Radiology of fibrosis part III: genitourinary system.

Fibrosis is a pathological process involving the abnormal deposition of connective tissue, resulting from improper tissue repair in response to sustained injury caused by hypoxia, infection, or physical damage. It can impact any organ, leading to their dysfunction and eventual failure. Additionally, tissue fibrosis plays an important role in carcinogenesis and the progression of cancer.Early and accurate diagnosis of organ fibrosis, coupled with regular surveillance, is essential for timely disease-modifying interventions, ultimately reducing mortality and enhancing quality of life. While extensive research has already been carried out on the topics of aberrant wound healing and fibrogenesis, we lack a thorough understanding of how their relationship reveals itself through modern imaging techniques.This paper focuses on fibrosis of the genito-urinary system, detailing relevant imaging technologies used for its detection and exploring future directions.

Clinical outcome in metastatic prostate cancer after primary radiotherapy.

PURPOSE: To describe a local radio-oncological treatment for patients with prostate cancer that metastasized to either the lymph nodes or distant regions. METHODS AND MATERIALS: We included 133 patients with prostate cancer that displayed either distant metastases (DM) or lymph node metastases alone (NM) and were treated between 2004 and 2019. All patients underwent computed tomography and a bone scan or 18F- or prostate-specific membrane antigen-targeted positron emission tomography. Patients received local external beam radiation therapy to the prostate to achieve local control (60-81.4 Gy to the prostate, and 45-50.4 Gy to pelvic lymph nodes), with either the 3D conformal (4-field box) or volumetric modulated arc therapy technique. A urologist prescribed additional therapy. RESULTS: We included 51 patients with DM and 82 patients with NM. The mean follow-up was 42 months for all patients. The groups were similar in T stage, initial prostate-specific antigen, histology, androgen deprivation therapy, age, treatment techniques, and prescribed doses, but different in lymph node inclusion and follow-up times. In the NM and DM groups, the 5­year biochemical recurrence-free rates were 52% and 24%, respectively (p < 0.0001); the 5­year disease-specific survival rates were 92% and 61%, respectively (p = 0.001); and the 5­year OS rates were 77% and 48%, respectively (p = 0.01). The groups had similar acute and late gastrointestinal and genitourinary side effects, except that late genitourinary side effects occurred significantly more frequently in the NM group (p = 0.01). CONCLUSIONS: DM was associated with significantly worse outcomes than NM. The long-term survival of patients with metastatic prostate cancer was low.

In sickness and in health: The functional role of extracellular vesicles in physiology and pathology in vivo: Part II: Pathology: Part II: Pathology.

It is clear from Part I of this series that extracellular vesicles (EVs) play a critical role in maintaining the homeostasis of most, if not all, normal physiological systems. However, the majority of our knowledge about EV signalling has come from studying them in disease. Indeed, EVs have consistently been associated with propagating disease pathophysiology. The analysis of EVs in biofluids, obtained in the clinic, has been an essential of the work to improve our understanding of their role in disease. However, to interfere with EV signalling for therapeutic gain, a more fundamental understanding of the mechanisms by which they contribute to pathogenic processes is required. Only by discovering how the EV populations in different biofluids change-size, number, and physicochemical composition-in clinical samples, may we then begin to unravel their functional roles in translational models in vitro and in vivo, which can then feedback to the clinic. In Part II of this review series, the functional role of EVs in pathology and disease will be discussed, with a focus on in vivo evidence and their potential to be used as both biomarkers and points of therapeutic intervention.

Prospective validation of stringent dose constraints for prostatic stereotactic radiation monotherapy: results of a single-arm phase II toxicity-oriented trial.

