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Gonzalez APG, Chovwen P, Myers S, Davids JS, Keshinro AO, Hill SS. Diversity, equity, and inclusion in colon and rectal surgery patient populations. Curr Probl Surg 2025; 65:101736. [PMID: 40128008 DOI: 10.1016/j.cpsurg.2025.101736] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/13/2024] [Accepted: 02/13/2025] [Indexed: 03/26/2025]
Affiliation(s)
| | - Praise Chovwen
- Department of Surgery, Cleveland Clinic Foundation, Cleveland, OH
| | - Sara Myers
- Department of Surgery, Boston Medical Center, Boston, MA
| | | | | | - Susanna S Hill
- Department of Surgery, Duke University Medical Center, Durham, NC.
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Karim A, Troester A, Mott SL, Arsoniadis E, Jensen C, Hassan I, Kandagatla P, Goffredo P. A Population-Level Validation of the New 9th Edition of the American Joint Commission on Cancer Staging System for Anal Squamous Cell Carcinoma. J Surg Oncol 2025; 131:481-488. [PMID: 39329174 DOI: 10.1002/jso.27926] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/24/2024] [Accepted: 09/08/2024] [Indexed: 09/28/2024]
Abstract
BACKGROUND AND OBJECTIVES The staging system for anal squamous cell carcinoma (ASCC) was recently revised, downstaging selected node-positive patients and upstaging some with larger tumors. We aimed to validate this staging system using a population-based cohort. METHODS The Surveillance, Epidemiology, and End Results database was analyzed to identify adult ASCC patients. Patients were staged according to the American Joint Committee on Cancer (AJCC) 8th and 9th edition systems. Survival probabilities were estimated using Kaplan-Meier curves. Cox regression models were utilized to estimate the effect of stage on overall (OS) and cancer-specific survival (CSS). RESULTS A total of 2117 patients were identified and staged based on the two AJCC classifications. At 24 months when comparing stage IIB versus stage IIIA, the 8th edition revealed an improved OS (79% vs. 88%) and CSS (84% vs. 91%) for stage IIIA disease, while the 9th edition restored the hierarchical OS (IIB 88% vs. IIIA 78%) and CSS (91% vs. 82%) order. CONCLUSIONS The hierarchical increase of the OS HRs, and nearly all CSS HRs, across disease stages validated the updated edition of the AJCC classification. Although this change may not have significant implication on the management of ASCC, it does provide better prognostication.
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Affiliation(s)
- Aos Karim
- Division of Colon & Rectal Surgery, Department of Surgery, University of Minnesota, Minneapolis, Minnesota, USA
| | - Alexander Troester
- Division of Colon & Rectal Surgery, Department of Surgery, University of Minnesota, Minneapolis, Minnesota, USA
| | - Sarah L Mott
- Holden Comprehensive Cancer Center, University of Iowa, Iowa City, Iowa, USA
| | - Elliot Arsoniadis
- Division of Colon & Rectal Surgery, Department of Surgery, University of Minnesota, Minneapolis, Minnesota, USA
| | | | - Imran Hassan
- Department of Surgery, University of Iowa, Iowa City, Iowa, USA
| | | | - Paolo Goffredo
- Division of Colon & Rectal Surgery, Department of Surgery, University of Minnesota, Minneapolis, Minnesota, USA
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Čulav I, Skerlev M, Starčević LŽ, Hrabač P, Ljubojević Hadžavdić S, Bešlić I, Lugović Mihić L. Human Papilloma Virus Infection in Men: A Specific Human Virome or a Specific Pathology? Genes (Basel) 2025; 16:230. [PMID: 40004559 PMCID: PMC11855728 DOI: 10.3390/genes16020230] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/29/2025] [Revised: 02/12/2025] [Accepted: 02/14/2025] [Indexed: 02/27/2025] Open
Abstract
BACKGROUND Human papillomavirus (HPV) infections in men remain under-researched despite their critical role in disease transmission and the increasing incidence of HPV-related cancers. This study investigates the clinical and molecular characteristics of anogenital HPV infections in men, emphasizing genotype prevalence, diagnostic methods, and lesion variability. METHODS A cross-sectional study was conducted on 70 men aged 18-65 years with clinically diagnosed anogenital HPV infection. Lesions were characterized by morphology and location. HPV DNA was analyzed using INNO-LiPA (INNOvative Line Probe Assay), Hybrid Capture II (HC II), and polymerase chain reaction (PCR) assays to determine genotype distribution. Associations between clinical features and HPV genotypes were assessed using multivariate statistical analyses. RESULTS Lesions varied in morphology, with verrucous (52.86%) and papular (30%) types being the most common. Localization patterns showed predominance on the penis radix (34.29%) and shaft (27.14%). Molecular testing revealed HPV DNA in 88.57% of the cases using INNO-LiPA, compared to 45% and 40% with HC II and PCR, respectively. Low-risk (LR) genotypes, particularly HPV6, dominated single infections, comprising 68.57% of the cases, while high-risk (HR) genotypes accounted for 20%. Mixed LR and HR infections were observed in 14.29% of the lesions, with greater diversity noted in distal genital regions. Notably, condyloma plana and lesions on the inner prepuce exhibited a higher prevalence of HR and mixed infections. Age and lesion duration showed trends toward older patients and longer disease duration in cases involving perianal and extragenital condylomas, though these findings were not statistically significant. No direct correlation between lesion type or localization and specific genotypes was identified, underscoring the heterogeneity of HPV clinical manifestations in men. CONCLUSIONS Anogenital HPV infections in men exhibit significant heterogeneity in lesion morphology, localization, and genotype distribution. HR HPV genotypes were detected in a notable proportion of benign lesions, underscoring their potential role in disease progression. INNO-LiPA proved superior in diagnostic accuracy, highlighting the need for standardized and cost-effective diagnostic approaches for men. Further research is crucial to elucidate HPV's clinical impact in men and inform prevention and treatment strategies.
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Affiliation(s)
- Ivana Čulav
- Department of Dermatology, Children’s Hospital Zagreb, 10000 Zagreb, Croatia
| | - Mihael Skerlev
- Medical School Zagreb, St. Catherine’s Special Hospital, University of Zagreb, 10000 Zagreb, Croatia; (M.S.); (S.L.H.)
| | - Lidija Žele Starčević
- Department of Clinical and Molecular Microbiology, Medical School Zagreb, University Hospital Center Zagreb, University of Zagreb, 10000 Zagreb, Croatia;
| | - Pero Hrabač
- Department of Medical Statistics, Epidemiology and Medical Informatics, Andrija Štampar School of Public Health, Medical School Zagreb, University of Zagreb, 10000 Zagreb, Croatia;
| | - Suzana Ljubojević Hadžavdić
- Medical School Zagreb, St. Catherine’s Special Hospital, University of Zagreb, 10000 Zagreb, Croatia; (M.S.); (S.L.H.)
| | - Iva Bešlić
- Department of Dermatovenereology, University Hospital Center Sestre Milosrdnice, 10000 Zagreb, Croatia;
| | - Liborija Lugović Mihić
- Department of Dermatovenereology, School of Dentistry Zagreb, University Hospital Center Sestre Milosrdnice, University of Zagreb, 10000 Zagreb, Croatia;
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Junejo MH, Oyebanji OI, Wang B, Cappello C, Wait B, Farrow E, Nathan M, Bowring J, Cuming T. Early detection of anal squamous cell carcinoma with the use of high-resolution anoscopy. Clin Exp Dermatol 2025; 50:395-398. [PMID: 39212481 DOI: 10.1093/ced/llae362] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/06/2024] [Revised: 06/24/2024] [Accepted: 08/26/2024] [Indexed: 09/04/2024]
Abstract
In the UK, few (12%) anal squamous cell carcinomas (aSCCs) are diagnosed early at stage 1 (T1N0M0). The Homerton Anogenital Neoplasia Service (HANS) is a highly specialized tertiary centre where high-resolution anoscopy (HRA) is performed to diagnose and treat anal intraepithelial neoplasia (AIN), a precursor to cancer. In some cases, aSCC (here defined as anal canal cancers and perianal cancers up to 5 cm from the anal verge) is found on referral for AIN; in others, aSCC may develop during management of AIN. We reviewed aSCC diagnoses at our specialist unit to establish whether HRA offers added value in the early detection of aSCC in a high-risk cohort. A cross-sectional analysis was performed of all primary aSCC diagnoses at HANS between January 2016 and June 2021. Patient records and histopathology and radiology reports were reviewed to define anal cancer stage per TNM classification (AJCC version 8). The results were compared with national anal cancer data published by the Office for National Statistics (AJCC version 8). Fifty-three aSCC diagnoses were made at HANS; 35 (66%) were stage 1 (14 prevalent, 21 incident), 11 (21%) stage 2 (9 prevalent, 2 incident) and 6 (11%) stage 3 (5 prevalent, 1 incident). None were stage 4, and one cancer was unstageable due to further management at another unit. By comparison, 5836 aSCCs were diagnosed in the UK between 2013 and 2017. Of these, 12.0% were stage 1, 22.8% stage 2, 33.0% stage 3 and 8.5% stage 4; 23.8% were unknown or unstageable. There was a statistically significant difference in the proportion of early (i.e. stage 1) HRA-detected cancers between HANS and national statistics (P < 0.001). Our results suggest that surveillance and examination within an HRA programme may lead to the detection of aSCC at an earlier stage, allowing for less morbid treatment and potentially lower mortality.
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Affiliation(s)
- Muhammad Hyder Junejo
- Department of Dermatology, Yale School of Medicine, New Haven, CT, USA
- Homerton Anogenital Neoplasia Service, Hackney, London, UK
| | | | - Baihan Wang
- Division of Psychiatry, University College London, London, UK
| | | | - Brenton Wait
- Homerton Anogenital Neoplasia Service, Hackney, London, UK
| | - Emily Farrow
- Homerton Anogenital Neoplasia Service, Hackney, London, UK
| | - Mayura Nathan
- Homerton Anogenital Neoplasia Service, Hackney, London, UK
| | - Julie Bowring
- Homerton Anogenital Neoplasia Service, Hackney, London, UK
| | - Tamzin Cuming
- Homerton Anogenital Neoplasia Service, Hackney, London, UK
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Jones BA, Chilakamarry S. Health Disparities and Anal Cancer. Surg Oncol Clin N Am 2025; 34:115-125. [PMID: 39547764 DOI: 10.1016/j.soc.2024.07.007] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2024]
Abstract
Health disparities are preventable differences in health outcomes that are experienced by disadvantaged patient populations. Disparities in prevention, incidence, treatment, and mortality exist among patients with anal cancer. Factors contributing to these disparities are found at the patient, provider, health system, and public policy levels. Future multilevel interventions targeted at each of these levels will provide opportunities to reduce these disparity gaps and improve anal cancer care for all patient populations.
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Affiliation(s)
- Bayley A Jones
- Department of Surgery, University of Texas Southwestern; Department of Surgery, University of Alabama at Birmingham
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English NC, Warden C. Epidemiology of Anal Cancer. Surg Oncol Clin N Am 2025; 34:11-19. [PMID: 39547763 DOI: 10.1016/j.soc.2024.07.011] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2024]
Abstract
Anal cancer is a rare disease, accounting for only 2% of all gastrointestinal tract malignancies. While individuals with advanced age (>50 years) and female sex have an increased risk of anal cancer, there has been a trend toward diagnosis at a younger age particularly among men who have sex with men, irrespective of their human immunodeficiency virus status. Histologically, approximately 85% of anal cancers are squamous cell carcinomas (ASCC). However, while more than 90% of ASCC is associated with oncogenic human papillomavirus, the temporal trends of anal cancer incidence modeled on national databases represent an unmet need for primary prevention.
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Affiliation(s)
| | - Claire Warden
- Department of General Surgery, University of Cape Town.
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7
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Ebrahimi F, Rasizadeh R, Jafari S, Baghi HB. Prevalence of HPV in anal cancer: exploring the role of infection and inflammation. Infect Agent Cancer 2024; 19:63. [PMID: 39696546 DOI: 10.1186/s13027-024-00624-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/29/2024] [Accepted: 11/27/2024] [Indexed: 12/20/2024] Open
Abstract
Anal cancer incidence is rising globally, driven primarily by human papillomavirus (HPV) infection. HPV, especially high-risk types 16 and 18, is considered a necessary cause of anal squamous cell carcinoma. Certain populations like people living with HIV, men who have sex with men, inflammatory bowel disease patients, smokers, and those with compromised immunity face elevated risk. Chronic inflammation facilitates viral persistence, cell transformation, and immune evasion through pathways involving the PD-1/PD-L1 axis. HIV coinfection further increases risk by impairing immune surveillance and epithelial integrity while promoting HPV oncogene expression. Understanding these inflammatory processes, including roles of CD8 + T cells and PD-1/PD-L1, could guide development of immunotherapies against anal cancer. This review summarizes current knowledge on inflammation's role in anal cancer pathogenesis and the interplay between HPV, HIV, and host immune factors.
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Affiliation(s)
- Fatemeh Ebrahimi
- Immunology Research Centre, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Reyhaneh Rasizadeh
- Immunology Research Centre, Tabriz University of Medical Sciences, Tabriz, Iran
- Department of Virology, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran
- Department of Animal Biology, Faculty of Natural Sciences, University of Tabriz, Tabriz, Iran
| | - Sajjad Jafari
- Department of Medical Microbiology and Virology, Faculty of Medicine, Urmia University of Medical Sciences, Urmia, Iran
| | - Hossein Bannazadeh Baghi
- Immunology Research Centre, Tabriz University of Medical Sciences, Tabriz, Iran.
- Department of Virology, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran.
- Infectious and Tropical Diseases Research Center, Tabriz University of Medical Sciences, PO Box 5165665931, Tabriz, Iran.
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Yamada K, Saiki Y, Sugimoto K, Iwasaki Y, Takano S, Tanaka M, Fukunaga M, Nakamura Y, Tsuji Y, Takano M, Ueno H, Sugihara K, Ajioka Y. The inguinal lymph nodes as regional lymph nodes in anal canal adenocarcinomas: a nationwide database analysis in Japan. Surg Today 2024; 54:1505-1513. [PMID: 38958723 DOI: 10.1007/s00595-024-02888-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/12/2024] [Accepted: 05/23/2024] [Indexed: 07/04/2024]
Abstract
PURPOSE To establish if it is appropriate to treat the inguinal lymph node (LN) of anal canal adenocarcinoma (ACA) as the intermediate LN according to the Japanese classification. METHODS The characteristics of 346 ACA patients were examined from the nationwide registry. The effect of LN dissection was evaluated using the therapeutic value index (TVI). Furthermore, the prognostic classification ability of N factors and stage was evaluated using Akaike's information criterion (AIC), the concordance index (C-index), and the 5-year overall survival (OS) rate. RESULTS The rate of metastasis of the inguinal LN was 7.5% and the TVI was 3.05. Evaluation using AIC and the C-index showed better results when the inguinal LN was treated as the intermediate LN. The 5-year OS rate for 66 patients with perirectal or intermediate LN metastasis, 7 with inguinal LN metastasis, and 13 with inguinal and perirectal or intermediate LN metastasis were 49.2%, 68.6%, and 47.6%, respectively. When inguinal LN metastases were treated as N3, the 5-year OS rates were 66.7% for those with T1N3 and T2N3 disease, and 49.2% for those with T3N3 disease. CONCLUSIONS The inguinal LN of ACA was evaluated and staged as the intermediate LN to devise an appropriate treatment strategy.
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Affiliation(s)
- Kazutaka Yamada
- Department of Surgery, Coloproctology Center Takano Hospital, 3-2-55 Oe, Chuo-ku, Kumamoto, 862-0971, Japan.
| | - Yasumitsu Saiki
- Department of Surgery, Coloproctology Center Takano Hospital, 3-2-55 Oe, Chuo-ku, Kumamoto, 862-0971, Japan
| | - Kosuke Sugimoto
- Division of Medical Information Research, Coloproctology Center Takano Hospital, Kumamoto, Japan
| | - Yuki Iwasaki
- Division of Medical Information Research, Coloproctology Center Takano Hospital, Kumamoto, Japan
| | - Shota Takano
- Department of Surgery, Coloproctology Center Takano Hospital, 3-2-55 Oe, Chuo-ku, Kumamoto, 862-0971, Japan
| | - Masafumi Tanaka
- Department of Surgery, Coloproctology Center Takano Hospital, 3-2-55 Oe, Chuo-ku, Kumamoto, 862-0971, Japan
| | - Mitsuko Fukunaga
- Department of Surgery, Coloproctology Center Takano Hospital, 3-2-55 Oe, Chuo-ku, Kumamoto, 862-0971, Japan
| | - Yasushi Nakamura
- Department of Surgery, Coloproctology Center Takano Hospital, 3-2-55 Oe, Chuo-ku, Kumamoto, 862-0971, Japan
| | - Yoriyuki Tsuji
- Department of Surgery, Coloproctology Center Takano Hospital, 3-2-55 Oe, Chuo-ku, Kumamoto, 862-0971, Japan
| | - Masahiro Takano
- Department of Surgery, Coloproctology Center Takano Hospital, 3-2-55 Oe, Chuo-ku, Kumamoto, 862-0971, Japan
| | - Hideki Ueno
- Department of Surgery, National Defense Medical College, Saitama, Japan
| | | | - Yoichi Ajioka
- Division of Molecular and Diagnostic Pathology, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan
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Paixão WHPD, Mendes GLQ, Silva DSD, Souza RGMLD, Araujo RODC, Meira KC, Jomar RT. SURVIVAL AND PROGNOSTIC FACTORS OF ANAL CANCER: A STUDY BASED ON DATA FROM THE HOSPITAL-BASED CANCER REGISTRY OF A HIGH-COMPLEXITY ONCOLOGY CARE CENTER. ARQUIVOS BRASILEIROS DE CIRURGIA DIGESTIVA : ABCD = BRAZILIAN ARCHIVES OF DIGESTIVE SURGERY 2024; 37:e1830. [PMID: 39475885 PMCID: PMC11520677 DOI: 10.1590/0102-6720202400037e1830] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 01/09/2024] [Accepted: 08/28/2024] [Indexed: 11/02/2024]
Abstract
BACKGROUND Anal cancer is a relatively rare disease, and there is a lack of survival data from low- and middle-income countries. AIMS The aim of this study was to investigate the survival rates and prognostic factors of anal cancer cases treated at a High-Complexity Oncology Care Center in Rio de Janeiro, Brazil. METHODS A retrospective cohort study was conducted involving 665 cases of squamous cell carcinoma of the anus/anal canal treated from 2000 to 2016. To estimate the 5-year overall survival probability and survival according to selected variables, the Kaplan-Meier method and the log-rank test were applied. To identify factors associated with survival, the Cox proportional hazards model, stratified by staging, was used to estimate hazard ratios (HR). Ninety-five percent confidence intervals (95%CI) were also calculated. RESULTS The overall survival probability was 62.20% (95%CI 57.90-66.20). Higher survival rates were observed in female cases, those with non-advanced staging, and those treated with chemoradiotherapy (p<0.001). Among cases with advanced staging, being female was a protective factor against death (HR=0.52; 95%CI 0.28-0.93). Compared to chemoradiotherapy, at least one type of treatment was identified as a risk factor: chemoradiotherapy + surgery among cases with non-advanced staging (HR=22.65; 95%CI 5.65-90.81), radiotherapy among cases with advanced staging (HR=2.71; 95%CI 1.39-5.30), and among cases with unknown staging, no treatment (HR=3.36; 95%CI 1.73-6.50), radiotherapy (HR=2.38; 95%CI 1.46-3.88), and radiotherapy + surgery (HR=3.99; 95%CI 1.20-13.27). CONCLUSIONS The findings support the superiority of chemoradiotherapy over other therapeutic modalities for anal cancer, resulting in increased survival and a better prognosis.
