Behandlung HPV-assoziierter analer Läsionen bei HIV-positiven Patienten – chirurgische Abtragung vs. topische Therapie mit Imiquimod

Author(s):  
Martin W. von Websky ◽  
Paul C. Wesselmann ◽  
Carolynne Schwarze-Zander ◽  
Tim Oliver Vilz ◽  
Burkhard Stoffels ◽  
...  

Zusammenfassung Hintergrund Regelmäßige proktologische Untersuchungen sind bei HIV+-Patienten aufgrund häufiger anorektaler Erkrankungen erforderlich. Insbesondere HPV-assoziierte Läsionen wie Condylomata acuminata (C. ac.) und anale Dysplasien (AIN) werden sowohl mit operativen Verfahren als auch mit topischer Therapie behandelt. Ziel der Arbeit Es sollte untersucht werden, ob sich chirurgische Abtragung und topische Therapie mit Imiquimod bez. Heilungsraten und Outcome bei HPV-assoziierten analen Läsionen unterscheiden und ob ein synergistischer Effekt vorliegt. Material und Methoden Es wurden bei 97 HIV+-Patienten alle proktologischen Untersuchungen und Therapiemaßnahmen über einen Zeitraum von 10 Jahren (11/2004 – 11/2015) retrospektiv untersucht. Insbesondere wurden Diagnose und Therapie von HPV-assoziierten analen Läsionen mit klinischem Outcome nach chirurgischer Abtragung und topischer Therapie mit Imiquimod analysiert. Ergebnisse Bei 53/97 (54%) HIV+-Patienten wurden HPV-assoziierte anale Läsionen festgestellt. Das mittlere Patientenalter betrug 41,0 ± 11,6 Jahre. Die HIV-Erkrankung war bei ca. der Hälfte der Patienten unter cART gut eingestellt (52 Patienten mit Viruslast < 40 Kopien [53,6%]). Im Verlauf wurden bei 7/53 Patienten mit C. ac. auch Low-Grade- und bei 18/53 Patienten High-Grade-AINs diagnostiziert. Eine vollständige Remission von C. ac. bzw. AIN nach einer Behandlung von 4 Wochen wurde als Erfolg gewertet. Die Erfolgsquote lag bei der Behandlung von C. ac. mit Imiquimod bei 5/25 (20,0%) vs. OP* 30/57 (52,6%, Mann-Whitney-U-Test p < 0,05) vs. OP+Imiquimod bei 7/15 (46,7%). Die Erfolgsquote lag bei der Behandlung von AIN mit Imiquimod bei 4/24 (16,7%) vs. OP* bei 47/83 (56,7%, Mann-Whitney-U-Test p < 0,05) vs. OP+Imiquimod bei 9/21 (42,8%). Es traten bei 7/92 Eingriffen chirurgische Komplikationen auf, davon 4 geringgradige und 2 signifikante Blutungen sowie eine Analvenenthrombose. Bei Imiquimod-Behandlung wurden lediglich einzelne Hautirritationen dokumentiert. Diskussion Eine operative Erstbehandlung von HPV-assoziierten analen Läsionen bei HIV+-Patienten ist einer topischen Therapie mit Imiquimod im Kurzzeitverlauf überlegen. Ein synergistischer Effekt konnte nicht festgestellt werden. Aufgrund der vorliegenden Ergebnisse unserer Studie empfehlen wir die operative Abtragung der HPV-assoziierten Läsionen bei HIV+-Patienten.

