ROAR-A: re-optimization based Online Adaptive Radiotherapy of anal cancer, a prospective phase II trial protocol.

BACKGROUND: Chemo-radiotherapy with curative intent for anal cancer has high complete remission rates, but acute treatment-related gastrointestinal (GI) toxicity is significant. Toxicity occurs due to irradiation of surrounding normal tissue. Current radiotherapy requires the addition of large planning margins to the radiation field to ensure target coverage regardless of the considerable organ motion in the pelvic region. This increases the irradiated volume and radiation dose to the surrounding normal tissue and thereby toxicity. Online adaptive radiotherapy uses artificial intelligence to adjust the treatment to the anatomy of the day. This allows for the reduction of planning margins, minimizing the irradiated volume and thereby radiation to the surrounding normal tissue.This study examines if cone beam computed tomography (CBCT)-guided oART with daily automated treatment re-planning can reduce acute gastrointestinal toxicity in patients with anal cancer. METHODS/DESIGN: The study is a prospective, single-arm, phase II trial conducted at Copenhagen University Hospital, Herlev and Gentofte, Denmark. 205 patients with local only or locally advanced anal cancer, referred for radiotherapy with or without chemotherapy with curative intent, are planned for inclusion. Toxicity and quality of life are reported with Common Terminology Criteria of Adverse Events and patient-reported outcome questionnaires, before, during, and after treatment. The primary endpoint is a reduction in the incidence of acute treatment-related grade ≥ 2 diarrhea from 36 to 25% after daily online adaptive radiotherapy compared to standard radiotherapy. Secondary endpoints include all acute and late toxicity, overall survival, and reduction in treatment interruptions. RESULTS: Accrual began in January 2022 and is expected to finish in January 2026. Primary endpoint results are expected to be available in April 2026. DISCUSSION: This is the first study utilizing online adaptive radiotherapy to treat anal cancer. We hope to determine whether there is a clinical benefit for the patients, with significant reductions in acute GI toxicity without compromising treatment efficacy. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT05438836. Danish Ethical Committee: H-21028093.

Coinfections with additional oncoviruses in HPV+ individuals: Status, function and potential clinical implications.

Oncovirus infections account for an estimated 12%-20% of human cancers worldwide. High-risk human papillomavirus (HPV) infection is the etiological agent of some malignancies such as cervical, oropharyngeal, anal, penile, vaginal, and vulvar cancers. However, HPV infection is not the only cause of these cancers or may not be sufficient to initiate cancer development. Actually, certain other risk factors including additional oncoviruses coinfections have been reported to increase the risk of patients exposed to HPV for developing different HPV-related cancers. In the current review, we summarize recent findings about coinfections with different oncoviruses in HPV+ patients from both clinical and mechanistic studies. We believe such efforts may lead to an interesting direction for improving our understanding and developing new treatments for virus-induced cancers.

Uterine retroversion and gluteal transposition flap for postoperative perineal evisceration after extralevator abdominoperineal resection.

Anal squamous cell carcinoma (ASCC) is the most common histological subtype of malignant tumor affecting the anal canal. Chemoradiotherapy (CRT) is the first-line treatment in nearly all cases, ensuring complete clinical response in up to 80% of patients. Abdominoperineal resection (APR) is typically reserved as salvage therapy in those patients with persistent or recurrent tumor after CRT. In locally advanced tumors, an extralevator abdominoperineal excision (ELAPE), which entails excision of the anal canal and levator muscles, might be indicated to obtain negative resection margins. In this setting, the combination of highly irradiated tissue and large surgical defect increases the risk of developing postoperative perineal wound complications. One of the most dreadful complications is perineal evisceration (PE), which requires immediate surgical treatment to avoid irreversibile organ damage. Different techniques have been described to prevent perineal complications after ELAPE, although none of them have reached consensus. In this technical note, we present a case of PE after ELAPE performed for a recurrent ASCC. Perineal evisceration was approached by combining a uterine retroversion with a gluteal transposition flap to obtain wound healing and reinforcement of the pelvic floor at once, when a mesh placement is not recommended.

Risk of anorectal cancer in patients with Crohn's disease and perianal fistula: a nationwide Danish cohort study.