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Chun SJ, Kim E, Jang WI, Kim MS, Kang HC, Kim BH, Chie EK. Prognostic Significance of Bulky Nodal Disease in Anal Cancer Management: A Multi-institutional Study. Cancer Res Treat 2024; 56:1197-1206. [PMID: 38605662 PMCID: PMC11491260 DOI: 10.4143/crt.2024.258] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/13/2024] [Accepted: 04/09/2024] [Indexed: 04/13/2024] Open
Abstract
PURPOSE This study aimed to assess the prognostic significance of bulky nodal involvement in patients with anal squamous cell carcinoma treated with definitive chemoradiotherapy. MATERIALS AND METHODS We retrospectively analyzed medical records of patients diagnosed with anal squamous cell carcinoma who underwent definitive chemoradiotherapy at three medical centers between 2004 and 2021. Exclusion criteria included distant metastasis at diagnosis, 2D radiotherapy, and salvage treatment for local relapse. Bulky N+ was defined as nodes with a long diameter of 2 cm or greater. RESULTS A total of 104 patients were included, comprising 51 with N0, 46 with non-bulky N+, and seven with bulky N+. The median follow-up duration was 54.0 months (range, 6.4 to 162.2 months). Estimated 5-year progression-free survival (PFS), loco-regional recurrence-free survival (LRRFS), and overall survival (OS) rates for patients with bulky N+ were 42.9%, 42.9%, and 47.6%, respectively. Bulky N+ was significantly associated with inferior PFS, LRRFS, and OS compared to patients without or with non-bulky N+, even after multivariate analysis. We proposed a new staging system incorporating bulky N+ as N2 category, with estimated 5-year LRRFS, PFS, and OS rates of 81.1%, 80.6%, and 86.2% for stage I, 67.7%, 60.9%, and 93.3% for stage II, and 42.9%, 42.9%, and 47.6% for stage III disease, enhancing the predictability of prognosis. CONCLUSION Patients with bulky nodal disease treated with standard chemoradiotherapy experienced poor survival outcomes, indicating the potential necessity for further treatment intensification.
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Affiliation(s)
- Seok-Joo Chun
- Department of Radiation Oncology, Seoul National University College of Medicine, Seoul, Korea
- Department of Radiation Oncology, Dongguk University Ilsan Hospital, Dongguk University College of Medicine, Goyang, Korea
| | - Eunji Kim
- Department of Radiation Oncology, Seoul Metropolitan Government Seoul National University Boramae Medical Center, Seoul, Korea
| | - Won Il Jang
- Department of Radiation Oncology, Korea Institute of Radiological and Medical Sciences, Seoul, Korea
| | - Mi-Sook Kim
- Department of Radiation Oncology, Korea Institute of Radiological and Medical Sciences, Seoul, Korea
| | - Hyun-Cheol Kang
- Department of Radiation Oncology, Seoul National University College of Medicine, Seoul, Korea
| | - Byoung Hyuck Kim
- Department of Radiation Oncology, Seoul National University College of Medicine, Seoul, Korea
- Department of Radiation Oncology, Seoul Metropolitan Government Seoul National University Boramae Medical Center, Seoul, Korea
| | - Eui Kyu Chie
- Department of Radiation Oncology, Seoul National University College of Medicine, Seoul, Korea
- Institute of Radiation Medicine, Medical Research Center, Seoul National University, Seoul, Korea
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DeZeeuw AK, Bassetti MF, Carchman EH, Heise CP, Hayden D, Lawson EH, Sanger CB, King R, LoConte NK, Lubner SJ, Kratz JD, Deming DA. Carboplatin and Paclitaxel Chemoradiation for Localized Anal Cancer in Patients Not Eligible for Mitomycin and 5-Fluorouracil. Cancers (Basel) 2024; 16:3062. [PMID: 39272920 PMCID: PMC11394111 DOI: 10.3390/cancers16173062] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/30/2024] [Revised: 08/29/2024] [Accepted: 08/29/2024] [Indexed: 09/15/2024] Open
Abstract
BACKGROUND Although squamous cell carcinoma of the anus (SCCA) is a relatively uncommon malignancy in the United States, it continues to increase in incidence. Treatment for locoregional disease includes mitomycin and 5-fluorouracil with radiation. This combination is associated with significant toxicity, limiting its use in patients who are older or have certain comorbidities. Carboplatin and paclitaxel (C/P) is an accepted treatment regimen for metastatic SCCA. We aim to evaluate the efficacy and toxicity of weekly C/P given with radiation for patients unable to receive standard chemoradiation for SCCA. METHODS From our cancer registry, adult patients who received weekly intravenous C/P concurrent with standard-dose radiation for localized SCCA were included in this study. Clinical response was determined based on the evidence of disease on imaging and/or anoscopy. Toxicities were graded according to the CTCAE v5. RESULTS Ten patients were included; eight were female, and the median age was 75.5 years (54-87). Six had T2 disease, and four had T3 tumors. Four had node-positive disease. The majority (70%) of patients were dosed at standard C (AUC 2) and P (50 mg/m2), with a limited subset requiring dose reduction for baseline performance status. Patients completed a mean of 78.3% (40-100%) of the intended treatments. A total of 89% of the patients achieved a complete clinical response. With a median follow-up of 25.8 months (3.4-50.4 months), 67% of the patients are alive and without recurrence. Two patients have had local recurrence, and one patient had metastatic progression. The most common toxicities of any grade included leukopenia (100%), anemia (100%), radiation dermatitis (100%), diarrhea (100%), and fatigue (100%). Grade 3 or higher toxicities included neutropenic fever (20%), neutropenia (30%), and anemia (30%). CONCLUSIONS This study demonstrates promising tolerability and efficacy for weekly C/P chemoradiation for patients with anal cancer unable to receive mitomycin and 5-fluorouracil. This regimen merits further investigation in prospective clinical trials.
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Affiliation(s)
- Alyssa K. DeZeeuw
- Division of Hematology, Medical Oncology, and Palliative Care, Department of Medicine, University of Wisconsin School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI 53792, USA; (A.K.D.); (N.K.L.); (S.J.L.); (J.D.K.)
| | - Michael F. Bassetti
- Carbone Cancer Center, University of Wisconsin, Madison, WI 53792, USA; (M.F.B.); (E.H.C.); (C.P.H.); (D.H.); (E.H.L.); (C.B.S.); (R.K.)
- Department of Human Oncology, University of Wisconsin School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI 53792, USA
| | - Evie H. Carchman
- Carbone Cancer Center, University of Wisconsin, Madison, WI 53792, USA; (M.F.B.); (E.H.C.); (C.P.H.); (D.H.); (E.H.L.); (C.B.S.); (R.K.)
- Division of Colorectal Surgery, Department of Surgery, University of Wisconsin School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI 53792, USA
- William S Middleton Memorial Veterans Hospital, Madison, WI 53705, USA
| | - Charles P. Heise
- Carbone Cancer Center, University of Wisconsin, Madison, WI 53792, USA; (M.F.B.); (E.H.C.); (C.P.H.); (D.H.); (E.H.L.); (C.B.S.); (R.K.)
- Division of Colorectal Surgery, Department of Surgery, University of Wisconsin School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI 53792, USA
| | - Dana Hayden
- Carbone Cancer Center, University of Wisconsin, Madison, WI 53792, USA; (M.F.B.); (E.H.C.); (C.P.H.); (D.H.); (E.H.L.); (C.B.S.); (R.K.)
- Division of Colorectal Surgery, Department of Surgery, University of Wisconsin School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI 53792, USA
| | - Elise H. Lawson
- Carbone Cancer Center, University of Wisconsin, Madison, WI 53792, USA; (M.F.B.); (E.H.C.); (C.P.H.); (D.H.); (E.H.L.); (C.B.S.); (R.K.)
- Division of Colorectal Surgery, Department of Surgery, University of Wisconsin School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI 53792, USA
| | - Cristina B. Sanger
- Carbone Cancer Center, University of Wisconsin, Madison, WI 53792, USA; (M.F.B.); (E.H.C.); (C.P.H.); (D.H.); (E.H.L.); (C.B.S.); (R.K.)
- Division of Colorectal Surgery, Department of Surgery, University of Wisconsin School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI 53792, USA
- William S Middleton Memorial Veterans Hospital, Madison, WI 53705, USA
| | - Ray King
- Carbone Cancer Center, University of Wisconsin, Madison, WI 53792, USA; (M.F.B.); (E.H.C.); (C.P.H.); (D.H.); (E.H.L.); (C.B.S.); (R.K.)
- Division of Colorectal Surgery, Department of Surgery, University of Wisconsin School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI 53792, USA
| | - Noelle K. LoConte
- Division of Hematology, Medical Oncology, and Palliative Care, Department of Medicine, University of Wisconsin School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI 53792, USA; (A.K.D.); (N.K.L.); (S.J.L.); (J.D.K.)
- Carbone Cancer Center, University of Wisconsin, Madison, WI 53792, USA; (M.F.B.); (E.H.C.); (C.P.H.); (D.H.); (E.H.L.); (C.B.S.); (R.K.)
| | - Sam J. Lubner
- Division of Hematology, Medical Oncology, and Palliative Care, Department of Medicine, University of Wisconsin School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI 53792, USA; (A.K.D.); (N.K.L.); (S.J.L.); (J.D.K.)
- Carbone Cancer Center, University of Wisconsin, Madison, WI 53792, USA; (M.F.B.); (E.H.C.); (C.P.H.); (D.H.); (E.H.L.); (C.B.S.); (R.K.)
| | - Jeremy D. Kratz
- Division of Hematology, Medical Oncology, and Palliative Care, Department of Medicine, University of Wisconsin School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI 53792, USA; (A.K.D.); (N.K.L.); (S.J.L.); (J.D.K.)
- Carbone Cancer Center, University of Wisconsin, Madison, WI 53792, USA; (M.F.B.); (E.H.C.); (C.P.H.); (D.H.); (E.H.L.); (C.B.S.); (R.K.)
- William S Middleton Memorial Veterans Hospital, Madison, WI 53705, USA
| | - Dustin A. Deming
- Division of Hematology, Medical Oncology, and Palliative Care, Department of Medicine, University of Wisconsin School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI 53792, USA; (A.K.D.); (N.K.L.); (S.J.L.); (J.D.K.)
- Carbone Cancer Center, University of Wisconsin, Madison, WI 53792, USA; (M.F.B.); (E.H.C.); (C.P.H.); (D.H.); (E.H.L.); (C.B.S.); (R.K.)
- McArdle Laboratory for Cancer Research, Department of Oncology, Madison, WI 53705, USA
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Temperley HC, Mac Curtain BM, O’Sullivan NJ, Mulhall C, Temperley TS, Mehigan BJ, Larkin JO, McCormick PH, Kerr C, Gallagher D, Bergin C, Gillham C, Kelly ME. Factors Influencing Outcomes and Survival in Anal Cancer. Curr Oncol 2024; 31:5151-5163. [PMID: 39330009 PMCID: PMC11431442 DOI: 10.3390/curroncol31090381] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/21/2024] [Revised: 08/27/2024] [Accepted: 08/30/2024] [Indexed: 09/28/2024] Open
Abstract
BACKGROUND We aim to ascertain prognostic factors in the current management of anal cancer within this study. METHODS We reviewed the management and outcomes of anal cancer cases over a seven-year period, inclusive (2016-2023). The primary objectives were to assess the demographic characteristics, clinical presentation, and outcomes of all anal cancer patients within our institution. Kaplan-Meier survival analysis was used to estimate survival differences between cohorts, with statistical significance determined using log-rank testing. Cox proportional hazards regression was utilised to identify prognostic factors. Cox regression hazard ratios were reported along with confidence intervals and p-values. RESULTS The median follow-up time for the study was 29.8 months. Seventy-five patients with anal cancer were included in this study, with 88% (66/75) being squamous cell carcinoma (SCC) and the majority having regional disease (82.7% (62/75)). The median age at diagnosis was 63.4 years (36-94). There was a female preponderance (57.3% (43/75)). In total, 84% (63/75) underwent definitive chemoradiation (dCRT), with 7/63 (11.1%) requiring a salvage abdomino-perineal resection (APR) for residual or recurrent disease. Adverse prognostic indicators include those with T4 disease hazard ratio = 3.81, (95% CI 1.13-12.83, * p = 0.04), poorly differentiated tumour disease HR = 3.37, (95% CI 1.13-10.02, * p = 0.04), having N2 nodal status HR = 5.03, (95% CI 1.11-22.8, * p = 0.04), and having metastatic disease at diagnosis HR = 5.8, (95% CI 1.28-26.42, * p = 0.02). CONCLUSION Presenting characteristics including stage, nodal, and differentiation status remain key prognostic indicators in those diagnosed with anal malignancy.
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Affiliation(s)
- Hugo C. Temperley
- Department of Radiology, St. James’s Hospital, D08 NHY1 Dublin, Ireland
- Department of Surgery, St. James’s Hospital, D08 NHY1 Dublin, Ireland
- Trinity St. James’s Cancer Institute, D08 NHY1 Dublin, Ireland
| | | | - Niall J. O’Sullivan
- Department of Radiology, St. James’s Hospital, D08 NHY1 Dublin, Ireland
- Department of Surgery, St. James’s Hospital, D08 NHY1 Dublin, Ireland
| | - Cormac Mulhall
- Department of Surgery, St. James’s Hospital, D08 NHY1 Dublin, Ireland
| | | | - Brian J. Mehigan
- Department of Surgery, St. James’s Hospital, D08 NHY1 Dublin, Ireland
| | - John O. Larkin
- Department of Surgery, St. James’s Hospital, D08 NHY1 Dublin, Ireland
| | - Paul H. McCormick
- Department of Surgery, St. James’s Hospital, D08 NHY1 Dublin, Ireland
| | - Colm Kerr
- Department of Infectious Diseases, St. James’s Hospital, D08 NHY1 Dublin, Ireland
| | - David Gallagher
- Department of Medical Oncology, St. James’s Hospital, D08 NHY1 Dublin, Ireland
- Department of Genetics, St. James’s Hospital, D08 NHY1 Dublin, Ireland
| | - Colm Bergin
- Department of Infectious Diseases, St. James’s Hospital, D08 NHY1 Dublin, Ireland
| | - Charles Gillham
- Department of Radiation Oncology, St. James’s Hospital, D08 NHY1 Dublin, Ireland
| | - Michael E. Kelly
- Department of Surgery, St. James’s Hospital, D08 NHY1 Dublin, Ireland
- Trinity St. James’s Cancer Institute, D08 NHY1 Dublin, Ireland
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Westerlinck P, Coucke P, Albert A. Development of a cancer risk model and mobile health application to inform the public about cancer risks and risk factors. Int J Med Inform 2024; 189:105503. [PMID: 38820648 DOI: 10.1016/j.ijmedinf.2024.105503] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/06/2024] [Revised: 05/21/2024] [Accepted: 05/25/2024] [Indexed: 06/02/2024]
Abstract
OBJECTIVE To develop and evaluate a mobile health application, the Cancer Risk Calculator (CRC), aimed at improving public health literacy by providing personalized information on cancer risks and preventive measures. MATERIALS AND METHODS The CRC was developed through a comprehensive process involving the identification of necessary content, integration of average cancer risks using data from reliable sources, creation of a novel risk model emphasizing modifiable factors, and the application's development for easy access. The application covers 38 cancer types, 18 subtypes, and approximately 790 risk factors, utilizing data from the Surveillance, Epidemiology, and End Results Program and scientific literature. RESULTS CRC offers users personalized risk assessments across a broad range of cancers, emphasizing modifiable risk factors to encourage preventive behaviors. It distinguishes itself by covering more cancer types and risk factors than existing tools, with preliminary user feedback indicating its utility in promoting health literacy and lifestyle changes. DISCUSSION The CRC application stands out as an innovative tool in health informatics, significantly enhancing public understanding of cancer risks. Its development underscores the potential of digital health technologies to bolster preventive healthcare strategies through improved health literacy. CONCLUSION The Cancer Risk Calculator is a pivotal development in mobile health technology, offering comprehensive and personalized insights into cancer risks and prevention. It serves as a valuable resource for public health education, facilitating informed decisions and lifestyle modifications for cancer prevention.
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Affiliation(s)
- Philippe Westerlinck
- Department of Radiation Oncology, University Hospital Centre (CHU), Liège, Belgium.
| | - Philippe Coucke
- Department of Radiation Oncology, University Hospital Centre (CHU), Liège, Belgium
| | - Adelin Albert
- Department of Biostatistics, University Hospital Centre (CHU), Liège, Belgium
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14
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Fuentes-Calvo KJ, Silva-Ramos CS, Arechavala-López SF, Aguilar-Ruiz F, Arias-Ruiz LF, Trejo-Ávila M. Pigmented basal cell carcinoma of the anus: a rare entity with diagnostic challenges. J Surg Case Rep 2024; 2024:rjae554. [PMID: 39211371 PMCID: PMC11358057 DOI: 10.1093/jscr/rjae554] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/27/2024] [Revised: 08/07/2024] [Accepted: 08/14/2024] [Indexed: 09/04/2024] Open
Abstract
Anal cancer is uncommon, comprising 2.2% of gastrointestinal cancers. Squamous cell carcinoma (SCC) is the most common; while perianal basal cell carcinoma (BCC) is rare, representing only 0.2% of anorectal malignancies. BCC, associated with sun exposure and immunosuppression, often resembles benign conditions and manifests as perianal ulcers or masses. Histologically, BCC exhibits basaloid tumor cells with distinct patterns. Despite its rarity, accurate diagnosis is crucial. We expose a case study of a 59-year-old male, previously healthy, that presented with hematochezia and perianal pain, leading to a diagnosis of lower gastrointestinal bleeding. Colonoscopy was needed, and a biopsy revealed an ulcerated, indurated lesion involving the left lateral hemorrhoidal bundle, diagnosed as pigmented basaloid carcinoma. Microscopic examination showed malignant nests of cells with peripheral nuclear palisading, melanocytes, and melanin pigment. Immunohistochemistry confirmed positivity for p63, CK5/6, and BCL2. Respect the treatment, due to the involvement of the anal sphincteric muscle, radiotherapy was chosen.
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Affiliation(s)
| | | | | | | | | | - Mario Trejo-Ávila
- Department of Colon and Rectal Surgery, Hospital Médica Sur, Mexico City, Mexico
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15
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Gambella A, Senetta R, Falco EC, Ricci AA, Mangherini L, Tampieri C, Fissore J, Orlando G, Manetta T, Mengozzi G, Mistrangelo M, Bertero L, Cassoni P. Prognostic and predictive role of YKL-40 in anal squamous cell carcinoma: a serological and tissue-based analysis in a multicentric cohort. Front Med (Lausanne) 2024; 11:1372195. [PMID: 39045410 PMCID: PMC11263350 DOI: 10.3389/fmed.2024.1372195] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/17/2024] [Accepted: 06/03/2024] [Indexed: 07/25/2024] Open
Abstract
Introduction Anal squamous cell carcinoma (ASC) is a rare gastrointestinal malignancy showing an increased incidence over the past decades. YKL-40 is an immune modulator and pro-angiogenetic factor that showed a promising prognostic and predictive potential in several malignancies, but limited data are available for ASC. This study aims to provide an extensive evaluation of the prognostic and predictive role of YKL-40 in a multicenter cohort of ASC patients. Methods We retrospectively retrieved 72 consecutive cases of ASC diagnosed between February 2011 and March 2021. Both serum and tissue protein expression of YKL-40 were assessed, the latter in ASC tumor cells and peritumor immune cells. Results Increased YKL-40 serum levels at the time of diagnosis were associated with older age (p = 0.035), presence of cardiovascular/metabolic comorbidities (p = 0.007), and death for any cause (p = 0.011). In addition, high serum levels of YKL-40 were associated with a poor prognosis (HR: 2.82, 95% CI: 1.01-7.84; p = 0.047). Protein expression of YKL-40 in ASC tumor cells was significantly associated with low tumor grade (p = 0.031), while the increased expression in peritumor immune cells was associated with a worse response of patients to chemoradiotherapy (p = 0.007). However, YKL-40 protein expression in ASC tumor cells or peritumor immune cells did not significantly impact patient overall survival. Discussion In conclusion, YKL-40 resulted a relevant prognostic (serum level) and predictive (tissue protein expression in peritumor immune cells) biomarker and can considerably improve ASC patient clinical management.
