Microscopic Adenomas Research Articles

Ethical issues of implementing artificial intelligence in medicine

Artificial intelligence (AI) systems are highly efficient. However, their implementation in medical practice is accompanied by a range of ethical issues. The black box problem is basic to the AI philosophy, although having its own specificity in relation to medicine. A selection of relevant papers for the last three years by citations and their analysis through PubMed and Google Scholar search engines was conducted to study the problems of the AI implementation in medicine. One of the central problems is that the algorithms to justify decisions are still unclear to doctors and patients. The lack of clear and reasonable principles of AI operation is called the black box problem. How can doctors rely on AI findings without enough data to explain a particular decision? Who will be responsible for the final decision in case of an adverse outcome (death or serious injury)? In routine practice, medical decisions are based on an integrative approach (understanding of pathophysiology and biochemistry and interpretation of past findings), clinical trials and cohort studies. AI may be used to build a plan for disease diagnosis and treatment, while not providing a convincing justification for specific decisions. This creates a black box, since the information that the AI considers important for making a conclusion is not always clear, nor is it clear how or why the AI reaches that conclusion. Thus, Juan M. Durn writes, Even if we claim to understand the principles underlying AI annotation and training, it is still difficult and often even impossible to understand the inner workings of such systems. The doctor can interpret or verify the results of these algorithms, but cannot explain how the algorithm arrived at its recommendations or diagnosis. Currently, AI models are trained to recognize microscopic adenomas and polyps in the colon. However, doctors still have insufficient understanding of how AI differentiates between different types of polyps despite the high accuracy, and the signs that are key to making an AI diagnosis remain unclear to experienced endoscopists. Another example is the biomarkers of colorectal cancer recognized by AI. The doctor does not know how algorithms determine the quantitative and qualitative criteria of detectable biomarkers to formulate a final diagnosis in each individual case, i.e., a black box of process pathology emerges. For the trust of doctors and patients to be earned, the processes underlying the work of AI must be deciphered and explained, describing how it is done sequentially, step by step, and a specific result is to be formulated. Although the black box algorithms cannot be called transparent, the possibility of applying these technologies in practical medicine is worth considering. Despite the above problems, the accuracy and efficiency of solutions does not allow to neglect the use of AI. On the contrary, this use is necessary. Emerging problems should serve as a basis for training and educating doctors to work with AI, expanding the scope of application and developing new diagnostic techniques.

ID: 3518361 EARLY RECURRENCE OF COLONIC POLYPS REDUCED WITH THERMAL ABLATION OF ENDOSCOPIC MUCOSAL RESECTION MARGINS: RETROSPECTIVE STUDY

The rate of residual adenoma after endoscopic mucosal resection (EMR) is an enduring challenge in endoscopic resection of large adenomatous polyps that is thought to be due to microscopic adenomas at the margin of the EMR site. A new technique involving ablation of EMR resection margins has been shown in recent studies to reduce recurrence of polyps ≥ 20mm. The aim of this study was to determine the effectiveness of this technique as an adjunct to EMR in clinical practice in a retrospective fashion.

774 SNARE TIP SOFT COAGULATION OF THE MARGINS OF THE POST ENDOSCOPIC MUCOSAL RESECTION (EMR) DEFECTS: A QUALITY IMPROVEMENT PROJECT IN PREVENTION OF ADENOMA RECURRENCE