PURPOSE: There are no safety-focused trials on stereotactic body radiotherapy (SBRT) for localized prostate cancer. This prospective 3­year phase II trial used binomial law to validate the safety and efficacy of SBRT with stringent organ at risk dose constraints that nevertheless permitted high planning target volume doses. METHODS: All consecutive ≥ 70-year-old patients with localized prostate adenocarcinoma who underwent SBRT between 2014 and 2018 at the National Radiotherapy Center in Luxembourg were included. Patients with low Cancer of Prostate Risk Assessment (CAPRA) scores (0-2) and intermediate scores (3-5) received 36.25 Gy. High-risk (6-10) patients received 37.5 Gy. Radiation was delivered in 5 fractions over 9 days with Cyberknife-M6™ (Accuray, Sunnyvale, CA, USA). Primary study outcome was Common Terminology Criteria for Adverse Events version 4 (CTCAEv4) genitourinary and rectal toxicity scores at last follow-up. Based on binomial law, SRBT was considered safe in this cohort of 110 patients if there were ≤ 2 severe toxicity (CTCAEv4 grade ≥ 3) cases. Secondary outcomes were biochemical progression-free survival (bPFS) and patient quality of life (QOL), as determined by the IPPS and the Urinary Incontinence QOL questionnaire. RESULTS: The first 110 patients who were accrued in a total cohort of 150 patients were included in this study and had a median follow-up of 36 months. Acute grade ≥ 3 toxicity never occurred. One transient late grade 3 case was observed. Thus, our SBRT program had an estimated severe toxicity rate of < 5% and was safe at the p < 0.05 level. Overall bPFS was 90%. QOL did not change relative to baseline. CONCLUSION: The trial validated our SBRT regimen since it was both safe and effective.

Primary Amyloidosis of the Genitourinary Tract.

CONTEXT.­: Amyloidosis is caused by the deposition of misfolded proteins as insoluble eosinophilic material in the extracellular tissues of the body, leading to impairment of organ function. It can be systemic or localized. Localized genitourinary tract amyloidosis is rare and can be incidentally seen; however, in some cases, it can be the only presenting disease. OBJECTIVE.­: To review the clinical presentation and pathologic findings related to primary amyloidosis of the urogenital system and highlight some of the associated pathologic findings based on our personal experience. DATA SOURCES.­: Published peer-reviewed literature and personal experience of the senior author. CONCLUSIONS.­: Primary localized amyloidosis within the urogenital tract can present as a neoplastic process and may be clinically and radiologically considered as a mass. Awareness of primary amyloidosis by pathologists and clinicians is required for accurate diagnosis and proper patient management.

Practical Molecular Testing in a Clinical Genitourinary Service.

CONTEXT.­: Molecular testing is increasingly playing a key role in the diagnosis, prognosis, and treatment of neoplasms of the genitourinary system. OBJECTIVE.­: To provide a general overview of the clinically relevant molecular tests available for neoplasms of the genitourinary tract. DATA SOURCES.­: Relevant medical literature indexed on PubMed. CONCLUSIONS.­: Understanding of the molecular oncology of genitourinary neoplasms is rapidly advancing, and the pathologist must be aware of the practical implications of molecular testing. While many genomic abnormalities are not yet clinically relevant, there is an increasing library of ancillary tests that may guide diagnosis, prognosis, and/or treatment of many neoplasms. Recurrent genomic abnormalities have been identified in many types of renal cell carcinoma, and some types of renal cell carcinoma are specifically defined by the molecular abnormality. Two major routes of developing urothelial carcinoma have been molecularly described. Recurrent translocations involving ETS family genes are found in approximately half of prostate cancer cases. Testicular germ cell tumors typically harbor i(12p). Penile neoplasms are often high-risk human papillomavirus-driven cancers. Nonetheless, even as genitourinary neoplasms are increasingly better understood at the molecular level, further research with eventual clinical validation is needed for optimal diagnosis, prognosis, and treatment of aggressive malignancies in the genitourinary tract.

Effects of secondary biological treatment plant effluent administration, as drinking water, to rats' urogenital system in relation to cadmium and lead accumulation.

