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In the review the role of HPV infection in development of diseases of anogenital area and methods of diagnostics and treatment of HPV infection of anogenital area is considered. Pathogenetic justification of application of preparations with immunomodulatory action is given in complex treatment of the diseases associated with HPV infection.

The review examined the role of HPV in anogenital diseases. There are presented modern data on the prevalence of anal intraepithelial neoplasia (AIN), HPV infection of the anal region among women at risk (cervical intraepithelial neoplasia - CIN, vulvar - VIN, vaginal - VaIN). There are considered methods of diagnosis of HPV-associated anogenital diseases. Analyzes the literature on the importance of the development of screening AIN in patientswith CIN, VIN, VaIN. There are presented data of the preliminary results of the research of HPV infection of the anal region in patients with genital neo-plasias, the data on different tropism of HPV to cervical epithelium and the epithelium of the anal region.

Introduction: Human papillomavirus (HPV) vaccination rates nationally are low. This study determined if an electronic point-of-care prompt in the retail clinic setting increases HPV vaccination rates among an eligible population.Study Design: An interrupted time series assessed change in weekly HPV vaccination rates with the introduction of an electronic point-of-care prompt and rate change in post-intervention period.Setting/participants: The study sites were two similar retail care clinics in Rochester, Minnesota. Participants were patients who presented to the retail clinics setting between the ages of 9 and 26 years from September 12, 2016, to September 30, 2017.Intervention: HPV vaccine (nonavalent) was made available at both retail clinics. Staff completed a 2-hour lecture on HPV vaccine and one-on-one training for use of the prompt. Pre- and post-intervention rates of HPV vaccination after initiation of electronic point-of-care prompt were measured. A satisfaction survey was given to all patients or parents/guardians between the ages of 9 and 26 years regardless of HPV vaccine status.Main Outcome Measures: HPV vaccination rates per week before and after the introduction of the electronic point-of-care prompt along with satisfaction with HPV vaccine availability and the point-of-care prompt in the retail clinic setting. Data analysis was completed January 2018.Results: The point-of-care prompt increased the median weekly HPV vaccination rate by 8.6 per 100 patient visits (95% CI=5.8, 11.5, p<0.001). Patients thought it was convenient having HPV vaccine available and helpful to be reminded of the need for HPV vaccine.Conclusions: This study demonstrates a significant increase of HPV vaccine rates in the retail clinic setting with use of a point-of-care prompt. [ABSTRACT FROM AUTHOR]

Background: Short-term studies have reported that the fecal immunochemical test (FIT) is less accurate in detecting proximal than distal colorectal neoplasia.Objective: To assess the long-term detection rates for advanced adenoma and colorectal cancer (CRC), according to anatomical location.Design: Retrospective study.Setting: Population-based, organized screening program in the Veneto region of Italy.Participants: Persons aged 50 to 69 years who completed 6 rounds of FIT screening.Measurements: At each screening round, the detection rates for advanced adenoma and cancer, as well as the proportional interval cancer rate (PICR), were calculated by anatomical location (proximal colon, distal colon, or rectum).Results: Between 2002 and 2014, a total of 123 347 participants had 441 647 FITs. The numbers of advanced adenomas and cancer cases detected, respectively, were 1704 and 200 in the proximal colon, 3703 and 324 in the distal colon, and 1220 and 209 in the rectum. Although the detection rate for proximal colon cancer declined only from the first to the second screening round (0.63 to 0.36 per 1000 screenees), the rate for both distal colon and rectal cancer steadily decreased across 6 rounds (distal colon, 1.65 in the first round to 0.17 in the sixth; rectum, 0.82 in the first round to 0.17 in the sixth). Similar trends were found for advanced adenoma (proximal colon, 5.32 in the first round to 4.22 in the sixth; distal colon, 15.2 in the first round to 5.02 in the sixth). Overall, 150 cases of interval cancer were diagnosed. The PICR was higher in the proximal colon (25.2% [95% CI, 19.9% to 31.5%]) than the distal colon (6.0% [CI, 3.9% to 8.9%]) or rectum (9.9% [CI, 6.9% to 13.7%]).Limitations: Participants with irregular attendance were censored. Those who had a false-positive result on a previous FIT but negative colonoscopy results were included in subsequent rounds.Conclusion: This FIT-based, multiple-round, long-term screening program had a negligible reduction in detection rates for neoplastic lesions in the proximal versus the distal colon after the first round. This was related to a higher PICR in the proximal colon and suboptimal efficacy in preventing the age-related proximal shifting of CRC.Primary Funding Source: None. [ABSTRACT FROM AUTHOR]

Objective: To describe ultrasound (US) and pathologic findings in 11 patients with multiple, synchronous lesions of different histology within the same testis.Materials and Methods: We reviewed US and pathologic findings in 11 patients with multiple, synchronous lesions of different histology within the same testis. Lesions were classified as separate or adjacent one to another and attempt was made to predict tumor type on their US textures. Pathologic review assessed presence of normal tissue between adjacent lesions and of Germ Cell Neoplasia In Situ in surrounding parenchyma. Nine cases were from files specifically dedicated to testicular tumors and estimated prevalence was calculated.Results: Two nodules were seen in nine patients and 3 in remaining two. Nine had tumors of different histology; two had one malignancy and one focal benign lesion. Germ Cell Neoplasia In Situ was seen in 7/11 cases. In dedicated archives, these lesions had 1.83% prevalence.Conclusion: Multiple focal lesions identified at imaging within the testis are not always of the same histology. This can be suspected in some cases basing on US texture. Recognition that lesions are multiple and an indication of their locations within the testis is the most important role of imaging and may help pathologists correctly sample the specimen to establish nature of each of them. Presence of multiple lesions is regarded as a contraindication to testicular sparing surgery. In two of our patients, one lesion was benign. Then, when the procedure is indicated all lesions have to be sampled and assessed by pathologists before deciding between conservative or radical technique. [ABSTRACT FROM AUTHOR]

