Risk For Development Of Carcinoma Research Articles

Comparison of the prognoses of laryngeal preneoplastic lesions based on Ljubljana and World Health Organization classifications.

The aim of this study is to evaluate the prognosis of patients with laryngeal preneoplastic lesions based on Ljubljana classification (LC), Revised LC, World Health Organization Dysplasia System (WHO-DS) 2005 and WHO-DS 2017. Patients diagnosed with a laryngeal preneoplastic lesion in our clinic between 2005 and 2018 were included in the study. Biopsy preparations of patients were reexamined by the pathology unit and classified based on LC, Revised LC, WHODS 2005, and WHO-DS 2017. Patients with carcinoma were identified during follow-up. The prognosis of preneoplastic lesions was statistically analyzed based on carcinoma development and duration using these four different classifications. Carcinoma developed in 16 of 142 patients after repeated biopsy. The risk for carcinoma development was found to be more statistically significant in atypical hyperplasia than in squamous cell hyperplasia and basal-parabasal cell hyperplasia according to LC (p: 0.027 and 0.035), no statistically significant difference was observed between squamous and basal-parabasal cell hyperplasia and CIS groups. The risk of carcinoma development was more statistically significant in high-grade squamous intraepithelial lesion (SIL) than in low-grade SIL according to revised LC (p: 0.04); in severe hyperplasia than in other groups according to WHO-DS 2005; and in highgrade dysplasia than in low-grade dysplasia according to WHO-DS 2017 (p: 0.013). The Cox regression analysis demonstrated that the risk of developing carcinoma statistically increased with age in all classifications, independent of the severity of dysplasia (p < 0.01). According to Cox regression analysis, there was no effect of sex on carcinoma development. : In revised classifications, such as the revised LC and WHO-DS 2017, it is seen that facilitating clinical use is achieved by reducing the number of subgroups by combining the subgroups that do not statistically differ in terms of carcinoma development.

Porphyromonas gingivalis W83 Membrane Components Induce Distinct Profiles of Metabolic Genes in Oral Squamous Carcinoma Cells.

Periodontitis, a chronic inflammatory disease is caused by a bacterial biofilm, affecting all periodontal tissues and structures. This chronic disease seems to be associated with cancer since, in general, inflammation intensifies the risk for carcinoma development and progression. Interactions between periodontal pathogens and the host immune response induce the onset of periodontitis and are responsible for its progression, among them Porphyromonas gingivalis (P. gingivalis), a Gram-negative anaerobic rod, capable of expressing a variety of virulence factors that is considered a keystone pathogen in periodontal biofilms. The aim of this study was to investigate the genome-wide impact of P. gingivalis W83 membranes on RNA expression of oral squamous carcinoma cells by transcriptome analysis. Human squamous cell carcinoma cells (SCC-25) were infected for 4 and 24 h with extracts from P. gingivalis W83 membrane, harvested, and RNA was extracted. RNA sequencing was performed, and differential gene expression and enrichment were analyzed using GO, KEGG, and REACTOME. The results of transcriptome analysis were validated using quantitative real-time PCR with selected genes. Differential gene expression analysis resulted in the upregulation of 15 genes and downregulation of 1 gene after 4 h. After 24 h, 61 genes were upregulated and 278 downregulated. GO, KEGG, and REACTONE enrichment analysis revealed a strong metabolic transcriptomic response signature, demonstrating altered gene expressions after 4 h and 24 h that mainly belong to cell metabolic pathways and replication. Real-time PCR of selected genes belonging to immune response, signaling, and metabolism revealed upregulated expression of CCL20, CXCL8, NFkBIA, TNFAIP3, TRAF5, CYP1A1, and NOD2. This work sheds light on the RNA transcriptome of human oral squamous carcinoma cells following stimulation with P. gingivalis membranes and identifies a strong metabolic gene expression response to this periodontal pathogen. The data provide a base for future studies of molecular and cellular interactions between P. gingivalis and oral epithelium to elucidate the basic mechanisms of periodontitis and the development of cancer.

Exposure of Human Skin Organoids to Low Genotoxic Stress Can Promote Epithelial-to-Mesenchymal Transition in Regenerating Keratinocyte Precursor Cells.