The aim of this study was to examine the effect of the secondary biological treatment plant effluent administration on the kidneys, urinary bladder, and testis of Wistar rats in relation to lead (Pb) and cadmium (Cd) accumulation, since such an effluent is used for irrigation of edible plants. Male Wistar rats, randomly assigned into 5 groups, were treated with domestic sewage effluent (DSE) for 24 months. Cadmium and lead concentrations in the DSE, rats' tissues, and urine were estimated by means of atomic spectroscopy. Lead was rapidly accumulated in high amounts in rats' kidney and to a lesser extent in the testis whereas Cd concentration was raised in all tissues examined. Deposition of Cd and Pd in the kidney of the rats resulted in profound damage over time. The results showed that long-term administration to DSE as drinking water exposes living organisms to urogenital stress related to heavy metal concentration and pH of the effluent.

Overall systematic approach to sepsis damages on urogenital tissues: protective power of lacosamide.

PURPOSE: The aim of the study was to evaluate the harmful effects of sepsis on the urogynecological tissues and the ability of Lacosamide (LCM) on Lipopolysaccharide (LPS)-induced cytokine production, oxidative stress and apoptotic pathways, in the experimental rat sepsis model. METHODS: Twenty-four female Wistar albino rats (12 months old) were divided into 3 groups as follows: control group (Group I) (0.1 ml/oral and i.p. saline, single dose), sepsis group (Group II) (5 mg/kg LPS, i.p. single dose) and sepsis + LCM group (Group III) (5 mg/kg LPS, i.p. single dose and 40 mg/kg LCM). Six hours after the last LPS administration, the animals were sacrificed. Subsequently, the analyses of urogenital tissues total oxidant/antioxidant status, histopathological and immunohistochemical analyses were performed. RESULTS: Total oxidant capacity (TOC) and oxidative stress index (OSI) values in the urogenital tissues were increased in the urogenital tissues in Group II [Total antioxidant capacity (TAC) was decreased] compared to group I (p < 0.05). LCM improved these values (p < 0.05). The immunohistochemical markers (Tumor Necrosis Factor-alpha (TNF-α), interleukin-1 beta (IL-1ß), heat shock protein 70 (HSP-70), C-reactive protein (CRP), Malondialdehyde (MDA) were significantly increased in Group II (p < 0.001). With the administration of LCM (Group III), the expressions of above-mentioned markers were markedly decreased (p < 0.001). Marked hyperemia and slight hemorrhages with neutrophil leukocyte infiltrations were seen histopathologically in Group II. LCM treatment ameliorated the pathological findings. CONCLUSION: These findings demonstrated that sepsis caused oxidative stress, apoptosis and inflammation in the urogenital tissues. We revealed that LCM ameliorated the damage caused by sepsis in urogenital tissue.

Topical estrogen prescribing patterns for urogenital atrophy among women with breast cancer: results of a national provider survey.

OBJECTIVE: The aim of the study was to evaluate knowledge, attitudes, and practice patterns of physicians prescribing topical estrogen for women with urogenital atrophy and a history of breast cancer. METHODS: A cross-sectional survey of breast surgeons, urogynecologists, and gynecologists was distributed via their professional societies: the American Society of Breast Surgeons (ASBrS), the American Urogynecologic Society (AUGS), and the Society of Gynecologic Surgeons (SGS). Providers reported level of comfort prescribing vaginal estrogen for urogenital symptoms for women with different categories of breast cancer and current treatment: estrogen receptor (ER) negative, ER positive no longer on endocrine therapy, and ER positive currently on adjuvant endocrine therapy. General knowledge questions assessed agreement on a 5-point Likert scale to statements about vaginal estrogen safety and pharmacology. RESULTS: A total of 820 physicians completed the survey: 437 responses from the ASBrS (response rate, 26.7%), 196 from AUGS (15%), and 187 from SGS (44.5%). The majority of physicians (84%), regardless of specialty, felt comfortable prescribing vaginal estrogen to women with a history of ER-negative cancer: 65.7% felt comfortable prescribing for women with ER-positive breast cancer no longer on endocrine therapy; 51.3% for women on an aromatase inhibitor; and 31.4% for women on tamoxifen. Urogynecologists were significantly more comfortable than breast surgeons prescribing vaginal estrogen for the lowest risk patients, whereas breast surgeons had the highest level of comfort for women currently on endocrine therapy. CONCLUSIONS: This study highlights heterogeneity in practice patterns both within and across specialties. The clinical variation seen in this study suggests providers may benefit from increased knowledge regarding vaginal estrogen.