AIM: Patients with Crohn's disease (CD) often suffer from perianal fistulizing disease. Their risk of anorectal cancer remains uncertain. We aimed to examine the long-term risk of anorectal cancer in a population-based cohort of CD patients with anorectal fistula. METHOD: Our study population covered all individuals (n = 7 987 520) aged 15+ years living in Denmark from 1978 to 2018. We identified all patients with CD and anorectal fistula in the Danish National Patient Register (NPR) and 50 matched noninflammatory bowel disease (IBD) individuals from the general population. Using Cox regression analyses, we examined the risk of anorectal cancer in CD fistula patients versus non-IBD individuals. All patients with CD were identified using codes from the International Classification of Diseases and their data extracted from the NPR. The main outcome measure was cases of anorectal cancer. RESULTS: A total of 2786 CD patients with anorectal fistula and 139 300 non-IBD individuals were followed for 1 553 917 person-years. During follow-up, anorectal cancer was observed in 19 CD patients (0.68%) and 340 non-IBD individuals (0.24%), corresponding to a 2.9-fold increased hazard ratio (HR) of anorectal cancer in CD fistula patients (95% CI 1.80-4.53), with a particularly high risk of anal cancer (HR 15.13, 95% CI 6.88-33.31) and a mean time from CD fistula diagnosis to anorectal cancer of 6.7 (SD 6.5) years. The risk was slightly higher in women than men and had no apparent relation to treatment with tumour necrosis factor-α inhibitors. Sensitivity analyses using CD nonfistula patients for comparison revealed similar results. Individual data on smoking and infection with human papilloma virus were not available. CONCLUSION: Patients with CD and anorectal fistula have a three-fold increased risk of anorectal cancer compared with the general population. The number needed to surveil to detect one case of anorectal cancer in this patient population was 2160 patients per year in patients with long-standing fistula (>6 years).

Feasibility Trial of Intensity Modulated Proton Therapy to Reduce Toxicity in Anal Cancer Patients.

PURPOSE: The purpose of this trial was to assess the patient and physician-reported toxicity in anal cancer patients undergoing definitive chemoradiation with intensity-modulated proton therapy (IMPT). METHODS: Patients with stage II and III anal cancer were treated with IMPT. All patients received 2 cycles of 5-fluorouracil and mitomycin concurrently with radiation. Toxicity was assessed at baseline, weekly during chemoradiation, and in follow-up using physician-graded common terminology criteria for adverse events (CTCAE) v 4.0 and PRO-CTCAE. The primary endpoint was to define point estimates and 95% CI for acute ≥ grade 2/3 gastrointestinal (GI), genitourinary (GU), dermatologic, and hematologic toxicity. The proportion of PRO-CTCAE questions scored ≥3 for each domain was compared with the baselinse. The proportion of ≥ grade 2 and ≥ grade 3 toxicities were compared with historic intensity-modulated radiotherapy patients treated on RTOG 0529. RESULTS: Fourteen patients were enrolled from 2017 to 2020. Rates of physician-reported GI, GU, dermatologic, and hematologic toxicity were not significantly different between patients treated with IMPT compared with patients treated with intensity-modulated radiotherapy. Rates of patient-reported dermatologic and GU toxicity were low at baseline with a peak at week 6 (91% and 58% PRO-CTCAE items ≥ grade 3, respectively) and normalization to baseline 3 months after IMPT. In contrast, the proportion of high-grade PRO-CTCAE GI scores was 40% at baseline, which persisted through 1-year posttreatment. CONCLUSIONS: Clinician-reported toxicity was not improved with IMPT in the context of this underpowered trial. High-grade GI symptoms persisted for 12 months and were similar to baseline. Additional measures are needed to minimize acute and chronic toxicity related to chemoradiation.

Anal High-risk Human Papillomavirus Infection, Squamous Intraepithelial Lesions, and Anal Cancer in Patients with Inflammatory Bowel Disease: A Systematic Review and Meta-analysis.