Background: Obesity and metabolic syndrome are risk factors for colorectal neoplasia (CRN). However, the association between metabolically healthy obese (MHO) or metabolically unhealthy non-obese (MUNO) status and the risk of CRN remains unclear.Aims: We aimed to elucidate the association between MHO or MUNO status and the risk of CRN.Methods: A total of 139,023 asymptomatic subjects who underwent a primary screening colonoscopy were categorized into 4 groups according to obesity and metabolic status: metabolically healthy non-obese (MHNO), MHO, MUNO, and metabolically unhealthy obese (MUO).Results: Mean participant age was 41.0 years, and the proportion of men was 65.3%. Among men, the risk of overall CRN increased in MHO (adjusted odds ratio [AOR] 1.22, 95% confidence intervals [CI] 1.12-1.33), MUNO (AOR 1.25, 95% CI 1.18-1.31), and MUO groups (AOR 1.47, 95% CI 1.40-1.54) compared with the MHNO group, whereas the risk of advanced CRN (ACRN) increased in MUNO (AOR 1.16, 95% CI 1.002-1.33) and MUO groups (AOR 1.49, 95% CI 1.31-1.70), but not in the MHO group (AOR 0.92, 95% CI 0.70-1.21). Moreover, among non-obese men, the risk of overall CRN and ACRN linearly increased with an increasing number of metabolic abnormalities. However, among women, only the MUO group had an increased risk of overall CRN (AOR 1.34, 95% CI 1.21-1.47) and no other significant associations were observed.Conclusions: Poor metabolic health, regardless of obesity, is an independent risk factor for CRN in men. Our results suggest that men with metabolic abnormalities should be considered as a high-risk group for colorectal cancer, even if they are not obese. [ABSTRACT FROM AUTHOR]

Objectives: HIV‐infected individuals are at increased risk of anal cancer. Screening for anal cancer precursors using high‐resolution anoscopy (HRA) may be clinically beneficial. In this study, we examined patient tolerability of this procedure. Methods: The acceptability of HRA was evaluated among HIV‐infected patients who completed a first‐time HRA between July 2008 and December 2013 at Kaiser Permanente Northern California. We reviewed electronic medical records to identify lack of HRA acceptability, which was defined as receipt of HRA with sedation, dispensation of opioid analgaesia, and/or an urgent care visit following HRA, and to evaluate factors associated with patients not returning for a recommended repeat HRA (proxy for HRA acceptability). HRA acceptability was also assessed via a survey mailed to patients who completed HRA between January 2014 and August 2014. Logistic regression was used to model lack of acceptability of initial HRA and likelihood of not returning for a repeat HRA. Results: Of 1857 HIV‐infected patients, 94 were prescribed opioids and one had an urgent care visit. Lack of HRA acceptability was more likely in patients with pre‐existing anal conditions [e.g. warts or fissure; adjusted odds ratio (aOR) 4.02; 95% confidence interval (CI) 2.4–6.7], those who had ever smoked (aOR 1.6; 95% CI 1.0–2.5) and women (aOR 5.3; 95% CI 1.6–17.5). Fifty per cent of patients returned for a repeat HRA, with younger patients less likely to return (per 10‐year age interval, aOR 0.8; 95% CI 0.7–0.9). Of 48 survey respondents, 91.7% reported acceptable pain levels and all reported willingness to return for a repeat HRA. Conclusions: HRA was generally well tolerated and may be an acceptable screening approach for patients at high risk of anal cancer. [ABSTRACT FROM AUTHOR]

Despite the progress made in the reduction of squamous cell carcinoma of the cervix, the incidence of anal squamous cell carcinoma (ASCC) has been increasing since 1992. While it remains an uncommon disease, the prevalence is climbing steadily. Among human immunodeficiency virus (HIV)-infected adults, especially men who have sex with men, ASCC is one of the more common non-AIDS-defining malignancies. The precursor lesion, anal intraepithelial neoplasia (AIN), is prevalent in the HIV-infected population. More than 90% of ASCCs are related to human papilloma virus (HPV), oncogenic types (HPV 16, 18). While the biology of HPV-related intraepithelial neoplasia is consistent in the anogenital area, the natural history of AIN is poorly understood and is not identical to cervical intraepithelial neoplasia (CIN). CIN is also considered an AIDS-defining malignancy, and the methods for screening and prevention of AIN are derived from the CIN literature. This article will discuss the epidemiology of ASCC and its association with HPV and the life cycle of the HPV, and the molecular changes that lead to clearance, productive infection, latency, and persistence. The immunology of HPV infection will discuss natural immunity, humoral and cellular immunity, and how the HPV virus evades and interferes with these mechanisms. We will also discuss high-risk factors for developing AIN in high-risk patient populations with relation to infections (HIV, HPV, and chlamydia infections), prolonged immunocompromised people, and sexual behavior and tobacco abuse. We will also discuss the pre- and post-HAART era and its effect on AINs and ASCC. Finally, we will discuss the importance of anal cytology and high-resolution anoscopy with and without biopsy in this high-risk population. [ABSTRACT FROM AUTHOR]