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Affiliation(s)
- Alessandro Gambella
- Pathology Unit, Department of Medical Sciences, University of Turin, Turin, Italy
| | - Rebecca Senetta
- Pathology Unit, Department of Oncology, University of Turin, Turin, Italy
| | | | - Alessia Andrea Ricci
- Pathology Unit, Department of Medical Sciences, University of Turin, Turin, Italy
| | - Luca Mangherini
- Pathology Unit, Department of Medical Sciences, University of Turin, Turin, Italy
| | - Cristian Tampieri
- Pathology Unit, Department of Medical Sciences, University of Turin, Turin, Italy
| | - Jessica Fissore
- Pathology Unit, Città della Salute e della Scienza University Hospital, Turin, Italy
| | - Giulia Orlando
- Pathology Unit, Department of Oncology, University of Turin, Turin, Italy
| | - Tilde Manetta
- Department of Laboratory Medicine, Città della Salute e della Scienza University Hospital, Turin, Italy
| | - Giulio Mengozzi
- Department of Laboratory Medicine, Città della Salute e della Scienza University Hospital, Turin, Italy
| | | | - Luca Bertero
- Pathology Unit, Department of Medical Sciences, University of Turin, Turin, Italy
| | - Paola Cassoni
- Pathology Unit, Department of Medical Sciences, University of Turin, Turin, Italy
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Ho VKY, Deijen CL, Hemmes B, van Erning FN, Snaebjornsson P, van Triest B, Grotenhuis BA. Trends in epidemiology and primary treatment of anal squamous cell carcinoma in the Netherlands (1990-2021). Int J Cancer 2024; 154:1569-1578. [PMID: 38151810 DOI: 10.1002/ijc.34811] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/24/2023] [Revised: 10/20/2023] [Accepted: 11/07/2023] [Indexed: 12/29/2023]
Abstract
A rapid increase in the incidence of anal squamous cell carcinoma (SCC) was reported in several countries over the past decades. This study assessed trends in epidemiology and primary treatment over a 32-year period (1990-2021) using the Netherlands Cancer Registry. The study population included 4273 patients, 44.2% male and 55.8% female (median age 63 years). The age-standardised incidence rate (European Standardised Rate, ESR) increased from 0.5 to 1.6 per 100,000, which entailed an average annual percentage change (AAPC) of 5.0% (95% confidence interval [CI]: 4.5%-5.8%). While incidence among females increased continuously over the total period (AAPC 4.9%; 95%CI: 4.4%-5.6%), to 1.8 per 100,000 ESR in 2021, incidence among males increased until 2016 (annual percentage change [APC] of 6.3%; 95%CI: 5.6%-10.7%), after which it seemed to stabilise (APC -2.1%; 95%CI: -16.8%-4.5%). Significant trends were also observed in distribution of age, tumour stage and primary treatment modalities. Five-year relative survival (RS) was estimated using the Pohar-Perme estimator, and this improved from 56.1% in 1990-1997 (95%CI: 49.3%-62.4%) to 67.9% in 2014-2021 (95%CI: 64.7%-70.9%), but remained poor for stage IV disease. Evaluation through a multivariable Poisson regression model demonstrated diagnosis in the most recent period to be independently associated with better RS, in addition to female sex, younger age, early disease stage and any treatment. In conclusion, the rising incidence of anal SCC seems to decline in males, but not in females, and advances in diagnostics and therapeutic management have likely contributed to improved prognosis.
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Affiliation(s)
- Vincent K Y Ho
- Department of Research & Development, Netherlands Comprehensive Cancer Organisation (IKNL), Utrecht, The Netherlands
| | - Charlotte L Deijen
- Department of Radiation Oncology, Netherlands Cancer Institute, Amsterdam, The Netherlands
| | - Birgit Hemmes
- Department of Research & Development, Netherlands Comprehensive Cancer Organisation (IKNL), Utrecht, The Netherlands
| | - Felice N van Erning
- Department of Research & Development, Netherlands Comprehensive Cancer Organisation (IKNL), Utrecht, The Netherlands
- Department of Surgery, Catharina Hospital, Eindhoven, The Netherlands
| | - Petur Snaebjornsson
- Department of Pathology, Netherlands Cancer Institute, Amsterdam, The Netherlands
- Faculty of Medicine, University of Iceland, Reykjavik, Iceland
| | - Baukelien van Triest
- Department of Radiation Oncology, Netherlands Cancer Institute, Amsterdam, The Netherlands
| | - Brechtje A Grotenhuis
- Department of Surgical Oncology, Netherlands Cancer Institute, Amsterdam, The Netherlands
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17
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Gopalani SV, Senkomago V, Rim SH, Saraiya M. Human papillomavirus-associated anal squamous cell carcinoma: sociodemographic, geographic, and county-level economic trends in incidence rates-United States, 2001-2019. J Natl Cancer Inst 2024; 116:275-282. [PMID: 37851397 DOI: 10.1093/jnci/djad214] [Citation(s) in RCA: 5] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/02/2023] [Revised: 09/25/2023] [Accepted: 10/11/2023] [Indexed: 10/19/2023] Open
Abstract
BACKGROUND Incidence of anal squamous cell carcinoma is increasing, but vaccination against human papillomavirus (HPV) and removal of precancerous anal lesions could prevent new cases. The overall HPV-associated cancer incidence is reported to be higher in rural populations and in counties with lower economic status. We assessed these differences specifically for HPV-associated anal squamous cell carcinoma and described the geographic, county-level economic, and sociodemographic variations in incidence rates and trends. METHODS We analyzed data from the US Cancer Statistics to assess age-standardized incidence rates of HPV-associated squamous cell carcinomas among adults aged 18 years and older from 2001 to 2019. We calculated rate ratios and 95% confidence intervals to examine differences in incidence rates. We also quantified changes in incidence rates over time using joinpoint regression. RESULTS From 2001 to 2019, 72 421 new cases of HPV-associated anal squamous cell carcinoma were diagnosed among women (2.8 per 100 000) and 37 147 among men (1.7 per 100 000). Age-standardized incidence rates were higher in the South compared with other census regions and in counties ranked in the bottom 25% and 25%-75% economically than in the top 25%. The overall incidence rate increased in women but remained stable in men during 2009-2019. Incidence rates increased in adults aged 50 years and older but decreased among those aged 40-44 years from 2001 to 2019 in women and from 2007 to 2019 in men. CONCLUSIONS There were inequities in HPV-associated anal squamous cell carcinoma incidence by geographic and county-level economic characteristics. Failure to improve vaccine and treatment equity may widen existing disparities.
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Affiliation(s)
- Sameer Vali Gopalani
- Division of Cancer Prevention and Control, Centers for Disease Control and Prevention, Atlanta, GA, USA
- Oak Ridge Institute for Science and Education, Oak Ridge, TN, USA
| | - Virginia Senkomago
- Division of Cancer Prevention and Control, Centers for Disease Control and Prevention, Atlanta, GA, USA
| | - Sun Hee Rim
- Division of Cancer Prevention and Control, Centers for Disease Control and Prevention, Atlanta, GA, USA
| | - Mona Saraiya
- Division of Cancer Prevention and Control, Centers for Disease Control and Prevention, Atlanta, GA, USA
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18
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Alawabdeh T, Abuhijlih R, Mohamed I, Alnasraween S, Ababneh H, Turfa R, Alsunna S, Khzouz Y, Abuhijla F. Analysis of definitive chemo-radiation outcomes in anal cancer: insights from a tertiary cancer center in the MENA Region. Front Oncol 2024; 13:1333558. [PMID: 38239656 PMCID: PMC10796166 DOI: 10.3389/fonc.2023.1333558] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/10/2023] [Accepted: 12/05/2023] [Indexed: 01/22/2024] Open
Abstract
BACKGROUND Outcomes of chemo-radiation (CRT) for anal cancer in Middle East and North Africa (MENA) are scarce. We aim to report treatment outcomes for anal cancer treated at tertiary cancer center, with a particular focus on patients managed with non-oncological surgery prior definitive CRT. METHODS We conducted a retrospective review of patients diagnosed with locally advanced anal carcinoma, who underwent definitive CRT King Hussein Cancer Center, from January 2007 till January 2020. Patient demographics and disease characteristics were extracted, and a univariate chi-squared test was employed to assess the impact of chemotherapy type, HPV status, and pre-treatment non-oncological surgery on outcomes, including complete remission (CR), disease-free survival (DFS), and overall survival (OS). Kaplan-Meier tests were employed to analyze the obtained survival data. RESULTS Among the 34 initially identified patients, 30 were eligible, 24 (80%) achieved CR. Notably, 20 out of 21 HPV positive patients achieved CR, versus 1 out 4 HPV-negative achieved CR, p=0.006The 5-years OS for HPV-positive patients was 89% compared with 25% for HPV-negative, p=0001. There was no statistical significant difference in patients outcomes as regard type of chemotherapy, radiation technique and non-oncologic resection prior to CRT. CONCLUSION Herein, we reported the first series of anal cancer from our region. CRT had yielded an oncologic outcome comparable with series in the literature. HPV-positive patients demonstrated better results. Moreover, we found non-oncologic resection prior to CRT did not seem to impact the outcomes. Further studies are warranted to overcome the limitations of our study.
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Affiliation(s)
- Tala Alawabdeh
- Department of Medical Oncology, King Hussein Cancer Center, Amman, Jordan
| | - Ramiz Abuhijlih
- Department of Radiation Oncology, King Hussein Cancer Center, Amman, Jordan
| | - Issa Mohamed
- Department of Radiation Oncology, King Hussein Cancer Center, Amman, Jordan
| | - Saif Alnasraween
- Department of Internal Medicine, University of Jordan School of Medicine, Amman, Jordan
| | - Hazem Ababneh
- Department of Radiation Oncology, Massachusetts General Hospital, Boston, MA, United States
| | - Reem Turfa
- Department of Medical Oncology, King Hussein Cancer Center, Amman, Jordan
| | - Sanad Alsunna
- Department of Internal Medicine, University of Jordan School of Medicine, Amman, Jordan
| | - Yacoub Khzouz
- Department of Pathology, King Hussein Cancer Center, Amman, Jordan
| | - Fawzi Abuhijla
- Department of Radiation Oncology, King Hussein Cancer Center, Amman, Jordan
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Cairns CA, Cross RK, Khambaty M, Bafford AC. Monitoring Patients With Inflammatory Bowel Disease at High Risk of Anal Cancer. Am J Gastroenterol 2024; 119:81-86. [PMID: 37721307 DOI: 10.14309/ajg.0000000000002503] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/16/2023] [Accepted: 09/05/2023] [Indexed: 09/19/2023]
Abstract
Anal cancer is a rare but deadly disease that disproportionately affects patients with inflammatory bowel disease (IBD). Rates of adenocarcinoma and human papillomavirus-related squamous cell carcinoma have been consistently demonstrated to be higher in patients with ulcerative colitis and Crohn's disease. Despite this increased risk, uniform screening, diagnosis, and treatment algorithms are lacking. This review describes the most recent literature surrounding anal cancer in the IBD population as well as the unique challenges inherent in diagnosing and treating this population. We conclude by proposing a new screening motif based off literature review and multidisciplinary clinical experience that aims to increase early detection of anal cancers in the IBD population.
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Affiliation(s)
- Cassandra A Cairns
- Department of Surgery, Division of General and Oncologic Surgery, University of Maryland School of Medicine, Baltimore, Maryland, USA
| | - Raymond K Cross
- Department of Medicine, Division of Gastroenterology and Hepatology, University of Maryland School of Medicine, Baltimore, Maryland, USA
| | - Mariam Khambaty
- Department of Medicine, Division of Infectious Diseases, University of Maryland School of Medicine, Baltimore, Maryland, USA
| | - Andrea C Bafford
- Department of Surgery, Division of Colon and Rectal Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
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20
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Joseph K, Balushi MA, Ghosh S, Stenson T, Abraham A, Elangovan A, Warkentin H, Paulson K, Tankel K, Usmani N, Severin D, Schiller D, Wong C, Mulder K, Doll C, King K, Nijjar T. Long-Term Patient-Reported Quality of Life of Anal Cancer Survivors Treated With Intensity Modulated Radiation Therapy and Concurrent Chemotherapy: Results From a Prospective Phase II Trial. Int J Radiat Oncol Biol Phys 2023; 117:434-445. [PMID: 37148982 DOI: 10.1016/j.ijrobp.2023.04.023] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/30/2023] [Revised: 03/12/2023] [Accepted: 04/18/2023] [Indexed: 05/08/2023]
Abstract
PURPOSE Intensity modulated radiation therapy (IMRT) has confirmed its superiority in improving acute treatment-related toxicities in anal cancer, without compromising tumor control. However, the effect of IMRT on long-term quality of life (QOL) is poorly documented. The study prospectively evaluated the long-term patient-reported QOL after IMRT-based chemoradiation in anal cancer. METHODS AND MATERIALS Fifty-eight patients treated with IMRT and concurrent 5 fluorouracil/mitomycin-C were enrolled in the study. A prespecified secondary endpoint was prospective evaluation of long-term QOL. Fifty-four patients underwent QOL evaluation at baseline, after treatment, and during follow-up until 60 months, with European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-C30 (EORTC QLQ-C30) scales and the Colorectal Cancer-Specific Quality Of Life Questionnaire (QLQ-CR29) scales. The QOL scores at baseline and posttreatment periods were compared. RESULTS For QLQ-C30, at 60 months, the mean scores of global health status, all functional scales, and all symptoms except diarrhea had improved, indicating normalization of QOL. Clinically and statistically significant improvements in the global health status (15.4; P = .003), role functioning (19.3; P = .0017), emotional functioning (18.9; P = .008), and social functioning (29.8; P ≤ .001) were observed. Diarrhea persisted as a concern over the years (P = .172). For European Organization for Research and Treatment of Cancer QLQ-CR29, rectal pain (-38.6; P = .001), mucous or blood discharge per rectum (-22.8; P = .005), and perianal soreness (-37.3; P ≤ .001) were improved both clinically and statistically. Clinically significant fecal leakage was reported by 16% of patients (5.6; P = .421). Volumes receiving 45 and 54 Gy were independent predictors for fecal incontinence. Clinically and statistically significant urinary incontinence occurred in 21% of patients (17.5; P = .014). Deterioration of dyspareunia was clinically significant (26.7; P = .099) at 60 months. CONCLUSIONS Compared with historical data, IMRT is associated with reduced long-term effects on QOL. The majority of patients treated with IMRT experienced clinically significant recovery of function and improvement in QOL over 5 years after completion of treatment. Specific toxicities such as chronic diarrhea, fecal incontinence, and urinary and sexual dysfunction were primarily responsible for deterioration of the long-term QOL. Future research aimed at reducing such toxicities is needed to further improve long-term QOL in anal cancer.
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Affiliation(s)
- Kurian Joseph
- Division of Radiation Oncology, Department of Oncology, University of Alberta & Cross Cancer Institute, Edmonton, Alberta, Canada.
| | - Mustafa Al Balushi
- Division of Radiation Oncology, Department of Oncology, University of Alberta & Cross Cancer Institute, Edmonton, Alberta, Canada
| | - Sunita Ghosh
- Division of Medical Oncology, Department of Oncology, University of Alberta & Cross Cancer Institute, Edmonton, Alberta, Canada
| | - Trevor Stenson
- Alberta Cancer Clinical Trials, Cross Cancer Institute, Edmonton, Alberta, Canada
| | - Aswin Abraham
- Division of Radiation Oncology, Department of Oncology, University of Alberta & Cross Cancer Institute, Edmonton, Alberta, Canada
| | - Arun Elangovan
- Division of Radiation Oncology, Department of Oncology, University of Alberta & Cross Cancer Institute, Edmonton, Alberta, Canada
| | - Heather Warkentin
- Alberta Cancer Clinical Trials, Cross Cancer Institute, Edmonton, Alberta, Canada
| | - Kim Paulson
- Division of Radiation Oncology, Department of Oncology, University of Alberta & Cross Cancer Institute, Edmonton, Alberta, Canada
| | - Keith Tankel
- Division of Radiation Oncology, Department of Oncology, University of Alberta & Cross Cancer Institute, Edmonton, Alberta, Canada
| | - Nawaid Usmani
- Division of Radiation Oncology, Department of Oncology, University of Alberta & Cross Cancer Institute, Edmonton, Alberta, Canada
| | - Diane Severin
- Division of Radiation Oncology, Department of Oncology, University of Alberta & Cross Cancer Institute, Edmonton, Alberta, Canada
| | - Dan Schiller
- Division of Medical Physics, Department of Oncology, University of Alberta & Cross Cancer Institute, Edmonton, Alberta, Canada
| | - Clarence Wong
- Division of General Surgery, Department of Surgery, University of Alberta, Edmonton, Canada; Division of Gastroenterology, Department of Medicine, University of Alberta, Edmonton, Canada
| | - Karen Mulder
- Division of Medical Oncology, Department of Oncology, University of Alberta & Cross Cancer Institute, Edmonton, Alberta, Canada
| | - Corinne Doll
- Division of Radiation Oncology, Department of Oncology, University of Calgary & Tom Baker Cancer Centre, Calgary, Alberta, Canada
| | - Karen King
- Division of Medical Oncology, Department of Oncology, University of Alberta & Cross Cancer Institute, Edmonton, Alberta, Canada
| | - Tirath Nijjar
- Division of Radiation Oncology, Department of Oncology, University of Alberta & Cross Cancer Institute, Edmonton, Alberta, Canada
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21
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Gul SK, Tepetam H, Yildiz F, Er I, Oksuz DC, Parvizi M, Ozden AS, Alicikus ZA, Sari SY, Alomari O, Gorken IB. Revisiting the Radical Radiotherapy-Radiochemotherapy Results in Anal Canal Cancers: (TROD Gastrointestinal Group Study 02-005). Clin Colorectal Cancer 2023; 22:318-326. [PMID: 37336706 DOI: 10.1016/j.clcc.2023.05.004] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/12/2023] [Revised: 05/10/2023] [Accepted: 05/15/2023] [Indexed: 06/21/2023]
Abstract
BACKGROUND AND AIM This study aimed to determine treatment outcomes and factors affecting prognosis in patients diagnosed with anal canal cancer who received radical radiotherapy (RT) or radiotherapy combined with chemotherapy (CT-RT) in radiation oncology centers in Turkey and compare the results with literature. MATERIAL AND METHOD The study included 193 patients with anal canal cancer reported between 1995 and 2019, of which 162 had complete data. The study was conducted in 11 radiation oncology centers, and a joint database was shared among them. Patients received radiotherapy doses of 45 Gy to 60 Gy. Data analysis was done using SPSS for Windows version 20. RESULTS Median follow-up was 48.51 months (2-214). All patients received radiotherapy, and 140 (86.4%) received concurrent chemotherapy. Radiotherapy doses of 50.4 Gy to 60 Gy were administered to 74 patients (45.7%) using 2-dimensional-3-dimensional (2D-3D) conformal therapy and 70 patients (43.2%) using intensity modulated radiotherapy technique (IMRT). Acute phase hematologic toxicity was observed in 62 patients (38.3%), and nonhematologic toxicity in 123 patients (75.9%). The 5-year overall survival (OS) rate was 75.1% and disease-specific survival (DSS) rate was 76.4%. OS without colostomy was achieved in 79,8 % at 5 years, and complete response in 112 patients (69.1%). OS rate was significantly higher in 142 patients with positive response (P < .000) and 112 with complete response (P < .000). Anemia (P < .002), local progression, and systemic progression (P < .000) resulted in lower OS (P < .002). In univariate analysis, factors affecting OS rate were: gender, age, stage, lymph node status, T stage, RT treatment duration, and treatment planning with PET fusion, which were found to be statistically significant. Completing radiotherapy in less than 45 days, concurrent chemotherapy, and continued administration of mitomycin and 5 FU as chemotherapy had a significant positive effect on overall survival. OS rate was higher in patients receiving RT dose of 58 Gy or less and undergoing IMRT planning in radiotherapy. IMRT was associated with lower acute and late side effects. CONCLUSION Radiochemotherapy is the primary treatment for anal canal cancer and advanced radiotherapy techniques may increase survival by reducing side effects and improving treatment continuation. Higher treatment doses require further investigation. The efficacy of treatment can be improved by including patients treated with modern radiotherapy techniques in multicenter prospective studies using new and more effective chemotherapy and immunotherapy agents.