Endoscopic mucosal resection is safe and effective technique for removal of large colorectal polyps (>20mm). Adenoma recurrence is one of the main limitations of EMR, which up to 20-55% recurrence occurs on first surveillance colonoscopy warranting systematic follow up program. Invisible microscopic adenoma at EMR site might be the cause of adenoma recurrence on follow up. Thermal ablation or burning of the margins with snare tip may eradicate the invisible micro-adenoma and decrease the adenoma recurrence. This was a quality improvement project with a main aim of reducing adenoma recurrence at first surveillance colonoscopy (SC1). This project was started on Nov 2016 with a video demonstration of snare tip soft coagulation of post EMR margins (by prof. Michael Bourke) to all EMR endoscopists at our hospital. All patients who were referred for EMR of large colorectal polyps (>20mm) were eligible for inclusion. After the polyp and visible adenoma islands were removed with standard technique; margins of post EMR defect was treated with snare tip soft coagulation using Olympus ESG at 20-80W. All five endoscopists with an extensive experience in EMR technique were involved. First surveillance colonoscopy was performed at 3-6 months with a biopsy of post EMR scar base. All the available STSC cases were compared with the consecutive EMR cases done prior to Nov 2016 matching with lesion size (as controls). Over median follow up of 6 months; 54 patients with STSC had completed first surveillance colonoscopy (SC1). Forty three percent were male, median age was 66 years, and median polyp size was 25mm. There were no differences between two groups (STSC vs non-STSC) in terms of age, sex, size of polyps, polyp histology, APC use, initial EMR site, adverse events, and procedure characteristics between EMR endoscopists except median follow up time. Adenoma recurrence in STSC group is significantly lower than non-STSC group (13% vs 32%, p=0.01) Table 1. Coagulation or burning of post EMR margins with snare tip significantly decreases adenoma recurrence. Implementation of this simple technique in routine practice may decrease the patient morbidity associated with frequent surveillance, and increase the EMR efficiency.Tabled 1Baseline characteristics and adenoma recurrence between STSC vs non-STSC groupVariablesSTSC=54Non-STSC=57P-valueAge, median (range)66 (49-81)67 (45-83)0.7aSex, Male (%)24 (43%)29 (52%)0.4bSize of polyp(mm), Median(range), mean (SD)25 (20-60), 28 (11)25 (20-60), 28 (11)0.9cFollow up, Median (range)6 (1-8)7 (3-28)0.01a**Site of polyp resection0.9bProximal Colon45 (83)47 (82)Distal Colon9 (17)10 (18)Polyp histology0.3bSessile serrated adenoma (SSA)25 (46)17 (30)Sessile serrated adenoma with HGD (SSA with HGD)1 (2)0 (0)Tubular adenoma (TA)13 (24)21 (37)Tubular adenoma with HGD (TA with HGD)2 (4)2 (4)Tubulovillous adenoma (TVA)9 (17)15 (26)Tubulovillous adenoma with HGD (TVA with HGD)2 (4)1 (2)Intramucosal carcinoma1 (2)1 (2)APC0 (0)2 (4)0.1bEndoscopists at initial EMR0.1bEndoscopists 123 (44)18 (32)Endoscopists 214 (23)10 (18)Endoscopists 35 (10)14 (25)Endoscopists 45 (10)5 (9)Endoscopists 55 (10)9 (16)Adverse Events0 (0)0 (0)-Adenoma Recurrence7 (13)18 (32)0.01b**Relative risk (95% CI)0.3 (0.11-0.82)3.1 (1.21-8.67)0.02**HGD: high grade dysplasia; EMR: endoscopic mucosal resection, SD: Standard deviation; non-STSC: no snare tip soft coagulation, STSC: Snare tip soft coagulation, a: Wilcoxon rank sums test; b: Chi Square test; c= Pair T-test; CI: Confidence Interval. Open table in a new tab

Clinical effectiveness of microscopic and neuroendoscopic endonasal transsphenoidal pituitary adenoma surgery in China: systematic review and Meta-analysis

Objective To evaluate the clinical effectiveness of microscopic and neuroendoscopic endonasal transsphenoidal pituitary adenoma resection in China.Methods The case-controlled trials of microscopic and neuroendoscopic endonasal transsphenoidal pituitary adenoma surgery were collected,and the systematic review and Meta-Analysis were conducted by revman 5.2 software.Results A total of 8 case-control trials involving 525 patients were included.As for the total resection rate and postoperative complications,significant differences were found between microscopic and neuroendoscopic endonasal transsphenoidal surgery (OR =0.41,95％ CI:0.25-0.67,P =0.0004; OR =1.90,95％ CI:1.24-2.91,P =0.003) respectively.Conclusions According to the available data,endoscopic transsphenoidal surgery provided favorable results in both tumour resection and control of complications in comparison with microscopic surgery. Key words: Pituitary neoplasms ; Microsurgery; Neuroendoscope ; Total resection rate ; Postoperative complications; Meta-analysis