Impact of bladder volume on acute genitourinary toxicity in intensity modulated radiotherapy for localized and locally advanced prostate cancer.

BACKGROUND AND PURPOSE: To evaluate the effect of changes in bladder volume during high-dose intensity-modulated-radiotherapy (IMRT) of prostate cancer on acute genitourinary (GU) toxicity and prospectively evaluate a simple biofeedback technique for reproducible bladder filling with the aim of reducing acute GU toxicity. METHODS: One hundred ninety-three patients were trained via a biofeedback mechanism to maintain a partially filled bladder with a reproducible volume of 200-300 cc at planning CT and subsequently at each fraction of radiotherapy. We prospectively analyzed whether and to what extent the patients' ability to maintain a certain bladder filling influenced the degree of acute GU toxicity and whether cut-off values could be differentiated. RESULTS: We demonstrated that the ability to reach a reproducible bladder volume above a threshold volume of 180 cc and maintain that volume via biofeedback throughout treatment predicts for a decrease in acute GU toxicity during curative high-dose IMRT of the prostate. Patients who were not able to reach a partial bladder filling to that cut-off value and were not able to maintain a partially filled bladder throughout treatment had a significantly higher risk of developing ≥grade 2 GU acute toxicity. CONCLUSION: Our results support the hypothesis that a biofeedback training for the patient is an easy-to-apply, useful, and cost-effective tool for reducing acute GU toxicity in high-dose IMRT of the prostate. Patients who are not able to reach and maintain a certain bladder volume during planning and treatment-two independent risk factors-might need special consideration.

Comparison of rRNA-based and DNA-based nucleic acid amplifications for detection of Chlamydia trachomatis, Neisseria gonorrhoeae, and Ureaplasma urealyticum in urogenital swabs.

BACKGROUND: Nucleic acid amplification tests (NAAT) are well-accepted in diagnosis and surveillance of sexually infectious pathogens worldwide. However, performance differences between a RNA-based NAAT and DNA-based NAAT are rarely reported. This study compares the performances of the RNA-based SAT (simultaneous amplification and testing) assay and the DNA-based quantitative real-time polymerase chain reaction (qPCR) assay. METHODS: A total of 123 urogenital swabs were collected from outpatients with suspected genital infections in our hospital. Chlamydia trachomatis (CT), Neisseria gonorrhoeae (NG), and Ureaplasma urealyticum (UU) in these swabs were simultaneously tested by SAT and qPCR. Any swabs were positive in the qPCR assay were further verified by following cloning and sequencing. All statistical analysis was performed using the SPSS software. RESULTS: When the concentrations of CT, NG, or UU were more than 1 × 103 copies/ml, 100% agreements between SAT and qPCR were observed regardless of the pathogen. No discrepancy was found. However, the sensitivity of SAT is significantly higher than qPCR in samples with concentration less than 1 × 103 copies/ml. When tested by SAT and qPCR, 57.14 and 28.57% were positive for CT, 46.15% and 0 were positive for NG, 80% and 0 were positive for UU, respectively. CONCLUSIONS: The SAT assay has better agreements and higher sensitivities when compared with the qPCR assay, and thus could be a better choice for screening, diagnosis, and surveillance of sexually transmitted diseases, especially for CT and NG.

Impact on genitourinary function and quality of life following focal irreversible electroporation of different prostate segments.