For the general population, medical diagnosis is a major cause of exposure to low genotoxic stress, as various imaging techniques deliver low doses of ionizing radiation. Our study investigated the consequences of low genotoxic stress on a keratinocyte precursor fraction that includes stem and progenitor cells, which are at risk for carcinoma development. Human skin organoids were bioengineered according to a clinically-relevant model, exposed to a single 50 mGy dose of γ rays, and then xeno-transplanted in nude mice to follow full epidermis generation in an in vivo context. Twenty days post-xenografting, mature skin grafts were sampled and analyzed by semi-quantitative immuno-histochemical methods. Pre-transplantation exposure to 50 mGy of immature human skin organoids did not compromise engraftment, but half of xenografts generated from irradiated precursors exhibited areas displaying focal dysplasia, originating from the basal layer of the epidermis. Characteristics of epithelial-to-mesenchymal transition (EMT) were documented in these dysplastic areas, including loss of basal cell polarity and cohesiveness, epithelial marker decreases, ectopic expression of the mesenchymal marker α-SMA and expression of the EMT promoter ZEB1. Taken together, these data show that a very low level of radiative stress in regenerating keratinocyte stem and precursor cells can induce a micro-environment that may constitute a favorable context for long-term carcinogenesis.

Diagnosis and Treatment of Gallbladder Polyps: Current Perspectives.

ABSTRACTIntroductionGallbladder polyps (GBPs) are generally harmless, but the planning of diagnosis and treatment of the GBP is of clinical importance due to the high mortality risk of delays in the diagnosis of gallbladder carcinomas that show polypoid development.Materials and methodsGBPs are usually incidentally detected during ultrasonographic (USG) examinations of the abdomen. The risk of carcinoma development from polypoid lesions in the literature is reported as 0-27%. There is no consensus about the management of the GBPs. Herein, we reviewed the contemporary data to update our knowledge about diagnosis and treatment of gallbladder polyps.ResultsPolyps can be identified in five different groups, primarily as neoplastic and non-neoplastic. Cholesterol polyps account for 60% of all cases. The most common (25%) benign polypoid lesions after cholesterol polyps are adenomyomas.ConclusionUltrasonography and endoscopic ultrasonography seems to be the most important tool in differential diagnosis and treatment. Ultrasonography should be repeated in every 3-12 months in cases that are thought to be risky. Nowadays, the most common treatment approach is to perform cholecystectomy in patients with polyps larger than 10 mm in diameter. Radical cholecystectomy and/or segmental liver resections should be planned in cases of malignancy.How to cite this articleDilek ON, Karsu S, et al. Diagnosis and Treatment of Gallbladder Polyps: Current Perspectives. Euroasian J Hepatogastroenterol 2019;9(1):40-48.

Topographic, histological and molecular study of aberrant crypt foci identified in human colon in different clinical groups.

Background/AimsAberrant crypt foci (ACF) are early microscopic lesions of the colonic mucosa, which can be detected by magnified chromoendoscopy. Herein, we have investigated whether ACF identified in different clinical groups can be differentiated based on their characteristics.MethodsMacroscopically unremarkable mucosal flaps were collected from 270 fresh colectomies and divided into 3 clinical groups: colorectal carcinoma (group A), disease controls having known pre-neoplastic potential (group Bc), and disease controls without risk of carcinoma development (group Bn). Topographic and histologic analysis, immunohistochemistry, and molecular studies (high-resolution melt curve analysis, real-time polymerase chain reaction, and Sanger sequencing) were conducted for certain neoplasia-associated markers.ResultsACF were seen in 107 cases, out of which 72 were left colonic ACF and 35 right colonic ACF (67.2% vs. 32.7%, P=0.02). The overall density of left colonic ACF was 0.97/cm, which was greater than the right colonic ACF density of 0.81/cm. Hypercrinia was present in 41 out of 72 left colonic ACF and in 14 out of 35 right colonic ACF (P=0.01). Immunohistochemical expression of p53 was also greater in left colonic ACF than in right colonic ACF (60.5% vs. 38.2%, P=0.03). However, ACF identified among the 3 clinical groups did not show any distinguishing topographic, histological, or genetic changes.ConclusionsLeft colonic ACF appear to be high-risk based on their morphological and prototypic tumor marker signature. ACF identified in different clinical groups do not show significant genotypic or topographic differences. Further detailed genetic studies are required to elucidate them further.

Barrett's esophagus. Correlation between flow cytometry and histology in detection of patients at risk for adenocarcinoma.