Inhibition of Aurora-B kinase activity confers antitumor efficacy in preclinical mouse models of early and advanced gastrointestinal neoplasia

The Aurora family of kinases, play a fundamental role in cell division and are overexpressed in several cancers including colon. The activity of barasertib-hQPA, a selective inhibitor of Aurora-B kinase (ABK) was investigated in a range of preclinical models of gastrointestinal cancer. Treatment with barasertib-hQPA produced anti-proliferative and cytotoxic effects across a panel of human colorectal cancer (CRC) cell lines in vitro. Prodrug, barasertib [48-h subcutaneous (s.c.) infusion; 150 mg/kg/day] inhibited the growth of SW620, Colo205, HCT116 human colorectal tumor xenografts in nude mice significantly (Student's t-test, P<0.05, n=10-12 per group). Flow cytometric analysis of single cells from disaggregated barasertib-treated SW620 tumors revealed a decrease in phosphorylated histone H3 (phH3) and an increase in tumor cells with ≥4N DNA content P<0.05). The activity of barasertib was then examined in ApcMin/+ mice, a spontaneous model of early intestinal neoplasia. Macroscopic evaluation of the small intestine revealed that barasertib treatment [25 mg/kg intra-peritoneal (i.p.) Q1Dx4 each week for 3 weeks] of 8-week old ApcMin/+ mice produced a 39% reduction in macroadenoma number (P=0.02) and a 43% reduction in overall adenoma burden (P=0.02) compared with vehicle-treated controls. Quantification of microscopic adenomas revealed a >64% reduction in the number of adenomas spanning more than one villus. Histological analysis of these adenomas revealed a number of distinct changes in barasertib-treated ApcMin/+ mice, including a 94% reduction in the proportion of phospho-histone H3-positive cells (P<0.001) and a 53% reduction in the number of cells per adenoma (P=0.001). These results provide a scientific rationale for investigating ABK inhibitors as a treatment for intestinal cancer.

Inflammatory bowel disease and familial adenomatous polyposis

BackgroundInflammatory bowel disease (IBD) and familial adenomatous polyposis (FAP) are uncommon diseases and both are associated with marked increased risk of colorectal cancer. MethodsWe present a patient diagnosed in parallel with ulcerative colitis and FAP. Mutational analysis of the APC germline and somatic DNA was performed by sequencing. ResultsThis patient's phenotype consisted of polyps only on the right side of the colon (cecum and ascending colon) whereas the area affected by ulcerative colitis (descending colon and rectum) was free of polyps on endoscopy and microscopic adenomas on histology. This raises the possibility that mosaicism or inflammation in the presence of active ulcerative colitis modified the phenotypic expression of adenomatous polyposis in the left colon. Mosaicism was excluded by DNA analysis. DiscussionThis case of a patient diagnosed with both inflammatory bowel disease and familial adenomatous polyposis offers potential insights into the distinct pathogenesis of cancer susceptibility within these syndromes, and suggests that a collision of phenotypes may influence their mutual presentation. Both of these conditions independently increase the risk of colorectal cancer.

Chemopreventive Effects of Pioglitazone on Chemically Induced Lung Carcinogenesis in Mice

Pioglitazone [(RS)-5-(4-[2-(5-ethylpyridin-2-yl)ethoxy]benzyl)thiazolidine-2,4-dione] is a ligand of nuclear receptor peroxisome proliferator-activated receptor γ that is approved for the treatment of type II diabetes mellitus. Activation of peroxisome proliferator-activated receptor γ has been associated with anticancer activities in a variety of cancer cell lines through inhibition of proliferation and promotion of apoptosis. We examined the effect of pioglitazone on lung cancer development in carcinogen-induced lung adenocarcinoma and squamous cell carcinoma (SCC). When pioglitazone was administered beginning 8 weeks after the first carcinogen treatment when microscopic adenomas already existed, pioglitazone significantly inhibited tumor load (sum of tumor volume per lung in average) by 64% (P < 0.05) in p53(wt/wt) mice and 50% (P < 0.05) in p53(wt/Ala135Val) mice in the lung adenocarcinoma model. Delayed administration of pioglitazone caused a limited (35%, P < 0.05) decrease in lung SCC. Induction of apoptosis occurred in both model systems. These data show that pioglitazone significantly inhibited progression of both adenocarcinoma and SCC in the two mouse model systems.