2021 ◽  
pp. 106689692110522
Author(s):  
Diego Montoya-Cerrillo ◽  
Laurence M. Briski ◽  
Merce Jorda ◽  
Oleksandr N. Kryvenko

Background Condyloma acuminatum is a squamous epithelial lesion which uncommonly involves the urinary tract. In this location, non-invasive papillary urothelial carcinoma constitutes one of the main differential diagnoses with significant prognostic and therapeutic implications. To date, no ancillary immunohistochemical stain has been described to differentiate these two entities. We assess the utility of cytokeratin 5/6 (CK5/6) and GATA-3 immunohistochemistry in distinguishing condyloma acuminatum from non-invasive papillary urothelial carcinoma. Design We reviewed 9 condylomata acuminata involving the urinary tract, 12 low-grade and 8 high-grade non-invasive papillary urothelial carcinomas. CK5/6 immunostaining was performed in all cases. GATA-3 immunostaining and low-risk human papilloma virus (HPV) chromogenic in situ hybridization was performed in all condyloma cases and 2 urothelial carcinomas with squamous differentiation. Results 8/9 condylomata acuminata were positive for low-risk HPV. All condylomata acuminata exhibited strong full-thickness cytoplasmic staining for CK5/6. In 10 of 12 low-grade non-invasive papillary urothelial carcinomas, CK5/6 expression was continuous and limited to the basal cell layer, while it was patchy and limited to the basal cell layer in all 8 high-grade non-invasive papillary urothelial carcinomas. Two low-grade non-invasive papillary urothelial carcinomas showed focal full-thickness CK5/6 expression in the areas of squamous differentiation. These 2 cases were negative for low-risk HPV. GATA-3 immunostaining was positive in all condylomata acuminata. Conclusions CK5/6 immunostaining is a useful and simple tool that can help separate low-grade and high-grade non-invasive papillary urothelial carcinomas from condyloma acuminatum involving the urothelium-lined organs. GATA-3 has no discriminatory role between condyloma acuminatum and papillary urothelial carcinomas.


1996 ◽  
Vol 35 (02) ◽  
pp. 42-52 ◽  
Author(s):  
R. Bares ◽  
U. Bull ◽  
A. Guhlmann ◽  
E. Moser ◽  
M. F. Wannenmacher ◽  
...  

Zusammenfassung Ziel: Es ist das Ziel der vorliegenden Arbeit, an Hand bisher publizierter Studienergebnisse eine Beurteilung des klinischen Stellenwertes von PET in der Onkologie zu erarbeiten. Methoden: Im Rahmen einer interdisziplinären Konferenz mit namhaften Experten wurde eine Wertung des gegenwärtigen Stands von PET in der Onkologie an Hand der in der Literatur dokumentierten Studienergebnisse erarbeitet. Angestrebt wurde eine differenzierte Bewertung von PET für die klinische Anwendung in fünf Klassen (1a, 1b, 2a, 2b, 3) von »angemessen« (1a), »akzeptabel« (1b), »hilfreich« (2a), »noch keine Bewertung möglich« (2b), »ohne Nutzen« (3). Ergebnisse: Für den klinischen Einsatz in der Onkologie ist 2-F18-Fluorodeoxyglukose (FDG) das Radiopharmakon der Wahl. PET ist klinisch in der Patientenversorgung zur Rezidivdiagnostik von high-grade Gliomen (FDG), low-grade Gliomen (C-11 Methionin oder F-18 Tyrosin), für die Dignitätsdiagnostik des peripheren Lungenrundherdes bei Risikopatienten sowie für die Diagnostik des Pankreaskarzioms indiziert (Indikation 1a). PET kann in der Patientenversorgung bei folgenden Indikationen (1b) eingesetzt werden: »low-grade« Gliome, Suche nach unbekanntem Primärtumor bei Kopf-Hals-Tumoren, Rezidivdiagnostik des nicht kleinzelligen Bronchialkarzinoms sowie des Rektumkarzinoms, Lymphknotenstaging beim nicht kleinzelligen Bronchial-Karzinom, Pan-kreas-Karzinom, muskelinvasiven Blasen-Karzinom und Hoden-Karzinom. Staging bei M. Hodgkin (Stad. I/II versus III), frühe Therapiekontrolle bei Resttumor und Rezidivdiagnostik bei M. Hodgkin und hochmalignen Non-Hodgkin-Lymphomen, Lymphknoten-Staging und Fern-metastasensuche beim malignen Melanom (Breslow >1,5 mm), Lymphknoten- und Fernmetastasen-Nachweis beim Schilddrüsen-Karzinommit erhöhtem hTg und nicht radiojodspeichernden Metastasen. Zahlreiche weitere Indikationen zeichnen sich bereits jetzt ab, sind jedoch noch weniger gut durch wissenschaftliche Studien belegt. Für die meisten Indikationen außerhalb wissenschaftlicher Studien ist eine individuelle Kosten-Nutzen-Betrachtung durch den verantwortlichen Arzt geboten. Schlußfolgerungen: Die metabolische Bildgebung von PET besitzt für eine Vielzahl onkologischer Fragestellungen prinzipielle Vorteile gegenüber der anatomisch-morphologisch orientierten Schnittbilddiagnostik. Für die klinische Indikationsstellung ist allerdings eine differenzierte Betrachtung der spezifischen Leistungsfähigkeit von PET geboten.