BACKGROUND: Ulcerative colitis [UC] and Crohn's disease [CD] can be associated with severe comorbidities, namely opportunistic infections and malignancies. We present the first systematic review and meta-analysis evaluating the burden of anal human papillomavirus disease in patients with UC and CD. METHODS: PubMed, Web of Science, and Scopus were searched until November 2022. Meta-analyses were performed using random effects models. The protocol was recorded at PROSPERO register with the number CRD42022356728. RESULTS: Six studies, including 78 711 patients with UC with a total follow-up of 518 969 person-years, described the anal cancer incidence rate. For anal cancer incidence rate in CD, six studies were selected, including 56 845 patients with a total follow-up of 671 899 person-years. The incidence of anal cancer was 10.2 [95% CI 4.3 - 23.7] per 100 000 person-years in UC and 7.7 [3.5 - 17.1] per 100 000 person-years in CD. A subgroup analysis of anal cancer in perianal CD, including 7105 patients, was calculated with incidence of 19.6 [12.2 - 31.6] per 100 000 person-years [three studies included]. Few studies described prevalence of anal cytological abnormalities [four studies including 349 patients] or high-risk human papillomavirus [three studies including 210 patients], with high heterogeneity. Prevalence of cytological abnormalities or high-risk human papillomavirus was not associated with pharmacological immunosuppression in the studies included. CONCLUSION: The incidence of anal cancer is higher in UC than in CD, with the exception of perianal CD. There are limited and heterogeneous data on anal high-risk human papillomavirus infection and squamous intraepithelial lesions prevalence in this population.

Human papillomavirus in the setting of immunodeficiency: Pathogenesis and the emergence of next-generation therapies to reduce the high associated cancer risk.

Human papillomavirus (HPV), a common sexually transmitted virus infecting mucosal or cutaneous stratified epithelia, is implicated in the rising of associated cancers worldwide. While HPV infection can be cleared by an adequate immune response, immunocompromised individuals can develop persistent, treatment-refractory, and progressive disease. Primary immunodeficiencies (PIDs) associated with HPV-related disease include inborn errors of GATA, EVER1/2, and CXCR4 mutations, resulting in defective cellular function. People living with secondary immunodeficiency (e.g. solid-organ transplants recipients of immunosuppression) and acquired immunodeficiency (e.g. concurrent human immunodeficiency virus (HIV) infection) are also at significant risk of HPV-related disease. Immunocompromised people are highly susceptible to the development of cutaneous and mucosal warts, and cervical, anogenital and oropharyngeal carcinomas. The specific mechanisms underlying high-risk HPV-driven cancer development in immunocompromised hosts are not well understood. Current treatments for HPV-related cancers include surgery with adjuvant chemotherapy and/or radiotherapy, with clinical trials underway to investigate the use of anti-PD-1 therapy. In the setting of HIV co-infection, persistent high-grade anal intraepithelial neoplasia can occur despite suppressive antiretroviral therapy, resulting in an ongoing risk for transformation to overt malignancy. Although therapeutic vaccines against HPV are under development, the efficacy of these in the setting of PID, secondary- or acquired- immunodeficiencies remains unclear. RNA-based therapeutic targeting of the HPV genome or mRNA transcript has become a promising next-generation therapeutic avenue. In this review, we summarise the current understanding of HPV pathogenesis, immune evasion, and malignant transformation, with a focus on key PIDs, secondary immunodeficiencies, and HIV infection. Current management and vaccine regimes are outlined in relation to HPV-driven cancer, and specifically, the need for more effective therapeutic strategies for immunocompromised hosts. The recent advances in RNA-based gene targeting including CRISPR and short interfering RNA (siRNA), and the potential application to HPV infection are of great interest. An increased understanding of both the dysregulated immune responses in immunocompromised hosts and of viral persistence is essential for the design of next-generation therapies to eliminate HPV persistence and cancer development in the most at-risk populations.

High-resolution anoscopy can diagnose precursors to anal cancer.

Anal cancer risk is increased in certain risk groups including people living with HIV (PLWH), especially in men who have sex with men, but also in organ transplant recipients and women with a history of cervical or vulva dysplasia or cancer. High-resolution anoscopy (HRA) is a tool to diagnose anal high-grade squamous intraepithelial lesions (HSIL), and HRA-guided treatment of anal HSIL has been shown to reduce the risk of anal cancer in PLWH. The purpose of this review is to increase the awareness of HRA but also of tertiary prevention by digital anal rectal examination.

[Implantation metastasis of colorectal adenocarcinoma in an anal fistula]. / Colorectalis adenocarcinoma implantációs áttéte végbélsipolyban.