Anal intraepithelial neoplasia (AIN) is the premalignant condition of the anal squamous tissue. It is associated with the human papilloma virus and is considered the transition prior to the invasive anal squamous cell carcinoma. It is typically asymptomatic and can be either an incidental finding after anorectal surgery or identified when high-risk patient populations are screened. Once AIN is diagnosed, the optimal management remains controversial, partly because the natural history of the disease is unclear. Surgical management of the disease has essentially been replaced by more conservative treatment options and can range from expectant management to topical therapy to photodynamic therapy. The aim of this article is to review the varied treatment options and to briefly review prevention strategies. [ABSTRACT FROM AUTHOR]

Anal squamous cell carcinoma is a relatively rare diagnosis, but its incidence has continued to rise. Anal squamous cell carcinoma and its precursor lesion, anal intraepithelial neoplasia (AIN), are human papillomavirus (HPV)-associated squamous neoplasias. High-risk HPV subtypes cause cellular proliferation in the anal transformation zone mucosa leading to similar dysplastic changes as seen in the cervix. Unified cytologic and histologic classification systems have emerged for all HPV-associated squamous lesions of the lower anogenital tract due to recent advancements in the understanding of these lesions. P16 immunohistochemical stain, a biomarker for HPV, is recommended in the diagnosis of HPV-associated lesions. The unity of terminology will aid in communication between pathologists and clinicians, ultimately leading to improved patient care. [ABSTRACT FROM AUTHOR]

Human papillomavirus (HPV) infection is responsible for 4.3% of the global cancer burden. Since 2006, current HPV vaccines have reduced the prevalence of the virus in adolescent girls, reduced the prevalence of genital warts, and been proven to reduce the progression of anal intraepithelial neoplasia in men. Herein, we review the epidemiology, virology, and immunology behind the prophylactic HPV vaccines and current recommendations for its use. We also review future immune therapies being trialed for use against HPV-related cancers including anal cancer. [ABSTRACT FROM AUTHOR]

Background Information on the performance of anal cytology in women who are high risk for human papillomavirus–related lesions and the factors that might influence cytology are largely lacking. Methods Retrospective study including all new referrals of women with a previous history of anogenital neoplasia from January 2012 to July 2017, with concomitant anal cytology and high-resolution anoscopy with or without biopsies. Results Six hundred and thirty six anal cytology samples and 323 biopsies obtained from 278 women were included. Overall sensitivity and specificity of "any abnormality" on anal cytology to predict any abnormality in histology was 47% (95% confidence interval [CI], 41%–54%) and 84% (95% CI, 73%–91%), respectively. For detecting high-grade squamous intraepithelial lesions (HSIL)/cancer, sensitivity was 71% (95% CI, 61%–79%) and specificity was 73% (95% CI, 66%–79%). There was a poor concordance between cytological and histological grades (κ = 0.147). Cytology had a higher sensitivity to predict HSIL/cancer in immunosuppressed vs nonimmunosuppressed patients (92% vs 60%, P =.002). The sensitivity for HSIL detection was higher when 2 or more quadrants were affected compared with 1 (86% vs 57%, P =.006). A previous history of vulvar HSIL/cancer (odds ratio [OR], 1.71, 1.08–2.73; P =.023), immunosuppression (OR, 1.88, 1.17–3.03; P =.009), and concomitant genital HSIL/cancer (OR, 2.51, 1.47–4.29; P =.001) were risk factors for abnormal cytology. Conclusions Women characteristics can influence the performance of anal cytology. The sensitivity for detecting anal HSIL/cancer was higher in those immunosuppressed and with more extensive disease. [ABSTRACT FROM AUTHOR]

Abstract: Aim: Chemoradiotherapy remains the first line of treatment for anal cancer with surgery reserved for cancer recurrence or persistence. The low incidence of anal cancer means that the numbers undergoing surgery is small with centralization for excision to regional cancer centres. We present our experience of abdominal perineal excision, with reconstruction of the perineal defect (APERR), within a tertiary centre. Method: Over a 15‐year period, data were collected retrospectively from notes of patients who underwent an APERR. The aim was to look at disease‐free and overall survival and complications associated with flap reconstruction. Results: In the study period, 29 patients [median age = 62 (range: 42–81; interquartile range: 54–68) years] underwent APERR. Median follow‐up was 77 (4–200) months. Thirteen patients died during follow‐up; eight from their disease, with a median survival time of 16 (4–63) months. Five‐year survival was 67%. Nine (31%) patients had recurrence during the follow up period; this was local (n = 2), regional (n = 4), distant (n = 2) or a combination (n = 1). Sixteen (55%) patients developed 24 complications, including nine (31%) flap complications and 10 (34%) parastomal hernias. Flap complications were flap failure (n = 1) requiring direct closure, flap dehiscence (n = 2), necrosis of flap tip (n = 1), wound infection (n = 4) and a bulky flap (n = 1) requiring liposuction. Conclusion: APERR of anal cancer is a feasible technique with excellent oncological treatment and acceptable long‐term complications, although a higher than expected rate of parastomal hernia was noted. [ABSTRACT FROM AUTHOR]