The value of endoscopic surveillance biopsy for dysplasia and carcinoma in patients with Barrett's esophagus is controversial. One reason is that the available histologic criteria are not adequate to separate patients with lesser degrees of dysplasia or predysplastic changes who are at increased risk for carcinoma and therefore require more frequent surveillance from those patients who are not at increased risk. We used flow cytometry and histology to evaluate 317 biopsy specimens from 64 consecutive patients who were in a cancer surveillance program for Barrett's esophagus and 3 additional patients with adenocarcinoma in Barrett's esophagus. Specimens from 10 patients had aneuploid cells; 9 of these had dysplasia or carcinoma, or both, but 1 patient had only specialized metaplastic epithelium. Twenty specimens ahd G2/tetraploid fractions greater than 6%; all 20 came from patients who had cancer or dysplasia, or were indefinite for dysplasia. All patients with dysplasia or adenocarcinoma had evidence of genomic instability (aneuploidy) or abnormalities of mucosal proliferation by flow cytometry, even when the dysplasia was focal or difficult to recognize histologically. In a small subset of patients with specialized metaplastic epithelium whose specimens were histologically negative or indefinite for dysplasia, the mucosa had aneuploid cell populations or proliferative abnormalities that were otherwise found only in dysplasia or carcinoma. Additional study may prove that this subset of patients merits more frequent endoscopic biopsy surveillance because of an increased risk for developing carcinoma. Because the abnormalities we have detected by flow cytometry correlate well with the conventional histologic diagnoses of dysplasia and carcinoma, they may prove to be a valuable objective adjunct in the diagnosis of dysplasia and carcinoma in Barrett's esophagus.

Role of podoplanin in potentially malignant disorders and oral squamous cell carcinoma and its correlation with lymphangiogenesis.

Oral squamous cell carcinoma (OSCC) ranks as one of the most common types of cancer and oral potentially malignant lesions (OPMLs) provides with an overall increased risk for development of carcinoma. As podoplanin expression is attracting interest as a marker for cancer diagnosis and prognosis, this study assesses the role of podoplanin expression in such lesions. Podoplanin expression and lymphatic vessel density (LVD) was determined using D2-40, a marker for podoplanin, in 70 diagnosed cases of potentially malignant lesions and OSCC. Normal epithelium showed negligible podoplanin expression, whereas the expression extended predominantly at the basal layer and the suprabasal layer or above at one or multiple areas in potentially malignant lesions. Podoplanin expression in OSCC showed two different patterns-diffuse and focal. A statistically significant increase in mean LVD was seen from normal epithelium to potentially malignant lesions (P < 0.001) and to OSCC (P < 0.022) while a non-significant increase was seen (P < 0.594) between OPMLs and OSCC. Overall no significant correlation was found between D2-40 epithelial positivity and LVD (P = 0.122). This study suggests the utility of podoplanin as a biomarker for cancer risk assessment as it detects the early changes and thus provides an additional value beyond current clinical and histopathological evaluations. Hence, podoplanin is suggested to be a marker of tumor initiation and to a lesser extent of tumor progression.

Abstract 4102: p27 as a biomarker and determinant of risk for endometrial carcinoma arising in the setting of obesity

Abstract Endometrial carcinoma exhibits the strongest association with obesity of any cancer. Tumor growth is driven by PI3K/AKT activation, and opposed by tumor suppressors, including the tuberous sclerosis complex (TSC) and p27, with inactivation of TSC2 and loss of cytoplasmic misloclization of p27 both being linked to PI3K/AKT signaling. However, little is known about the involvement of p27 in the development of endometrial carcinoma arising in the setting of obesity, expecially its role in early disease progression. We found that p27 was moderatley-to-severely reduced in both “normal” endometrial glands as well as endometrial hyperplasia of obese women. Obese Tsc-2-deficient Eker rats similarly developed endometrial hyperplasia with a high frequency and short latency, and like obese women, endometrial hyperplasia that developed in obese rats exhibited loss of p27. In Eker rats, even a short duration of caloric restriction (2-4 months of age) reduced weight, increased adiponectin and lowered leptin to produce favorable leptin:adiponectin ratio, and reduced circulating insulin levels. Caloric restriction also increased p27 levels, primarily in the nucleus, and significantly decreased endometrial hyperplasia incidence by up to 50%. These data demonstrate that in the setting of obesity, loss of p27 occurs very early in progression to carcinoma. Importantly, p27 can be modulated along with weight by diet, and perhaps other lifestyle interventions that decrease risk for development of carcinoma, suggesting it may be a useful biomarker, and possible determinant of risk for endometrial carcinoma in the setting of obesity. Citation Format: Adrienne S. McCampbell, Megan L. Mittlestedt, Ruhee Dere, Lijun Zhou, Bojana Djordjevic, Pamela T. Soliman, Qian Zhang, Caimiao Wei, Stephen D. Hursting, Karen H. Lu, Cheryl L. Walker, Russell R. Broaddus. p27 as a biomarker and determinant of risk for endometrial carcinoma arising in the setting of obesity. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 4102. doi:10.1158/1538-7445.AM2014-4102