In our case report, we describe a rare form of metastatic colorectal carcinoma, in which tumor cells spread intraluminally and metastasis occurs with implantation mechanism far from the primary tumor. A 43-year-old male patient developed perianal abscess. After surgical intervention a fistula-in-ano appeared at the site of the abscess. Fistulotomy was performed in another hospital. A few months later, we admitted him to our department with an abnormal tissue proliferation appearing in the surgical area. Histology confirmed adenocarcinoma. Colonoscopy detected tissue proliferation in the sigmoid colon, causing a subtotal stenosis. Laparoscopic rectosigmoid resection and per anum tumor excision were performed. Detailed histological examination confirmed the same mucinous adenocarcinoma in the colon and the anorectal malformation. In this case, implantation mechanism is likely in the development of a synchronous tumor at the site of the fistula-in-ano. Implantation metastasis is considered rare, only a few cases have been reported in the international literature so far. We are not aware of any similar case reported from Hungary. Orv Hetil. 2023; 164(3): 110-113.

Perianal Crohn's Disease and the Development of Colorectal and Anal Cancer: A Systematic Review and Meta-analysis.

BACKGROUND AND AIMS: The aim of this systematic review was to assess the literature on the incidence and risk factors for colorectal cancer and anal cancer in patients with perianal Crohn's disease. METHOD: A systematic review of the literature was performed using PubMed, Embase and Google Scholar. A meta-analysis was then conducted using a random-effects model. RESULTS: Five studies were included in the systematic review. Of the total patients, 26.5% had perianal Crohn's disease. The median follow-up was 6 years. In total, 127 cases of colorectal cancer were found [0.43% of the included Crohn's disease patients]. Perianal involvement was present in 50% of colorectal cancer patients [0.89% of the population]. Three of the studies specified the cancer to be rectal or anal, which were present in 68 and 24 cases [0.3% and 0.1% of patients], respectively. In a subgroup analysis of rectal and anal cancer, perianal involvement was most frequent in anal cancer, accounting for 46% of the cases. In the rectal cancer group, 37% had perianal involvement. The higher incidence of colorectal cancer in patients with perianal Crohn's disease was confirmed in a meta-analysis. CONCLUSION: Half of the patients with colorectal cancer and anal cancer were found to have perianal Crohn's disease. In patients with perianal involvement, there was a higher percentage of anal cancer compared with rectal cancer. These results support the theory that patients with perianal Crohn's disease are at increased risk for developing colorectal and anal cancer. Studies collecting more detailed data regarding patients and their cancers are needed to further specify the disease course.

One-Drop Serum Screening Test for Anal Cancer in Men via Infrared Attenuated Total Reflection Spectroscopy.

Rare cancers are a challenge for clinical practice, the treatment experience at major centers to which rare cancers are referred is limited and are the most difficult to diagnose. Research to identify causes or develop prevention and early detection strategies is extremely challenging. Anal cancer is an example of a rare cancer, with the human papillomavirus (HPV) infection being the most important risk factor associated. In the early stages, anal cancer does not exhibit evident symptoms. This disease is diagnosed by means of anoscopy, which diagnoses some cases of early cancer; nevertheless, sensitivity of this test ranges between 47 and 89%. Therefore, the development of new, effective, and evidence-based screening methodologies for the early detection of rare cancers is of great relevance. In this study, the potential of ATR-FTIR spectroscopy has been explored as a sensitive, nondestructive, and inexpensive analytical method for developing disease screening platforms in serum. Spectral differences were found in the regions of 1700-1100 and 1700-1400 cm-1 between the control group and the anal cancer group related to the presence of proteins and nucleic acids. The chemometric analysis presented differences in the spectral fingerprints for both spectral regions with a high sensitivity ranging from 95.2 to 99.9% and a specificity ranging from 99.2 to 100%. This is the first step that we report for a methodology that is fast, nondestructive, and easy to perform, and the high sensitivity and specificity of the method are the basis for extensive research studies to implement these technologies in the clinical field.

Treatment of Anal High-Grade Squamous Intraepithelial Lesions to Prevent Anal Cancer.