Huge renal cyst with parietal renal cell carcinoma, osseous metaplasia and a papillary adenoma: a case report with unique clinicopathological features and literature review

The unique clinicopathological features of a giant solitary renal cyst with a parietal clear cell carcinoma in contiguity with a focus of osseous metaplasia and a papillary adenoma are reported. Ultrasonography and computed tomography showed a single cyst with a focal wall irregularity. During surgery, a frozen section revealed the presence of a renal cell carcinoma of clear cell type, so a nephrectomy was performed. After extensive pathological sampling of the cyst's wall, a focus of osseous metaplasia in contiguity with the main tumour and a microscopic papillary adenoma were found. Diagnostic implications for the present case are discussed within a pertinent literature review.

Microscopic Papillary Adenoma as a Cause of Recurrent Acute Pancreatitis

Microscopic Papillary Adenoma as a Cause of Recurrent Acute Pancreatitis

Role of peroxisome proliferator-activated receptor-alpha (PPARalpha) in bezafibrate-induced hepatocarcinogenesis and cholestasis.

Prolonged administration of peroxisome proliferators to rodents typically leads to hepatocarcinogenesis. Peroxisome proliferator-activated receptor-alpha (PPARalpha) is required to mediate alterations in PPARalpha target gene expression, repress apoptosis, enhance replicative DNA synthesis, oxidative stress to DNA and hepatocarcinogenesis induced by the relatively specific PPARalpha agonist, Wy-14,643. Interestingly, administration of the less specific PPARalpha agonist, bezafibrate, leads to a modest induction of PPARalpha target genes in the absence of PPARalpha expression. In these studies, the role of PPARalpha in modulating hepatocarcinogenesis induced by long-term feeding of 0.5% bezafibrate was examined in wild-type (+/+) and PPARalpha-null (-/-) mice. The average liver weight was significantly higher in (+/+) and (-/-) mice fed bezafibrate than controls, but this effect was considerably less in (-/-) mice as compared with similarly treated (+/+) mice. Increased levels of mRNA encoding cell cycle regulatory proteins and DNA repair enzymes were found in (+/+) mice fed bezafibrate, and this effect was not found in (-/-) mice. In mice fed bezafibrate for 1 year, preneoplastic foci, adenomas and a hepatocellular carcinoma were found in (+/+) mice, while only a single microscopic adenoma was found in one (-/-) mouse. This effect was observed in both Sv/129 and C57BL/6N strains of mice, although only preneoplastic foci were observed in the latter strain. Interestingly, hepatic cholestasis was observed in 100% of the bezafibrate-fed (-/-) mice, and this was accompanied by significantly elevated hepatic expression of mRNA encoding bile salt export pump and lower expression of mRNA encoding cytochrome P450 7A1, consistent with enhanced activation of the bile acid receptor, farnesoid X receptor. Results from these studies demonstrate that the PPARalpha is required to mediate hepatocarcinogenesis induced by bezafibrate, and that PPARalpha protects against potential cholestasis.

Lack of prolactin receptor signaling in mice results in lactotroph proliferation and prolactinomas by dopamine-dependent and -independent mechanisms.