Abstract Anal squamous cell carcinoma (SCC) is a rare cancer and accounts for approximately 4% of all cancers of the lower alimentary tract. The dominant etiology is infection with human papilloma virus (HPV), which is the most common sexually transmitted disease in the United States. Integration of HPV DNA into the host genome seems to be the driving mechanism behind carcinogenesis. Vaccines directed against oncogenic HPV serotypes exist, and their utility for preventing anal neoplasia is under investigation. Additional risk factors for developing SCC include HIV infection, anal receptive intercourse, smoking, and immunosuppression. Patients with known anal intraepithelial neoplasia (AIN) must be carefully screened with periodic digital rectal exam and anoscopy. The most common presenting symptom is bleeding, with up to one third of patients presenting asymptomatic. Once tissue diagnosis is made, staging of primary tumor is accomplished with either MRI or transanal ultrasound. Distant disease is evaluated with CT of chest abdomen and pelvis vs whole body PET/CT. The gold standard treatment for stage I-III disease remains the Nigro protocol, first described in 1974. Stage I disease not involving sphincter may be treated with local excision. Distant disease is treated with systemic chemotherapy with radiation reserved for locoregional symptoms. Careful surveillance is mandatory after completion of chemoradiation. Salvage abdominoperineal resection can achieve locoregional control in up to 77% of patients with persistent or recurrent disease. Morbidity is high, mostly owing to wound complications, and as such a flap reconstruction of the perineum is warranted. [ABSTRACT FROM AUTHOR]

Anal intraepithelial neoplasia (AIN) and anal squamous cell carcinoma (ASCC) are on the rise in the United States, especially among men who have sex with men, HIV-positive or other immunocompromised patients, and women with a history of cervical, vaginal, or vulvar cancer. Strong evidence supports the human papillomavirus as the causative factor in anal dysplasia; reducing the risk of HPV infection can reduce rates of ASCC. High-risk patients should be screened for AIN, but no universal screening guidelines exist, and more studies are needed to develop a national protocol for screening and management of patients with AIN. [ABSTRACT FROM AUTHOR]

Background: There is uncertainty as to the appropriate follow-up of patients who test positive on multimarker stool DNA (sDNA) testing and have a colonoscopy without neoplasia.Aims: To determine the prevalence of missed colonic or occult upper gastrointestinal neoplasia in patients with an apparent false positive sDNA.Methods: We prospectively identified 30 patients who tested positive with a commercially available sDNA followed by colonoscopy without neoplastic lesions. Patients were invited to undergo repeat sDNA at 11-29 months after the initial test followed by repeat colonoscopy and upper endoscopy. We determined the presence of neoplastic lesions on repeat evaluation stratified by results of repeat sDNA.Results: Twelve patients were restudied. Seven patients had a negative second sDNA test and a normal second colonoscopy and upper endoscopy. In contrast, 5 of 12 subjects had a persistently positive second sDNA test, and 3 had positive findings, including a 3-cm sessile transverse colon adenoma with high-grade dysplasia, a 2-cm right colon sessile serrated adenoma with dysplasia, and a nonadvanced colon adenoma (p = 0.045). These corresponded to a positive predictive value of 0.60 (95% CI 0.17-1.00) and a negative predictive value of 1.00 (95% CI 1.00-1.00) for the second sDNA test. In addition, the medical records of all 30 subjects with apparent false positive testing were reviewed and no documented cases of malignant tumors were recorded.Conclusions: Repeat positive sDNA testing may identify a subset of patients with missed or occult colorectal neoplasia after negative colonoscopy for an initially positive sDNA. High-quality colonoscopy with careful attention to the right colon in patients with positive sDNA is critically important and may avoid false negative colonoscopy. [ABSTRACT FROM AUTHOR]

Abstract: Background: Esophago‐gastric junction (EGJ) outflow obstruction is of unclear significance. Rapid drink challenge (RDC) test is easy to perform during esophageal high resolution manometry. We aimed to assess the yield of RDC test in patients with EGJ outflow obstruction. Methods: Manometry studies of patients with EGJ outflow obstruction according to the Chicago Classification v3.0 were retrospectively reviewed. Pan‐esophageal pressurization (PEP), esophageal shortening, and pressure gradient across the EGJ were analyzed during RDC test (200‐mL free drinking in sitting position) and compared according to the causes of EGJ outflow obstruction determined by charts review. Key Results: Seventy‐five patients (29 males, mean age 62 years) were included. Causes of EGJ outflow obstruction were previous esophago‐gastric surgery (40%), incomplete form of achalasia (7%), mediastinal neoplasia (7%), other associated conditions (21%), and undetermined (25%). Rapid drink challenge test was successfully performed in 70 patients and associated with PEP and shortening in 41% and 13%, respectively. The causes of EGJ outflow obstruction were similarly distributed in patients with and without PEP during RDC test. Esophageal shortening tended to be more likely in patients with definitive findings of obstruction (achalasia, previous surgery, neoplasia) than in the others. Dysphagia was more severe in patients with PEP and/or shortening during RDC test compared to those without. Conclusions & Inferences: Pan‐esophageal pressurization and esophageal shortening were associated with symptoms severity but did not predict the cause of this disorder. Further prospective studies are necessary to determine if RDC test could help to select patients who might benefit from treatment. [ABSTRACT FROM AUTHOR]