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Affiliation(s)
- Sule Karabulut Gul
- Department of Radiation Oncology, University of Health Sciences, Dr. Lutfi Kirdar Kartal Training and Research Hospital, Istanbul, Turkey.
| | - Huseyin Tepetam
- Department of Radiation Oncology, University of Health Sciences, Dr. Lutfi Kirdar Kartal Training and Research Hospital, Istanbul, Turkey
| | - Ferah Yildiz
- Department of Radiation Oncology, Faculty of Medicine, Hacettepe University, Ankara, Turkey
| | - Ilhami Er
- Department of Radiation Oncology, Izmir Katip Celebi University, Ataturk Training and Research Hospital, Izmir, Turkey
| | - Didem Colpan Oksuz
- Istanbul University Department of Radiation Oncology, Hospital of Cerrahpasa school of Medicine, Istanbul, Turkey
| | - Murtaza Parvizi
- Department of Radiation Oncology, Manisa State Hospital, Manisa, Turkey
| | - Ayse Sevgi Ozden
- Department of Radiation Oncology, University of Health Sciences, Dr. Lutfi Kirdar Kartal Training and Research Hospital, Istanbul, Turkey
| | | | - Sezin Yuce Sari
- Department of Radiation Oncology, Faculty of Medicine, Hacettepe University, Ankara, Turkey
| | - Omar Alomari
- Hamidiye International School of Medicine, University of Health Sciences, Istanbul, Turkey
| | - Ilknur Bilkay Gorken
- Department of Radiation Oncology, Dokuz Eylul University Faculty of Medicine, Izmir, Turkey
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22
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Janczewski LM, Faski J, Nelson H, Gollub MJ, Eng C, Brierley JD, Palefsky JM, Goldberg RM, Washington MK, Asare EA, Goodman KA. Survival outcomes used to generate version 9 American Joint Committee on Cancer staging system for anal cancer. CA Cancer J Clin 2023; 73:516-523. [PMID: 37114458 DOI: 10.3322/caac.21780] [Citation(s) in RCA: 15] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/17/2023] [Revised: 03/09/2023] [Accepted: 03/20/2023] [Indexed: 04/29/2023] Open
Abstract
The American Joint Committee on Cancer (AJCC) staging system for all cancer sites, including anal cancer, is the standard for cancer staging in the United States. The AJCC staging criteria are dynamic, and periodic updates are conducted to optimize AJCC staging definitions through a panel of experts charged with evaluating new evidence to implement changes. With greater availability of large data sets, the AJCC has since restructured and updated its processes, incorporating prospectively collected data to validate stage group revisions in the version 9 AJCC staging system, including anal cancer. Survival analysis using AJCC eighth edition staging guidelines revealed a lack of hierarchical order in which stage IIIA anal cancer was associated with a better prognosis than stage IIB disease, suggesting that, for anal cancer, tumor (T) category has a greater effect on survival than lymph node (N) category. Accordingly, version 9 stage groups have been appropriately adjusted to reflect contemporary long-term outcomes. This article highlights the changes to the now published AJCC staging system for anal cancer, which: (1) redefined stage IIB as T1-T2N1M0 disease, (2) redefined stage IIIA as T3N0-N1M0 disease, and (3) eliminated stage 0 disease from its guidelines altogether.
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Affiliation(s)
- Lauren M Janczewski
- Department of Surgery, Feinberg School of Medicine at Northwestern University, Chicago, Illinois, USA
- American College of Surgeons Cancer Programs, Chicago, Illinois, USA
| | - Joseph Faski
- American College of Surgeons Cancer Programs, Chicago, Illinois, USA
| | - Heidi Nelson
- American College of Surgeons Cancer Programs, Chicago, Illinois, USA
| | - Marc J Gollub
- Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, New York, USA
| | - Cathy Eng
- Division of Hematology and Oncology, Department of Medicine, Vanderbilt-Ingram Cancer Center, Nashville, Tennessee, USA
| | - James D Brierley
- Radiation Medicine Program, Princess Margaret Cancer Centre, University of Toronto, Toronto, Ontario, Canada
| | - Joel M Palefsky
- Department of Medicine, University of California, San Francisco, California, USA
| | - Richard M Goldberg
- West Virginia University Cancer Institute, Morgantown, West Virginia, USA
| | - M Kay Washington
- Department of Pathology, Microbiology, and Immunology, Vanderbilt University School of Medicine, Nashville, Tennessee, USA
| | - Elliot A Asare
- Department of Surgery, University of Utah Huntsman Cancer Institute, Salt Lake City, Utah, USA
| | - Karyn A Goodman
- Department of Radiation Oncology, Icahn School of Medicine at Mount Sinai, New York, New York, USA
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23
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Yamada K, Shiraishi K, Takashima A, Takayanagi D, Saiki Y, Takano S, Tanaka M, Fukunaga M, Sugimoto K, Iwasaki Y, Nakamura Y, Kuwahara D, Tsuji Y, Takano M, Sugihara K, Ajioka Y. Characteristics of anal canal squamous cell carcinoma as an HPV-associated cancer in Japan. Int J Clin Oncol 2023; 28:990-998. [PMID: 37115427 DOI: 10.1007/s10147-023-02339-5] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/28/2023] [Accepted: 04/06/2023] [Indexed: 04/29/2023]
Abstract
The definition of the anal canal was revised in the TNM classification (8th edition). The Japanese Society for Cancer of the Colon and Rectum (JSCCR) conducted a retrospective multi-institutional study to clarify the characteristics of anal canal cancer (ACC) in Japan. The diagnoses of 1781 patients treated for ACC were squamous cell carcimoma (SCC; n = 428; 24.0%), adenosquamous cell carcinoma (n = 7; 0.4%), and adenocarcinoma (n = 1260; 70.7%). Anal carcinoma is associated with human papillomavirus (HPV) infection and is risk factor for anal SCC. Among 40 cases analyzed at Takano Hospital and 47 cases analyzed at National Cancer Center Hospital, 34 cases (85.0%) and 40 cases (85.1%), respectively were infected with HPV; HPV-16 was the most common genotype (79.4% and 82.5%). In the JSCCR retrospective multi-institutional study, the prognosis analysis by stage was performed for anal SCC cases (202 cases treated by CRT and 91 cases treated by surgery). The 5-year overall survival (OS) rates by stage did not differ between the two treatment groups to a statistically significant extent. Regarding the results of cancer treatment of patients who underwent HPV infection tests, although the 5-year OS rates by stage did not differ to a statistically significant extent due to the small number of cases, HPV-positive patients had better survival. While an HPV vaccine for anal canal SCC has already been approved internationally, HPV vaccination has already been implemented in Japan as a national immunization program for young women but not for men at present. An HPV vaccination for men is urgently needed.
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Affiliation(s)
- Kazutaka Yamada
- Department of Surgery, Coloproctology Center Takano Hospital, 3-2-55 Oe, Chuo-ku, Kumamoto, 862-0971, Japan.
| | - Kouya Shiraishi
- Division of Genome Biology, National Cancer Center Research Institute, 5-1-1 Tsukiji, Chuo-ku, Tokyo, 104-0045, Japan
| | - Atsuo Takashima
- Department of Gastrointestinal Medical Oncology, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo, 104-0045, Japan
| | - Daisuke Takayanagi
- Division of Genome Biology, National Cancer Center Research Institute, 5-1-1 Tsukiji, Chuo-ku, Tokyo, 104-0045, Japan
| | - Yasumitsu Saiki
- Department of Surgery, Coloproctology Center Takano Hospital, 3-2-55 Oe, Chuo-ku, Kumamoto, 862-0971, Japan
| | - Shota Takano
- Department of Surgery, Coloproctology Center Takano Hospital, 3-2-55 Oe, Chuo-ku, Kumamoto, 862-0971, Japan
| | - Masafumi Tanaka
- Department of Surgery, Coloproctology Center Takano Hospital, 3-2-55 Oe, Chuo-ku, Kumamoto, 862-0971, Japan
| | - Mitsuko Fukunaga
- Department of Surgery, Coloproctology Center Takano Hospital, 3-2-55 Oe, Chuo-ku, Kumamoto, 862-0971, Japan
| | - Kosuke Sugimoto
- Division of Medical Information Research, Coloproctology Center Takano Hospital, 3-2-55 Oe, Chuo-ku, Kumamoto, 862-0971, Japan
| | - Yuki Iwasaki
- Division of Medical Information Research, Coloproctology Center Takano Hospital, 3-2-55 Oe, Chuo-ku, Kumamoto, 862-0971, Japan
| | - Yasushi Nakamura
- Department of Surgery, Coloproctology Center Takano Hospital, 3-2-55 Oe, Chuo-ku, Kumamoto, 862-0971, Japan
| | - Daisaku Kuwahara
- Department of Surgery, Coloproctology Center Takano Hospital, 3-2-55 Oe, Chuo-ku, Kumamoto, 862-0971, Japan
| | - Yoriyuki Tsuji
- Department of Surgery, Coloproctology Center Takano Hospital, 3-2-55 Oe, Chuo-ku, Kumamoto, 862-0971, Japan
| | - Masahiro Takano
- Department of Surgery, Coloproctology Center Takano Hospital, 3-2-55 Oe, Chuo-ku, Kumamoto, 862-0971, Japan
| | - Kenichi Sugihara
- Tokyo Medical and Dental University, 1-5-45, Yushima, Bunkyo-ku, Tokyo, 113-8510, Japan
| | - Yoichi Ajioka
- Division of Molecular and Diagnostic Pathology, Niigata University Graduate School of Medical and Dental Sciences, 757 Ichibancho, Asahimachi-dori, Chuo Ward, Niigata, 951-8510, Japan
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24
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Shegog R, Savas LS, Frost EL, Thormaehlen LC, Teague T, Steffy J, Healy CM, Shay LA, Preston S, Vernon SW. Adaptation and Formative Evaluation of Online Decision Support to Implement Evidence-Based Strategies to Increase HPV Vaccination Rates in Pediatric Clinics. Vaccines (Basel) 2023; 11:1270. [PMID: 37515085 PMCID: PMC10383429 DOI: 10.3390/vaccines11071270] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/02/2023] [Revised: 07/11/2023] [Accepted: 07/19/2023] [Indexed: 07/30/2023] Open
Abstract
Human papilloma virus (HPV) vaccination rates remain below national goals in the United States despite the availability of evidence-based strategies to increase rates. The Adolescent Vaccination Program (AVP) is a multi-component intervention demonstrated to increase HPV vaccination rates in pediatric clinics through the implementation of six evidence-based strategies. The purpose of this study, conducted in Houston, Texas, from 2019-2021, was to adapt the AVP into an online decision support implementation tool for standalone use and to evaluate its feasibility for use in community clinics. Phase 1 (Adaptation) comprised clinic interviews (n = 23), literature review, Adolescent Vaccination Program Implementation Tool (AVP-IT) design documentation, and AVP-IT development. Phase 2 (Evaluation) comprised usability testing with healthcare providers (HCPs) (n = 5) and feasibility testing in community-based clinics (n = 2). AVP-IT decision support provides an Action Plan with tailored guidance on implementing six evidence-based strategies (immunization champions, assessment and feedback, continuing education, provider prompts, parent reminders, and parent education). HCPs rated the AVP-IT as acceptable, credible, easy, helpful, impactful, and appealing (≥80% agreement). They rated AVP-IT supported implementation as easier and more effective compared to usual practice (p ≤ 0.05). The clinic-based AVP-IT uses facilitated strategy implementation by 3-month follow-up. The AVP-IT promises accessible, utilitarian, and scalable decision support on strategies to increase HPV vaccination rates in pediatric clinic settings. Further feasibility and efficacy testing is indicated.
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Affiliation(s)
- Ross Shegog
- Department of Health Promotion and Behavioral Sciences, University of Texas School of Public Health, Houston, TX 77030, USA
| | - Lara S Savas
- Department of Health Promotion and Behavioral Sciences, University of Texas School of Public Health, Houston, TX 77030, USA
| | - Erica L Frost
- Department of Health Promotion and Behavioral Sciences, University of Texas School of Public Health, Houston, TX 77030, USA
| | - Laura C Thormaehlen
- Department of Health Promotion and Behavioral Sciences, University of Texas School of Public Health, Houston, TX 77030, USA
| | - Travis Teague
- Department of Health Promotion and Behavioral Sciences, University of Texas School of Public Health, Houston, TX 77030, USA
| | - Jack Steffy
- Department of Anthropology, Washington University in St. Louis, St. Louis, MO 63130, USA
| | - Catherine Mary Healy
- Department of Pediatrics, Infectious Diseases Section, Baylor College of Medicine, Houston, TX 77030, USA
| | - Laura Aubree Shay
- Department of Health Promotion and Behavioral Sciences, University of Texas School of Public Health, Houston, TX 77030, USA
| | - Sharice Preston
- Department of Health Promotion and Behavioral Sciences, University of Texas School of Public Health, Houston, TX 77030, USA
| | - Sally W Vernon
- Department of Health Promotion and Behavioral Sciences, University of Texas School of Public Health, Houston, TX 77030, USA
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25
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Comeau D, Johnson C, Bouhamdani N. Review of current 2SLGBTQIA+ inequities in the Canadian health care system. Front Public Health 2023; 11:1183284. [PMID: 37533535 PMCID: PMC10392841 DOI: 10.3389/fpubh.2023.1183284] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/09/2023] [Accepted: 07/03/2023] [Indexed: 08/04/2023] Open
Abstract
Gender identity and sexual orientation are determinants of health that can contribute to health inequities. In the 2SLGBTQIA+ community, belonging to a sexual and/or gender minority group leads to a higher risk of negative health outcomes such as depression, anxiety, and cancer, as well as maladaptive behaviors leading to poorer health outcomes such as substance abuse and risky sexual behavior. Empirical evidence suggests that inequities in terms of accessibility to health care, quality of care, inclusivity, and satisfaction of care, are pervasive and entrenched in the health care system. A better understanding of the current Canadian health care context for individuals of the 2SLGBTQIA+ community is imperative to inform public policy and develop sensitive public health interventions to make meaningful headway in reducing inequity. Our search strategy was Canadian-centric and aimed at highlighting the current state of 2SLGBTQIA+ health inequities in Canada. Discrimination, patient care and access to care, education and training of health care professionals, and crucial changes at the systemic and infrastructure levels have been identified as main themes in the literature. Furthermore, we describe health care-related disparities in the 2SLGBTQIA+ community, and present available resources and guidelines that can guide healthcare providers in narrowing the gap in inequities. Herein, the lack of training for both clinical and non-clinical staff has been identified as the most critical issue influencing health care systems. Researchers, educators, and practitioners should invest in health care professional training and future research should evaluate the effectiveness of interventions on staff attitudinal changes toward the 2SLGBTQIA+ community and the impact on patient outcomes.
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Affiliation(s)
- Dominique Comeau
- Vitalité Health Network, Dr. Georges-L.-Dumont University Hospital Center, Research Sector, Moncton, NB, Canada
| | - Claire Johnson
- School of Public Policy Studies, Université de Moncton, Moncton, NB, Canada
| | - Nadia Bouhamdani
- Vitalité Health Network, Dr. Georges-L.-Dumont University Hospital Center, Research Sector, Moncton, NB, Canada
- Medicine and Health Sciences Faculty, Université de Sherbrooke, Sherbrooke, QC, Canada
- Centre de Formation Médicale du Nouveau-Brunswick, Université de Moncton, Moncton, NB, Canada
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26
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Parra-Lara LG, Arango-Ibañez JP, Martínez-Arboleda JJ, Bravo JC, Zambrano ÁR, Collazos P, Andino F, Badillo A, Estrada S, Rosso F. Survival of patients living with HIV and cancer in Cali, Colombia. Colomb Med (Cali) 2023; 54:e2015558. [PMID: 38098512 PMCID: PMC10719985 DOI: 10.25100/cm.v54i3.5588] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/13/2023] [Revised: 08/22/2023] [Accepted: 09/21/2023] [Indexed: 12/17/2023] Open
Abstract
Background People living with HIV have an increased risk of cancer compared to the general population. However, with the increase in life expectancy and advances in antiretroviral therapy, the survival of patients with cancer and HIV has changed. Objective To determine the survival of patients living with HIV and cancer in Cali, Colombia. Methods A retrospective cohort study was conducted at the Fundación Valle del Lili, Cali, Colombia. Data from the HIV database was crossed with data from the hospital and population-based cancer registries between 2011-2019. Patients <18 years, limited available clinical information on the diagnosis and treatment of HIV and cancer, and non-oncological tumor diagnosis were excluded. Results A total of 173 patients were included. The frequencies of AIDS-defining neoplasms were: Non-Hodgkin lymphoma (42.8%), Kaposi sarcoma (27.8%), and cervical cancer (4.6%). Overall survival was 76.4% (95% CI 68.9-82.3) at five years. Poorer survival was found in patients with AIDS-defining infections (56.9% vs. 77.8%, p=0.027) and non-AIDS-defining infections (57.8% vs. 84.2%, p=0.013), while there was better survival in patients who received antiretroviral therapy (65.9% vs. 17.9%, p=0.021) and oncological treatment (66.7% vs. 35.4%, p<0.001). The presence of non-AIDS-defining infections increases the risk of dying (HR = 2.39, 95% CI 1.05-5.46, p=0.038), while oncological treatment decreases it (HR = 0.33, 95% CI 0.14-0.80, p=0.014). Conclusions In people living with HIV, Non-Hodgkin lymphoma and Kaposi sarcoma are the most common neoplasms. Factors such as AIDS-associated and non-AIDS-associated infections have been identified as determinants of survival. Cancer treatment seems to improve survival.
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Affiliation(s)
- Luis Gabriel Parra-Lara
- Universidad Icesi, Facultad de Ciencias de la Salud, Cali, Colombia
- Fundación Valle del Lili, Centro de Investigaciones Clínicas (CIC), Cali, Colombia
| | | | | | - Juan C. Bravo
- Fundación Valle del Lili, Departamento de Patología y Laboratorio Clínico, Cali, Colombia
| | - Ángela R. Zambrano
- Fundación Valle del Lili, Departamento de Medicina Interna, Servicio de Hematología & Oncología Clínica, Cali, Colombia
| | - Paola Collazos
- Universidad del Valle, Facultad de Salud, Registro Poblacional de Cáncer de Cali (RPCC), Cali, Colombia
| | - Francisco Andino
- Universidad Católica de Santiago de Guayaquil, Guayaquil, Ecuador
| | - Angélica Badillo
- Fundación Valle del Lili, Centro de Investigaciones Clínicas (CIC), Cali, Colombia
| | - Sebastián Estrada
- Fundación Valle del Lili, Centro de Investigaciones Clínicas (CIC), Cali, Colombia
| | - Fernando Rosso
- Universidad Icesi, Facultad de Ciencias de la Salud, Cali, Colombia
- Fundación Valle del Lili, Centro de Investigaciones Clínicas (CIC), Cali, Colombia
- Fundación Valle del Lili, Departamento de Medicina Interna, Servicio de Infectología, Cali, Colombia
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27
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Roji AM, Namiq KF, Radley S, Ismail T, Hejmadi R, Taniere P, Geh JI. Management of small (T1-T2) anal margin squamous cell carcinoma: clinical outcomes following local excision alone. Colorectal Dis 2023; 25:1403-1413. [PMID: 37029622 DOI: 10.1111/codi.16562] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/12/2022] [Revised: 01/28/2023] [Accepted: 03/08/2023] [Indexed: 04/09/2023]
Abstract
AIM Squamous cell carcinomas of the anus are normally treated with synchronous chemoradiotherapy (CRT). Small, localized anal margin tumours may be adequately treated by local excision (LE) alone. This study aims to investigate the outcomes of patients with anal margin tumours treated with LE alone, reserving the use of CRT for salvage on local recurrence (LR). METHODS Patients with small, localized (stage I/IIA) anal margin tumours treated by LE from October 1999 to September 2018 were identified. The effect of tumour size and resection margin on LR risk was analysed. Outcomes of overall survival and disease-free survival were measured. RESULTS Fifty-five patients with anal margin tumours were identified. Overall 5-year LR, overall survival and disease-free survival rates were 8%, 86% and 82% respectively. Of the seven LRs, five were successfully salvaged with CRT with no further recurrence and two were not fit for CRT. Resection margins in non-fragmented tumours and tumour size did not significantly influence LR risk. CONCLUSIONS Most small, localized anal margin tumours can be adequately treated by LE alone with low LR rates. Most patients who developed LR were salvaged using CRT, with no cancer-related deaths reported.