Hypothalamic dopamine inhibits pituitary prolactin secretion and proliferation of prolactin-producing lactotroph cells by activating lactotroph dopamine D2 receptors (D2Rs). Conversely, prolactin (PRL) stimulates hypothalamic dopamine neurons via PRL receptors (PRLRs) in a short-loop feedback circuit. We used Drd2(-/-) and Prlr(-/-) mutant mice to bypass this feedback and investigate possible dopamine-independent effects of PRL on lactotroph function. The absence of either receptor induced hyperprolactinemia and large prolactinomas in females. Small macroadenomas developed in aged Prlr(-/-) males, but only microscopic adenomas were found in Drd2(-/-) male mice. Pharmacologic studies in Prlr(-/-) mice with D2R agonists and antagonists demonstrated a significant loss of endogenous dopamine tone, i.e., constitutive inhibitory signaling by the D2R, in the pituitary. However, Prlr(-/-) mice exhibited more profound hyperprolactinemia and larger tumors than did age-matched Drd2(-/-) mice, and there were additive effects in compound homozygous mutant male mice. In vitro, PRL treatment markedly inhibited the proliferation of wild-type female and male Drd2(-/-) lactotrophs, but had no effect on female Drd2(-/-) lactotrophs, suggesting a downregulation or desensitization of PRLR in response to chronic hyperprolactinemia. We conclude that PRL inhibits lactotrophs by two distinct mechanisms: (a) indirectly by activation of hypothalamic dopamine neurons and (b) directly within the pituitary in a dopamine-independent fashion.

Lack of prolactin receptor signaling in mice results in lactotroph proliferation and prolactinomas by dopamine-dependent and -independent mechanisms

Hypothalamic dopamine inhibits pituitary prolactin secretion and proliferation of prolactin-producing lactotroph cells by activating lactotroph dopamine D2 receptors (D2Rs). Conversely, prolactin (PRL) stimulates hypothalamic dopamine neurons via PRL receptors (PRLRs) in a short-loop feedback circuit. We used Drd2–/– and Prlr–/– mutant mice to bypass this feedback and investigate possible dopamine-independent effects of PRL on lactotroph function. The absence of either receptor induced hyperprolactinemia and large prolactinomas in females. Small macroadenomas developed in aged Prlr–/– males, but only microscopic adenomas were found in Drd2–/– male mice. Pharmacologic studies in Prlr–/– mice with D2R agonists and antagonists demonstrated a significant loss of endogenous dopamine tone, i.e., constitutive inhibitory signaling by the D2R, in the pituitary. However, Prlr–/– mice exhibited more profound hyperprolactinemia and larger tumors than did age-matched Drd2–/– mice, and there were additive effects in compound homozygous mutant male mice. In vitro, PRL treatment markedly inhibited the proliferation of wild-type female and male Drd2–/– lactotrophs, but had no effect on female Drd2–/– lactotrophs, suggesting a downregulation or desensitization of PRLR in response to chronic hyperprolactinemia. We conclude that PRL inhibits lactotrophs by two distinct mechanisms: (a) indirectly by activation of hypothalamic dopamine neurons and (b) directly within the pituitary in a dopamine-independent fashion.

Detection of dysplastic intestinal adenomas using enzyme-sensing molecular beacons in mice

Background & Aims:Proteases play key roles in the pathogenesis of tumor growth and invasioN. This study assesses the expression of cathepsin B in dysplastic adenomatous polypS.Methods:Aged Apcmin/+ mice served as an experimental model for familial adenomatous polyposiS. The 4 experimental groups consisted of (a) animals injected with a novel activatablE. cathepsin B sensing near infrared fluorescence (NIRF) imaging probe; (b) animals injected with a nonspecific NIRF; (c) uninjected control animals; and (d) non-APCMin/+ mice injected with the cathepsin B probE. Lesions were analyzed by immunohistochemistrY. Western blottinG. reverse transcription-polymerase chain reactioN. and optical imaginG.Results:Cathepsin B was consistently overexpressed in adenomatous polypS. When mice were injected intravenously with the cathepsin reporter probE. intestinal adenomas became highly fluorescent indicative of high cathepsin B enzyme activitY. Even microscopic adenomas were readily detectable by fluorescencE. but not lighT. imaginG. The smallest lesion detectable measured 50 μm in diameteR. Adenomas in the indocyanine green and/or noninjected group were only barely detectable above the backgrounD.Conclusions: The current experimental study shows that cathepsin B is up-regulated in a mouse model of adenomatous polyposiS. Cathepsin B activity can be used as a biomarker to readily identify such lesionS. particularly when contrasted against normal adjacent mucosa. This detection technology can be adapted to endoscopy or tomographic optical imaging methods for screening of suspicious lesions and potentially for molecular profiling in vivo.