2014 ◽  
Vol 23 (2) ◽  
pp. 161-170 ◽  
Author(s):  
Claudiu Margaritescu ◽  
Daniel Pirici ◽  
Irina Cherciu ◽  
Alexandru Barbalan ◽  
Tatiana Cârtâna ◽  
...  

Background & Aims: Colorectal cancer represents the third most common malignancy and the fourth most common cause of cancer death worldwide. The existence of drug-resistant colon cancer stem cells is thought to be one of the most important reasons behind treatment failure in colon cancer, their existence putatively leading to metastasis and recurrences. The aim of our study was to investigate the immunoexpression patterns of CD133 and CD166 in colon carcinoma, both individually and in combination, assessing their significance as prognostic markers.Methods. A total of 45 retrospective colon adenocarcinoma cases were investigated by enzymatic and multiple fluorescence immunohistochemistry for their CD133 and CD166 expression and colocalization.Results. Both CD133 and CD166 were expressed to different extents in all cancer specimens, with apredominant cytoplasmic pattern for CD133 and a more obvious membranous-like pattern for CD166.Overall, when comparing their reactivity for the tumoral tissue, CD166 expression areas seemed to be smaller than those of CD133. However, there was a direct correlation between CD133 and CD166 expression levels throughout the entire spectrum of lesions, with higher values for dysplastic lesions. Colocalization of CD133/ CD166 was obvious at the level of cells membranes, with higher coeficients in high grade dysplasia, followed by well and moderate differentiated tumours.Conclusions. CD133/CD166 colocalization is an early event occurring in colon tumorigenesis, with thehighest coeficients recorded for patients with high grade dysplasia, followed by well differentiated tumours. Thus, we consider that the coexpression of these two markers could be useful for further prognostic andtherapeutically stratification of patients with colon cancer.Abbreviations: AJCC - American Joint Committee on Cancer; CCD - charge-coupled device camera sensor; CD133 - prominin-1 (PROM1); CD166 - Activated Leukocyte Cell Adhesion Molecule (ALCAM); CRC - colorectal cancer; CSC - cancer stem cells; DAB - 3,3'-diaminobenzidine chromogen; DAPI - 4',6-diamidino- 2-phenylindole; HE - Hematoxylin and eosin staining; HGD - high grade dysplasia; HRP - horseradish peroxidase; LGD - low grade dysplasia; SDS - sodium dodecyl sulfate*Part of this work has been accepted as a poster presentation at the Digestive Disease Week (DDW) meeting, Chicago, IL, USA May 3-6, 2014


2019 ◽  
Vol 65 (1) ◽  
pp. 56-62
Author(s):  
Alisa Villert ◽  
Larisa Kolomiets ◽  
Natalya Yunusova ◽  
Yevgeniya Fesik