BACKGROUND: The incidence of anal cancer is substantially higher among persons living with the human immunodeficiency virus (HIV) than in the general population. Similar to cervical cancer, anal cancer is preceded by high-grade squamous intraepithelial lesions (HSILs). Treatment for cervical HSIL reduces progression to cervical cancer; however, data from prospective studies of treatment for anal HSIL to prevent anal cancer are lacking. METHODS: We conducted a phase 3 trial at 25 U.S. sites. Persons living with HIV who were 35 years of age or older and who had biopsy-proven anal HSIL were randomly assigned, in a 1:1 ratio, to receive either HSIL treatment or active monitoring without treatment. Treatment included office-based ablative procedures, ablation or excision under anesthesia, or the administration of topical fluorouracil or imiquimod. The primary outcome was progression to anal cancer in a time-to-event analysis. Participants in the treatment group were treated until HSIL was completely resolved. All the participants underwent high-resolution anoscopy at least every 6 months; biopsy was also performed for suspected ongoing HSIL in the treatment group, annually in the active-monitoring group, or any time there was concern for cancer. RESULTS: Of 4459 participants who underwent randomization, 4446 (99.7%) were included in the analysis of the time to progression to cancer. With a median follow-up of 25.8 months, 9 cases were diagnosed in the treatment group (173 per 100,000 person-years; 95% confidence interval [CI], 90 to 332) and 21 cases in the active-monitoring group (402 per 100,000 person-years; 95% CI, 262 to 616). The rate of progression to anal cancer was lower in the treatment group than in the active-monitoring group by 57% (95% CI, 6 to 80; P = 0.03 by log-rank test). CONCLUSIONS: Among participants with biopsy-proven anal HSIL, the risk of anal cancer was significantly lower with treatment for anal HSIL than with active monitoring. (Funded by the National Cancer Institute; ClinicalTrials.gov number, NCT02135419.).

Acute toxicity and patient-reported outcomes in anal canal cancer: results of a pilot study.

INTRODUCTION: Anal canal cancer (ACC) is uncommon. The gold standard of care is chemoradiotherapy treatment. However, this treatment is associated with considerable acute and late side effects. The aim of this pilot study was to evaluate acute toxicity and patient-reported outcomes (PRO) in these patients from planning to 3 months after treatment. METHODS: Sixteen patients were recruited to this prospective observational study from March 2015 to December 2017. All patients received volumetric modulated arc therapy (VMAT) in 30#. Toxicity data were graded by a Radiation Oncologist using the Common Terminology Criteria for Adverse Effects (CTCAE) version 4 at planning, weekly during treatment, 6-week and 3-month post-treatment. PRO data were collected using the EORTC QLQ C30 and CR29 questionnaires completed by patients at planning, mid and end treatment and 3-month post-treatment. RESULTS: The majority of toxicity and PRO items peaked in severity at the end of treatment (week 6). Skin was the only item where >50% of patients had ≥ grade 2 toxicity at any point with 75% having ≥ grade 2 at week 6. Patient-reported embarrassment significantly increased over time (P < 0.001). No meaningful relationships were found between PRO and CTCAE results. CONCLUSION: After reaching their maximum severity at the end of treatment, the majority of toxicity and PRO items approached baseline levels by 3-month post-treatment. The results of this study suggest that PROs are an important complementary tool to CTCAE and provide greater understanding of patients' perception of treatment side effects.

Carcinogenesis and Cancer Progression in De Novo Anal Squamous Cell Carcinoma After Organ Transplantation: A Systematic Review.

Our aim was to perform a comprehensive literature review on the pathogenesis of squamous anal cancerin patients after solid-organ transplant. Medical databases were consulted until June 1, 2020, for potentially relevant publications.All studies on pathogenesis of de novo anal squamous cell carcinoma in solid-organ transplant recipients were included. Two researchers independently performed study selection, quality assessment, and data extraction and analysis. Twenty-one studies were included.None ofthe selected papers had been solely focused on carcinogenesis. Most ofthe studies identified human papillomavirus infection and immunosuppression to be significantly correlated with the development of de novo anal cancer in adult solid organ transplant recipients. CD4+ T-cell depletion and inactivation oftumor suppressor pathways were mainly implicated. All solid-organ transplant recipients, especially those who were human papillomavirus positive, were shown to be at increased risk for the development of posttransplant anal cancer. Further studies are needed to determine the specific mechanisms of pathogenesis according to different solid-organ transplant populations.

