Solid organ transplant recipients are at high risk for developing skin malignancies due to prolonged immunosuppression. The field of transplant dermatology (TD) has experienced a surge in research and clinical advancements, yet there is no quantitative evaluation estimating the impact of TD literature.

Identify and characterize the most frequently cited TD articles.

Institute For Scientific Information Web of Science was used to identify the 50 most cited research articles in TD. Results were reviewed by 3 independent authors. A network analysis was performed to assess collaboration patterns among coauthors.

Top articles held a combined total of 12,114 citations. The top-cited article was "Cancer incidence before and after kidney transplantation," by Vajdic and colleagues in the Journal of the American Medical Association (2006) with 872 citations. A total of 22 countries and 221 institutions were represented.

This bibliometric analysis offers a detailed overview of the most cited manuscripts in TD and illustrates the discoveries steering TD research and practice.

Routine pre-transplant evaluations for heart or lung recipients often include upper and lower gastrointestinal endoscopies. However, given that these patients frequently have significant and multiple comorbidities, the risk-benefit ratio of endoscopy with sedation remains uncertain.

We conducted a retrospective chart review of all patients who underwent esophagogastroduodenoscopy (EGD) and/or colonoscopy as part of the pre-transplant evaluation for heart (HTX) or lung transplantation (LuTX) at our center over a 10-year period. All procedures were performed with either anesthesiologist-assisted sedation or general anesthesia (72%) or physician-assisted sedation (28%). The primary outcomes included the prevalence of pre/neoplastic lesions and the rate of adverse events, classified according to the American Society of Gastrointestinal Endoscopy.

A total of 315 patients (70% male, median age 55 years) were included, with ASA grades 3 (31%) and 4 (69%). Of these, 90% underwent both EGD and colonoscopy. While no neoplasia or findings relevant to transplantation were detected on EGD, a single rectal malignant pedunculated polyp was identified and curatively removed via colonoscopy (G2 pT1 L0 V0 R0). The adenoma detection rate during colonoscopy was 25%, including a 7% rate of advanced adenomas, with six additional lesions (< 10 mm) exhibiting high-grade dysplasia. Conversely, severe adverse events occurred in 2.5% of cases, involving both cardiovascular and colonoscopy-related complications. These included two cases of severe hypotension and bradyarrhythmia requiring cardiovascular resuscitation, with one resulting in death (0.3% mortality). Additionally, one splenic rupture, two colonic perforations, and two cases of severe post-polypectomy bleeding were observed.

The routine requirement for upper and lower gastrointestinal endoscopy as a screening measure before heart or lung transplantation should be reconsidered due to its unfavorable risk-benefit profile. An individualized approach should be taken.

There is limited evidence of potential associations between body mass index (BMI) and risk of vulvar and vaginal cancer. We explored these associations in a large cohort of Norwegian women.

The analytical dataset included 889,441 women aged 16-75 years at baseline in 1963-1975. Multivariable Cox regression analyses were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for the associations between BMI and vulvar and vaginal cancer incidence.

During 30.1 million person-years of follow-up, 1748 incident vulvar and 408 incident vaginal cancer cases occurred. The HRs (95% CIs) for vulvar cancer for a BMI of 15- < 18.5, 18.5- < 25, 25- < 30, 30- < 35, ≥ 35 were 0.62 (0.38-1.01), 1.00 (reference), 1.23 (1.10-1.40), 1.43 (1.23-1.66) and 1.72 (1.35-2.20, ptrend < 0.001), and per 5 kg/m2 increment was 1.20 (1.13-1.26). The corresponding HRs (95% CIs) for vaginal cancer were 1.05 (0.52-2.15), 1.00, 0.89 (0.71-1.12), 0.95 (0.68-1.34), and 2.01 (1.29-3.13, ptrend < 0.001), respectively, and per 5 kg/m2 was 1.11 (0.99-1.25). The HR (95% CI) per 5 kg/m2 increase in BMI at ages 16-29 was 1.28 (1.07-1.54, n = 250 cases) for vulvar and 1.53 (1.11-2.11, n = 66 cases) for vaginal cancers. The HR (95% CI) per 5 kg/m2 for early-onset (< 50 years age at diagnosis) vulvar cancer was 0.92 (0.66-1.28, n = 87 cases) and 1.70 (1.05-2.76, n = 21 cases) for vaginal cancer.

These results further support the associations between higher BMI and increased risk of vulvar and vaginal cancers, with suggestive stronger associations between BMI in early adulthood for both cancers and for early-onset vaginal cancer. Further studies are needed to elucidate these findings and investigate the underlying mechanisms.

The pathophysiology of the development of anal cancer is thought to be linked to chronic inflammation, a possible consequence of infections with human papillomavirus (HPV) or HIV, or inflammation from inflammatory bowel disease. Anal HPV-induced carcinogenesis bears similarities to its cervical counterpart via viral integration into the host genome and the development of precursor lesions termed anal intraepithelial neoplasia. HPV-16 and -18 are the most common HPV genotypes associated with anal cancer. Other risk factors for the development of anal cancer include chronic immunosuppression, sexual activity and sexually transmitted diseases, female gender, history of anogenital dysplasia, and smoking.

Anal cancer is an uncommon disease in a sensitive region of the body that benefits from early and systematic workup and treatment. Main modalities for workup include history, physical examination, and MRI. PET scan and computed tomography scan are helpful in assessing spread of disease. High-resolution anoscopy may be useful in identifying precancerous lesions but come with a high-learning curve.

