal carcinoma and but also in adenoma. Moreover, a screening panel of CYP1B1 in combination with nuclear β-catenin was the most suitable marker pair to screen for colorectal carcinoma based on this study.     

112例溃疡性结肠炎的内镜和临床分析

回顾性分析过去13年经结肠镜检查并结合临床、活检符合溃疡性结肠炎(UC)诊断的112例结肠炎病例,占结肠镜检总数的3.01％。症状以腹泻(95.5％％)和腹痛(60.7％)为主,中毒性巨结肠和肠外表现少见。肠镜下糜烂和溃疡最多见(96.4％),其次是充血水肿、其它有质脆易出血、血管网模糊、粗糙颗粒感和假息肉。与病变范围广泛者相比,病变限制在直肠及乙状结肠的UC的病情轻、合并症和非典型增生少见。     

Adherence to surveillance guidelines for dysplasia and colorectal carcinoma in ulcerative and Crohn''s colitis patients in the Netherlands

AIM: To study adherence to the widely accepted surveillance guidelines for patients with long-standing colitis in the Netherlands. METHODS: A questionnaire was sent to all 244 gastroenterologists in the Netherlands. RESULTS: The response rate was 63%. Of all gastroenterologists, 95% performed endoscopic surveillance in ulcerative colitis (UC) patients and 65% in patients with Crohn's colitis. The American Gastroenterological Association (AGA) guidelines were followed by 27%, while 27% and 46% followed their local hospital protocol or no specific protocol, respectively. The surveillance was correctly initiated in cases of pancolitis by 53%, and in cases of left-sided colitis by 44% of the gastroenterologists. Although guidelines recommend 4 biopsies every 10 cm, less than 30 biopsies per colonoscopy were taken by 73% of the responders. Only 31%, 68% and 58% of the gastroenterologists referred patients for colectomy when low-grade dysplasia, high-grade dysplasia (HGD) or Dysplasia Associated Lesion or Mass (DALM) was present, respectively. CONCLUSION: Most Dutch gastroenterologists perform endoscopic surveillance without following international recommended guidelines. This practice potentially leads to a decreased sensitivity for dysplasia, rendering screening for colorectal cancer in this population highly ineffective.     

The Role of the Human Papillomavirus in the Pathogenesis of Schneiderian Inverted Papillomas: An Analytic Overview of the Evidence

Background Evidence of an etiological role for human papillomavirus (HPV) in Schneiderian inverted papillomas IP arose in the late 1980’s; yet almost three decades later, the association between HPV and IP has yet to be universally accepted. This is probably due to the disparate HPV detection rates in IP reported in the literature. We analyzed the weight of published data in order to address the following questions: why do the HPV detection rates in IP vary so greatly? What is the relationship between low-risk (LR) and high-risk (HR) HPV types and HPV detection rates in IP? Is there a relationship between the presence and type of HPV in IP and recurrence and malignant progression? Materials and methods A search using the Pubmed search engine was performed to identify studies published in English from 01/87 through 12/06 using the MeSH terms ‘‘HPV’’ and ‘‘Inverted”, “Exophytic”, “Oncocytic Schneiderian” or “Fungiform papilloma’’. Data was abstracted from publications including histology, HPV target, HPV type, method of detection, etc. HPV results were stratified by histology and other variables. Tests for heterogeneity (between-study variability) were conducted, and weighted prevalence (WP) estimates and 95% confidence intervals (CI) were calculated using a random-effects inverse-variance model stratified on study. The association between HPV IP recurrence was estimated by random-effects inverse-variance weighted odds ratio (OR). Results Weighted estimates revealed similar detection rates across detection methods, 26.8% (95%CI 16.4–37.2%) by ISH, 25.2% (95%CI 14.7–35.6%) by consensus PCR, and 23.6% (95%CI 12.2–35.0%) by type-specific PCR. A preponderance of HPV 6/11 is found in IP as compared to HPV 16/18; the overall unadjusted ratio of LR to high-risk HR HPV types is 2.8:1 The HPV detection rates significantly increase (Wald t-test P < 0.02) in IPs with high-grade dysplasia (WP 55.8%, 95%CI 30.5-81.0%) and carcinoma (WP 55.1%, 95%CI 37.0–73.2%) as compared to IPs with no dysplasia or mild dysplasia (WP 22.3%, 95%CI 15.9–28.6%). Furthermore, the preponderance of LR HPV in benign IP (ratio LR/HR = 4.8:1) shifts in dysplastic and malignant IP. The LR/HR ratio is 1.1:1 for IPs with high-grade dysplasias, this ratio is inverted to favor HR HPV (1:2.4) for malignant IP. Recurrences developed in 44 of 236 patients; HPV was detected in 27 of 44 IPs (WP 57.9%, 95%CI 31.6–84.2%) that developed recurrences and in 24 of 192 IPs (WP 9.7%, 95%CI 4.4–15.0%) that did not develop recurrence. The presence of HPV was significantly associated with the likelihood of developing recurrence (weighted OR of 10.2, 95%CI 3.2–32.8). Conclusions We hypothesize that LR HPV may induce IP formation, and then are lost as infected cells are shed, as a “hit and run” phenomenon. HPV detection rates increase in dysplastic IP and SCC-ex-IP with increasing ratio of HR to LR HPV types, compared to nondysplastic IP. We believe that one explanation for the variation in HPV detection rates between different studies may be the actual histologic composition of the cohort. That is, if one series contains a higher frequency of dysplastic and malignant IP, it may have a higher detection rate than another series which contains only nondysplastic IP. We hypothesize that the higher rates of HPV detection in dysplastic and malignant IP may be related to HPV integration. The implication of this is that HPV sub-type testing may identify patients at risk for recurrence, or progression to dysplasia and malignancy, and thus may impact surveillance protocols.     

CO2 laser therapy in malignant and premalignant lesions of the larynx

Twenty-nine patients have undergone CO₂ laser surgery for dysplasia or for malignant disease of the larynx. Nine patients treated for dysplasia show no signs of recurrence and, of 20 patients treated for malignant disease of the larynx, 14 are currently alive. From these results it is possible to define the indications for laser surgery and to show that there may be advantages in combining laser surgery with other forms of treatment for malignant disease.