Anal cancer: an essay on etiology, risk conditions, vulnerability, and care of carriers / Câncer anal: um ensaio sobre etiologia, condições de risco, vulnerabilidade e cuidados aos portadores

Introduction: The incidence of anal cancer is influenced by individual factors and socially determined conditions of vulnerability. In Brazil, it has increased in recent decades. A probable explanation for the growing incidence is the low coverage of screening and prevention programs. Objective: The aim of this study was to reflect on risk factors, the need for early diagnosis, and care of people with anal cancer and to associate social vulnerability in the understanding of illness and care in the Unified Health System (SUS). Methods: This is a systematic literature review with consultations carried out in open electronic databases: SciELO, Digital Library of Theses and Dissertations, and CAPES Publications Portal. The descriptors used were "anal cancer," "anal cytology," "anal cancer precursor lesions," "primary prevention," "integrality in health," and "public health policies." Results: Ensuring access to services is a common guideline in the literature. Based on the recovered references, two axes of analysis were built: in the first, ideas to reflect on care with collective health approaches were systematized, mainly on the etiology, biological risk factors, and conditions of vulnerability for cancer development to which the subjects are exposed. In the second, ideas to propose care technologies are put forward, with evidence from similar protocols and policies, especially the "Cervical Cancer Control Program," which deals with a pathology with cytohistological and etiological similarities, risk factors, diagnostic techniques, and skilled health professionals. Conclusion: The reviewed sources point to the possibility of incorporating, as a SUS policy, large-scale actions of prevention, screening, and early diagnosis, to qualify and expand the initiatives of promotion and care. The professional cytotechnologist can be a decisive factor in the implementation of the care policy, expanding assistance to the population and qualifying the services.

Introdução: O câncer anal tem incidência influenciada por fatores individuais e condições de vulnerabilidade socialmente determinadas. No Brasil, apresentou crescimento nas últimas décadas. Uma provável explicação para a incidência é a baixa abrangência dos programas de rastreamento e prevenção. Objetivo: Refletir sobre fatores de risco, necessidade de diagnóstico precoce e cuidado às pessoas com câncer anal, bem como compreender a relação entre vulnerabilidade social, adoecimento e cuidados no Sistema Único de Saúde (SUS). Métodos: Trata-se de uma revisão sistemática da literatura, com consultas realizadas em bases de dados eletrônicas abertas: SciELO, Biblioteca Digital de Teses e Dissertações e Portal de Periódicos CAPES. Os descritores utilizados foram "câncer anal", "citologia anal", "lesões precursoras do câncer anal", "prevenção primária", "integralidade em saúde" e "políticas públicas de saúde". Resultados: A garantia de acesso aos serviços é orientação comum na literatura. Com base nas referências recuperadas, foram construídos dois eixos de análise: no primeiro, foram sistematizadas ideias para refletir sobre o cuidado com abordagens da saúde coletiva, principalmente sobre a etiologia, fatores de riscos biológicos e condições de vulnerabilidades para desenvolvimento do câncer ao qual os sujeitos estão expostos. No segundo, foram sistematizadas ideias para propor tecnologias de cuidado, com evidências de protocolos e políticas modelo, principalmente o Programa de Controle de Câncer de Colo do Útero, que trata de patologia com semelhanças cito-histológicas e etiológicas, considerando fatores de risco, boas técnicas para diagnóstico e a qualificação dos profissionais de saúde habilitados. Conclusão: As fontes revisadas apontam a possibilidade de se incorporar, como política do Sistema Único de Saúde, ações de prevenção, rastreio e diagnóstico precoce em ampla escala, a fim de qualificar e expandir as iniciativas de promoção e atenção ao público. O profissional citotécnico pode ser um fator decisivo na implantação da política de cuidado, ampliando a assistência à população e qualificando os serviços prestados.

Metformin use and the risk of anal intraepithelial neoplasia in type II diabetic patients.