Advances in immunosuppressive therapy and postoperative management have greatly improved the graft and patient survival rates after kidney transplantation; however, the incidence of post-transplant malignant tumors is increasing. Post-renal transplantation malignant tumors are associated with renal failure, immunosuppression, and viral infections. Moreover, the risk of developing cancer is higher in kidney transplant recipients than in the general population, and the tendency to develop cancer is affected by the background and environment of each patient. Recently, cancer after kidney transplantation has become the leading cause of death in Japan. Owing to the aggressive nature and poor prognosis of genitourinary malignancies, it is crucial to understand their epidemiology, risk factors, and best practices in kidney transplant recipients. This review has a special emphasis on the epidemiology, risk factors, and treatment protocols of genitourinary malignancies in kidney transplant recipients to enhance our understanding of the appropriate management strategies. Optimal immunosuppressive therapy and cancer management for these patients remain controversial, but adherence to the general guidelines is recommended.

Limited data exists concerning the post lung transplantation outcomes of patients diagnosed with myelodysplastic syndrome (MDS). We delineate the clinical trajectories and outcomes for 3 patients with MDS and Short Telomere Syndrome (STS) who underwent lung transplantation. Our findings suggest that patients with STS and low-risk MDS, especially those harboring the SF3B1 mutation, tolerated standard immunosuppression and antimicrobial prophylaxis well without significant deviation from a typical post-transplant course. Therefore, individuals with low-risk MDS should not be automatically excluded from lung transplantation consideration. Post-transplant monitoring is crucial to promptly detect and manage cytopenias. Conversely, our patient, diagnosed with high-risk MDS post-transplantation faced a poor prognosis, with severe cytopenias limiting immunosuppression treatment and resulting in rejection. Thus, abundance of caution is warranted when contemplating lung transplantation for individuals with high-risk MDS and STS. Further research is necessary to validate these findings.

Tissue or organ damage due to severe injuries or chronic diseases can adversely affect the quality of life. Current treatments rely on organ or tissue transplantation which has limitations including unavailability of donors, ethical issues, or immune rejection after transplantations. These limitations can be addressed by tissue regeneration which involves the development of bioactive scaffolds closely mimicking the extracellular matrix (ECM). One of the major components of ECM is the laminin protein which supports several tissues associated with important organs. In this direction, peptide-based hydrogels can effectively mimic the essential characteristics of laminin. While several reports have discussed the structure of laminin, the potential of laminin-derived peptide hydrogels as effective biomaterial for tissue engineering applications is yet to be discussed. In this context, the current review focuses on the structure of laminin and its role as an essential ECM protein. Further, the potential of short peptide hydrogels in mimicking the crucial properties of laminin is proposed. The review further highlights the significance of bioactive hydrogels inspired by laminin - in addressing numerous tissue engineering applications including angiogenesis, neural, skeletal muscle, liver, and adipose tissue regeneration along with a brief outlook on the future applications of these laminin-based hydrogels.

The incidence of thyroid nodules has increased as diagnostic imaging has become more prevalent, but the management in transplant candidates, a high-risk population because of the need for chronic immunosuppression, has not been described. We sought to review our institution's approach to thyroid nodules incidentally found during pretransplant workup.

A multisite retrospective review was performed of pretransplant patients with incidental thyroid nodules diagnosed between 2011 and 2021. Demographics, nodule characteristics, treatment timeline, and oncologic outcomes were collected. Patients diagnosed before and after 2017 were compared to evaluate how adoption of Thyroid Imaging Reporting and Data System and expansion of a dedicated transplant center were correlated with changes in patient management.

A total of 10,340 patients underwent abdominal transplant, 236 had incidental thyroid nodules. After 2017, radiology recommendations for biopsy decreased from 39% to 29% (P = 0.174) and fewer biopsies were performed, 45%-33% (P = 0.055). Time between imaging and biopsy was significantly shorter after 2017, from 14 mo to 4 (P = 0.038). Overall time from imaging to transplant was also significantly reduced, from 31 mo to 11 (P < 0.001). Thirty-one (13.1%) patients underwent thyroid surgery before transplant and four (1.7%) patients after.

In the recent years, thyroid biopsy rates for thyroid incidentalomas found during pretransplant workup have decreased and more closely match imaging-based guideline recommendations. Patients who required biopsy obtained them sooner and underwent transplant surgery sooner. Guideline-driven thyroid incidentaloma workup for the pretransplant population allows for timely and appropriate cancer care while avoiding unnecessary delays in transplant.

Solid organ transplant recipients have an elevated risk of cancer following organ transplantation than the age-adjusted general population. We assessed incidence of head and neck squamous cell carcinoma (HNSCC) in heart, lung, and liver recipients.

This retrospective cohort study included 124,966 patients from the United States Scientific Registry of Transplant Recipients (SRTR) database who received heart, lung, or liver transplantation between 1991 and 2010. Follow-up data were available until 2018. Patients with prevalent HNSCC at transplantation were excluded. Incident cases of HNSCC post organ transplantation were identified, and incidence rates (per 100,000 person-years) were reported by gender, race, organ type, year and age at organ transplantation.

The majority of patients received liver transplantation (58.64 %), followed by heart (28.64 %), and lung (12.72 %) transplantation. During follow-up, 4.14 % patients developed HNSCC. Overall incidence rate of HNSCC was 426.76 per 100,000 person-years. Male recipients had a higher HNSCC incidence rate than female recipients (571.8 and 177.0 per 100,000 person-years, respectively). Lung recipients had the highest overall HNSCC incidence rate (1273.6 per 100,000 person-years), followed by heart (644.2 per 100,000 person-years), and liver recipients (207.1 per 100,000 person-years). Overall, an increase in HNSCC incidence rate was observed with increase in age at organ transplantation. An increase in incidence rates of HNSCC over time was observed in lung recipients; however, incidence rates decreased over time in heart recipients.

Solid organ transplant recipients have a high incidence of HNSCC following organ transplantation, and the incidence varies by type of organ received.