Telomere dysfunction and evolution of intestinal carcinoma in mice and humans.

Telomerase activation is a common feature of advanced human cancers and facilitates the malignant transformation of cultured human cells and in mice. These experimental observations are in accord with the presence of robust telomerase activity in more advanced stages of human colorectal carcinogenesis. However, the occurrence of colon carcinomas in telomerase RNA (Terc)-null, p53-mutant mice has revealed complex interactions between telomere dynamics, checkpoint responses and carcinogenesis. We therefore sought to determine whether telomere dysfunction exerts differential effects on cancer initiation versus progression of mouse and human intestinal neoplasia. In successive generations of ApcMin Terc-/- mice, progressive telomere dysfunction led to an increase in initiated lesions (microscopic adenomas), yet a significant decline in the multiplicity and size of macroscopic adenomas. That telomere dysfunction also contributes to human colorectal carcinogenesis is supported by the appearance of anaphase bridges (a correlate of telomere dysfunction) at the adenoma-early carcinoma transition, a transition recognized for marked chromosomal instability. Together, these data are consistent with a model in which telomere dysfunction promotes the chromosomal instability that drives early carcinogenesis, while telomerase activation restores genomic stability to a level permissive for tumor progression. We propose that early and transient telomere dysfunction is a major mechanism underlying chromosomal instability of human cancer.

Toxicology of mono-, di-, and triethanolamine.

The chemistry, biochemistry, toxicity, and industrial use of monoethanolamine (MEA), diethanolamine (DEA), and triethanolamine (TEA) are reviewed. The dual function groups, amino and hydroxyl, make them useful in cutting fluids and as intermediates in the production of surfactants, soaps, salts, corrosion control inhibitors, and in pharmaceutical and miscellaneous applications. In 1995, the annual U.S. production capacity for ethanolamines was 447,727 metric tons. The principal route of exposure is through skin, with some exposure occurring by inhalation of vapor and aerosols. MEA, DEA, and TEA in water penetrate rat skin at the rate of 2.9 x 10(-3), 4.36 x 10(-3) and 18 x 10(-3) cm/hr, respectively. MEA, DEA, and TEA are water-soluble ammonia derivatives, with pHs of 9-11 in water and pHa values of 9.3, 8.8, and 7.7, respectively. They are irritating to the skin, eyes, and respiratory tract, with MEA being the worst irritant, followed by DEA and TEA. The acute oral LD50s are 2.74 g/kg for MEA, 1.82 g/kg for DEA, and 2.34 g/kg for TEA (of bw), with most deaths occurring within 4 d of administration. MEA is present in nature as a nitrogenous base in phospholipids. These lipids, composed of glycerol, two fatty acid esters, phosphoric acid, and MEA, are the building blocks of biomembranes in animals. MEA is methylated to form choline, another important nitrogenous base in phospholipids and an essential vitamin. The rat dietary choline requirement is 10 mg kg-1 d-1; 30-d oral administration of MEA (160-2670 mg kg-1 d-1) to rats produced "altered" liver and kidney weights in animals ingesting 640 mg kg-1 d-1 or greater. Death occurred at dosages of 1280 mg kg-1 d-1. No treatment-related effects were noted in dogs administered as much as 22 mg kg-1 d-1 for 2 yr. DEA is not metabolized or readily eliminated from the liver or kidneys. At high tissue concentrations, DEA substitutes for MEA in phospholipids and is methylated to form phospholipids composed of N-methyl and N, N-dimethyl DEA. Dietary intake of DEA by rats for 13 wk at levels greater than 90 mg kg-1 d-1 resulted in degenerative changes in renal tubular epithelial cells and fatty degeneration of the liver. Similar effects were noted in drinking water studies. The findings are believed to be due to alterations in the structure and function of biomembranes brought about by the incorporation of DEA and methylated DEA in headgroups. TEA is not metabolized in the liver or incorporated into phospholipids. TEA, however, is readily eliminated in urine. Repeated oral administration to rats (7 d/wk, 24 wk) at dose levels up to and including 1600 mg kg-1 d-1 produced histopathological changes restricted to kidney and liver. Lesions in the liver consisted of cloudy swelling and occasional fatty changes, while cloudy swelling of the convoluted tubules and loop of Henle were observed in kidneys. Chronic administration (2 yr) of TEA in drinking water (0, 1%, or 2% w/v; 525 and 1100 mg kg-1 d-1 in males and 910 and 1970 mg kg-1 d-1 in females) depressed body and kidney weights in F-344 rats. Histopathological findings consisted of an "acceleration of so-called chronic nephropathy" commonly found in the kidneys of aging F-344 rats. In B6C3F1 mice, chronic administration of TEA in drinking water (0, 1%, or 2%) produced no significant change in terminal body weights between treated and control animals or gross pathological changes. TEA was not considered to be carcinogenic. Systemic effects in rats chronically administered TEA dermally (0, 32, 64, or 125 mg kg-1 d-1 in males; 0, 63, 125, or 250 mg kg-1 d-1 in females) 5 d/wk for 2 yr were primarily limited to hyperplasia of renal tubular epithelium and small microscopic adenomas. In a companion mouse dermal study, the most significant change was associated with nonneoplastic changes in livers of male mice consistent with chronic bacterial hepatitis.