PURPOSE: We aimed to evaluate the genitourinary function and quality of life (QoL) following the ablation of different prostate segments with irreversible electroporation (IRE) for localized prostate cancer (PCa). METHODS: Sixty patients who received primary focal IRE for organ-confined PCa were recruited for this study. Patients were evaluated for genitourinary function and QoL per prostate segment treated (anterior vs. posterior, apex vs. base vs. apex-to-base, unilateral vs. bilateral). IRE system settings and patient characteristics were compared between patients with preserved vs. those with impaired erectile function and urinary continence. Data were prospectively collected at baseline, 3, 6, and 12 months using the expanded prostate cancer index composite, American Urological Association symptom score, SF-12 physical and mental component summary surveys. Difference over time within segments per questionnaire was evaluated using the Wilcoxon's signed rank test. Outcome differences between segments were assessed using covariance models. Baseline measurements included questionnaire scores, age, and prostate volume. RESULTS: There were no statistically significant changes over time for overall urinary (P = 0.07-0.89), bowel (P = 0.06-0.79), physical (P = 0.18-0.71) and mental (P = 0.45-0.94) QoL scores within each segment. Deterioration of sexual function scores was observed at 6 months within each segment (P = 0.001-0.16). There were no statistically significant differences in QoL scores between prostate segments (P = 0.08-0.97). Older patients or those with poor baseline sexual function at time of treatment were associated with a greater risk of developing erectile dysfunction. CONCLUSION: IRE is a feasible modality for all prostate segments without any significantly different effect on the QoL outcomes. Older patients and those with poor sexual function need to be counseled regarding the risk of erectile dysfunction.

[MORPHOLOGICAL CHANGES OF THE UROGENITAL SYSTEM INTERNAL STRUCTURE AT MODELING OF PORTAL HYPERTENSION IN RATS].

Portal hypertension is a constant companion of numerous diseases in gastroenterology, vascular surgery, cardiology, and hematology with grave consequences for the health and life of patients. The development of portal hypertension leads to significant violations of hemodynamics in the liver vessels and the development of arterial and venous hypertrophy, stasis of blood in the vessels of the portal tract. In the experiment on rats, portal hypertension was simulated in an original way with the following study of the peculiarities of morphological changes in the internal structure of the kidneys and gonads in males as a manifestation of a violation of systemic hemodynamics. The decrease of the renal artery throughput in portal hypertension, dystrophic changes in the epithelium against the background of venous congestion, paravazal polymorphocytic infiltration and proliferation of the connective tissue have been identified.

Diagnosis of congenital and acquired focal lesions in the neck, abdomen, and pelvis with contrast-enhanced ultrasound: a pictorial essay.

Contrast-enhanced ultrasound (CEUS) is a versatile imaging modality that improves the diagnostic potential of conventional ultrasound. It allows for portable imaging at the bedside. In this paper, we illustrate how CEUS can be used in evaluating several focal lesions in the pediatric population, including liver hemangioma, telangiectasias, splenic hamartomas, and bladder lesions. We describe the ultrasound findings and contrast enhancement patterns associated with these lesions. Findings are correlated with MRI, CT, and/or pathology when available. This paper demonstrates the value of CEUS in improving characterization of many focal lesions in the pediatric population. CONCLUSION: CEUS is a valuable bedside technique for use in the pediatric population to evaluate focal lesions in various organs, and will allow for safe, more efficient diagnostic imaging. What is Known: • CEUS offers many advantages over CT and MRI and is underutilized in the United States. • It is only FDA approved for vesicoureteral reflux and liver in the pediatric population. However, off label uses are well described. What is New: • This pictorial essay describes ultrasound findings and contrast enhancement patterns associated with liver hemangioma, liver telangiectasia, splenic hamartoma, hemorrhagic ovarian cyst, urachal remnant, spinning top urethras, and kaposiform hemangioendothelioma. • We demonstrate the utility of CEUS in expanding the diagnostic potential of conventional ultrasound.