Predictive Value of Dysplasia Grading and DNA Ploidy in Malignant Transformation of Oral Potentially Malignant Disorders

Dysplasia grading is widely used to assess risk of transformation in oral potentially malignant disorders despite limited data on predictive value. DNA ploidy analysis has been proposed as an alternative. This study examines the prognostic value for both tests used in a routine diagnostic setting to inform clinical management. A retrospective study of conventional dysplasia grading was conducted on 1,401 patients. DNA ploidy analysis was conducted on a subset of 273 patients and results correlated with clinical information, pathologic diagnosis, and outcome over 5 to 15 years. Malignant transformation occurred in 32 of 273 patients (12%) and, of these, 20 (63%) of preexisting index lesions were aneuploid. Of 241 patients not developing carcinoma, only 39 (16%) of index lesions were aneuploid. Epithelial dysplasia correlated with DNA ploidy status (P < 0.001). The overall positive predictive value for malignant transformation by DNA aneuploidy was 38.5% (sensitivity 65.2% and specificity 75%) and by severe dysplasia grade 39.5% (sensitivity 30% and specificity 98%). DNA diploid and tetraploid status had negative predictive value of 90% to 96%. Combining DNA ploidy analysis with dysplasia grading gives a higher predictive value than either technique alone. Each of three traditional dysplasia grades predicts a significantly different risk of carcinoma development and time to transformation. DNA ploidy analysis had equivalent predictive value and also detected additional risk lesions in the absence of dysplasia.

Long-term follow-up of human papillomavirus vaccine efficacy

Oncogenic, high-risk human papillomaviruses (HPV) have, in less than four decades, become the showcase of translational science. Harald zur Hausen first suggested the concept of oncogenic high-risk HPV in 1975, before confirming HPV’s link to cervical cancer in 1983; work which led to him being awarded the 2008 Nobel Prize for physiology and medicine [1,2]. Then, between 1996 and 2001 HPV were proven to cause increased risk for later development of carcinomas of the uterine cervix, other anogenital sites and the oropharynx [3–5], before being shown to be preventable between 2002 and 2012. In clinical trials, efficacy of the two licensed vaccines against genital infections with the two most important high-risk HPV types, 16/18, and their neoplastic sequelae – most notably cervical intraepithelial neoplasia grades 2/3 (CIN2/3) – have been between 97 and 100% with tight, albeit overlapping 95% CIs (for a recent review of this topic, see the 2012 work by Lehtinen et al. [6]). Overall, vaccine efficacy (VE) against CIN3 also appears to be almost too good to be true (>93%), but numbers of incident clinical trials or cancer-registry follow up-based end point cases are still limited. So far, observations of VE against the most stringent cervical adenocarcinoma in situ, as well as CIN3 end points, are based on small numbers [6,7]. These, and other still missing HPV-associated cancer end points, need to be verified in the future. It is especially important to verify and exploit wide-spread cross-protectivity of the currently licensed vaccine(s) against a number of oncogenic HPV types and their sequelae [8]. A substantial lag period existed in gathering convincing evidence on the impact of hepatitis B virus vaccination programs, implemented in 1984 in Taiwan and Alaska on hepatocellular carcinoma, since it was 25 years before a 90–100% reduction in the hepatocellular carcin incidence was achieved [9,10]. In the case of HPV, an even longer lag period in completing this kind of a chain of evidence via national HPV vaccination programs was imminent. This is because the age-peaks of high-risk HPV infections and cervical cancer are between 18 and 22 and at approximately 45 years of age, respectively [11]. Thus, from vaccination of early adolescents it would take 30 years to start to see the impact of HPV vaccination on cervical cancer incidence, and long-term follow up of sizeable population-based clinical trial cohorts, enrolled approximately 10 years ago in Costa Rica, Finland and the Scandinavian countries, is pivotal [12,13]. The major flaw in the originally US FDA-approved CIN2 surrogate end point is that it has proven to be irreproducible and unstable [14,15], which makes inferences on the probable HPV VE against overall invasive cervical cancer (ICC) vague. It is, however, not only about getting convincing evidence on the VE against ICC, but evidence on the VE against other HPV-associated cancers as well.