Heart transplant patients have an increased risk of developing cancer. Patients who underwent HTx between 1985 and 2017 were included. Detection of cancer was obtained by cross-checking the study population with the Swedish Cancer-Registry and the Cause-of-Death-Registry. A total of 664 patients were followed for a median of 7.7 years. In all, 231 malignancies were diagnosed in 138 patients. Compared to the general population the excess risk of cancer following HTx was 6.2-fold calculated as the standardized incidence ratio (SIR) and 2.9-fold after exclusion of non-melanoma skin cancer (NMSC). The most common malignancies were NMSC, non-Hodgins lymphoma, and lung cancer. There was no significant difference in overall survival between those with and without a history of cancer before HTx (p = 0.53). During a median follow-up of 7.7 years, 19% of HTx recipients developed cancer, 6.2-fold higher relative to the general population, and 2.9-fold higher when excluding NMSC. Risk factors for malignancies (excluding NMSC) included previous smoking, hypertension and prolonged ischemic time; and for NMSC, increasing age, seronegative CMV-donors, and azathioprine. A previous cancer in selected recipients results in similar survival compared to those without cancer prior to HTx.

Lung transplantation (LTx) is a well-known treatment for end-stage lung disease. This study aimed to report the incidence of cancer after LTx and long-term outcome among lung transplant recipients with a pretransplant diagnosis of cancer. Patients who underwent LTx between 1990-2016 were included in the study. Detection of cancer was obtained by cross-checking the study population with the Swedish Cancer Registry and the Cause-of-Death registry. A total of 614 patients were followed for a median of 5.1 years. In all, 159 malignancies were diagnosed. The excess risk of cancer or standardized incidence ratio (SIR) following LTx was 5.6-fold compared to the general Swedish population. The most common malignancies were non-melanoma skin cancer (NMSC) (SIR 76.5 (95%CI 61.7-94.8); non-Hodgkin lymphoma (SIR 23.5, 95%CI 14.8-37.2); and lung cancer (SIR 8.89, 95%CI 5.67-13.9). There was no significant difference in overall survival between those with and without a history of cancer before LTx (p = 0.56). In total, 159 malignancies were identified after LTx, which was a 5.6-fold higher relative to the general population. A history of previous cancer yields similar survival in selected recipients, compared to those without cancer prior to LTx.

Chronic kidney disease (CKD) has been correlated with certain pathological conditions such as cardiovascular diseases and other renal-related dysfunctions. Some other reports suggested an association between CKD and the development of certain solid cancers. Therefore, we aimed to generate this narrative review to present the available literature on the risk of solid cancer development in CKD patient populations. We explored the associations between CKD, organ transplantation, and the development of specific solid organ tumors such as kidney, thyroid, lung, breast, bladder, gastric, and prostate cancers. In conclusion, the previous reports showed an increase in the risk of certain solid cancers such as kidney, lung, bladder, and possibly breast cancer in CKD patients and transplant recipients. On the other hand, thyroid, gastric, and prostate cancers showed unclear association with CKD. Despite the suggested impact of smoking and immunosuppression on the development of cancers in CKD patients, more studies are needed to elucidate the mechanism and the risk factors that might be related to the development of cancer in CKD patients.

De novo malignancies (DNMs) are a major adverse event after solid organ transplantation; however, their characteristics and recent trends after living-donor liver transplantation (LDLT) remain unclear.

We retrospectively reviewed 1781 primary LDLT recipients (1990-2020) and annually calculated standardized incidence ratios (SIRs) of DNMs compared to the age-adjusted Japanese general population.

After 21 845 person-years follow-up, 153 DNM lesions (8.6%) were identified in 131 patients (7.4%). The incidence was 0.007 person-years. DNMs included 81 post-transplant lymphoproliferative disorders (PTLDs), 14 colorectal, 12 lung, and 12 gastric cancers, and so on. Comorbid DNMs significantly worsened recipient survival than those without (p < .001). The 5- and 10-year recipient survival after DNM diagnosis were 65% and 58%, respectively. Notably, SIR1993-1995: 8.12 (95% CI: 3.71-15.4, p < .001) and SIR1996-1998: 3.11 (1.34-6.12, p = .01) were significantly high, but had decreased time-dependently to SIR2005-2007: 1.31 (0.68-2.29, p = .42) and SIR2008-2010: 1.34 (0.75-2.20, p = .33), indicating no longer significant difference in DNMs development. Currently, however, SIR2014-2016: 2.27 (1.54-3.22, p < .001) and SIR2017-2019: 2.07 (1.40-2.96, p < .001) have become significantly higher again, reflecting recent aging of recipients (>50 years) and resultant increases in non-PTLD DNMs. Furthermore, characteristically in LDLT, the fewer the donor-recipient HLA-mismatches, the less the post-transplant DNMs development.

DNM development after LDLT was significantly higher than in the general population due to higher PTLD incidence (1993-1998), but once became equivalent (2005-2013), then significantly increased again (2014-2019) due to recent recipient aging and resultant increase in solid cancers.

Patients after renal transplantation are susceptible to secondary malignancies, including anal squamous cell carcinoma. Chemoradiotherapy is the standard treatment for anal squamous cell carcinoma; however, typical irradiation fields for anal cancer encompass a transplanted kidney located in the right iliac fossa, which causes complete renal dysfunction. Thus, typical irradiation fields are not feasible for this population. Additionally, standard concurrent chemotherapy demonstrates nephrotoxicity. Here, we report a case of modified definitive chemoradiotherapy for a 40-year-old patient with locally advanced perianal squamous cell carcinoma after renal transplantation whose abdominoperineal resection was difficult because of a history of repeated open surgeries and long-term steroids. We modified the cranial side of the elective nodal irradiation fields in this case to spare the transplanted kidney, considering the lymph chains of the perianal tumor. We then used continuous 5-fluorouracil to avoid nephrotoxicity of mitomycin C, considering his life expectancy. Modified definitive chemoradiotherapy achieved complete remission with expected toxicities. Now, approximately five years after the procedure, the patient remains disease-free, preserving anal and renal function. Definitive chemoradiotherapy using modified irradiation fields and chemotherapy may be an option for patients with anal squamous cell carcinoma after renal transplantation.