Objective This study aimed to demonstrate the predictive value of miR-21-5p, miR-34a, and human telomerase RNA component (hTERC) in cervical cancer (CC) development and evaluated their potential possibility for future clinical applications. Methods Specimens were collected from the normal cervix, cervical intraepithelial neoplasia (CIN) I, CIN II/III, cervical squamous cell carcinoma. Cytological evaluations and histopathologic examinations were conducted in all subjects, along with the assessment of human papillomavirus (HPV) DNA. The expression levels of the miR-21-5p and miR-34a were detected by RT-PCR. hTERC amplification was detected by dual-color interphase fluorescence in situ hybridization (FISH). Then miRNA, hTERC expressions were compared with the cytological and histologic examination. Results Compared to that in the benign samples, the expression of miR-21-5p and miR-34a in abnormal samples was significantly upregulated and downregulated, gradually corresponding to the severity of cervical lesions (P < 0.05). There was a trend toward an increasing amplification of hTERC with the increasing severity of cervical lesions. miR-21-5p and miR-34a expression, and hTERC amplification were more specific than HPV positivity in differentiating low-grade cervical disorders from high-grade ones (P < 0.05). Conclusions MiR-21-5p upregulation, miR-34a downregulation, and hTERC amplification were associated with the aggressive progression of CC, which suggests that miR-21-5p, miR-34a and hTERC might serve as surrogate markers for CC progression and potential molecular targets for blockage of the development of CC. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the prevalence of anal intraepithelial lesions and associated risk factors in women with cervical neoplasia.Methods: The present cross-sectional study enrolled patients with intraepithelial or invasive cervical neoplasia who had been referred to the lower genital tract pathology outpatient department of the Instituto de Medicina Integral Prof. Fernando Figueira, Recife, Brazil, between December 1, 2008, and December 31, 2009; patients with HIV infections were excluded. All participants underwent anal cytology and high-resolution anoscopy; sociodemographic and clinical risk factors were identified using multivariate analysis.Results: There were 324 patients included and 37 (11.4%) had anal intraepithelial neoplasia. Factors associated with anal intraepithelial neoplasia in the multivariate analysis were being older than 35 years of age (P=0.002), having completed no more than 4 years of education (P=0.012), anomalous anal cytology (P=0.003), and anomalous high-resolution anoscopy findings (P<0.001); subclinical HPV lesions on vulvoscopy (P=0.057) were not associated with anal intraepithelial neoplasia.Conclusion: The prevalence of anal intraepithelial neoplasia was high among patients with cervical neoplasia who did not have HIV, particularly patients older than 35 years. [ABSTRACT FROM AUTHOR]

Background: Canine Transmissible Venereal Tumor (cTVT) is a neoplasia that affects mainly the genital organs of dogs, but can rich extragenital sites as well. It's a tumor characterized microscopically by the presence of vacuolized round cells. Transmission occurs by implantation of these cells in non-affected tissues and the treatment is based on vincristine chemotherapy. Cases: Case 1. A 5-year-old intact male Poodle, presenting an increase volume of nasal plane came for veterinary care at a private veterinary clinic. The animal had bilateral bloody nasal secretion and dyspnea. The external genitalia had no alterations. The cytological evaluation confirmed cTVT. Treatment with vincristine sulfate weekly showed a rapid response with improvement of the respiratory condition, total remission of the mass and absence of neoplastic cells in cytology. Case 2. A 5-year-old mixed-breed canine bitch, weighing 6.7 kg, was brought to the State University of Santa Cruz Veterinary Hospital (UESC-VH), showing an increase volume in the nasal plan region, with complaints about sneezing, nasal bleeding, respiratory distress with approximately 4 months of evolution. The owner informed that the mother of these female dog, that lived in the same environment, died a month before the beginning of clinical signs of the bitch of this case, and showed a reddish vaginal mass with intense bleeding. Intranasal exfoliative cytology showed moderately cellular sample compatible with cTVT. The treatment with vincristine sulphate for 6 weeks, showed completely remission of all clinical signs. Case 3. A 3-year-old mixed-breed male dog was brought to the UESC-VH with a reddish, friable mass located in the left eye. The citology confirmed the clinical suspicion of cTVT. After six weekly sessions of chemotherapy with vincristine sulfate, the tumor regressed and a new cytological evaluation was performed, without visible of tumor cells. By the end of the treatment, the dog was diagnosed with phitisis bulbi, and one year later, due to recurrent ulcerative keratitis, the enucleation was performed and the histopathological examination of the eye did not identify the presence of tumor cells. Discussion: Two of the dogs cited in this report had freely streets access, without supervision of the owners, and they are likely to have contracted cTVT on one of those occasions. The animal's care style acts as a risk factor for the development of neoplasia. Regarding the third animal, the close contact with another female dog, who had compatible vaginal cTVT clinical signs was probably the factor that determined the transmission. None of the animals cited in this report had lesions on their external genitalia. The extragenital presentation may be attributed to the social behavior of licking and sniffing the genitalia of carrier animals, which may lead to the natural implantation of the viable cells of the cTVT into the ocular and nasal mucosa. About the clinical signs manifested, in the cases of involvement of the nasal structures, the main signs described in literature are bloody nasal secretion, sneezing, dyspnea and increased nasal plane volume, and are similar to those observed in the animals cited in this report. In the case of ocular cTVT, the increase volume with impairment and deformity of all ocular structures, as well as pain and pruritus corroborate with the clinical findings observed in the literature. The cytopathological test was the diagnostic tool used in all cases cited in this report and the cytopathological findings corroborates with those described in the literature. Vincristine sulfate is the drug of choice for the treatment of cTVT cases, and in the dogs of this report, this drug was successfully used leading to complete remission of lesions and clinical signs, as observed in other studies. [ABSTRACT FROM AUTHOR]