The rectal ‘no man's land’ and sphincter preservation during rectal excision

Colorectal surgeons are familiar with the ‘holy plane’ as the key to total mesorectal excision (TME). Although this has revolutionized the surgical treatment of rectal cancer1, another term should now be introduced into the surgical lexicon – the rectal ‘no man’s land’. This is the area of the distal rectum that lies within the pelvic floor musculature. It cannot usually be reached from the abdomen and has been relatively inviolate as far as surgical exploration is concerned, although its anterior compartment has been accessed by the coloproctologist and gynaecologist during rectocele repair and by the urologist during perineal prostatectomy. This region varies in length depending on age, sex and body habitus. It is this variability that determines the length of retained diseased rectal cuff (ranging from a few millimetres to several centimetres) during restorative proctocolectomy for ulcerative colitis. Retention of long lengths may mar the functional result and increases the risk of carcinoma development, particularly in the presence of dysplasia2. To avoid such a potential disaster, coloproctologists either resort to mucosectomy and transanal anastomosis or panproctocolectomy. Both have drawbacks; mucosectomy may be incomplete, risks damage to the underlying internal sphincter and may cause incontinence, whereas after panproctocolectomy the patient is left with a permanent stoma3,4. Similarly, in low rectal cancer, if tumour clearance does not leave sufficient rectal stump to facilitate a stapled anastomosis, the sphincter-saving resection is invariably abandoned in favour of an abdominoperineal excision. It is interesting to note that even in the modern era of stapling up to 52 per cent of patients undergoing surgery for rectal cancer may still be left with a permanent stoma5. Although a minority of surgeons in such circumstances may attempt a partial sphincter-conserving procedure, notably the intersphincteric approach, concerns about technical difficulty, tumour clearance and functional outcome have limited its use6–8. If access could be obtained easily to the crucial few centimetres of distal rectum lying between the superior border of the levator ani which forms the pelvic floor within the abdomen and the anorectal junction in the perineum, it should be feasible to preserve the sphincteric apparatus virtually intact. By doing so it might be possible to increase the proportion of sphincter-saving resections without jeopardizing cure. Such an approach has been developed and should significantly reduce the need for a permanent stoma in patientswith benign and malignant rectal disease. So how can this ‘no man’s land’ be explored? For many years urologists used the anterior compartment of this space for the perineal approach to prostatectomy. As a result of elegant anatomical studies, Walsh9 demonstrated the feasibility of excising the prostate without damaging the nervi erigentes that enter the prostate at its inferolateral poles. To access the prostate, the dissection by necessity is in the rectoprostatic plane and begins above the external sphincter. Gynaecologists also pointed theway by using the rectovaginal plane in the course of posterior colporrhaphy, albeit by entering this space via the posterior vaginal wall. Both groups take great pains to avoid damage to the anterior wall of the rectum during dissection and of course have no desire to mobilize it. Dissection in the rectovaginal/ prostatic plane has been used in the development of an operation for rectal intussusception (the Express procedure)10. During development of this procedure it was realized that the rectum and mesorectum could be mobilized completely within the funnel of the pelvic floor musculature, and that the ‘no man’s land’ could be used for sphincter preservation. It was also demonstrated that the length of the rectum contained within this muscular funnel varied significantly. Although this variation was anatomical in that it was fixed according to body habitus, it was also obvious that some variation was operator dependent. Thus, in the course of an anterior resection for low rectal cancer, the extent of rectal mobilization down to the pelvic floor via the abdomen differs according to the surgeon’s skill and perseverance, compounded by anatomical variation and the shape of the pelvis. This in turn influences the length of rectum and mesorectum that remains for construction of the colorectal anastomosis. Exploitation of the rectal

Radiation-induced cutaneous carcinoma of the head and neck: is there an early role for p53 mutations?