Invasive graft biopsies assess the efficacy of immunosuppression through lagging indicators of transplant rejection. We report on a microporous scaffold implant as a minimally invasive immunological niche to assay rejection before graft injury. Adoptive transfer of T cells into Rag2-/- mice with mismatched allografts induced acute cellular allograft rejection (ACAR), with subsequent validation in wild-type animals. Following murine heart or skin transplantation, scaffold implants accumulate predominantly innate immune cells. The scaffold enables frequent biopsy, and gene expression analyses identified biomarkers of ACAR before clinical signs of graft injury. This gene signature distinguishes ACAR and immunodeficient respiratory infection before injury onset, indicating the specificity of the biomarkers to differentiate ACAR from other inflammatory insult. Overall, this implantable scaffold enables remote evaluation of the early risk of rejection, which could potentially be used to reduce the frequency of routine graft biopsy, reduce toxicities by personalizing immunosuppression, and prolong transplant life.

Solid organ transplantation is a crucial treatment for patients who have reached the end stage of heart, lung, kidney, or liver failure. However, the likelihood of developing cancer post-transplantation increases. Additionally, primary malignant tumors remain a major obstacle to the long-term survival of transplanted organs. Therefore, it is essential to investigate effective therapies that can boost the immune system's ability to combat cancer and prevent allograft rejection. We established a mouse orthotopic liver tumor model and conducted allogeneic heterotopic heart transplantation. Various treatments were administered, and survival curves were generated using the Kaplan-Meier method. We also collected graft samples and measured inflammatory cytokine levels in the serum using an inflammatory array. The specificity of the histochemical techniques was tested by staining sections. We administered a combination therapy of phosphoinositide 3-kinase/mammalian target of rapamycin (PI3K/mTOR) dual inhibitor BEZ235 and Lactobacillus rhamnosus HN001 to primary liver cancer model mice with cardiac allografts. Consistent with our prior findings, L. rhamnosus HN001 alleviated the intestinal flora imbalance caused by BEZ235. Our previous research confirmed that the combination of BEZ235 and L. rhamnosus HN001 significantly prolonged cardiac transplant survival.

We observed that the combination of phosphoinositide 3-kinase/mammalian target of rapamycin (PI3K/mTOR) dual inhibitor BEZ235 and Lactobacillus rhamnosus HN001 notably prolonged cardiac transplant survival while also inhibiting the progression of primary liver cancer. The combination therapy was efficacious in treating antitumor immunity and allograft rejection, as demonstrated by the efficacy results. We also found that this phenomenon was accompanied by the regulation of inflammatory IL-6 expression. Our study presents a novel and effective therapeutic approach to address antitumor immunity and prevent allograft rejection.

Introduction: Post-transplant malignancy is a significant cause of morbidity and mortality following kidney transplantation often emerging after medium- to long-term follow-up. To understand the risk factors for the development of de novo post-transplant malignancy (DPTM), this study aimed to assess the incidence, risk factors, and outcomes of DPTM at a single nephrology centre over two decades. Methods: This retrospective cohort study included 963 kidney transplant recipients who underwent kidney transplantation between January 2000 and December 2020 and followed up over a median follow-up of 7.1 years (IQR 3.9-11.4). Cox regression models were used to identify the significant risk factors of DPTM development, the association of DPTM with graft survival, and mortality with a functioning graft. Results: In total, 8.1% of transplant recipients developed DPTM, and the DPTM incidence rate was 14.7 per 100 patient-years. There was a higher mean age observed in the DPTM group (53 vs. 47 years, p < 0.001). The most affected organ systems were genitourinary (32.1%), gastrointestinal (24.4%), and lymphoproliferative (20.5%). Multivariate Cox analysis identified older age at transplant (aHR 9.51, 95%CI: 2.60-34.87, p < 0.001) and pre-existing glomerulonephritis (aHR 3.27, 95%CI: 1.10-9.77, p = 0.03) as significant risk factors for DPTM. Older age was significantly associated with poorer graft survival (aHR 8.71, 95%CI: 3.77-20.20, p < 0.001). When age was excluded from the multivariate Cox model, DPTM emerged as a significant risk factor for poor survival (aHR 1.76, 95%CI: 1.17-2.63, p = 0.006). Conclusion: These findings underscore the need for tailored screening, prevention, and management strategies to address DPTM in an aging and immunosuppressed kidney transplant population.

Successful allogeneic human pluripotent stem cell (hPSC)-derived therapies must overcome immunological rejection by the recipient. To build reagents to define these barriers, we genetically ablated β2M, TAP1, CIITA, CD74, MICA, and MICB to limit expression of HLA-I, HLA-II, and natural killer (NK) cell activating ligands in hPSCs. Transplantation of these cells that also expressed covalent single chain trimers of Qa1 and H2-Kb to inhibit NK cells and CD55, Crry, and CD59 to inhibit complement deposition led to persistent teratomas in wild-type mice. Transplantation of HLA-deficient hPSCs into mice genetically deficient in complement and depleted of NK cells also led to persistent teratomas. Thus, T cell, NK cell, and complement evasion are necessary to prevent immunological rejection of hPSCs and their progeny. These cells and versions expressing human orthologs of immune evasion factors can be used to define cell type-specific immune barriers and conduct preclinical testing in immunocompetent mouse models.