Prediction of acute gastrointestinal and genitourinary radiation toxicity in prostate cancer patients using lymphocyte microRNA.

BACKGROUND: To search for novel biomarkers that can predict acute radiation toxicity, we conducted microRNA expression analysis of peripheral blood lymphocytes (PBLs). METHODS: The discovery cohort was 69 patients with localized adenocarcinoma of the prostate who received intensity-modulated radiation therapy between October 2007 and October 2010. The validation cohort was 72 patients treated with low-dose-rate brachytherapy between May 2008 and March 2014. After13 microRNAs were selected by TaqMan® Array analysis in a preliminary experiment, expression of these microRNAs in all samples was analyzed by RT-PCR. RESULTS: In the discovery cohort, the average prostate volume, the rectal volume receiving 70 Gy, and expression of miR-410 and miR-221 were significant risk factors for Grade 1-2 gastrointestinal toxicity. Receiver operating characteristic analysis showed that the area under the curve (AUC) was 0.807. The maximum dose to the urinary bladder, prostate volume, pretreatment urinary function score, and miR-99a and miR-221 expression were risk factors for Grade 2 genitourinary toxicity. The corresponding AUC was 0.796. In the validation cohort, reproducibility of these markers was confirmed for gastrointestinal toxicity, but not for genitourinary toxicity. CONCLUSION: Combining radiation dose parameters with microRNA expression in PBLs may be useful for predicting acute gastrointestinal toxicity of radiation therapy, thus contributing to personalized treatment of prostate cancer.

Pathological findings in the red fox (Vulpes vulpes), stone marten (Martes foina) and raccoon dog (Nyctereutes procyonoides), with special emphasis on infectious and zoonotic agents in Northern Germany.

Anthropogenic landscape changes contributed to the reduction of availability of habitats to wild animals. Hence, the presence of wild terrestrial carnivores in urban and peri-urban sites has increased considerably over the years implying an increased risk of interspecies spillover of infectious diseases and the transmission of zoonoses. The present study provides a detailed characterisation of the health status of the red fox (Vulpes vulpes), stone marten (Martes foina) and raccoon dog (Nyctereutes procyonoides) in their natural rural and peri-urban habitats in Schleswig-Holstein, Germany between November 2013 and January 2016 with focus on zoonoses and infectious diseases that are potentially threatening to other wildlife or domestic animal species. 79 red foxes, 17 stone martens and 10 raccoon dogs were collected from traps or hunts. In order to detect morphological changes and potential infectious diseases, necropsy and pathohistological work-up was performed. Additionally, in selected animals immunohistochemistry (influenza A virus, parvovirus, feline leukemia virus, Borna disease virus, tick-borne encephalitis, canine adenovirus, Neospora caninum, Toxoplasma gondii and Listeria monocytogenes), next-generation sequencing, polymerase chain reaction (fox circovirus) and serum-neutralisation analysis (canine distemper virus) were performed. Furthermore, all animals were screened for fox rabies virus (immunofluorescence), canine distemper virus (immunohistochemistry) and Aujeszky's disease (virus cultivation). The most important findings included encephalitis (n = 16) and pneumonia (n = 20). None of the investigations revealed a specific cause for the observed morphological alterations except for one animal with an elevated serum titer of 1:160 for canine distemper. Animals displayed macroscopically and/or histopathologically detectable infections with parasites, including Taenia sp., Toxocara sp. and Alaria alata. In summary, wildlife predators carry zoonotic parasitic disease and suffer from inflammatory diseases of yet unknown etiology, possibly bearing infectious potential for other animal species and humans. This study highlights the value of monitoring terrestrial wildlife following the "One Health" notion, to estimate the incidence and the possible spread of zoonotic pathogens and to avoid animal to animal spillover as well as transmission to humans.

Diagnosing Urogenital Schistosomiasis: Dealing with Diminishing Returns.