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Affiliation(s)
- A M Roji
- Queen Elizabeth Hospital, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK
| | - K F Namiq
- Queen Elizabeth Hospital, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK
- School of Cancer Sciences, University of Birmingham, Birmingham, UK
| | - S Radley
- Queen Elizabeth Hospital, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK
| | - T Ismail
- Queen Elizabeth Hospital, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK
| | - R Hejmadi
- Queen Elizabeth Hospital, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK
| | - P Taniere
- Queen Elizabeth Hospital, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK
| | - J I Geh
- Queen Elizabeth Hospital, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK
- School of Cancer Sciences, University of Birmingham, Birmingham, UK
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28
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Rosado C, Fernandes ÂR, Rodrigues AG, Lisboa C. Impact of Human Papillomavirus Vaccination on Male Disease: A Systematic Review. Vaccines (Basel) 2023; 11:1083. [PMID: 37376472 DOI: 10.3390/vaccines11061083] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/05/2023] [Revised: 06/08/2023] [Accepted: 06/08/2023] [Indexed: 06/29/2023] Open
Abstract
Human papillomavirus (HPV)-related diseases are highly prevalent in men worldwide, comprising external anogenital condyloma, anal intraepithelial neoplasia (AIN), penile intraepithelial neoplasia (PIN), and anogenital and oropharyngeal cancers. There is exceptionally low vaccine coverage in the male population. Only 4% of men were fully vaccinated, worldwide, as of 2019. The aim of this review is to assess the impact of HPV vaccination on male disease. Three databases (MEDLINE, Web of Science, Scopus) and Clinical Trials.gov were searched. We included thirteen studies, eight randomized controlled trials (RCTs), and five cohorts, comprising a total of 14,239 participants. Regarding anal disease, seven studies reported HPV vaccine efficacy ranging from 91.1% to 93.1% against AIN1, and ranging from 89.6% to 91.7% against AIN2|3 and anal cancer. Five studies showed an efficacy against genital condyloma of 89.9% in HPV-naïve males, varying between 66.7% and 67.2% in intention-to-treat populations. Studies reporting no efficacy have included older participants. These results support vaccination of young men previously infected, beyond HPV-naïve males. The evidence quality was moderate to low for most outcomes, namely genital diseases. RCTs are needed to assess the efficacy of HPV vaccination on male oropharyngeal cancer.
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Affiliation(s)
- Catarina Rosado
- Division of Microbiology, Department of Pathology, Faculty of Medicine, University of Porto, 4200-039 Porto, Portugal
| | - Ângela Rita Fernandes
- Division of Microbiology, Department of Pathology, Faculty of Medicine, University of Porto, 4200-039 Porto, Portugal
| | - Acácio Gonçalves Rodrigues
- Division of Microbiology, Department of Pathology, Faculty of Medicine, University of Porto, 4200-039 Porto, Portugal
- CINTESIS@RISE, Center of Health Technology and Services Research/Rede de Investigação em Saúde, Faculty of Medicine, University of Porto, 4200-319 Porto, Portugal
| | - Carmen Lisboa
- Division of Microbiology, Department of Pathology, Faculty of Medicine, University of Porto, 4200-039 Porto, Portugal
- CINTESIS@RISE, Center of Health Technology and Services Research/Rede de Investigação em Saúde, Faculty of Medicine, University of Porto, 4200-319 Porto, Portugal
- Department of Dermatology and Venereology, Centro Hospitalar Universitário São João, 4200-319 Porto, Portugal
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29
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Ejaz M, Ekström AM, Ali TS, Salazar M, Ahmed A, Ali D, Haroon A, Siddiqi S. Integration of human papillomavirus associated anal cancer screening into HIV care and treatment program in Pakistan: perceptions of policymakers, managers, and care providers. BMC Public Health 2023; 23:1034. [PMID: 37259085 DOI: 10.1186/s12889-023-15896-1] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/09/2022] [Accepted: 05/15/2023] [Indexed: 06/02/2023] Open
Abstract
BACKGROUND The incidence of anal cancer, largely associated with anal human papillomavirus (HPV) infection, is increasing among men who have sex with men (MSM), and transgender women living with or without HIV. Screening for anal cancer to detect anal precancerous lesions in high-risk groups is an important opportunity for prevention but still lacking in many low-and-middle-income countries. The aim of this study was to explore the readiness of Pakistan's healthcare system to integrate anal cancer and HPV screening into a national HIV program, as perceived by policymakers, health managers, and healthcare providers. DESIGN This qualitative study using key-informant interviews with participants influence in policy making, implementation and advocacy from public and private sector were conducted between March 2021 to August 2021 in Karachi Pakistan. METHODS Key informants were purposely selected from different domains of the healthcare system responsible for the target group of interest, MSM and transgender-women in general and people living with HIV in particular. A total of 18 key informants, at different levels of seniority were recruited from governmental and non-governmental organizations, high-level infectious disease healthcare managers, and United Nations Program representatives. Qualitative content analysis was used to identify the manifest and latent themes, based on socioecological framework. RESULTS The results were grouped into five major themes; (1) The policy context and priorities, (2) Health systems factors, (3) Community environment, (4) Healthcare setting & providers and (5) Individual-level obstacles. The policy actors expressed their concerns about their limited voice in country's health and health related priority setting. Informants reported a lack of political will and suggested that government should bring a change in the paradigm of healthcare service delivery from reactive to proactive approach. Although, participants unanimously favored integration of HPV preventive services into existing HIV program, they also identified several service delivery barriers including trained workforce shortage, limited capacity of information technology, lack of supplies needed for screening, lack of financing, and lack of services that could meet key-populations needs. Participants also predicted other implementation challenges such as stigma, social victimization, and systemic discrimination against at-risk groups at healthcare facilities. CONCLUSION Although policy makers and health providers in Pakistan saw a clear need to scale-up and integrate anal cancer screening for key populations, the feasibility of this is dependent on political will, financing, anti-stigma and discrimination interventions and health system efficiency.
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Affiliation(s)
- Muslima Ejaz
- Department of Global Public Health, Karolinska Institutet Stockholm, Widerströmska Huset 18 A 171 77, Stockholm, Sweden.
- Department of Community Health Sciences, Aga Khan University, Stadium Road, P.O. Box 3500, Karachi, 74800, Pakistan.
| | - Anna Mia Ekström
- Department of Global Public Health, Karolinska Institutet Stockholm, Widerströmska Huset 18 A 171 77, Stockholm, Sweden
- Department of Infectious Diseases, South Central Hospital, Stockholm, Sweden
| | | | - Mariano Salazar
- Department of Global Public Health, Karolinska Institutet Stockholm, Widerströmska Huset 18 A 171 77, Stockholm, Sweden
| | - Alyan Ahmed
- Department of Community Health Sciences, Aga Khan University, Stadium Road, P.O. Box 3500, Karachi, 74800, Pakistan
| | - Dania Ali
- Department of Community Health Sciences, Aga Khan University, Stadium Road, P.O. Box 3500, Karachi, 74800, Pakistan
| | - Ayman Haroon
- Department of Biostatistics and Epidemiology, School of Public Health, Boston University, Boston, MA, USA
| | - Sameen Siddiqi
- Department of Community Health Sciences, Aga Khan University, Stadium Road, P.O. Box 3500, Karachi, 74800, Pakistan
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Rotondi M, Facondo G, Mossa S, Vullo G, Angelicone I, Valeriani M, Osti MF. Comparative analysis of toxicity in patients with anal cancer undergoing definitive simultaneous integrated boost (SIB) or sequential integrated boost (SeqB) radiotherapy. Int J Colorectal Dis 2023; 38:125. [PMID: 37171509 PMCID: PMC10181964 DOI: 10.1007/s00384-023-04411-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 04/24/2023] [Indexed: 05/13/2023]
Abstract
PURPOSE To compare toxicity of radiotherapy (RT) with concomitant chemotherapy (CHT) in patients (pts) with anal cancer treated with simultaneous integrated boost (SIB) versus sequential boost (SeqB). METHODS Sixty-six patients were treated from 2007 to 2021. Thirty patients underwent to SeqB concurrent to CHT and 37 to SIB-group. Toxicity assessment has been considered in acute and in late toxicities for gastrointestinal (GI), genitourinary (GU), cutaneous (CU) districts, according to Common Terminology Criteria for Adverse Events (CTCAE), Version 5.0. The Wexner scale among summary scoring systems has been used as a tool to measure fecal incontinence. The chi-square test for ordinal variables were used to evaluate the association between patient and treatment characteristics and acute or late severe toxicity. Univariable logistic regression models were fit to evaluate predictive factors associated with fecal incontinence. RESULTS Median follow-up was 61.5 months (IQR, 27.1-121.7 months) for all patients. Severe acute toxicity (≥ G2) was observed in 49 patients (74.2%). Late toxicity (≥ G2) occurred in 13 cases (19.6%). In assessment of cutaneous toxicity, there was also a significant reduction in ≥ G1 in SIB group with 29 patients (80.5%) vs SeqB group with 29 patients (96.6%) (p-value = 0.046). Of both groups 11 patients (16.6%) developed fecal incontinence, 8 (22%) in the SIB group and 3 (10%) in the SeqB. CONCLUSION SIB for anal cancer treatment results in reduced acute and late cutaneous toxicity compared to SeqB. According to our results the rate of other acute and late toxicities are low and comparable between the two groups.
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Affiliation(s)
- Margherita Rotondi
- Department of Medicine and Surgery and Translational Medicine, Radiotherapy Oncology, Sapienza University of Rome, St. Andrea Hospital, 00189, Rome, Italy
| | - Giuseppe Facondo
- Department of Medicine and Surgery and Translational Medicine, Radiotherapy Oncology, Sapienza University of Rome, St. Andrea Hospital, 00189, Rome, Italy.
| | - Stefano Mossa
- Department of Medicine and Surgery and Translational Medicine, Radiotherapy Oncology, Sapienza University of Rome, St. Andrea Hospital, 00189, Rome, Italy
| | - Gianluca Vullo
- Department of Medicine and Surgery and Translational Medicine, Radiotherapy Oncology, Sapienza University of Rome, St. Andrea Hospital, 00189, Rome, Italy
| | - Ilaria Angelicone
- Department of Medicine and Surgery and Translational Medicine, Radiotherapy Oncology, Sapienza University of Rome, St. Andrea Hospital, 00189, Rome, Italy
| | - Maurizio Valeriani
- Department of Medicine and Surgery and Translational Medicine, Radiotherapy Oncology, Sapienza University of Rome, St. Andrea Hospital, 00189, Rome, Italy
| | - Mattia Falchetto Osti
- Department of Medicine and Surgery and Translational Medicine, Radiotherapy Oncology, Sapienza University of Rome, St. Andrea Hospital, 00189, Rome, Italy
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Roeder F, Jensen AD, Lindel K, Mattke M, Wolf F, Gerum S. Geriatric Radiation Oncology: What We Know and What Can We Do Better? Clin Interv Aging 2023; 18:689-711. [PMID: 37168037 PMCID: PMC10166100 DOI: 10.2147/cia.s365495] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/21/2022] [Accepted: 04/22/2023] [Indexed: 05/13/2023] Open
Abstract
Elderly patients represent a growing subgroup of cancer patients for whom the role of radiation therapy is poorly defined. Older patients are still clearly underrepresented in clinical trials, resulting in very limited high-level evidence. Moreover, elderly patients are less likely to receive radiation therapy in similar clinical scenarios compared to younger patients. However, there is no clear evidence for a generally reduced radiation tolerance with increasing age. Modern radiation techniques have clearly reduced acute and late side effects, thus extending the boundaries of the possible regarding treatment intensity in elderly or frail patients. Hypofractionated regimens have further decreased the socioeconomic burden of radiation treatments by reducing the overall treatment time. The current review aims at summarizing the existing data for the use of radiation therapy or chemoradiation in elderly patients focusing on the main cancer types. It provides an overview of treatment tolerability and outcomes with current standard radiation therapy regimens, including possible predictive factors in the elderly population. Strategies for patient selection for standard or tailored radiation therapy approaches based on age, performance score or comorbidity, including the use of prediction tests or geriatric assessments, are discussed. Current and future possibilities for improvements of routine care and creation of high-level evidence in elderly patients receiving radiation therapy are highlighted.
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Affiliation(s)
- Falk Roeder
- Department of Radiation Therapy and Radiation Oncology, Paracelsus Medical University Hospital, Salzburg, Austria
| | - Alexandra D Jensen
- Department of Radiation Oncology, University Hospital Marburg-Giessen, Giessen, Germany
| | - Katja Lindel
- Department of Radiation Oncology, Städtisches Klinikum, Karlsruhe, Germany
| | - Matthias Mattke
- Department of Radiation Therapy and Radiation Oncology, Paracelsus Medical University Hospital, Salzburg, Austria
| | - Frank Wolf
- Department of Radiation Therapy and Radiation Oncology, Paracelsus Medical University Hospital, Salzburg, Austria
| | - Sabine Gerum
- Department of Radiation Therapy and Radiation Oncology, Paracelsus Medical University Hospital, Salzburg, Austria
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Hewavisenti RV, Arena J, Ahlenstiel CL, Sasson SC. Human papillomavirus in the setting of immunodeficiency: Pathogenesis and the emergence of next-generation therapies to reduce the high associated cancer risk. Front Immunol 2023; 14:1112513. [PMID: 36960048 PMCID: PMC10027931 DOI: 10.3389/fimmu.2023.1112513] [Citation(s) in RCA: 38] [Impact Index Per Article: 19.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/30/2022] [Accepted: 02/03/2023] [Indexed: 03/09/2023] Open
Abstract
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.
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Affiliation(s)
- Rehana V. Hewavisenti
- Immunovirology and Pathogenesis Program, The Kirby Institute, The University of New South Wales, Sydney, NSW, Australia
| | - Joshua Arena
- Immunovirology and Pathogenesis Program, The Kirby Institute, The University of New South Wales, Sydney, NSW, Australia
- UNSW RNA Institute, The University of New South Wales, Sydney, NSW, Australia
| | - Chantelle L. Ahlenstiel
- Immunovirology and Pathogenesis Program, The Kirby Institute, The University of New South Wales, Sydney, NSW, Australia
- UNSW RNA Institute, The University of New South Wales, Sydney, NSW, Australia
| | - Sarah C. Sasson
- Immunovirology and Pathogenesis Program, The Kirby Institute, The University of New South Wales, Sydney, NSW, Australia
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Kumar P, Del Rosario M, Chang J, Ziogas A, Jafari MD, Bristow RE, Tanjasiri SP, Zell JA. Population-Based Analysis of National Comprehensive Cancer Network (NCCN) Guideline Adherence for Patients with Anal Squamous Cell Carcinoma in California. Cancers (Basel) 2023; 15:cancers15051465. [PMID: 36900256 PMCID: PMC10000877 DOI: 10.3390/cancers15051465] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/07/2023] [Revised: 02/17/2023] [Accepted: 02/20/2023] [Indexed: 03/02/2023] Open
Abstract
PURPOSE We analyzed adherence to the National Comprehensive Cancer Network treatment guidelines for anal squamous cell carcinoma in California and the associated impacts on survival. METHODS This was a retrospective study of patients in the California Cancer Registry aged 18 to 79 years with recent diagnoses of anal squamous cell carcinoma. Predefined criteria were used to determine adherence. Adjusted odds ratios and 95% confidence intervals were estimated for those receiving adherent care. Disease-specific survival (DSS) and overall survival (OS) were examined with a Cox proportional hazards model. RESULTS 4740 patients were analyzed. Female sex was positively associated with adherent care. Medicaid status and low socioeconomic status were negatively associated with adherent care. Non-adherent care was associated with worse OS (Adjusted HR 1.87, 95% CI = 1.66, 2.12, p < 0.0001). DSS was worse in patients receiving non-adherent care (Adjusted HR 1.96, 95% CI = 1.56, 2.46, p < 0.0001). Female sex was associated with improved DSS and OS. Black race, Medicare/Medicaid, and low socioeconomic status were associated with worse OS. CONCLUSIONS Male patients, those with Medicaid insurance, or those with low socioeconomic status are less likely to receive adherent care. Adherent care was associated with improved DSS and OS in anal carcinoma patients.
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Affiliation(s)
- Priyanka Kumar
- Department of Internal Medicine, University of California, Irvine, CA 92868-3201, USA
- Correspondence: ; Tel.: +1-714-456-5691; Fax: +1-714-456-8874
| | | | - Jenny Chang
- Department of Internal Medicine, University of California, Irvine, CA 92868-3201, USA
| | - Argyrios Ziogas
- Department of Internal Medicine, University of California, Irvine, CA 92868-3201, USA
| | - Mehraneh D. Jafari
- Department of Surgery, Section of Colon and Rectal Surgery, Weill Cornell Medicine, New York, NY 10065, USA
| | - Robert E. Bristow
- Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, University of California, Irvine, CA 92868-3201, USA
| | - Sora Park Tanjasiri
- Department of Epidemiology & Biostatistics, University of California, Irvine, CA 92868-3201, USA
- Division of Hematology-Oncology, Department of Medicine, University of California, Irvine, CA 92868-3201, USA
| | - Jason A. Zell
- Division of Hematology-Oncology, Department of Medicine, University of California, Irvine, CA 92868-3201, USA
- Chao Family Comprehensive Cancer Center, University of California, Irvine, CA 92868-3201, USA
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Gunder LC, Moyer TH, Johnson HR, Auyeung AS, Leverson GE, Zhang W, Matkowskyj KA, Carchman EH. Anal Cancer Prevention Through the Topical Use of Single or Dual PI3K/mTOR Inhibitors. J Surg Res 2023; 282:137-146. [PMID: 36274448 DOI: 10.1016/j.jss.2022.09.025] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/06/2022] [Revised: 08/29/2022] [Accepted: 09/26/2022] [Indexed: 11/23/2022]
Abstract
INTRODUCTION Anal dysplasia and anal cancer are major health problems. This study seeks to determine if inhibition of mTOR and/or PI3K pathways is effective at anal cancer prevention in mice with/without established precancerous lesions of the anus (anal dysplasia). METHODS K14E6/E7 mice were entered into the study at 5 wk, 15 wk, or 25 wk of age. Mice were treated with a topical carcinogen, 7,12-Dimethylbenz[a]anthracene (DMBA), which ensures carcinoma development within 20 wk. Treatment groups included: no treatment, DMBA only, topical Pictilisib (PI3K inhibitor) with/without DMBA, topical Sapanisertib (mTOR inhibitor) with/without DMBA, and topical Samotolisib (dual PI3K/mTOR inhibitor) with/without DMBA. Mice underwent weekly observations for anal tumor development (tumor-free survival). After 20 wk of treatment, anal tissue was harvested and evaluated histologically for squamous cell carcinoma (SqCC). RESULTS All topical treatments in conjunction with DMBA increased tumor-free survival in mice that started treatment at 15 wk of age when compared to DMBA-only treatment, except for Pictilisib + DMBA in males. Topical Sapanisertib increased tumor-free survival in mice regardless of starting treatment age. When examining tissue for microscopic evidence of SqCC, only topical Samotolisib in males decreased SqCC in the 15 wk starting mice. CONCLUSIONS Sapanisertib, the mTOR inhibitor, had the greatest effect, in terms of increasing tumor-free survival, regardless of starting time point or sex. Unlike the other treatments, Samotolisib, the dual PI3K/mTOR inhibitor, decreased microscopic evidence of SqCC when starting treatment at 15 wk of age but only in male mice.
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Affiliation(s)
- Laura C Gunder
- University of Wisconsin-Madison, School of Medicine and Public Health, Department of Surgery, 5148 Wisconsin Institute for Medical Research (WIMR), Madison, Wisconsin
| | - Tyra H Moyer
- University of Wisconsin-Madison, School of Medicine and Public Health, Department of Surgery, 5148 Wisconsin Institute for Medical Research (WIMR), Madison, Wisconsin
| | - Hillary R Johnson
- University of Wisconsin-Madison, School of Medicine and Public Health, Department of Surgery, 5148 Wisconsin Institute for Medical Research (WIMR), Madison, Wisconsin
| | - Andrew S Auyeung
- University of Wisconsin-Madison, School of Medicine and Public Health, Department of Surgery, 5148 Wisconsin Institute for Medical Research (WIMR), Madison, Wisconsin
| | - Glen E Leverson
- University of Wisconsin-Madison, School of Medicine and Public Health, Department of Surgery, 5148 Wisconsin Institute for Medical Research (WIMR), Madison, Wisconsin
| | - Wei Zhang
- University of Wisconsin-Madison, Department of Pathology and Laboratory Medicine, 3170 UW Medical Foundation Centennial Building (MFCB), Madison, Wisconsin; University of Wisconsin-Madison, Carbone Cancer Center, Madison, Wisconsin
| | - Kristina A Matkowskyj
- University of Wisconsin-Madison, Department of Pathology and Laboratory Medicine, 3170 UW Medical Foundation Centennial Building (MFCB), Madison, Wisconsin; William S. Middleton Memorial Veterans Hospital, Madison, Wisconsin; University of Wisconsin-Madison, Carbone Cancer Center, Madison, Wisconsin
| | - Evie H Carchman
- University of Wisconsin-Madison, School of Medicine and Public Health, Department of Surgery, 5148 Wisconsin Institute for Medical Research (WIMR), Madison, Wisconsin; William S. Middleton Memorial Veterans Hospital, Madison, Wisconsin; University of Wisconsin-Madison, Carbone Cancer Center, Madison, Wisconsin.