BACKGROUND Malignancy after kidney transplantation (MKT) remains a leading cause of death in transplant recipients and over the past few decades there have been many reports on this topic. However, the task of extracting crucial information from intricate events poses a significant challenge in guiding clinical work. Hence, bibliometrics was employed to summarize and predict the future in this study. MATERIAL AND METHODS Reviews and articles on MKT were extracted from the Web of Science Core Collection (WoSCC) and were analyzed by the software VOSviewer, CiteSpace, Scimago Graphica, and R package Bibliometrix for bibliometric analysis. RESULTS The analysis considered 5700 publications from 28 647 authors and 4924 institutions across 100 countries, spanning the years 1970-2022. Reference co-citation analysis showed that "renal cell carcinoma", "skin cancer", "post-transplant lymphoproliferative disorder" and "COVID-19 vaccine" were research hotspots. Keywords that co-occurred early were "immunosuppressant", "cancer", "Epstein-Barr virus", "squamous cell carcinoma", and "infection", etc., while "impact","risk factor", "outcomes", "mortality", "management" frequently co-occurred later. From 2020 to 2022, newly emerging keywords such as "SARS-CoV-2" and "COVID-19", together with citation bursts for "immune checkpoint inhibitors" and "ipilimumab," were observed. CONCLUSIONS The focus of MKT-related studies has evolved from exploring the spectrum, risk factors, and outcomes of MKT, to examining the pathogenesis, individualized screening, prevention, and treatment, including appropriate use of immune checkpoint inhibitors. Reports of renal transplant recipients infected with SARS-CoV-2 or COVID-19 have also gained attention since 2019. These suggest that individualized management remains a frontier for research and a future direction in MKT topics.

Post-transplant lymphoproliferative disorder (PTLD) is one of the most common malignancies affecting solid organ transplant recipients. The disease is frequently associated with Epstein-Barr virus (EBV) infection (70% of cases) and cases are often delineated by EBV positivity status. The oncogenesis of EBV-positive PTLD is well-described in the literature; however, the etiology of the EBV-negative subtype is poorly understood. This report describes a case of EBV-negative PTLD developing in a combined kidney-pancreas transplant recipient with an incidental finding of untreated chronic hepatitis C virus (HCV). Our experience suggests an association between HCV and EBV-negative PTLD. Additional well-designed studies are needed to further investigate this association.

Targeted screening programs for patients at high risk for anal squamous-cell carcinoma have been proposed; however, the evidence in support of screening remains unclear.

This study aimed to determine whether screening high-risk patients (predominantly those living with HIV) detected squamous-cell carcinoma at an earlier stage compared to the routine practice of not screening.

This is a cohort study.

This study was conducted at a quaternary care center in Canada.

Included patients were at least 18 years old with a pathologic diagnosis of invasive anal squamous-cell carcinoma between 2002 and 2022.

Patients diagnosed through a high-risk screening program were compared to those who did not undergo screening.

The primary outcome was clinical stage at presentation, categorized as T1N0M0 vs other. Secondary outcomes included treatments received, treatment failure, and overall survival.

A total of 612 patients with anal squamous-cell carcinoma were included, with 26 of those patients diagnosed through a screening program. Patients with screen-detected cancers had greater odds of presenting with T1N0M0 tumors compared to unscreened patients (18 [69.2%] vs 84 [14.3%]; adjusted OR 9.95; 95% CI, 3.95-25.08). A propensity score-matched sensitivity analysis found similar results (OR 11.13; 95% CI, 4.67-26.52). Screened patients had greater odds of treatment with wide local excision alone, as opposed to any combination of chemotherapy, radiation therapy, and surgery (3 [12.5%] vs 18 [3.2%]; OR 4.38; 95% CI, 1.20-16.04). There were no statistically significant differences in treatment failure or overall survival between groups.

The small number of screened patients limits the power of the analysis.

Screening for anal squamous-cell carcinoma among high-risk populations detects cancers at an earlier stage. Patients with screen-detected cancers also had a greater likelihood of being candidates for wide local excision alone, which may have spared them the morbidity associated with chemoradiotherapy or abdominoperineal resection. See Video Abstract.

ANTECEDENTES:Se han propuesto programas de cribado dirigidos a pacientes con alto riesgo de carcinoma anal de células escamosas; sin embargo, la evidencia a favor de la detección sigue sin estar clara.OBJETIVO:Este estudio tuvo como objetivo determinar si el cribado de pacientes de alto riesgo (predominantemente aquellos que viven con el VIH) detectó el carcinoma de células escamosas en una etapa más temprana en comparación con la práctica habitual de no cribado.DISEÑO:Este es un estudio de cohortes.CONFIGURACIÓN:Este estudio se realizó en un centro de atención cuaternaria en Canadá.PACIENTES:Los pacientes incluidos tenían al menos 18 años con un diagnóstico patológico de carcinoma de células escamosas anal invasivo entre 2002 y 2022.INTERVENCIONES:Los pacientes diagnosticados mediante un programa de cribado de alto riesgo se compararon con aquellos que no se sometieron a cribado.PRINCIPALES MEDIDAS DE RESULTADO:El resultado primario fue el estadio clínico en la presentación, categorizado como T1N0M0 versus otro. Los resultados secundarios incluyeron los tratamientos recibidos, el fracaso del tratamiento y la supervivencia general.RESULTADOS:Se incluyeron un total de 612 pacientes con carcinoma anal de células escamosas, con 26 de esos pacientes diagnosticados a través de un programa de cribado. Los pacientes con cánceres detectados mediante cribado tenían mayores probabilidades de presentar tumores T1N0M0 en comparación con los pacientes no cribados (18 [69.2%] frente a 84 [14.3%]; razón de probabilidad ajustada 9.95; intervalo de confianza del 95 % 3.95 -25.08). Un análisis de sensibilidad emparejado por puntaje de propensión encontró resultados similares (odds ratio 11.13; intervalo de confianza del 95% 4.67 -26.52; p < 0.001). Los pacientes examinados tenían mayores probabilidades de recibir tratamiento con escisión local amplia sola, en comparación con cualquier combinación de quimioterapia, radiación y cirugía (3 [12.5%] frente a 18 [3.2%]; razón de probabilidad 4.38; intervalo de confianza del 95 % 1.20 -16.04). No hubo diferencias estadísticamente significativas en el fracaso del tratamiento o la supervivencia global entre los grupos.LIMITACIONES:El pequeño número de pacientes evaluados limita el poder del análisis.CONCLUSIONES:La detección del carcinoma anal de células escamosas entre las poblaciones de alto riesgo detecta los cánceres en una etapa más temprana. Los pacientes con cánceres detectados mediante cribado también tenían una mayor probabilidad de ser candidatos para una escisión local amplia sola, lo que puede haberles evitado la morbilidad asociada con la quimiorradioterapia o la resección abdominoperineal. (Traducción --Dr. Aurian Garcia Gonzalez ).