The aging of the on-dialysis population raises the issue of whether to propose elderly patients for kidney transplantation and how to manage their immunosuppression. This study aimed to analyze the outcome of kidney transplantation on an Italian series of elderly recipients. We included in this retrospective study all patients over 60 years, receiving a deceased-donor kidney transplantation from January 2004 to December 2014 in two north Italian Centers. We analyzed the correlation of recipient age with graft's and patient's survival, delayed graft function, acute cellular rejection ( ACR), surgical complications, infections, and glomerular filtration rate. Four hundred and fifty-two patients with a median age of 65 years were included in the study. One-, 3-, and 5-year patient's and graft's survival were, respectively, of 98.7%, 93%, 89% and 94.4%, 87.9%, 81.4%. The increasing recipient age was an independent risk factor only for the patient's ( P=.008) and graft's survival ( P=.002). ACR and neoplasia were also associated to a worse graft survival. The reduced graft survival in elderly kidney recipients seems to be related more to the increasing recipient's age than to the donor's features. In this population, the optimization of organ allocation and immunosuppression may be the key factors to endorse improvements. [ABSTRACT FROM AUTHOR]

Objective. Anal cytology is being increasingly used as part of anal cancer screening in patients at high risk for anal neoplasia. Most studies in anal cytology have focused on correlating the abnormal anal Pap smear with histopathologic outcomes. The aim of this study was to document histopathologic or repeat anal cytology outcomes in patients with unsatisfactory cytology. Materials and Methods. Unsatisfactory anal Pap tests in high risk male patients were correlated with follow-up histopathologic diagnoses or cytology. Results. 1205 anal tests were performed during the study period and 214 (17.8%) were unsatisfactory. Adequate follow-up cytology was available in 75 cases and revealed epithelial cell abnormality (ECA) in 40% [30/75] (atypical squamous cells of undetermined significance (ASCUS) [20%] and low-grade squamous intraepithelial lesions (LGSIL) [20%]) and was negative for intraepithelial lesion or malignancy (NILM) in 60% [45/75] of cases. 28.7% of unsatisfactory Pap smears had unsatisfactory repeat cytology. Histopathological follow-up on these unsatisfactory Pap smears revealed anal intraepithelial neoplasia (AIN) 1 and AIN 2/3 or 2/3+ in 39% and 18% of the total number of biopsy cases, respectively. Conclusions. High risk male patients with unsatisfactory Pap smears are at significant risk of epithelial cell abnormality and histopathologically verifiable anal intraepithelial lesions. [ABSTRACT FROM AUTHOR]

Background: Safety and immunogenicity of the quadrivalent human papillomavirus (qHPV) vaccine were evaluated in HIV-positive Spanish MSM. The prevalence of High Squamous Intraepithelial Lesions (HSIL) and genotypes of high-risk human papillomavirus (HR-HPV) were also determined, as well as risk factors associated with the presence of HR-HPV in anal mucosa. Methods: This is a randomised, double blind, placebo-controlled trial of the quadrivalent HPV (qHPV) vaccine. The study enrolled from May 2012 to May 2014. Vaccine and placebo were administered at 0, 2 and 6 months (V1, V2, V3 clinical visits). Vaccine antibody titres were evaluated at 7 months. Cytology (Thin Prep® Pap Test), HPV PCR genotyping (Linear Array HPV Genotyping Test), and high-resolution anoscopy (Zeiss 150 fc© colposcope) were performed at V1. Results: Patients (n = 162; mean age 37.9 years) were screened for inclusion; 14.2% had HSIL, 73.1% HR-HPV and 4.5% simultaneous infection with HPV16 and 18. Study participants (n = 129) were randomized to qHPV vaccine or placebo. The most common adverse event was injection-site pain predominating in the placebo group [the first dose (83.6% vs. 56.1%; p = 0.0001]; the second dose (87.8% vs. 98.4%; p = 0.0001); the third dose (67.7% vs. 91.9%; p = 0.0001). The vaccine did not influence either the viral load of HIV or the levels of CD4. Of those vaccinated, 76% had antibodies to HPV vs. 30.2% of those receiving placebo (p = 0.0001). In the multivariate analysis, Older age was associated with lower HR-HPV infection (RR 0.97; 95% CI 0.96-0.99), and risk factor were viral load of HIV >200 copies/µL (RR 1.42 95% CI 1.17-1.73) and early commencement of sexual activity (RR 1.35; 95% CI 1.001-1.811). Conclusions: This trial showed significantly higher anti-HR-HPV antibody titres in vaccinated individuals than in unvaccinated controls. There were no serious adverse events attributable to the vaccine. In our cohort, 1 of every 7 patients had HSIL and the prevalence of combined infection by genotypes 16 and 18 was low. This suggests that patients could benefit from receiving qHPV vaccine. Older age was the main protective factor against HR-HPV infection, and non-suppressed HIV viremia was a risk factor. Clinical trial registration: ISRCTN14732216 (http://www.isrctn.com/ISRCTN14732216). [ABSTRACT FROM AUTHOR]