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Sun J, Wiley D, Barrett BW, Hsu H, Palella FJ, Kwait J, Martinson J, D'Souza G. Comparison of anal pre-cancer screening strategies among men who have sex with men. Int J STD AIDS 2023; 34:87-97. [PMID: 36380689 PMCID: PMC9942485 DOI: 10.1177/09564624221137974] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022]
Abstract
PURPOSE Comparison of anal pre-cancer screening strategies in men who have sex with men (MSM). METHODS MSM in the Multicenter AIDS Cohort Study underwent repeated anal cytology (aCyt), oncogenic human papillomavirus (oncHPV) testing. A subset received High-Resolution Anoscopy (HRA). We evaluated three screening strategies for their ability to predict anal histological High-Grade Squamous Intraepithelial lesion (HSIL): single aCyt, sequential aCyt, and oncHPV co-testing. Multivariable logistic regression models evaluated risk of HSIL among participants undergoing HRA within 5 years of screening. Sensitivity and specificity were estimated among participants with HRA, and results corrected for verification bias using weighted generalized estimating equations. RESULTS There were 1426 MSM with aCyt screening (48% people with HIV [PWH]) and 428 that underwent HRA. Median age was 57 years, 14% of PWH had CD4< 350 cells/mm3. HSIL probability was higher in MSM with one (39%, p < 0.01) or two abnormal aCyt results (46%, p < 0.01), versus those with normal aCyt (23-24%). Among men with abnormal aCyt, men with oncHPV+ had significantly higher risk than those who were oncHPV- (47% vs. 16%, p < 0.01). Specificity was modest with single aCyt+ (50%) but increased with sequential aCyt+ (79%) or oncHPV+ (67%). Sensitivity was high with single oncHPV+ (88%), moderate with single aCyt+ (66%) and oncHPV+ co-testing (61%), and low with sequential aCyt+ (39%). After correcting for potential verification bias, specificity increased and sensitivity decreased, but inferences were similar. CONCLUSION None of the screening strategies evaluated had both sufficient specificity and sensitivity to warrant routine widespread use.
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Affiliation(s)
- Jing Sun
- Department of Epidemiology, 25802Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA
| | | | - Benjamin W Barrett
- Department of Epidemiology, 25802Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA
| | - Hilary Hsu
- School of Nursing, 8783UCLA, Los Angeles, CA, USA
| | - Frank J Palella
- Division of Infectious Diseases, 12244Northwestern University Feinberg School of Medicine, Chicago, IL, USA
| | | | - Jeremy Martinson
- Department of Infectious Diseases and Microbiology, 51303University of Pittsburgh Graduate School of Public Health, Pittsburgh, PA, USA
| | - Gypsyamber D'Souza
- Department of Epidemiology, 25802Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA
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Pfister NT, Cao Y, Schlafstein AJ, Switchenko J, Patel PR, McDonald MW, Tian S, Landry JC, Alese OB, Gunthel C, Lin JY. Factors Affecting Clinical Outcomes Among Patients Infected With HIV and Anal Cancer Treated With Modern Definitive Chemotherapy and Radiation Therapy. Adv Radiat Oncol 2022; 8:101155. [PMID: 36845623 PMCID: PMC9943777 DOI: 10.1016/j.adro.2022.101155] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/16/2022] [Accepted: 12/09/2022] [Indexed: 12/27/2022] Open
Abstract
Purpose Anal cancer affects a disproportionate percentage of persons infected with human immunodeficiency virus (HIV). We analyzed a cohort of patients with HIV and anal cancer who received modern radiation therapy (RT) and concurrent chemotherapy to assess whether certain factors are associated with poor oncologic outcomes. Patients and Methods We performed a retrospective chart review of 75 consecutive patients with HIV infection and anal cancer who received definitive chemotherapy and RT from 2008 to 2018 at a single academic institution. Local recurrence, overall survival, changes in CD4 counts, and toxicities were investigated. Results Most patients were male (92%) with large representation from Black patients (77%). The median pretreatment CD4 count was 280 cells/mm3, which was persistently lower at 6 and 12 months' posttreatment, 87 cells/mm3 and 182 cells/mm3, respectively (P < .001). Most (92%) patients received intensity modulated RT; median dose was 54 Gy (Range, 46.8-59.4 Gy). At a median follow-up 5.4 years (Range, 4.37-6.21 years), 20 (27%) patients had disease recurrence and 10 (13%) had isolated local failures. Nine patients died due to progressive disease. In multivariable analysis, clinically node negative involvement was significantly associated with better overall survival (hazard ratio, 0.39; 95% confidence interval, 0.16-1.00, P = .049). Acute grade 2 and 3 skin toxicities were common, at 83% and 19%, respectively. Acute grade 2 and 3 gastrointestinal toxicities were 9% and 3%, respectively. Acute grade 3 hematologic toxicity was 20%, and one grade 5 toxicity was reported. Several late grade 3 toxicities persisted: gastrointestinal (24%), skin (17%), and hematologic (6%). Two late grade 5 toxicities were noted. Conclusions Most patients with HIV and anal cancer did not experience local recurrence; however, acute and late toxicities were common. CD4 counts at 6 and 12 months' posttreatment remained lower than pretreatment CD4 counts. Further attention to treatment of the HIV-infected population is needed.
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Affiliation(s)
- Neil T. Pfister
- Department of Radiation Oncology, Winship Cancer Institute, Emory University School of Medicine, Atlanta, Georgia
| | - Yichun Cao
- Department of Biostatistics and Bioinformatics, Emory University Rollins School of Public Health, Atlanta, Georgia
| | - Ashely J. Schlafstein
- Department of Radiation Oncology, Winship Cancer Institute, Emory University School of Medicine, Atlanta, Georgia
| | - Jeffrey Switchenko
- Department of Biostatistics and Bioinformatics, Emory University Rollins School of Public Health, Atlanta, Georgia
| | - Pretesh R. Patel
- Department of Radiation Oncology, Winship Cancer Institute, Emory University School of Medicine, Atlanta, Georgia
| | - Mark W. McDonald
- Department of Radiation Oncology, Winship Cancer Institute, Emory University School of Medicine, Atlanta, Georgia
| | - Sibo Tian
- Department of Radiation Oncology, Winship Cancer Institute, Emory University School of Medicine, Atlanta, Georgia
| | - Jerome C. Landry
- Department of Radiation Oncology, Winship Cancer Institute, Emory University School of Medicine, Atlanta, Georgia
| | - Olatunji B. Alese
- Department of Hematology and Medical Oncology, Winship Cancer Institute, Emory University School of Medicine, Atlanta, Georgia
| | - Clifford Gunthel
- Department of Medicine – Infectious Diseases Program, Emory University School of Medicine, Atlanta, Georgia
| | - Jolinta Y. Lin
- Department of Radiation Oncology, Winship Cancer Institute, Emory University School of Medicine, Atlanta, Georgia,Corresponding author: Jolinta Y. Lin, MD
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Taylor JP, Wei IH, Smith JJ, Tin AL, Aiken N, Vickers AJ, Romesser PB, Crane CH, Widmar M, Nash GM, Weiser MR, Paty PB, Garcia-Aguilar J, Pappou E. Assessment of Patient-Reported Outcomes in Patients With Anal Squamous-Cell Cancer Undergoing Combined Modality Therapy. Dis Colon Rectum 2022; 65:1448-1455. [PMID: 36102865 PMCID: PMC9851905 DOI: 10.1097/dcr.0000000000002600] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
BACKGROUND There is limited knowledge on long-term bowel, sexual, and urinary function after combined modality therapy for anal squamous-cell cancer. OBJECTIVE This study aimed to evaluate long-term changes in patients treated with combined modality. DESIGN This was a retrospective study of prospectively collected patient-reported outcome surveys. SETTING This study was conducted at a single institution. PATIENTS There were 143 patients with stage I to III anal cancer who were treated with chemoradiation and had completed the survey. MAIN OUTCOME MEASURES This study included patient-reported outcomes reflecting bowel, sexual, and urinary function. RESULTS Thirty-nine percent of patients had major low anterior resection syndrome at baseline. Major low anterior resection syndrome remained stable (38%; 95% CI, 31%-46%) with no change over time (OR 0.95; 95% CI, 0.74-1.21; p = 0.7). Higher rates of major low anterior resection syndrome were observed for patients who had major low anterior resection syndrome at baseline (OR 20.7; 95% CI 4.70-91.3; p < 0.001) and for females (OR 2.14; 95% CI, 1.01-4.56; p = 0.047). On 5-point scales, we saw a nonsignificant increased level of sexual arousal during sexual activity after therapy for women (β for 1 year = 0.15; 95% CI, -0.01 to 0.32; p = 0.072) and nonsignificant decreased confidence in getting and keeping an erection after therapy for men (β for 1 year = -0.33; 95% CI, -0.66 to 0.00; p = 0.053). LIMITATIONS This was a single-institution study and only patients who answered the questionnaire were included in the study. CONCLUSIONS A significant proportion of patients have major low anterior resection syndrome at baseline and after successful treatment for anal cancer. Having major low anterior resection syndrome at baseline was the biggest predictor of having major low anterior resection syndrome after treatment. Bowel, sexual, and urinary function did not improve over time up to 2 years after end of treatment. Physicians should counsel their patients before treatment that baseline poor bowel function is a risk factor for posttreatment bowel dysfunction. See Video Abstract at http://links.lww.com/DCR/C29 . EVALUACIN DE LOS RESULTADOS INFORMADOS POR LOS PACIENTES CON CNCER ANAL DE CLULAS ESCAMOSAS QUE SE SOMETEN A UNA TERAPIA DE MODALIDAD COMBINADA ANTECEDENTES:Existe un conocimiento limitado sobre la función intestinal, sexual y urinaria a largo plazo después de la terapia de modalidad combinada para el cáncer anal de células escamosas.OBJETIVO:Evaluar los cambios a largo plazo en la función intestinal, sexual y urinaria en pacientes tratados con modalidad combinada.DISEÑO:Este fue un estudio retrospectivo de encuestas de resultados informadas por pacientes recolectadas prospectivamente.ESCENARIO:Institución única.PACIENTES:Fueron 143 pacientes con cáncer anal en estadio I-III que fueron tratados con quimiorradiación y completaron la encuesta.PRINCIPALES MEDIDAS DE RESULTADO:Resultados reportados por el paciente que reflejan la función intestinal, sexual, y urinaria.RESULTADOS:Treinta y nueve por ciento de los pacientes tenían puntajes importantes de síndrome de resección anterior bajo al inicio del estudio. Las puntuaciones del síndrome de resección anterior baja mayor permanecieron estables (38 %; IC del 95%: 31 %, 46 %) sin cambios con el tiempo (OR 0,95, IC del 95%: 0,74, 1,21, p = 0,7). Se observaron tasas más altas de puntuaciones del síndrome de resección anterior baja mayor para los pacientes que tenían puntuaciones del síndrome de resección anterior baja mayor desde el inicio (OR 20,7; IC del 95%: 4,70; 91,3, p < 0,001) y para las mujeres (OR 2,14; IC del 95%: 1,01, 4,56; p = 0,047). En escalas de 5 puntos, observamos un aumento no significativo del nivel de excitación sexual durante la actividad sexual después de la terapia para las mujeres (β durante 1 año = 0,15; IC del 95%: -0,01, 0,32; p = 0,072) y una disminución no significativa de la confianza en lograr y mantener una erección después de la terapia para hombres (β para 1 año = -0,33; IC del 95%: -0,66, 0,00; p = 0,053).LIMITACIONES:Este es un estudio de una sola institución. Solo se incluyeron en el estudio los pacientes que contestaron el cuestionario.CONCLUSIONES:Una proporción significativa de pacientes tienen puntajes de síndrome de resección anterior muy bajos al inicio del estudio y después de un tratamiento exitoso para el cáncer anal. Tener puntajes de síndrome de resección anterior bajos importantes al inicio del estudio fue el predictor más importante de tener puntajes de síndrome de resección anterior bajos importantes después del tratamiento. La función intestinal, sexual y urinaria no mejoró con el tiempo hasta 2 años después de finalizar el tratamiento. Los médicos deben aconsejar a sus pacientes antes del tratamiento que la mala función intestinal inicial es un factor de riesgo para la disfunción intestinal posterior al tratamiento. Consulte Video Resumen en http://links.lww.com/DCR/C29 . (Traducción-Dr. Yolanda Colorado ).
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Affiliation(s)
- James P. Taylor
- Department of Colon and Rectal Surgery, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, New York
| | - Iris H. Wei
- Department of Colon and Rectal Surgery, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, New York
| | - J. Joshua Smith
- Department of Colon and Rectal Surgery, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, New York
| | - Amy L. Tin
- Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, New York
| | - Nate Aiken
- Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, New York
| | - Andrew J. Vickers
- Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, New York
| | - Paul B. Romesser
- Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, New York
| | - Christopher H. Crane
- Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, New York
| | - Maria Widmar
- Department of Colon and Rectal Surgery, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, New York
| | - Garrett M. Nash
- Department of Colon and Rectal Surgery, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, New York
| | - Martin R. Weiser
- Department of Colon and Rectal Surgery, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, New York
| | - Philip B. Paty
- Department of Colon and Rectal Surgery, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, New York
| | - Julio Garcia-Aguilar
- Department of Colon and Rectal Surgery, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, New York
| | - Emmanouil Pappou
- Department of Colon and Rectal Surgery, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, New York
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Franco P, Porreca A, Mantello G, Valvo F, Gasparini L, Slim N, Manfrida S, De Felice F, Gerardi MA, Vagge S, Krengli M, Palazzari E, Osti MF, Gonnelli A, Catalano G, Pittoni P, Ivaldi GB, Lupattelli M, Rosetto ME, Niespolo RM, Guido A, Durante O, Macchia G, Munoz F, El Khouzai B, Lucido MR, Arcadipane F, Casadei Gardini A, Maria D'Angelillo R, Gambacorta MA, Genovesi D, Di Nicola M, Caravatta L. External validation of a composite bio-humoral index in anal cancer patients undergoing concurrent chemoradiation. Radiother Oncol 2022; 177:9-15. [PMID: 36273737 DOI: 10.1016/j.radonc.2022.10.015] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/24/2022] [Revised: 09/25/2022] [Accepted: 10/14/2022] [Indexed: 11/06/2022]
Abstract
BACKGROUND AND PURPOSE A prognostic scoring system based on laboratory inflammation parameters, [Hemo-Eosinophils-Inflammation (HEI) index], including baseline hemoglobin level, the systemic inflammatory index and eosinophil count was recently proposed in patients with squamous cell carcinoma of the anus (ASCC). HEI was shown to discriminate disease-free (DFS) and overall (OS) survival in ASCC patients treated with concurrent chemoradiation (CRT). We tested the accuracy of the model on a multicentric cohort for external validation. MATERIALS AND METHODS Patients treated with CRT were enrolled. The Kaplan-Meier curves for DFS and OS based on HEI risk group were calculated and the log-rank test was used. Cox proportional hazards models were used to assess the prognostic factors for DFS and OS. The exponential of the regression coefficients provided an estimate of the hazard ratio (HR). For model discrimination, we determined Harrell's C-index, Gönen & Heller K Index and the explained variation on the log relative hazard scale. RESULTS A total of 877 patients was available. Proportional hazards were adjusted for age, gender, tumor-stage, and chemotherapy. Two-year DFS was 77 %(95 %CI:72.0-82.4) and 88.3 %(95 %CI:84.8-92.0 %) in the HEI high- and low- risk groups. Two-year OS was 87.8 %(95 %CI:83.7-92.0) and 94.2 %(95 %CI:91.5-97). Multivariate Cox proportional hazards model showed a HR = 2.02(95 %CI:1.25-3.26; p = 0.004) for the HEI high-risk group with respect to OS and a HR = 1.53(95 %CI:1.04-2.24; p = 0.029) for DFS. Harrel C-indexes were 0.68 and 0.66 in the validation dataset, for OS and DFS. Gonen-Heller K indexes were 0.67 and 0.71, respectively. CONCLUSION The HEI index proved to be a prognosticator in ASCC patients treated with CRT. Model discrimination in the external validation cohort was acceptable.
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Affiliation(s)
- Pierfrancesco Franco
- Division of Radiation Oncology, Department of Translational Medicine, University of Eastern Piedmont, and University Hospital "Maggiore della Carità", Novara, Italy.
| | - Annamaria Porreca
- Laboratory of Biostatistics, Department of Medical, Oral and Biotechnological Sciences, "G. D'Annunzio" University of Chieti-Pescara, Chieti, Italy.
| | - Giovanna Mantello
- Department of Oncology and Radiotherapy, Azienda Ospedaliero Universitaria Ospedali Riuniti, Ancona, Italy.
| | - Francesca Valvo
- Radiotherapy Unit, Clinical Department, CNAO National Center for Oncological Hadrontherapy, Pavia, Italy.
| | - Lucrezia Gasparini
- Radiation Oncology Unit, "SS Annunziata" Hospital, "G. d'Annunzio" University, Via Dei Vestini, 66100, Chieti, Italy.
| | - Najla Slim
- Department of Radiotherapy, IRCCS San Raffaele Scientific Institute, Milan, Italy.
| | - Stefania Manfrida
- "A. Gemelli" IRCCS, UOC di Radioterapia Oncologica, Dipartimento di Diagnostica per Immagini, Radioterapia Oncologica ed Ematologia, Fondazione Policlinico Universitario, 00168 Roma, Italy.
| | - Francesca De Felice
- Department of Radiotherapy, Policlinico Umberto I, "Sapienza" University of Rome, Rome, Italy.
| | - Marianna A Gerardi
- Department of Radiotherapy, IEO European Institute of Oncology, IRCCS, Milan, Italy.
| | - Stefano Vagge
- Department of Radiation Oncology, IRCCS Ospedale Policlinico San Martino, Genoa, Italy.
| | - Marco Krengli
- Division of Radiation Oncology, Department of Translational Medicine, University of Eastern Piedmont, and University Hospital "Maggiore della Carità", Novara, Italy.
| | - Elisa Palazzari
- Radiation Oncology Department, Oncological Referral Center, Aviano, Italy.
| | - Mattia Falchetto Osti
- Unit of Radiation Oncology, Sant'Andrea Hospital, Sapienza University of Rome, 00100 Rome, Italy.
| | - Alessandra Gonnelli
- Department of Radiotherapy, Azienda Ospedaliero-Universitaria Pisana, Pisa, Italy.
| | - Gianpiero Catalano
- Radiation Oncology Center, IRCCS Multimedica, Sesto San Giovanni, Italy.
| | - Patrizia Pittoni
- Radiation Oncology Unit, Asst Lariana, Ospedale di Como, Como, Italy.
| | | | - Marco Lupattelli
- Radiation Oncology Section, University of Perugia and Perugia General Hospital, 06156, Perugia, Italy.
| | | | | | - Alessandra Guido
- Radiation Oncology, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy.
| | - Oreste Durante
- Azienda Ospedaliera SS. Antonio e Biagio e Cesare Arrigo, Alessandria, Italy.
| | - Gabriella Macchia
- Radiation Oncology Unit, Gemelli Molise Hospital - Università Cattolica del Sacro Cuore, Campobasso, Italy.
| | - Fernando Munoz
- Department of Radiotherapy, Azienda U. S. L. della Valle d'Aosta, 11100, Aosta, Italy.
| | - Badr El Khouzai
- Radiotherapy and Nuclear Medicine Unit, Veneto Institute of Oncology-IRCCS, Padova, Italy.
| | | | - Francesca Arcadipane
- Radiation Oncology, AOU Citta' della Salute e della Scienza, Presidio San Giovanni Antica Sede, Torino, Italy.
| | - Andrea Casadei Gardini
- Department of Medical Oncology, Università Vita-Salute, San Raffaele Hospital IRCCS, 20019 Milan, Italy.
| | - Rolando Maria D'Angelillo
- Radiation Oncology, Department of Biomedicine and Prevention, University of Rome Tor Vergata, Rome, Italy.
| | - Maria Antonietta Gambacorta
- "A. Gemelli" IRCCS, UOC di Radioterapia Oncologica, Dipartimento di Diagnostica per Immagini, Radioterapia Oncologica ed Ematologia, Fondazione Policlinico Universitario, 00168 Roma, Italy.
| | - Domenico Genovesi
- Radiation Oncology Unit, "SS Annunziata" Hospital, "G. d'Annunzio" University, Via Dei Vestini, 66100, Chieti, Italy; Department of Neuroscience, Imaging and Clinical Sciences, "G. D'Annunzio" University of Chieti-Pescara, Chieti, Italy.
| | - Marta Di Nicola
- Laboratory of Biostatistics, Department of Medical, Oral and Biotechnological Sciences, "G. D'Annunzio" University of Chieti-Pescara, Chieti, Italy.
| | - Luciana Caravatta
- Radiation Oncology Unit, "SS Annunziata" Hospital, "G. d'Annunzio" University, Via Dei Vestini, 66100, Chieti, Italy.