Cancer is the second leading cause of death among the adult population following cardiovascular diseases. Prevention and earlier diagnosis are among the cornerstones in the management of malignancies. Albuminuria is a diagnostic criterion for chronic kidney disease and has been associated with multiple conditions including cardiovascular diseases and systemic inflammation while the association between albuminuria and malignancy has been inadequately addressed. Large-scale observational studies with long follow-up periods demonstrate a statistically significant association between albuminuria and overall malignancy incidence, especially urothelial malignancy incidence. However, the underlying pathophysiology linking these two entities is not a straightforward causal relationship but most likely a multidirectional relationship including a causal link. In this narrative review, we evaluate the clinical studies investigating the association between albuminuria and malignancy along with potential underlying mechanisms linking them. We also summarize data on the impact of treatment modalities prescribed for albuminuria and/or proteinuria on the prevention or prognosis of malignancies.

Kidney transplant patients require careful management of immunosuppression to avoid rejection while minimizing the risk of infection and malignancy for the best long-term outcome. The gold standard for monitoring allograft status and immunosuppression adequacy is a kidney biopsy, but this is invasive and costly. Conventional methods of allograft monitoring, such as serum creatinine level, are non-specific. Although they alert physicians to the need to evaluate graft dysfunction, by the time there is a clinical abnormality, allograft damage may have already occurred. The development of novel and non-invasive methods of evaluating allograft status are important to improving graft outcomes. This review summarizes the available conventional and novel methods for monitoring allograft status after kidney transplant. Novel and less invasive methods include gene expression, cell-free DNA, urinary biomarkers, and the use of artificial intelligence. The optimal method to manage patients after kidney transplant is still being investigated. The development of less invasive methods to assess allograft function has the potential to improve patient outcomes and allow for a more personalized approach to immunosuppression management.

The Centers for Disease Control and Prevention sponsored a project conducted by the American College of Obstetricians and Gynecologists to develop educational materials for clinicians on the prevention and early diagnosis of gynecologic cancers. For this final module, focusing on the cancers of the lower anogenital tract (vulva, vagina, and anus), a panel of experts in evidence assessment from the Society for Academic Specialists in General Obstetrics and Gynecology, ASCCP, and the Society of Gynecologic Oncology reviewed relevant literature and current guidelines. Panel members conducted structured literature reviews, which were then reviewed by other panel members. Representatives from stakeholder professional and patient advocacy organizations met virtually in September 2022 to review and provide comment. This article is the executive summary of the review. It covers prevention, early diagnosis, and special considerations of lower anogenital tract cancer. Knowledge gaps are summarized to provide guidance for future research.

Although the association between post-transplant malignancy (PTM) and immunosuppressive therapy after organ transplantation has been studied, an integrated review of PTM after lung transplantation is lacking. We investigated the incidence and types of de novo PTM and its impact on survival following double lung transplantation (DLT). The incidence and type of PTM as well as the annual and cumulative risks of each malignancy after DLT were analyzed. The overall survival (OS) of recipients with or without PTM was compared by the Kaplan-Meier survival method and landmark analysis. There were 5,629 cases (23.52%) with 27 types of PTMs and incidences and OS varied according to the types of PTMs. The recipients with PTM showed a significantly longer OS than those without PTM (p < 0.001). However, while the recipients with PTM showed significantly better OS at 3, and 5 years (p < 0.001, p = 0.007), it was worse at the 10-year landmark time (p = 0.013). And the single PTM group showed a worse OS rate than the multiple PTM group (p < 0.001). This comprehensive report on PTM following DLT can help understand the risks and timing of PTM to improve the implementation of screening and treatment.

A relative lack of molecular and clinical studies compared to other lymphoid cancers has historically made it difficult to determine optimal management approaches in post-transplant lymphoproliferative disorder (PTLD). We sought to better define the "state of the science" in PTLD by examining recent advances in risk assessment, genomic profiling, and trials of PTLD-directed therapy.

Several major clinical trials highlight risk-stratified sequential therapy incorporating rituximab with or without chemotherapy as a rational treatment strategy in patients with CD20+ PTLD who do not respond to reduction of immunosuppression alone. Epstein Barr virus (EBV)-targeted cytotoxic lymphocytes are a promising approach in patients with relapsed/refractory EBV+ PTLD, but dedicated clinical trials should determine how autologous chimeric antigen receptor T cell therapy (CAR-T) may be safely administered to PTLD patients. Sequencing studies underscore the important effect of EBV infection on PTLD pathogenesis, but comprehensive genomic and tumor microenvironment profiling are needed to identify biomarkers that predict response to treatment in this clinically heterogeneous disease.