High prevalence of adenomas and microadenomas of the duodenal papilla and periampullary region in patients with familial adenomatous polyposis.

Patients with familial adenomatous polyposis (FAP) are traditionally considered to be at high risk for duodenal-papillary and periampullary adenomas and cancer. To evaluate prospectively the prevalence, histology and clinical significance of ampullary and periampullary macroscopic and microscopic lesions in our population of affected patients. Three gastroenterological departments of northern Italian hospitals. Twenty-five affected patients were carefully investigated over a 24-month period by end-viewing and side-viewing upper panendoscopy. Biopsies were performed on representative macroscopic lesions and randomly on normal-appearing papillary and periampullary mucosa. Seven patients had macroscopic adenomas of the duodenal papilla, three of the periampullary region and five at both sites (cumulative prevalence 40%). An additional six patients had macroadenomas in the rest of the duodenum (overall prevalence 64%). Microscopic adenomas were identified in nine and two patients in the papilla and periampullary region, respectively, and in three at both sites (overall prevalence 44%). Thus, a total of 17 (68%) patients presented macro- or microadenomas at these locations. The prevalence rose to 72%, when a further patient with macroadenomas in the rest of the duodenum only was included. Malignancy was not encountered and severe dysplasia was observed only in a macroadenoma of the second duodenal portion. A higher frequency of macroadenomas in the papilla and periampullary region was significantly correlated with the presence and number of such lesions in the rest of the duodenum (P = 0.04). No other significant association was detected either between micro- or macroadenomas at different sites or with the demographic, clinical and pathological features. This study confirms that the duodenal papilla and periampullary region are sites with high prevalence of macro- and microscopic adenomas in patients with FAP. However, our data do not seem to support a higher frequency and malignancy potential of such lesions as compared to polyps in the rest of the duodenum. Nevertheless, these findings warrant a periodic, careful examination of the duodenum with either end-viewing or side-viewing endoscopy, the need for random biopsies of the papilla and periampullary region and the removal of any larger or rapidly growing lesions detected.