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Women with Cervical High-Risk Human Papillomavirus: Be Aware of Your Anus! The ANGY Cross-Sectional Clinical Study. Cancers (Basel) 2022; 14:cancers14205096. [PMID: 36291879 PMCID: PMC9600245 DOI: 10.3390/cancers14205096] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/19/2022] [Revised: 10/03/2022] [Accepted: 10/17/2022] [Indexed: 12/24/2022] Open
Abstract
Anogenital human papillomaviruses (HPV) are highly prevalent in sexually active populations, with HR-HPV being associated with dysplasia and cancers. The consequences of cervical HPV infection are well-known, whereas those of the anus are less clear. The correlation of cervical and anal HPVs with the increasing number of anal cancers in women has not been studied yet. The objective of our prospective study was to determine whether cervical and anal HPV correlated in a cohort of women recruited in a university hospital in Switzerland. Recruitment was conducted in the gynecology clinic, the colposcopy clinic, and the HIV clinic. Cervical and anal HPV genotyping and cytology were performed. Overall, 275 patients were included (360 were initially planned), and among them, 102 (37%) had cervical HR-HPV. Patients with cervical HR-HPV compared to patients without cervical HR-HPV were significantly younger (39 vs. 44 yrs, p < 0.001), had earlier sexual intercourse (17.2 vs. 18.3 yrs, p < 0.01), had more sexual partners (2.9 vs. 2.2, p < 0.0001), more dysplastic cervical cytology findings (42% vs. 19%, p < 0.0001) and higher prevalence of anal HR-HPV (59% vs. 24%, p < 0.0001). Furthermore, the HR-HPV group reported more anal intercourse (44% vs. 29%, p < 0.015). Multivariate analysis retained anal HR-HPV as independent risk factor for cervical HR-HPV (OR3.3, CI 1.2−9.0, p = 0.02). The results of this study emphasize that it is of upmost importance to screen women for anal HR-HPV when diagnosing cervical HR-HPV.
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Rathi R, Sanshita, Kumar A, Vishvakarma V, Huanbutta K, Singh I, Sangnim T. Advancements in Rectal Drug Delivery Systems: Clinical Trials, and Patents Perspective. Pharmaceutics 2022; 14:2210. [PMID: 36297645 PMCID: PMC9609333 DOI: 10.3390/pharmaceutics14102210] [Citation(s) in RCA: 17] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/10/2022] [Revised: 10/12/2022] [Accepted: 10/13/2022] [Indexed: 07/30/2023] Open
Abstract
The rectal route is an effective route for the local and systemic delivery of active pharmaceutical ingredients. The environment of the rectum is relatively constant with low enzymatic activity and is favorable for drugs having poor oral absorption, extensive first-pass metabolism, gastric irritation, stability issues in the gastric environment, localized activity, and for drugs that cannot be administered by other routes. The present review addresses the rectal physiology, rectal diseases, and pharmaceutical factors influencing rectal delivery of drugs and discusses different rectal drug delivery systems including suppositories, suspensions, microspheres, nanoparticles, liposomes, tablets, and hydrogels. Clinical trials on various rectal drug delivery systems are presented in tabular form. Applications of different novel drug delivery carriers viz. nanoparticles, liposomes, solid lipid nanoparticles, microspheres, transferosomes, nano-niosomes, and nanomicelles have been discussed and demonstrated for their potential use in rectal administration. Various opportunities and challenges for rectal delivery including recent advancements and patented formulations for rectal drug delivery have also been included.
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Affiliation(s)
- Ritu Rathi
- Chitkara College of Pharmacy, Chitkara University, Rajpura 140401, India
| | - Sanshita
- Chitkara College of Pharmacy, Chitkara University, Rajpura 140401, India
| | - Alpesh Kumar
- Chitkara College of Pharmacy, Chitkara University, Rajpura 140401, India
| | | | | | - Inderbir Singh
- Chitkara College of Pharmacy, Chitkara University, Rajpura 140401, India
| | - Tanikan Sangnim
- Faculty of Pharmaceutical Sciences, Burapha University, Chonburi 20131, Thailand
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Atallah RP, Zhang Y, Zakka K, Jiang R, Huang Z, Shaib WL, Diab M, Akce M, Wu C, El-Rayes BF, Alese OB. Role of local therapy in the management of patients with metastatic anal squamous cell carcinoma: a National Cancer Database study. J Gastrointest Oncol 2022; 13:2306-2321. [PMID: 36388688 PMCID: PMC9660037 DOI: 10.21037/jgo-22-125] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/28/2022] [Accepted: 07/04/2022] [Indexed: 10/10/2023] Open
Abstract
BACKGROUND About 10-20% of patients with anal squamous cell carcinoma (SCCa) present with metastatic disease and are usually treated with systemic chemotherapy. However, primary tumor control is crucial as local failure is associated with significant morbidity. Using the largest cohort to date, we report the impact of local therapy on survival among patients with metastatic anal SCCa. METHODS Data were collected from US hospitals that contributed to the National Cancer Database (NCDB) between 2004 and 2015. Patients who did not receive palliative systemic chemotherapy were excluded from analysis. Univariate (UVA) and multivariable analyses (MVA) were performed to identify factors associated with patient outcome. Kaplan-Meier analysis and Cox proportional hazards models were used to evaluate the association between tumor/patient characteristics and overall survival (OS). RESULTS A total of 1,160 patients were identified over the 12 years of study. Median age was 57 years. Majority were female (64.9%), non-Hispanic Whites (79.1%) and had Charlson-Deyo Score of 0 (83.6%). Most common metastatic sites were liver (25.9%), lung (11.6%) and bone (8.5%). More than 79% of the patients had received radiation to the primary site, and 10.4% underwent surgical resection for local control. Use of local therapy correlated closely with OS on MVA (HR 0.66; 0.55-0.79; P<0.001), with a 12-month and 5-year OS rates of 72.8% and 25.7% respectively, compared with 61.1% and 14.6% for patients treated with chemotherapy only. Poor prognostic factors included male gender (HR 1.44; 1.24-1.67; P<0.001), age >70 years (HR 1.28; 1.02-1.62; P=0.034), lack of health insurance (HR 1.32; 1.02-1.71; P=0.034), and cloacogenic zone location (HR 4.02; 1.43-11.30; P=0.008). There was no benefit from abdominoperineal resection (mOS =19.7 months; HR 1.05; 0.48-2.29; P=0.909), but both local resection of the primary (mOS =24.8 months, HR 0.48; 0.29-0.80; P=0.005) and palliative radiation (mOS =22.6 months; HR 0.66; 0.55-0.79; P<0.001) were associated with improved OS. CONCLUSIONS In addition to systemic therapy, resection of the primary tumor or palliative radiation improved OS in patients with anal SCCa. Patients unlikely to benefit from local control were those >70 years of age, male, lack of health insurance and cloacogenic carcinoma.
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Affiliation(s)
- Rami P. Atallah
- Department of Hematology and Oncology, Winship Cancer Institute of Emory University, Atlanta, GA, USA
| | - Yining Zhang
- Winship Data and Technology Applications Shared Resource, Emory University, Atlanta, GA, USA
| | | | - Renjian Jiang
- Winship Data and Technology Applications Shared Resource, Emory University, Atlanta, GA, USA
| | - Zhonglu Huang
- Winship Data and Technology Applications Shared Resource, Emory University, Atlanta, GA, USA
| | - Walid L. Shaib
- Department of Hematology and Oncology, Winship Cancer Institute of Emory University, Atlanta, GA, USA
| | - Maria Diab
- Department of Hematology and Oncology, Winship Cancer Institute of Emory University, Atlanta, GA, USA
| | - Mehmet Akce
- Department of Hematology and Oncology, Winship Cancer Institute of Emory University, Atlanta, GA, USA
| | - Christina Wu
- Department of Hematology and Oncology, Winship Cancer Institute of Emory University, Atlanta, GA, USA
| | - Bassel F. El-Rayes
- Department of Hematology and Oncology, Winship Cancer Institute of Emory University, Atlanta, GA, USA
| | - Olatunji B. Alese
- Department of Hematology and Oncology, Winship Cancer Institute of Emory University, Atlanta, GA, USA
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ORUÇ AF, KARABULUT GUL S. Anal canal cancers. JOURNAL OF HEALTH SCIENCES AND MEDICINE 2022. [DOI: 10.32322/jhsm.1054519] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/05/2022] Open
Abstract
Although anal canal cancer is rare, its incidence has increased in the last 30 years, especially in young men. The most common pathological type is squamous cell carcinoma. Definitive histopathological diagnosis is made by biopsy. “American Joint Committee on Cancer” (AJCC) TNM staging is used for staging. The standard approach in treatment is radiochemotherapy, and surgery is applied in persistent or recurrent failure.
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43
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Bushara O, Weinberg SE, Finkelman BS, Jiang H, Krogh K, Sun L, Halverson AL, Jennings LJ, Liao J, Yang GY. The Effect of Human Immunodeficiency Virus and Human Papillomavirus Strain Diversity on the Progression of Anal Squamous Intraepithelial Lesions. Hum Pathol 2022; 128:20-30. [PMID: 35803414 DOI: 10.1016/j.humpath.2022.06.025] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/17/2022] [Revised: 06/26/2022] [Accepted: 06/30/2022] [Indexed: 11/17/2022]
Abstract
Anal squamous cell carcinoma (SCC) is a human papillomavirus (HPV)-mediated malignancy with increasing incidence. HIV infection is a significant risk factor for anal SCC, however it is unknown if HIV infection alters anal lesion progression and HPV strain profile. This study aims to determine whether HIV co-infection is associated with progression of HPV-mediated anal lesions and on their HPV strain diversity. This is a retrospective cohort study of adults with anal squamous intraepithelial lesion (SIL) who presented for anorectal sampling between 2010-2019. Using the full cohort, we performed clinicopathologic epidemiologic analysis of HIV co-infection on lesion progression. Using a subset of patients, we conducted molecular analysis of HPV strain diversity as related to HIV status and progression. Our cohort included 2203 individuals, of which 940 (43%) were HIV+. HIV+ status was associated with faster progression at all levels of dysplasia. Our molecular cohort included 329 adults, of which 190 (57.8%) were HIV+. HIV+ status was associated with higher HPV strain diversity (median: 7 [5-9] vs. median: 4 [4-6], P<0.001). Latent class analysis identified specific HPV strain signatures associated with progression. We demonstrate that HIV+ individuals had faster rates of anal SIL progression and that almost all HPV strains were more prevalent in anal samples from HIV+ adults. Our results imply that HIV+ adults with anal SIL should undergo more frequent screening and obtain HPV genotyping at initial presentation, as it shows value as a biomarker of lesion progression.
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Affiliation(s)
- Omar Bushara
- Department of Pathology, Northwestern University Feinberg School of Medicine, 303 E Chicago Avenue, Chicago, IL, 60611 USA
| | - Samuel Edward Weinberg
- Department of Pathology, Northwestern University Feinberg School of Medicine, 303 E Chicago Avenue, Chicago, IL, 60611 USA
| | - Brian Steven Finkelman
- Department of Pathology, Northwestern University Feinberg School of Medicine, 303 E Chicago Avenue, Chicago, IL, 60611 USA
| | - Hongmei Jiang
- Department of Statistics, Northwestern University, 2006 Sheridan Road, Evanston, IL, 60208 USA
| | - Katrina Krogh
- Department of Pathology, Northwestern University Feinberg School of Medicine, 303 E Chicago Avenue, Chicago, IL, 60611 USA
| | - Leyu Sun
- Department of Pathology, Northwestern University Feinberg School of Medicine, 303 E Chicago Avenue, Chicago, IL, 60611 USA
| | - Amy L Halverson
- Department of Surgery, Northwestern University Feinberg School of Medicine, 303 E, Chicago Avenue, Chicago, IL, 60611 USA
| | - Lawrence J Jennings
- Department of Pathology, Northwestern University Feinberg School of Medicine, 303 E Chicago Avenue, Chicago, IL, 60611 USA
| | - Jie Liao
- Department of Pathology, Northwestern University Feinberg School of Medicine, 303 E Chicago Avenue, Chicago, IL, 60611 USA
| | - Guang-Yu Yang
- Department of Pathology, Northwestern University Feinberg School of Medicine, 303 E Chicago Avenue, Chicago, IL, 60611 USA.
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Wells J, Flowers L, Mehta CC, Chandler R, Knott R, McDonnell Holstad M, Watkins Bruner D. Follow-Up to High-Resolution Anoscopy After Abnormal Anal Cytology in People Living with HIV. AIDS Patient Care STDS 2022; 36:263-271. [PMID: 35727648 PMCID: PMC9464048 DOI: 10.1089/apc.2022.0057] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/04/2023] Open
Abstract
Current expert recommendations suggest anal cytology followed by high-resolution anoscopy (HRA) for biopsy and histological confirmation may be beneficial in cancer prevention, especially in people living with HIV (PLWH). Guided by the social ecological model, the purpose of this study was to examine sociodemographic and clinical variables, individual-level factors (depression, HIV/AIDS-related stigma, and health beliefs) and interpersonal-level factors (social support) related to time to HRA follow-up after abnormal anal cytology. We enrolled 150 PLWH from a large HIV community clinic, with on-site HRA availability, in Atlanta, GA. The median age was 46 years (interquartile range of 37-52), 78.5% identified as African American/Black, and 88.6% identified as born male. The average length of follow-up to HRA after abnormal anal cytology was 380.6 days (standard deviation = 317.23). Only 24.3% (n = 39) of the sample had an HRA within 6 months after an abnormal anal cytology, whereas 57% of the sample had an HRA within 12 months. HIV/AIDS-related stigma [odds ratio (OR) 0.54, 95% confidence interval (CI) 0.33-0.90] and health motivation (OR 0.80, 95% CI 0.67-0.95) were associated with time to HRA follow-up ≤6 months. For HRA follow-up ≤12 months, we found anal cytology [high-grade squamous intraepithelial lesions/atypical squamous cells of undetermined significance cannot exclude HSIL (HSIL/ASCUS-H) vs. low-grade squamous intraepithelial lesions (LSIL) OR = 0.05, 95% CI 0.00-0.70; atypical squamous cells of undetermined significance (ASCUS) vs. LSIL OR = 0.12, 95% CI 0.02-0.64] and health motivation (OR = 0.86, 95% CI 0.65-0.99) were associated. Findings from this study can inform strategies to improve follow-up care after abnormal anal cytology at an individual and interpersonal level in efforts to decrease anal cancer morbidity and mortality.
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Affiliation(s)
- Jessica Wells
- Nell Hodgson Woodruff School of Nursing, Emory University, Atlanta, Georgia, USA.,Address correspondence to: Jessica Wells, PhD, RN, WHNP-BC, FAAN, Nell Hodgson Woodruff School of Nursing, Emory University, 1520 Clifton Road, NE, RM. 230, Atlanta, GA 30324, USA
| | - Lisa Flowers
- Department of Gynecology and Obstetrics, Emory University School of Medicine, Atlanta, Georgia, USA
| | - C. Christina Mehta
- Division of Infectious Diseases, Emory University School of Medicine, Atlanta, Georgia, USA
| | - Rasheeta Chandler
- Nell Hodgson Woodruff School of Nursing, Emory University, Atlanta, Georgia, USA
| | - Robert Knott
- Nell Hodgson Woodruff School of Nursing, Emory University, Atlanta, Georgia, USA
| | | | - Deborah Watkins Bruner
- Office of the Senior Vice President of Research, Emory University, Atlanta, Georgia, USA
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Vieira GV, Somera dos Santos F, Lepique AP, da Fonseca CK, Innocentini LMAR, Braz-Silva PH, Quintana SM, Sales KU. Proteases and HPV-Induced Carcinogenesis. Cancers (Basel) 2022; 14:cancers14133038. [PMID: 35804810 PMCID: PMC9264903 DOI: 10.3390/cancers14133038] [Citation(s) in RCA: 13] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/05/2022] [Revised: 06/01/2022] [Accepted: 06/15/2022] [Indexed: 02/04/2023] Open
Abstract
Simple Summary Human papillomavirus (HPV) infection is a sexually transmitted disease with high prevalence worldwide. Although most HPV infections do not lead to cancer, some HPV types are correlated with the majority of cervical cancers, and with some anogenital and oropharyngeal cancers. Moreover, enzymes known as proteases play an essential role in the pathogenic process in HPV-induced carcinogenesis. This review highlights the role of proteases and recent epidemiological data regarding HPV-dependent carcinogenesis. Abstract Persistent infection with Human papillomavirus (HPV) is the main etiologic factor for pre-malignant and malignant cervical lesions. Moreover, HPV is also associated with oropharynx and other anogenital carcinomas. Cancer-causing HPV viruses classified as group 1 carcinogens include 12 HPV types, with HPV 16 and 18 being the most prevalent. High-risk HPVs express two oncoproteins, E6 and E7, the products of which are responsible for the inhibition of p53 and pRB proteins, respectively, in human keratinocytes and cellular immortalization. p53 and pRB are pleiotropic proteins that regulate the activity of several signaling pathways and gene expression. Among the important factors that are augmented in HPV-mediated carcinogenesis, proteases not only control processes involved in cellular carcinogenesis but also control the microenvironment. For instance, genetic polymorphisms of matrix metalloproteinase 1 (MMP-1) are associated with carcinoma invasiveness. Similarly, the serine protease inhibitors hepatocyte growth factor activator inhibitor-1 (HAI-1) and -2 (HAI-2) have been identified as prognostic markers for HPV-dependent cervical carcinomas. This review highlights the most crucial mechanisms involved in HPV-dependent carcinogenesis, and includes a section on the proteolytic cascades that are important for the progression of this disease and their impact on patient health, treatment, and survival.
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Affiliation(s)
- Gabriel Viliod Vieira
- Department of Cell and Molecular Biology and Pathogenic Bioagents, Ribeirao Preto Medical School, University of Sao Paulo, Ribeirao Preto 14049-900, SP, Brazil; (G.V.V.); (C.K.d.F.); (L.M.A.R.I.)
| | - Fernanda Somera dos Santos
- Department of Gynecology and Obstetrics, Ribeirao Preto Medical School, University of Sao Paulo, Ribeirao Preto 14049-900, SP, Brazil; (F.S.d.S.); (S.M.Q.)
| | - Ana Paula Lepique
- Department of Immunology, Biomedical Sciences Institute, University of Sao Paulo, Sao Paulo 05508-000, SP, Brazil;
| | - Carol Kobori da Fonseca
- Department of Cell and Molecular Biology and Pathogenic Bioagents, Ribeirao Preto Medical School, University of Sao Paulo, Ribeirao Preto 14049-900, SP, Brazil; (G.V.V.); (C.K.d.F.); (L.M.A.R.I.)
| | - Lara Maria Alencar Ramos Innocentini
- Department of Cell and Molecular Biology and Pathogenic Bioagents, Ribeirao Preto Medical School, University of Sao Paulo, Ribeirao Preto 14049-900, SP, Brazil; (G.V.V.); (C.K.d.F.); (L.M.A.R.I.)