Histological features and genetic profiles of gastric metaplastic tissue are well characterized in humans but not in dogs. The objective of this retrospective study was to better characterize the metaplastic tissue observed adjacent to canine gastric carcinoma. The histological specimens of 91 dogs diagnosed with gastric carcinoma were re-evaluated and Alcian Blue PAS staining at pH 2.5 was performed to find areas of intestinal metaplasia. Metaplasia was histologically classified according to Jass and Filipe classification. From samples with at least one focus of metaplasia, three sections were prepared for histochemical and immunohistochemical staining for p53 and c-erb 2 proteins. 35 of the 91 specimens demonstrated areas of intestinal metaplasia (27% complete and 11% incomplete). Nuclear positive immunolabeling for p53 was detected in 21 out of 35 cases of intestinal metaplasia. Immunohistochemical staining for c-erb 2 was detected in 31 out of 35 cases of intestinal metaplasia. There was a statistically significant correlation between c-erb2 and p53 expression in metaplastic tissue and in the adjacent neoplasia. [ABSTRACT FROM AUTHOR]

Anal squamous cell carcinoma (SCC) is the fourth most prevalent cancer in human immunodeficiency virus (HIV)-infected men who have sex with men (MSM). Human papillomavirus (HPV) has been detected in over 90% of anal carcinoma biopsy specimens from MSM, and is considered a necessary, but alone, insufficient factor for carcinogenesis. Anal intraepithelial neoplasia (AIN) may be precursive for SCC, and screening cytology with referral of persons with abnormality for high-resolution anoscopy-guided biopsy, and AIN treatment, has been recommended for prevention. In the absence of either randomized controlled trials or surveillance data demonstrating a reduction in anal SCC incidence, these recommendations were based on analogy with cervical cancer. HPV-mediated genetic changes associated with cervical cancer, and aneuploidy, have been documented in AIN. However, little data exist on the rate of AIN progression to SCC. The treatment of AIN is frequently prolonged and not curative, and if routinized in the care of HIV-infected MSM, would likely be recurring well into their sixth decade of life. Clinical trials demonstrating a reduction in invasive anal carcinoma incidence, as well as acceptable morbidity with repeated AIN destruction, are needed before asking our patients to commit to routine treatment. [ABSTRACT FROM AUTHOR]

Simultaneous canine mammary tumours ( CMTs) are frequently reported in the literature, but few studies have addressed their biological relationship in detail or performed statistical assessments. In this study, 269 canine mammary gland tumours from 216 dogs were categorized using an extended histopathological classification, where semiquantitative and binomial scales enumerated morphological parameters of the tumours. The classification facilitated a statistical study of the biological relationship between simultaneous within-dog tumours. Seventy-seven percent of the dogs had single tumours and 23% had simultaneous tumours. Sixty-one percent of the neoplasias were benign, with complex adenoma as the most frequent diagnosis and 39% were malignant, with complex carcinoma as the most common malignancy. Simultaneous tumours within dogs more often had equal diagnoses and neoplastic level (benign or malignant) than would be expected by chance alone, as compared with random pairs of single tumours from different dogs. This statistically supported finding indicated the presence of a biological relationship between simultaneous tumours. [ABSTRACT FROM AUTHOR]

Background Infection with high-risk human papillomaviruses (HPVs) can lead to development of cancer of the head and neck and anogenital regions. G-rich sequences found in genomes of high-risk HPVs can fold into non-canonical secondary structures that could serve as 3D motifs distinct from double-stranded DNA and present recognition sites for ligands and opportunity for gene expression modulation. Methods Combination of UV, CD and NMR spectroscopy and PAGE electrophoresis were used as they offer complementary insights into structural changes of G-rich oligonucleotides. Results G-rich region of HPV16 is shown to preferentially form hairpin structures, while regions of HPV18, HPV52 and HPV58 fold into four-stranded DNA structures called G-quadruplexes. Single nucleotide polymorphisms found in G-rich sequences have been found to promote formation of hairpin structures of HPV16 and have affected number of species formed in G-rich region of HPV52, whereas they have exhibited minimal effect on the formation of HPV18 and HPV58 G-quadruplex structures. These structural changes were reflected in differences in apparent thermal stabilities. Conclusions Potential of G-rich sequences as drug targets was evaluated based on the results of the current study. HPV16 and HPV18 are considered less appropriate targets due to several single nucleotide polymorphisms and low stability, respectively. On the other hand, HPV52 and HPV58 could be used for small-molecule mediated stabilization. General significance G-rich sequences occurring in high-risk HPVs can fold into hairpin and G-quadruplex structures that could be potentially utilized as drug targets. This article is part of a Special Issue entitled "G-quadruplex" Guest Editor: Dr. Concetta Giancola and Dr. Daniela Montesarchio. [ABSTRACT FROM AUTHOR]