Actinic keratoses and cutaneous squamous cell carcinomas are associated with infections with human papillomavirus of genus beta (betaHPV) in immunosuppressed patients. To date, targeted therapy against betaHPV-associated skin cancer does not exist because of the large number of betaHPV without defined high-risk types. In this study, we hypothesized that the activation of innate antiviral immunity in the skin, asymptomatically infected with betaHPV, induces an antitumor response by in situ autovaccination and prevents the formation of betaHPV-associated skin cancer. To test this, we used the preclinical keratin-14-HPV8 transgenic mouse model, which develops skin tumors after mechanical wounding. Remarkably, treatment with the antiviral immune response activating polyinosinic-polycytidylic acid (poly[I:C]) completely prevented cutaneous tumor growth. The induction of the IFN-induced genes Cxcl10 and Ifit1 by poly(I:C) depended on MDA5 activation. Increased numbers of total and activated CD4 and CD8 T cells were detected in poly(I:C)-treated skin. T cells were found in the skin of poly(I:C)-treated mice but not in the skin tumors of untreated mice. T-cell depletion showed a predominant role of CD4 T cells in poly(I:C)-mediated tumor prevention. Our findings identify the MDA5 ligand poly(I:C) as a promising candidate for in situ autovaccination approaches, which might serve as a treatment strategy against betaHPV-related skin diseases.

We conducted this review to offer a comprehensive search and up-to-date overview of the currently available information about the probability risk of colorectal cancer among chronic kidney disease patients.

We performed a systematic review and meta-analysis following Preferred Reporting Items for Systematic Reviews (PRISMA) and meta-analysis guidelines. We identified, reviewed, and extracted from Scopus, PubMed, EMBASE, and Komaki Databases for research publications on chronic kidney disease and colorectal cancer published between February 2016 and January 2023. We meta-analyzed the prevalence of colorectal cancer with chronic kidney disease. We ran a random effect meta-regression. Risk-of-bias assessment was evaluated using the Newcastle-Ottawa Scale. The systematic review was registered with PROSPERO (CRD42023400983).

The risk of CRC in chronic kidney diseases was reported in 50 research studies, which included 4,337,966 people from 16 different countries. SIR of CRC was obtained from 14 studies and showed a significant relationship between CRC with CKD patients, with a pooled SIR of 1.33; 95% CI (1.30-1.36), with higher heterogeneity (Q = 121.82, P < 0.001, and I2 = 86.9%). Metaregression showed that there was no significant correlation between the risk of CRC and the proportion of males or age.

Overall, this study shows that patients with chronic kidney disease have a significantly increased risk of colorectal cancer. More studies with larger sample sizes, and robust surveillance are needed.

The success of solid organ transplant has steadily improved which has led to a unique set of post-transplant issues. The rates of de novo cancer in the solid organ transplant recipient population are higher than those in the general population. There is growing evidence that breast and gynecologic cancers may have a higher mortality rate in post-transplant patients. Cervical and vulvovaginal cancers specifically have a significantly higher mortality in this population. Despite this increased mortality risk, there is currently no consistent standard in screening and identifying these cancers in post-transplant patients. Breast, ovarian and endometrial cancers do not appear to have significantly increased incidence. However, the data on these cancers remains limited. Further studies are needed to determine if more aggressive screening strategies would be of benefit for these cancers. Here we review the cancer incidence, mortality risk and current screening methods associated with breast and gynecologic cancers in the post-solid organ transplant population.

Photosensitizing properties of hydrochlorothiazide may increase skin cancer risk. To date, study findings on the association between hydrochlorothiazide use and skin cancer risk are inconsistent, notably regarding confounding and dose-response. The aim of this study was to investigate the association between hydrochlorothiazide use and incidence of skin cancer in a cohort of unselected Caucasian adults, taking dosing into account. As part of the PharmLines Initiative, which links data from the Lifelines Cohort Study and prescription database IADB.nl, patients aged ≥ 40 years were included from Lifelines, a prospective population-based cohort study in the north of the Netherlands. Skin cancer incidence was compared between subjects starting hydrochlorothiazide treatment (n = 608), subjects starting treatment with other antihypertensives (n = 508), and non-antihypertensive long-term medication users (n = 1,710). Cox regression analyses were performed to obtain hazard ratios, adjusted for potential confounders. The risk of any skin cancer, keratinocyte carcinoma, basal cell carcinoma and squamous cell carcinoma was not significantly increased in general hydrochlorothiazide users. A clear association was observed between high cumulative hydrochlorothiazide use (≥ 5,000 defined daily dose; ≥ 125,000 mg) and the risk of any skin cancer (adjusted hazard ratio 5.32, 95% confidence interval (95% CI) 2.40-11.81), keratinocyte carcinoma (adjusted hazard ratio 7.31, 95% CI 3.12-17.13), basal cell carcinoma (adjusted hazard ratio 7.72, 95% CI 3.11-19.16) and squamous cell carcinoma (adjusted hazard ratio 19.63, 95% CI 3.12-123.56). These findings should lead to awareness with high use of hydrochlorothiazide in Caucasian adults.

To provide a narrative review of anogenital screening for human papillomavirus in solid organ transplant recipients.

Keyword searches of PubMed and Ovid MEDLINE databases were performed. Keywords included human papillomavirus, malignancy, cervical cancer, Pap smear, solid organ transplant, and immunosuppression. Manual searches were also conducted of other relevant journals and reference lists of primary articles.