Chromosome abnormalities in colorectal adenomas: Two cytogenetic subgroups characterized by deletion of 1 p and numerical aberrations

Cytogenetic analysis of short-term cultures from 34 benign colorectal polyps, all histologically verified as adenomas, revealed clonal chromosome aberrations in 21 of them. Eight polyps had structural rearrangements, whereas only numerical changes were found in 13. A combination of structural and numerical chromosomal aberrations was found in three polyps. The most common numerical change was gain of chromosome 7, found either as the sole anomaly (five polyps), together with other numerical changes (six polyps), or together with structural rearrangements (two polyps). Other recurrent numerical changes were +20, +13, and monosomy 18, found in six, five, and two adenomas, respectively. Rearrangement of chromosome 1 was the most common structural change. Abnormalities involving lp were seen in six adenomas, leading to visible loss of material in three. One adenoma had one clone with a large and another with a small 1p deletion. In three adenomas, del(1)(p36) was the only cytogenetic aberration, supporting the authors' previous conclusion that loss of one or more gene loci in band lp36 is a common early change in colorectal tumorigenesis. Chromosome 8 was involved in structural changes in two adenomas; in one this led to loss of 8p and in the other to gain of 8q. The cytogenetic findings did not correlate in a statistically significant manner with clinicopathologic parameters, such as grade of dysplasia, macroscopic or microscopic adenoma structure, tumor size and location, or the patients' sex and age.

Spontaneous Renal Cell Tumors in Long‐Evans Cinnamon Rats

Neoplastic lesions of the kidneys in untreated Long‐Evans Cinnamon (LEC) rats of 57–118 weeks old (85 males and 34 females) and male F344 rats of 64–93 weeks old (59 males) were examined histologically. The incidences of renal cell tumors in male and female LEC rats were 6/80 (8%) in weeks 57–65, 3/19 (16%) in weeks 66–75, 3/8 (38%) in weeks 76–105 and 7/12 (58%) in weeks 106–118. Of these tumors, 13 were microscopic adenomas and 7 were renal cell carcinomas. The copper content of the kidneys was about three times higher in LEC rats than in F344 rats (P<0.001), but the iron content of the kidneys was similar in the two strains.

The expression of stage-specific embryonic antigen 1 in the noncancerous colorectal epithelia of familial polyposis coli.

The epithelial expression of carbohydrate antigen, stage-specific embryonic antigen 1 (SSEA-1) was examined immunohistochemically in noncancerous specimens from patients with familial polyposis coli, and compared with the colorectal epithelia from patients with sporadic colorectal cancer. In mucosa remote from carcinoma of sporadic cases, SSEA-1 was expressed only faintly in the lower crypts. In mucosa adjacent to carcinoma of sporadic cases, SSEA-1 was expressed not only in the lower crypts but also in the upper crypts. These results corresponded to those observed in the authors' previous study. In the flat mucosa of familial polyposis coli cases, SSEA-1 was detected not only in the lower crypts, but also in both upper crypts and the surface epithelium in contrast with the flat mucosa of sporadic cases. The staining pattern in the upper crypts of the flat mucosa of familial polyposis coli cases was very similar to that of the mucosa adjacent to carcinoma of sporadic cases, but was stronger and more diffuse in the surface epithelium. In microscopic adenomas, SSEA-1 was expressed diffusely. These results demonstrate that the flat mucosa of patients with familial polyposis coli shows preneoplastic changes similar to those in the mucosa adjacent to carcinoma of sporadic cases, and that SSEA-1 is related to adenoma formation in the early stage of carcinogenesis in the colorectum. In addition, the results suggest that immunohistochemical studies of flat mucosa may be useful for the early detection of high-risk individuals in a familial polyposis coli family.

Acquired cystic disease of the kidney in association with chronic ambulatory peritoneal dialysis.

A combined necropsy and ultrasound study in patients with end-stage renal disease treated exclusively by peritoneal dialysis revealed acquired cystic disease of the kidney (ACDK) in five of 15 necropsies and in one of seven sonograms from living patients. Two benign microscopic adenomas were also found in the first group of patients. No malignant renal tumors or hemorrhagic complications were detected. The cause of the cyst formation is clearly related to chronic renal failure rather than dialysis per se, as one patient had cysts prior to CAPD and seven of 41 patients with end-stage renal disease in the predialysis era were found to have renal cysts on postmortem examination. This study shows that ACDK is not uncommon in patients with chronic renal failure treated by chronic ambulatory peritoneal dialysis.