- Clinical Hospital of Ribeirao Preto Medical School, University of São Paulo, Ribeirao Preto 14049-900, SP, Brazil
| | - Paulo Henrique Braz-Silva
- Department of Stomatology, School of Dentistry, University of Sao Paulo, São Paulo 05508-000, SP, Brazil;
- Laboratory of Virology, Institute of Tropical Medicine of Sao Paulo, School of Medicine, University of Sao Paulo, Sao Paulo 05403-000, SP, Brazil
| | - Silvana Maria Quintana
- Department of Gynecology and Obstetrics, Ribeirao Preto Medical School, University of Sao Paulo, Ribeirao Preto 14049-900, SP, Brazil; (F.S.d.S.); (S.M.Q.)
| | - Katiuchia Uzzun Sales
- Department of Cell and Molecular Biology and Pathogenic Bioagents, Ribeirao Preto Medical School, University of Sao Paulo, Ribeirao Preto 14049-900, SP, Brazil; (G.V.V.); (C.K.d.F.); (L.M.A.R.I.)
- Correspondence: ; Tel.: +55-16-3315-9113
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Chan PSF, Fang Y, Chidgey A, Fong F, Ip M, Wang Z. Would Chinese Men Who Have Sex With Men Take Up Human Papillomavirus (HPV) Screening as an Alternative Prevention Strategy to HPV Vaccination? Front Med (Lausanne) 2022; 9:904873. [PMID: 35721088 PMCID: PMC9205561 DOI: 10.3389/fmed.2022.904873] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/26/2022] [Accepted: 05/09/2022] [Indexed: 11/13/2022] Open
Abstract
Background Men who have sex with men (MSM) are at high risk for human papillomavirus (HPV) infection. A community-based organization (CBO)-private clinic service model promoting HPV vaccination among MSM was implemented in Hong Kong. The aim of this study was to evaluate the effectiveness of this service model in increasing HPV screening among MSM. Methods This was a secondary analysis of the CBO-private clinic service model in increasing HPV screening among MSM. Participants were Hong Kong Chinese-speaking MSM aged 18–45 years who had never received HPV vaccination. All participants completed a telephone survey at baseline before receiving online intervention promoting HPV vaccination and completed another telephone survey 12 months afterward. Results A total of 350 participants completed a baseline telephone survey and received interventions promoting HPV vaccination. Among 274 participants being followed up at Month 12, 33 (12.0%) received any type of HPV screening during the study period. Such uptake rate was similar to the prevalence of HPV screening in the past year measured at baseline (12.0 vs. 9.9%, p = 0.43). More MSM preferred HPV vaccination or HPV vaccination plus HPV screening, and very few preferred HPV screening alone. After adjusting for significant baseline characteristics, higher perceived susceptibility to HPV (adjusted odds ratio (AOR): 1.16, 95% confidence interval (CI): 1.00–1.34) and receiving HPV vaccination during the study period (AOR: 7.03, 95% CI: 3.07–16.13) were significantly associated with higher HPV screening uptake. Conclusions The CBO-private clinic service model promoting HPV vaccination had limited impact in increasing HPV screening among MSM in Hong Kong. MSM in Hong Kong may not use HPV screening as an alternative prevention strategy to HPV vaccination. Future programs preventing HPV-related diseases among MSM in Hong Kong should focus on HPV vaccination promotion.
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Affiliation(s)
- Paul Shing-fong Chan
- Jockey Club School of Public Health and Primary Care, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, Hong Kong SAR, China
| | - Yuan Fang
- Department of Health and Physical Education, The Education University of Hong Kong, Hong Kong, Hong Kong SAR, China
| | | | | | - Mary Ip
- Jockey Club School of Public Health and Primary Care, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, Hong Kong SAR, China
| | - Zixin Wang
- Jockey Club School of Public Health and Primary Care, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, Hong Kong SAR, China
- *Correspondence: Zixin Wang
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Selimagic A, Dozic A, Husic-Selimovic A, Tucakovic N, Cehajic A, Subo A, Spahic A, Vanis N. The Role of Inflammation in Anal Cancer. Diseases 2022; 10:27. [PMID: 35645248 PMCID: PMC9149845 DOI: 10.3390/diseases10020027] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/04/2022] [Revised: 05/01/2022] [Accepted: 05/04/2022] [Indexed: 11/16/2022] Open
Abstract
The aim of this article was to present a summary of the current resources available in the literature regarding the role of inflammation in anal cancer development. Anal cancer is relatively uncommon, accounting for about 2.7% of all reported gastrointestinal cancers in the United States. However, the importance of understanding the pathogenesis and risk factors for anal cancer has been recognized over the last several decades due to a noticed increase in incidence worldwide. Infections, autoimmune diseases, and inflammatory diseases of unknown etiology cause chronic inflammation that promotes tumorigenesis. The association between chronic inflammation and cancer development is widely accepted. It is based on different pathophysiological mechanisms that lead to cellular transformation and changes in immunological response, allowing tumor cells to avoid apoptosis and immune surveillance. However, there are still many molecular and cellular mechanisms that remain largely unexplored. Further studies on this topic could be of tremendous significance in elucidating anal cancer pathogenesis and developing immunotherapeutic approaches for its treatment.
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Affiliation(s)
- Amir Selimagic
- Department of Gastroenterohepatology, General Hospital “Prim. dr. Abdulah Nakas”, 71 000 Sarajevo, Bosnia and Herzegovina; (A.H.-S.); (N.T.); (A.C.)
| | - Ada Dozic
- Department of Internal Medicine, General Hospital “Prim. dr. Abdulah Nakas”, 71 000 Sarajevo, Bosnia and Herzegovina; (A.D.); (A.S.); (A.S.); (N.V.)
| | - Azra Husic-Selimovic
- Department of Gastroenterohepatology, General Hospital “Prim. dr. Abdulah Nakas”, 71 000 Sarajevo, Bosnia and Herzegovina; (A.H.-S.); (N.T.); (A.C.)
| | - Nijaz Tucakovic
- Department of Gastroenterohepatology, General Hospital “Prim. dr. Abdulah Nakas”, 71 000 Sarajevo, Bosnia and Herzegovina; (A.H.-S.); (N.T.); (A.C.)
| | - Amir Cehajic
- Department of Gastroenterohepatology, General Hospital “Prim. dr. Abdulah Nakas”, 71 000 Sarajevo, Bosnia and Herzegovina; (A.H.-S.); (N.T.); (A.C.)
| | - Anela Subo
- Department of Internal Medicine, General Hospital “Prim. dr. Abdulah Nakas”, 71 000 Sarajevo, Bosnia and Herzegovina; (A.D.); (A.S.); (A.S.); (N.V.)
| | - Azra Spahic
- Department of Internal Medicine, General Hospital “Prim. dr. Abdulah Nakas”, 71 000 Sarajevo, Bosnia and Herzegovina; (A.D.); (A.S.); (A.S.); (N.V.)
| | - Nedim Vanis
- Department of Internal Medicine, General Hospital “Prim. dr. Abdulah Nakas”, 71 000 Sarajevo, Bosnia and Herzegovina; (A.D.); (A.S.); (A.S.); (N.V.)
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Impact of Definitive Chemoradiation on Quality-of-Life Changes for Patients With Anal Cancer: Long-term Results of a Prospective Study. Dis Colon Rectum 2022; 65:642-653. [PMID: 35067501 DOI: 10.1097/dcr.0000000000002385] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
BACKGROUND Maintaining and improving quality of life (QOL) are important goals of anal cancer management. This disease is generally curable, with many long-term survivors. OBJECTIVE Long-term QOL after chemoradiation for patients with anal cancer was evaluated. DESIGN This was a prospective cohort study. SETTINGS This study used data from a prospective study of patients with anal cancer who were treated with chemoradiation between 2008 and 2013. PATIENTS Patients with anal cancer who were treated with image-guided intensity-modulated radiation therapy were included. INTERVENTIONS English-speaking patients completed European Organization for Research and Treatment of Cancer cancer-specific (C30) and site-specific (CR29) QOL questionnaires at baseline, at end of radiation, at 3 and 6 months, and then annually. MAIN OUTCOMES MEASURES Long-term QOL was evaluated clinically (a change in score of ≥10 points was considered clinically significant) and statistically (using repeated-measurement analysis) by comparing the subscale scores at 1, 2, and 3 years with baseline scores. Subanalysis compared patients who received a radiation dose of 45 to 54 Gy versus 63 Gy. RESULTS Ninety-six patients were included (median follow-up of 56.5 months). The symptom and functional scales showed a clinically significant decline at the end of treatment with improvement by 3 months after treatment. There was a long-term statistically significant decline in dyspnea, body image, bowel embarrassment, fecal incontinence, and hair loss, and there was long-term statistically and clinically significant worsening of impotence. Higher radiation dose (63 Gy) was not associated with significantly worse QOL. LIMITATIONS Limitations included single-institution, single-arm study design, and lack of dose reconstruction (ie, analyses were based on prescribed, rather than delivered, dose). CONCLUSIONS Patients with anal cancer treated with chemoradiation reported recovery of overall QOL to baseline levels. Specific symptoms remained bothersome, emphasizing the need to address and manage the chemoradiation-induced symptoms, during treatment and in the long term. See Video Abstract at http://links.lww.com/DCR/B905. IMPACTO DE LA QUIMIORRADIACIN DEFINITIVA EN CAMBIOS EN LA CALIDAD DE VIDA DE LOS PACIENTES CON CNCER ANAL RESULTADOS A LARGO PLAZO DE UN ESTUDIO PROSPECTIVE ANTECEDENTES:Mantener y mejorar la calidad de vida son objetivos importantes del tratamiento del cáncer anal, ya que esta enfermedad generalmente es curable, con muchos sobrevivientes a largo plazo.OBJETIVO:Se evaluó la calidad de vida a largo plazo después de la quimiorradiación en pacientes con cáncer anal.DISEÑO:Este fue un estudio de cohorte prospectivo.ENTORNO CLINICO:Utilizamos datos de un estudio prospectivo en pacientes con cáncer anal tratados con quimiorradiación entre 2008-2013.PACIENTES:Los pacientes con cáncer anal fueron tratados con radioterapia de intensidad modulada guiada por imágenes.INTERVENCIONES:Los pacientes de habla inglesa completaron los cuestionarios de calidad de vida específicos de cáncer (C30) y específicos del sitio (CR29) de la Organización Europea para la Investigación y el Tratamiento del Cáncer al inicio, al final de la radiación, 3 y 6 meses, y luego anualmente.PRINCIPALES MEDIDAS DE RESULTADOS:Se evaluó a largo plazo la calidad de vida clínicamente (un cambio en la puntuación de ≥10 puntos se consideraron clínicamente significativo) y estadísticamente (usando análisis de medición repetida) comparando las subescalas de puntuación al 1, 2, y 3 años. Con puntuaciones de referencia. El subanálisis comparó pacientes que recibieron 45-54 Gy versus 63 Gy.RESULTADOS:Se incluyeron un total de 96 pacientes (mediana de seguimiento: 56,5 meses). La mayoría de las escalas funcionales y de síntomas mostraron una disminución clínicamente significativa al final del tratamiento con una mejoría a los 3 meses posteriores al tratamiento. Hubo una disminución estadísticamente significativa a largo plazo en disnea, imagen corporal, vergüenza intestinal, incontinencia fecal y pérdida de cabello; y hubo un empeoramiento a largo plazo estadística y clínicamente significativo en impotencia. La dosis de radiación más alta (63 Gy) no se asoció con una calidad de vida significativamente peor.LIMITACIONES:Institución única, diseño de estudio de un solo brazo y falta de recomposición de la dosis (es decir, los análisis se basan en la dosis prescrita, en lugar de la administrada).CONCLUSIÓNES:Los pacientes con cáncer anal tratados con quimiorradiación reportaron una recuperación de la QOL en general a los niveles de base. Síntomas específicos siguieron siendo molestos, lo que enfatiza la necesidad de resolver y tartar los síntomas inducidos por la quimiorradiación no solo durante el tratamiento, sino a largo plazo. Consulte Video Resumen en http://links.lww.com/DCR/B905. (Traducción- Dr. Francisco M. Abarca-Rendon).
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Trends in incidence and survival from anal cancer and incidence of high-grade anal intraepithelial neoplasia in Denmark. Cancer Epidemiol 2022; 77:102099. [DOI: 10.1016/j.canep.2022.102099] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/02/2021] [Revised: 01/05/2022] [Accepted: 01/06/2022] [Indexed: 11/21/2022]
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Yamada K, Saiki Y, Komori K, Shiomi A, Ueno M, Ito M, Hida K, Yamamoto S, Shiozawa M, Ishihara S, Kanemitsu Y, Ueno H, Kinjo T, Maeda K, Kawamura J, Fujita F, Takahashi K, Mizushima T, Shimada Y, Sasaki S, Sunami E, Ishida F, Hirata K, Ohnuma S, Funahashi K, Watanabe J, Kinugasa Y, Yamaguchi S, Hashiguchi Y, Ikeda M, Sudo T, Komatsu Y, Koda K, Sakamoto K, Okajima M, Ishida H, Hisamatsu Y, Masuda T, Mori S, Minami K, Hasegawa S, Endo S, Iwashita A, Hamada M, Ajioka Y, Usuku K, Ikeda T, Sugihara K. Characteristics of anal canal cancer in Japan. Cancer Med 2022; 11:2735-2743. [PMID: 35274487 PMCID: PMC9302302 DOI: 10.1002/cam4.4631] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/06/2021] [Revised: 01/07/2022] [Accepted: 01/20/2022] [Indexed: 01/06/2023] Open
Abstract
Anal canal cancer (ACC) has been reported to be an uncommon cancer in Japan, as in the USA, Europe, and Australia. This retrospective multi‐institutional study was conducted to clarify the characteristics of ACC in Japan. First, the histological ACC type cases treated between 1991 and 2015 were collected. A detailed analysis of the characteristics of anal canal squamous cell carcinoma (SCC) cases was then conducted. The results of the histological types revealed that of the 1781 ACC cases, 435 cases (24.4%) including seven cases of adenosquamous cell carcinomas were SCC and 1260 cases (70.7%) were adenocarcinoma. However, the most common histological type reported in the USA, Europe, and Australia is SCC. Most ACC cases are adenocarcinomas and there is a low incidence of SCC in Japan which is different from the above‐mentioned countries. Moreover, we reclassified T4 into the following two groups based on tumor size: T4a (tumor diameter of 5 cm or less) and T4b (tumor diameter of more than 5 cm). The results of the TNM classification of SCC revealed that the hazard ratio (HR) to T1 of T2, T3, T4a, and T4b was 2.45, 2.28, 2.89, and 4.97, respectively. As T4b cases had a worse prognosis than T4a cases, we propose that T4 for anal canal SCC in Japan be subclassified into T4a and T4b.
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Affiliation(s)
- Kazutaka Yamada
- Department of Surgery, Coloproctology Center Takano Hospital, Kumamoto, Japan
| | - Yasumitsu Saiki
- Department of Surgery, Coloproctology Center Takano Hospital, Kumamoto, Japan
| | - Koji Komori
- Department of Gastroenterological Surgery, Aichi Cancer Center Hospital, Aichi, Japan
| | - Akio Shiomi
- Division of Colon and Rectal Surgery, Shizuoka Cancer Center Hospital, Shizuoka, Japan
| | - Masashi Ueno
- Department of Gastroenterological Surgery, Cancer Institute Hospital of the Japanese Foundation for Cancer Research, Tokyo, Japan
| | - Masaaki Ito
- Department of Colorectal Surgery, National Cancer Center Hospital East, Chiba, Japan
| | - Koya Hida
- Department of Surgery, Kyoto University Hospital, Kyoto, Japan
| | - Seiichiro Yamamoto
- Department of Gastroenterological Surgery, Tokai University School of Medicine, Kanagawa, Japan
| | - Manabu Shiozawa
- Department of Gastrointestinal Surgery, Kanagawa Cancer Center, Kanagawa, Japan
| | - Soichiro Ishihara
- Department of Surgical Oncology, The University of Tokyo, Tokyo, Japan
| | - Yukihide Kanemitsu
- Department of Colorectal Surgery, National Cancer Center Hospital, Tokyo, Japan
| | - Hideki Ueno
- Department of Surgery, National Defense Medical College, Saitama, Japan
| | - Tatsuya Kinjo
- Department of Digestive and General Surgery, Graduate School of Medicine, University of Ryukyus, Okinawa, Japan
| | - Kotaro Maeda
- International Medical Center, Fujita Health University Hospital, Aichi, Japan
| | - Junichiro Kawamura
- Department of Surgery, Kindai University Faculty of Medicine, Osaka, Japan
| | - Fumihiko Fujita
- Department of Surgery, Kurume University School of Medicine, Fukuoka, Japan
| | - Keiichi Takahashi
- Department of Surgery, Tokyo Metropolitan Cancer and Infectious Diseases Center Komagome Hospital, Tokyo, Japan
| | - Tsunekazu Mizushima
- Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Osaka, Japan
| | - Yasuhiro Shimada
- Department of Clinical Oncology, Kochi Health Sciences Center, Kochi, Japan
| | - Shin Sasaki
- Department of Coloproctological Surgery, Japanese Red Cross Medical Center, Tokyo, Japan
| | - Eiji Sunami
- Department of Surgery, Kyorin University Faculty of Medicine, Tokyo, Japan
| | - Fumio Ishida
- Digestive Disease Center, Showa University Northern Yokohama Hospital, Kanagawa, Japan
| | - Keiji Hirata
- Department of Surgery1, School of Medicine, University of Occupational and Environmental Health, Fukuoka, Japan
| | - Shinobu Ohnuma
- Department of Surgery, Tohoku University Graduate School of Medicine, Miyagi, Japan
| | - Kimihiko Funahashi
- Department of Gastroenterological Surgery, Toho University Omori Medical Center, Tokyo, Japan
| | - Jun Watanabe
- Department of Surgery, Gastroenterological Center, Yokohama City University Medical Center, Kanagawa, Japan
| | - Yusuke Kinugasa
- Department of Gastrointestinal Surgery, Tokyo Medical and Dental University, Tokyo, Japan
| | - Shigeki Yamaguchi
- Department of Gastroenterological Surgery, Saitama Medical University International Medical Center, Saitama, Japan
| | - Yojiro Hashiguchi
- Department of Surgery, Teikyo University School of Medicine, Tokyo, Japan
| | - Masataka Ikeda
- Division of Lower Gastrointestinal Surgery, Department of Surgery, Hyogo College of Medicine, Hyogo, Japan
| | - Takeshi Sudo
- Department of Gastroenterological Surgery, Yamagata Prefectural Central Hospital, Yamagata, Japan
| | - Yoshito Komatsu
- Department of Cancer Center, Hokkaido University Hospital, Hokkaido, Japan
| | - Keiji Koda
- Department of Surgery, Teikyo University Chiba Medical Center, Chiba, Japan
| | - Kazuhiro Sakamoto
- Department of Coloproctological Surgery, Juntendo University Faculty of Medicine, Tokyo, Japan
| | - Masazumi Okajima
- Department of Surgery, Hiroshima City Hiroshima Citizens Hospital, Hiroshima, Japan
| | - Hideyuki Ishida
- Department of Digestive Tract and General Surgery, Saitama Medical Center, Saitama Medical University, Saitama, Japan
| | - Yuichi Hisamatsu
- Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Taiki Masuda
- Department of Surgery, Tokyo Metropolitan Hiroo Hospital, Tokyo, Japan
| | - Shinichiro Mori
- Department of Digestive Surgery, Breast and Thyroid Surgery, Graduate School of Medicine and Dental Sciences, Kagoshima University, Kagoshima, Japan
| | - Kazuhito Minami
- Department of Surgery, Matsuyama Red Cross Hospital, Ehime, Japan
| | - Seiji Hasegawa
- Department of Surgery, Saiseikai Yokohamashi Nanbu Hospital, Kanagawa, Japan
| | - Shungo Endo
- Department of Coloproctology, Aizu Medical Center, Fukushima Medical University, Fukushima, Japan
| | - Akinori Iwashita
- Department of Pathology, Fukuoka University Chikushi Hospital, Fukuoka, Japan
| | - Madoka Hamada
- Division of Gastrointestinal Surgery, Kansai Medical University Hospital, Osaka, Japan
| | - Yoichi Ajioka
- Division of Molecular and Diagnostic Pathology, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan
| | - Koichiro Usuku
- Department of Medical Information Sciences and Administration Planning, Kumamoto University Hospital, Kumamoto, Japan
| | - Tokunori Ikeda
- Department of Medical Information Sciences and Administration Planning, Kumamoto University Hospital, Kumamoto, Japan
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