Forty-one studies, articles, or clinical practice guidelines across 25 years of literature were included. Eligible literature was written in English or offered an English translation.

Human papillomavirus-related anogenital malignancies disproportionately affect transplant recipients compared to the general population. Evidence-based guidelines for cervical cancer screening and prevention in transplant patients are lacking. Current practice guidelines generally agree on increased Pap screening for transplant recipients compared to the general population. However, recommended screening frequency differs between organizations and amongst medical specialties. Vaccination against HPV remains the most effective strategy to prevent HPV-driven pre-malignant and malignant lesions.

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.

There is a growing need to better understand the risk of malignancy in the multiple sclerosis (MS) population, particularly given the relatively recent and widespread introduction of immunomodulating disease modifying therapies (DMTs). Multiple sclerosis disproportionately affects women, and the risk of gynecological malignancies, specifically cervical pre-cancer and cancer, are of particular concern. The causal relationship between persistent human papillomavirus (HPV) infection and cervical cancer has been definitively established. To date, there is limited data on the effect of MS DMTs on the risk of persistent HPV infection and subsequent progression to cervical pre-cancer and cancer. This review evaluates the risk of cervical pre-cancer and cancer in women with MS, including the risk conferred by DMTs. We examine additional factors, specific to the MS population, that alter the risk of developing cervical cancer including participation in HPV vaccination and cervical screening programs.

Immune-mediated hypersensitivities such as autoimmunity, allergy, and allogeneic graft rejection are treated with therapeutics that suppress the immune system, and the lack of specificity is associated with significant side effects. The delivery of disease-relevant antigens (Ags) by carrier systems such as poly(lactide-co-glycolide) nanoparticles (PLG-Ag) and carbodiimide (ECDI)-fixed splenocytes (SP-Ag) has demonstrated Ag-specific tolerance induction in model systems of these diseases. Despite therapeutic outcomes by both platforms, tolerance is conferred with different efficacy. This investigation evaluated Ag loading and total particle dose of PLG-Ag on Ag presentation in a coculture system of dendritic cells (DCs) and Ag-restricted T cells, with SP-Ag employed as a control. CD25 expression was observed in nearly all T cells even at low concentrations of PLG-Ag, indicating efficient presentation of Ag by dendritic cells. However, the secretion of IL-2, Th1, and Th2 cytokines (IFNγ and IL-4, respectively) varied depending on PLG-Ag concentration and Ag loading. Concentration escalation of soluble Ag resulted in an increase in IL-2 and IFNγ and a decrease in IL-4. Treatment with PLG-Ag followed a similar trend but with lower levels of IL-2 and IFNγ secreted. Transcriptional Activity CEll ARrays (TRACER) were employed to measure the real-time transcription factor (TF) activity in Ag-presenting DCs. The kinetics and magnitude of TF activity was dependent on the Ag delivery method, concentration, and Ag loading. Ag positively regulated IRF1 activity and, as carriers, NPs and ECDI-treated SP negatively regulated this signaling. The effect of Ag loading and dose on tolerance induction were corroborated in vivo using the delayed-type hypersensitivity (DTH) and experimental autoimmune encephalomyelitis (EAE) mouse models where a threshold of 8 μg/mg Ag loading and 0.5 mg PLG-Ag dose were required for tolerance. Together, the effect of Ag loading and dosing on in vitro and in vivo immune regulation provide useful insights for translating Ag-carrier systems for the clinical treatment of immune disorders.

During the last four decades, development of effective immunosuppressants has significantly improved short-term results of organ transplantation. However, long-term results have not been satisfactory due to chronic rejection or complications caused by immunosuppressive drugs. Therefore, induction of immunological tolerance of the transplanted organ is considered essential to improve the long-term results. Despite numerous tolerance strategies that have been successful in murine models, inducing hematopoietic chimerism through donor hematopoietic stem cell transplantation is the only method that reproducibly induces kidney allograft tolerance in nonhuman primates or humans. Combining kidney and hematopoietic stem cell transplantation to achieve allograft tolerance has now been attempted with different chimerism strategies. This review summarizes the status of current clinical trials on the induction of allograft tolerance. We also summarize recent studies to extend the chimerism approach to deceased donor transplant recipients.

PTLD is a rare but severe complication of hematopoietic or solid organ transplant recipients, with variable incidence and timing of occurrence depending on different patient-, therapy-, and transplant-related factors. The pathogenesis of PTLD is complex, with most cases of early PLTD having a strong association with Epstein-Barr virus (EBV) infection and the iatrogenic, immunosuppression-related decrease in T-cell immune surveillance. Without appropriate T-cell response, EBV-infected B cells persist and proliferate, resulting in malignant transformation. Classification is based on the histologic subtype and ranges from nondestructive hyperplasias to monoclonal aggressive lymphomas, with the most common subtype being diffuse large B-cell lymphoma-like PTLD. Management focuses on prevention of PTLD development, as well as therapy for active disease. Treatment is largely based on the histologic subtype. However, given lack of clinical trials providing evidence-based data on PLTD therapy-related outcomes, there are no specific management guidelines. In this review, we discuss the pathogenesis, histologic classification, and risk factors of PTLD. We further focus on common preventive and frontline treatment modalities, as well as describe the application of novel therapies for PLTD and elaborate on potential challenges in therapy.

Several infections can predispose to certain malignancies in different body parts. These infections include viral, bacterial, and fungal pathogens. Imaging plays a vital role in the diagnosis, staging, and management of these neoplastic conditions. Furthermore, it can help in differentiating infection-related non-neoplastic processes that can mimic malignancies. Both radiologists and clinicians should be familiar with these conditions. This review discusses the epidemiology, pathogenesis, and imaging features of infection-related tumors.