Little is known about the molecular mechanisms underlying ionizing radiation-induced carcinogenesis of the skin. To investigate the possible role of p53 in radiodermatitis and in the development of radiation-induced cutaneous carcinomas. The study group comprised six patients affected by cutaneous carcinomas arising in radiodermatitis (one squamous cell carcinoma and five basal cell carcinomas), and seven patients presenting only chronic radiodermatitis. Skin specimens were evaluated for p53 immunohistochemical expression. Using laser-assisted microdissection, areas with different p53 immunoreactivity were separately submitted to DNA isolation and p53 gene analysis. In the majority of cases (9/12, 75%), p53 immunoreactivity was detected in radiation-damaged epidermis. In carcinomas p53 oncoprotein was expressed by several neoplastic cells in one case (16.7%%), or by nearly all neoplastic cells in four (66.7%). SSCP band shifts were detected in 9/25 samples (36%) microdissected from irradiated epidermis and in 3/6 (50%) carcinomas. DNA sequencing demonstrated two repeatedly found mutations: a G deletion at codon 244 and an A-->G transition at codon 205, as well as hallmarks of ultraviolet mutagenic action, including a C-->T transition occurring at a dipyrimidine site and a CC-->TT tandem double-base transition. Our data indicate that irradiation induces significant p53 alterations that may be relevant in the modification of epithelial maturation processes and may be responsible for the high risk for development of carcinomas in radiodermatitis.

Barrett's esophagus is characterized by expression of gastric-type mucins (MUC5AC, MUC6) and TFF peptides (TFF1 and TFF2), but the risk of carcinoma development may be indicated by the intestinal-type mucin, MUC2

Barrett's esophagus (BE) consists of metaplastic epithelium of the esophagus, generally diagnosed by mucin histochemistry. We aimed to determine which mucins were expressed in BE, and to relate their expression to BE pathology. Archival biopsies of 4 patient groups were selected, based on standard histochemistry: BE without inflammation, BE with inflammation, ulcerating BE, and BE with dysplasia. Sections were stained by immunohistochemistry for secretory mucins (MUC2, MUC5AC, MUC5B, and MUC6), the proliferation marker Ki-67, and mucin-associated trefoil factor family (TFF) peptides (TFF1, TFF2, and TFF3). MUC5AC and TFF2 were expressed at similar high levels in each clinical group. Intestinal metaplasia (IM), detected both histochemically and by the intestinal mucin MUC2, was lowest in inflamed BE. The expression of the intestinal-type TFF3 did not differ among the groups. Ulcerating BE was distinguished by very low expression of MUC6 and MUC5B, but very high expression of TFF1. Proliferation was not different among the groups. In the total group of BE patients, H. pylori infection of the stomach correlated with decreased TFF2 expression in the BE epithelium. We conclude that BE is best characterized by the specific expression of the gastric-type markers, MUC5AC, MUC6, TFF1, and TFF2. Ulcerating BE constitutes the most distinguished group with respect to mucin and TFF expression. Of the intestinal markers, MUC2 is very specific for IM in BE, whereas TFF3 is not a marker for IM. The low occurrence of IM in inflamed BE suggests that these patients may have the lowest risk of developing carcinoma. Hum Pathol 33:660-668. Copyright 2002, Elsevier Science (USA). All rights reserved.

Each Barrett's esophagus expresses gastric type mucins and trefoil factors, whereas the risk of carcinoma development may be indicated by the intestinal type MUC2

Each Barrett's esophagus expresses gastric type mucins and trefoil factors, whereas the risk of carcinoma development may be indicated by the intestinal type MUC2

Each Barrett's esophagus expresses gastric type mucins and trefoil factors, whereas the risk of carcinoma development may be indicated by the intestinal type MUC2

Each Barrett's esophagus expresses gastric type mucins and trefoil factors, whereas the risk of carcinoma development may be indicated by the intestinal type MUC2

Duodenal adenomatosis in familial adenomatous polyposis. DAF Project Group.

In order to evaluate the prevalence of duodenal adenomas in familial adenomatous polyposis (FAP) and the risk of carcinoma development, a multicenter study was initiated in Denmark, Finland, Holland, Norway and Sweden, which have national polyposis registers with an almost complete registration. Patients aged 20 years or more are being examined with biennial gastroduodenoscopy during 1990-2000. Multiple duodenal biopsies are examined by one pathologist from each country, and the endoscopic and histological criteria of Spigelman have been adopted. At the end of August 1992, 312 patients with a median age of 37 years (range 20-86) had completed their first endoscopy. The duodenum was examined in 310 patients, of whom 199 (64%) had duodenal adenomas. Twenty-two patients (11% of all patients with duodenal adenomas) had no endoscopically visible polyps. One patient had an asymptomatic adenocarcinoma. The Spigelman stage worsened significantly (P < 0.05) with time from the diagnosis of FAP, which may suggest an increasing risk of carcinoma by time.