AIM: Emerging evidence has suggested that metformin may be protective against the development of human-papillomavirus-related cancers. Anal intraepithelial neoplasia (AIN) is highly associated with human papillomavirus infection and a precancerous status of anal cancer. The aim of this study was to investigate the relationship between metformin usage and the development of AIN in a large national sample. METHODOLOGY: The IBM MarketScan dataset was used to design a nested case-control study from 2010 to 2017. Patients aged 18-65 years with type 2 diabetes mellitus (DM) were evaluated, and cases of AIN were identified. Four controls were randomly selected in the risk set of each case by using incidence density sampling. The association between metformin usage and AIN was assessed using multivariate logistic regression modelling. RESULTS: A total of 258 patients with type 2 DM were diagnosed with AIN during the study interval, and these were matched to 1032 control patients without a diagnosis of AIN. Patients who developed AIN had 38% lower odds of prior metformin use compared to those without a history of AIN (P < 0.01) and this finding remained robust after adjusting for age, sex, human immunodeficiency virus infection and DM complications (P = 0.02). Patients with AIN had 56% lower odds of long-term metformin use compared to control patients (P = 0.01). CONCLUSIONS: An AIN diagnosis in patients with DM is associated with 56% lower likelihood of prior metformin use. This relationship suggests that metformin could potentially play a protective role against AIN. Prospective studies in non-diabetic patients are warranted to examine these findings further.

Associations between hepatitis B virus exposure and the risk of extrahepatic digestive system cancers: A hospital-based, case-control study (SIGES).

OBJECTIVES: This case-control study was aimed to investigate associations between HBV infection and extrahepatic digestive system cancers. METHODS: The patients of gastric, small intestinal, colonic, rectal, anal, biliary tract, and pancreatic cancers were retrospectively collected between 2016.5 and 2017.12. Simultaneously, the healthy controls were collected from the health check-up registry, and cancer-free status was confirmed based on medical records. Propensity score matching was performed to reduce bias. Multinomial logit model and conditional logistic regression model were used to assess the risk of individual cancer according to HBV serological markers and classifications. RESULTS: Totally, 4748 patients involving seven cancers, and 57,499 controls were included. After matching, HBsAg was associated with increased risk of gastric cancer (aOR = 1.39, 95% CI: 1.05-1.85), and anti-HBs served as a protective factor for gastric (aOR = 0.72, 95% CI: 0.61-0.85), colonic (aOR = 0.73, 95% CI: 0.60-0.89), rectal (aOR = 0.73, 95% CI: 0.63-0.85), and pancreatic (aOR = 0.58, 95% CI: 0.42-0.82) cancers. Compared to subgroups with non-infection and vaccination status, inactive HBsAg carriers and active HBV infection subgroup were correlated with gastric carcinogenesis (aOR = 1.41, 95% CI: 1.03-1.93). However, no clear association was found between HBV infection and other cancers. CONCLUSIONS: HBV infection was potentially associated with an increased risk of gastric cancer. The development mechanism of HBV-associated gastric cancer needs to investigate further.

Cronkhite-Canada syndrome associated with perianal condyloma acuminatum with malignant transformation: A case report.

RATIONALE: Cronkhite-Canada syndrome (CCS) is a rare non-familial polyposis syndrome characterized by multiple gastrointestinal polyps with the ectodermal triad. To date, many complications of CCS have been reported in the literature, but perianal condyloma acuminatum with malignant transformation has not been included. PATIENT CONCERNS: This report presents the case of a 52-year-old Chinese man who presented with diarrhea, loss of appetite, and weight loss. He developed skin pigmentation and atrophy of the fingernails and toenails. Upper gastrointestinal endoscopy, colonoscopy, capsule endoscopy, and enteroscopy revealed diffuse polyps along the entire digestive tract. Histopathological examination revealed polyps of different pathological types dominated by hamartoma. Physical examination revealed a crissum cauliflower-like neoplasm (2.5 × 2.0 cm). After perianal tumor resection, pathology suggested that this was a perianal condylomatous lesion with malignant transformation, as well as well-differentiated squamous cell carcinoma. DIAGNOSES: These clinical features and endoscopic findings were consistent with CCS which associated with perianal condyloma acuminatum with malignant transformation. INTERVENTION: Clinical remission was achieved with glucocorticoid, azathioprine, and nutritional support. OUTCOME: At the 4-year follow-up, the patient had no diarrhea or loss of appetite, had gained 13 kg in weight, and the perianal tumor had not recurred. LESSONS: No previous report has described CCS in a patient with perianal condyloma acuminatum with malignant transformation. As both conditions are related to immune disorders, their occurrence may be correlated.