Purpose: Radiofrequency ablation (RFA) effectively treats esophageal high-grade dysplasia, but its efficacy in treating anal canal high-grade squamous intraepithelial lesions (HSILs) is unsubstantiated. This prospective study assessed the safety and efficacy of applying hemi-circumferential RFA to anal canal HSIL. Methods: Twenty-one HIV-negative participants with HSIL occupying ≤ half the anal canal circumference were treated with hemi-circumferential anal canal RFA. Participants were assessed every 3 months for 12 months with high-resolution anoscopy; recurrence in the treatment zone was re-treated with focal RFA. Results: Twenty-one participants with a mean of 1.7 lesions (range 1-4) enrolled and completed the trial. Six (29 %) participants had recurrent HSIL within the treated hemi-circumference within 1 year. Four participants (19 %) had persistence of an index lesion at 3 months. One (2.9 %) index HSIL persisted again at 12 months. No participants had more than two RFA treatments. KM curve-predicted HSIL-free survival within the treatment zone at 1 year was 76 % (95 % CI 52-89 %). Comparing the first 7 and last 14 participants, the predicted 1-year HSIL-free survivals are 43 % (95 % CI 10-73 %) and 93 % (95 % CI 59-99 %), respectively ( p = 0.008), suggesting a learning curve with the treating physician. Multivariable analysis showed decreased recurrence in the last 14 participants (HR 0.02; 95 % CI 0.001-0.63) while increasing BMI increased recurrence (HR 1.43, 95 % CI 1.01-2.01). No participants had device or procedure-related serious adverse events, anal stricture, or heavy bleeding. Conclusions: Hemi-circumferential RFA yielded a high rate of anal HSIL eradication in HIV-negative patients at 1 year with minimal adverse events. Lesion persistence was probably related to incomplete initial ablation. [ABSTRACT FROM AUTHOR]

NK cells, which contribute to immune defense against certain viral infections and neoplasia, are emerging as modifiers of chronic immunologic diseases including transplant rejection and autoimmune diseases. Immunobiology and genetic studies have implicated NK cells as a modifier of Crohn's disease, a condition often treated with thiopurine agents such as 6-mercaptopurine (6-MP). Here, we demonstrate that thiopurines mediate NK cell apoptosis via a caspase 3 and 9 inclusive pathway, and that this process is triggered by thiopurine-mediated inhibition of Rac1. We also show that CD patients in clinical remission maintained on 6-MP have decreased NK cell Rac1 activity, and decreased NK cell numbers in their intestinal biopsies. These observations suggest that thiopurine targeting of NK cells may be a previously unappreciated therapeutic action of these agents in IBD. [ABSTRACT FROM AUTHOR]

Background: Prostate cancer involving the rectal wall is rare and may lead to diagnostic pitfalls. Case presentation: Out of 9504 patients with rectal tumors between January 2003 and January 2015, 9 patients (elderly with a mean age of 74 years) with prostate cancer involving the rectal wall were clinically misdiagnosed with rectal cancer. The lesions were located in the rectum, and included 3 circumferential rectal masses, 1 ulceration lesion, 1 crater-like mass, and 4 protruding lesions. Specimens were acquired using biopsy, fine needle aspiration, or resection. The initial symptoms of these patients included rectal urgency, bowel obstruction, and lower gastrointestinal bleeding. Prostate-related symptoms were not obvious. Histologically, 2 cases showed cancer cell invasion in the mucosa, 1 showed transmural invasion from the mucosa to subserosal soft tissues, and 7 cases had submucosa and muscularis propria involvement. All the 9 cases had muscularis propria involvement. However, there were no intraepithelial neoplasias in the mucosal layer, which is reminiscent of rectal carcinoma. The tumors consisted of small-sized or foamy cells that formed acinus-like, duct-like, and cribriform-like structures. We conducted histological staining and an immunohistochemical analysis for CDX-2, prostate-specific antigen (PSA), P504s, villin, carcinoembryonic antigen, CK-pan, cytokeratin 20, and Ki-67. All tumors were PSA and CK-pan positive, 5 of 9 tumors were P504s-positive, and all tumors were negative for the other markers. All patients underwent standard therapy for prostate cancer after the definitive pathological diagnosis. As of March 31, 2015, 8 patients were alive and 1 had died of prostate cancer 6 months posttreatment. Conclusions: Adenocarcinoma appearing in the rectal wall is not always rectal carcinoma. It is necessary to perform a differential diagnosis for prostate cancer in cases of rectal malignant tumors in elderly male patients. Any treatment should be postponed until the final definitive diagnosis is reached. [ABSTRACT FROM AUTHOR]

Background and Aim Colorectal cancer (CRC) incidence is rising among <50-year olds. The objective of this study was to determine screening colonoscopy outcomes among 40- to 49-year olds, which are currently limited. Methods Asymptomatic 40- to 49-year olds underwent one time CRC screening colonoscopy at The Chinese University of Hong Kong between 2007 and 2011. Screening outcomes, including prevalence, distribution, and predictive factors for overall and specifically proximal colorectal neoplasia were determined. Results Among 1133 ethnic Chinese, colorectal neoplasia prevalence was 20.5%. In men, distal adenomas were associated with proximal colorectal neoplasia. Men, advancing age, a first degree relative (FDR) with CRC, and diabetes mellitus were independently associated with colorectal neoplasia. A colorectal neoplasia was three times more likely to be found in a 45- to 49-year-old man with FDR of CRC compared with a 40- to 44-year-old woman without a FDR of CRC. The numbers needed to screen one colorectal neoplasia, and one advanced neoplasm in the highest risk group of 45- to 49-year-old men with FDR with CRC were 2.8 (95% CI: 2.2-4.4) and 18.5 (95% CI: 8.9-39.2), respectively. Conclusions Colorectal neoplasia prevalence in this 40- to 49-year-old Chinese cohort was higher than previous studies. Men, advancing age, FDR with CRC, and diabetes mellitus, can be used to risk stratify for neoplasia development. Men 45-49 years old with FDR with CRC represented the highest risk subgroup, with the lowest number needed to screen. [ABSTRACT FROM AUTHOR]

A letter to the editor on findings of vulvar intraepithelial neoplasia, findings of vulvar intraepithelial neoplasia, a subtype of in situ squamous cell carcinoma (SCC), is presented.