Urogenital schistosomiasis, caused by Schistosoma haematobium, is the most prevalent form of schistosomiasis affecting humans, and can result in severe bladder, kidney, ureteral, and genital pathologies. Chronic infection with S. haematobium has been linked with bladder cancer and increased risk for HIV infection. As mass drug administration with praziquantel increases in an attempt to transition from control to elimination of schistosomiasis, the need for updated, more sensitive diagnostic tools becomes more apparent, especially for use in areas of low infection intensity and for individuals with light infections. Here, we review established and investigational diagnostic tests utilized for urogenital schistosomiasis, highlighting new insights and recent advances.

Intravaginal Chlamydia trachomatis Challenge Infection Elicits TH1 and TH17 Immune Responses in Mice That Promote Pathogen Clearance and Genital Tract Damage.

While ascension of Chlamydia trachomatis into the upper genital tract of women can cause pelvic inflammatory disease and Fallopian tube damage, most infections elicit no symptoms or overt upper genital tract pathology. Consistent with this asymptomatic clinical presentation, genital C. trachomatis infection of women generates robust TH2 immunity. As an animal model that modeled this response would be invaluable for delineating bacterial pathogenesis and human host defenses, herein we explored if pathogen-specific TH2 immunity is similarly elicited by intravaginal (ivag) infection of mice with oculogenital C. trachomatis serovars. Analogous to clinical infection, ascension of primary C. trachomatis infection into the mouse upper genital tract produced no obvious tissue damage. Clearance of ivag challenge infection was mediated by interferon (IFN)-γ-producing CD4+ T cells, while IFN-γ signaling blockade concomitant with a single ivag challenge promoted tissue damage by enhancing Chlamydia-specific TH17 immunity. Likewise, IFN-γ and IL-17 signaling blockade or CD4+ T cell depletion eliminated the genital pathology produced in untreated controls by multiple ivag challenge infections. Conversely, we were unable to detect formation of pathogen-specific TH2 immunity in C. trachomatis-infected mice. Together, our work revealed C. trachomatis infection of mice generates TH1 and TH17 immune responses that promote pathogen clearance and immunopathological tissue damage. Absence of Chlamydia-specific TH2 immunity in these mice newly highlights the need to identify experimental models of C. trachomatis genital infection that more closely recapitulate the human host response.

Genital invasion or perigenital spread may pose a risk of marginal misses for Intensity Modulated Radiotherapy (IMRT) in anal cancer.

BACKGROUND: While intensity modulated radiotherapy (IMRT) in anal cancer is feasible and improves high-dose conformality, the current RTOG/AGITG contouring atlas and planning guidelines lack specific instructions on how to proceed with external genitalia. Meanwhile, the RTOG-Protocol 0529 explicitly recommends genital sparing on the basis of specific genital dose constraints. Recent pattern-of-relapse studies based on conventional techniques suggest that marginal miss might be a potential consequence of genital sparing. Our goal is to outline the potential scope and increase the awareness for this clinical issue. METHODS: We present and discuss four patients with perigenital spread in anal cancer in both early and advanced stages (three at time of first diagnosis and one in form of relapse). Genital/perigenital spread was observed once as direct genital infiltration and thrice in form of perigenital lymphatic spread. RESULTS: We review the available data regarding the potential consequences of genital sparing in anal cancer. Pattern-of-relapse studies in anal cancer after conventional radiotherapy and the current use of IMRT in anal cancer are equivocal but suggest that genital sparing may occasionally result in marginal miss. An obvious hypothesis suggested by our report is that perigenital lymphovascular invasion might be associated with manifest inguinal N+ disease. CONCLUSIONS: Local failure has low salvage rates in recent anal cancer treatment series. Perigenital spread may pose a risk of marginal misses in IMRT in anal cancer. To prevent marginal misses, meticulous pattern-of-relapse analyses of controlled IMRT-series are warranted. Until their publication, genital sparing should be applied with caution, PET/CT should be used when possible and meeting genital dose constraints should not be prioritized over CTV coverage, especially (but not only) in stage T3/4 and N+ disease.