Gross Cystic Disease

Gross cystic disease elevates risk for the subsequent development of carcinoma of the breast when there is a positive family history of breast cancer. This relationship probably does not hold true for women with no family history. A single cyst that has been aspirated successfully does not increase risk in the absence of ductal or lobular hyperplasia, with or without atypia, when biopsy has allowed the pathologist to make this diagnosis. Multiple, recurring cysts probably elevate risk, but this may be related to the high incidence of epithelial hyperplasia found in association with apocrine metaplasia, the forerunner of gross cystic disease.

Juvenile Papillomatosis of the Breast: A Follow-Up Study of 41 Patients Having Biopsies Before 1979

Juvenile papillomatosis (JP) is a benign proliferative breast tumor rarely found in women older than 30 years of age that may exhibit considerable histologic atypia. Often these findings would be regarded as precancerous in older patients. Rarely, carcinoma and JP have been coexistent at diagnosis, but little is known about the risk for development of carcinoma after excisional biopsy of JP. To examine this issue, the authors reviewed a series of 41 patients with JP who had biopsies between 1960 and 1978 with a median follow-up of 14 years. Age at diagnosis ranged from 15 to 35 years (median, 19 years), whereas at last follow-up the patients were 22-48 years old (median, 36 years). Overall, 21 (58%) reported a positive family history for breast carcinoma, with mothers and maternal aunts being at highest risk. Six had bilateral JP. Subsequent breast carcinoma was diagnosed in four (10%) of the patients with JP. All of these patients were unusual because they had recurrent and bilateral JP. In two instances the changes were multifocal. Each had a positive family history for breast carcinoma. In this series, none of the patients with nonrecurrent unilateral, unicentric JP has thus far had subsequent mammary carcinoma develop. When counseling the JP patient one should take care not to exaggerate her near term risk for development of carcinoma. The present data suggest that concern should be greatest for women with a positive family history and recurrent bilateral JP.

Effect of antireflux operation on Barrett's mucosa

Regression of Barrett's epithelium after antireflux operations remains a controversial topic. We evaluated the effect of antireflux procedures in patients with Barrett's esophagus on the regression of columnar epithelium and dysplasia and its potential protective effect on the subsequent development of carcinoma. Of the 241 patients with Barrett's esophagus treated at the Lahey Clinic from 1973 to 1989, 37 patients underwent an antireflux operation. Regression was defined at histological evidence of regenerating squamous mucosa that completely or partially replaced the columnar epithelium. Improvement in lower esophageal sphincter pressure to 12 mm Hg or greater occurred in 19 of 26 patients (73%) who had perioperative manometry. Symptomatic relief of esophagitis occurred in 34 of 37 patients (92%). Four patients had partial regression with regenerating squamous mucosa juxtaposed with areas of columnar epithelium. Carcinoma developed in 3 of 37 patients (8.1%). One patient had recurrence of severe symptoms of reflux esophagitis before development of carcinoma. Patients with Barrett' s esophagus who have undergone a successful antireflux operation with symptomatic relief and evidence of improvement in lower esophageal sphincter pressures rarely show regression of Barrett's mucosa and may still be at risk for development of carcinoma. Therefore, the indications for antireflux operation in Barrett's esophagus should remain the same as for other patients with gastroesophageal reflux, but yearly endoscopic and histological surveillance should be continued postoperatively.

Duodenal adenomas in familial adenomatous polyposis: their structure and cellular composition with particular reference to endocrine hyperplasia

134 duodenal biopsies from 14 patients with familial adenomatous polyposis were evaluated by light microscopy for the presence of adenoma. Staining reactions for endocrine cells were applied. 90 biopsies contained adenoma, almost all of the tubular type (98%) with dysplasia, ranging from mild to moderate. Accompanying hyperplasia of argyrophil and argentaffin endocrine cells was found in 91% and 64% of the adenomas, respectively. Based on histological criteria it is concluded that the risk of carcinoma development in the duodenum could equal that in colon and rectum. The observation of endocrine hyperplasia is new, and further investigations are needed before the significance of this finding can be evaluated.