High-grade ovarian carcinoma is a histopathological diagnosis, however, at the molecular level, ovarian cancer represents a heterogeneous group of diseases. Studies aimed at identifying molecular genetic subtypes of ovarian cancer are conducted in order to find the answer to the question: can different molecular subgroups influence the choice of treatment? One of the achievements in this trend is the recognition of the dualistic model that categorizes various types of ovarian cancer into two groups designated high-grade (HG) and low-grade (LG) tumors. However, the tumor genome sequencing data suggest the existence of 6 ovarian carcinoma subtypes, including two LG and four HG subtypes. Subtype C1 exhibits a high stromal response and the lowest survival. Subtypes C2 and C4 demonstrate higher number of intratumoral CD3 + cells, lower stromal gene expression and better survival than sybtype C1. Subtype C5 (mesenchymal) is characterized by mesenchymal cells, over-expression of N-cadherin and P-cadherin, low expression of differentiation markers, and lower survival rates than C2 and C4. The use of a consensus algorithm to determine the subtype allows identification of only a minority of ovarian carcinomas (approximately 25%) therefore, the practical importance of this classification requires additional research. There is evidence that it makes sense to randomize tumors into groups with altered expression of angiogenic genes and groups with overexpression of the immune response genes, as in the angiogenic group there is a comparative superiority in terms of survival. The administration of bevacizumab in the angiogenic group improves survival, while the administration of bevacizumab in the immune group even worsens the outcome. Molecular subtypes with worse survival rates (proliferative and mesenchymal) also benefit most from bevacizumab treatment. This review focuses on some of the advances in understanding molecular, cellular, and genetic changes in ovarian carcinomas with the results achieved so far regarding the formulation of molecular subtypes of ovarian cancer, however further studies are needed.


2020 ◽  
Vol 16 (1) ◽  
pp. 18-22
Author(s):  
Eronmwon E. Gbinigie ◽  
Joshua Fogel ◽  
Maggie Tetrokalashvili

Background: Clinicians commonly perform colposcopy directed biopsies on patients with low grade squamous intraepithelial lesion (LSIL) on PAP cytology even when not consistent with clinical guidelines. Objective: We study the association of PAP cytology screening results with cervical intra-epithelia neoplasia (CIN) 2-3 high-grade dysplasia, as confirmed by colposcopy-directed biopsy. Methods: A retrospective study of 263 women with an abnormality on the PAP smear. Multinomial logistic regression was performed with predictors of PAP cytology screening results with the outcome variable of colposcopy-directed biopsy. Results: High grade squamous intraepithelial lesion (HSIL) had significantly increased relative risk for CIN 2-3 (RR: 9.85, 95% CI: 1.84, 52.79, p=0.008). LSIL was not significantly associated with CIN 2-3. In the comparisons of negative with CIN-1, both HSIL and LSIL were not significantly associated with a negative biopsy. Conclusion: HSIL is associated with cervical dysplasia of CIN 2-3 while LSIL is not associated with cervical dysplasia of CIN 2-3. We do not recommend routine biopsies in patients with LSIL cytologic abnormalities unless additional compelling factors exist.


2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Maike Grootenhaar ◽  
Dominique Lamers ◽  
Karin Kamphuis-van Ulzen ◽  
Ivo de Blaauw ◽  
Edward C. Tan

Abstract Background Non-operative management (NOM) is generally accepted as a treatment method of traumatic paediatric splenic rupture. However, considerable variations in management exist. This study analyses local trends in aetiology and management of paediatric splenic injuries and evaluates the implementation of the guidelines proposed by the American Paediatric Surgical Association (APSA) in a level 1 trauma centre. Methods The charts of paediatric patients with blunt splenic injury (BSI) who were admitted or transferred to a level 1 trauma centre between 2003 and 2020 were retrospectively assessed. Information pertaining to demographics, mechanism of injury, injury description, associated injuries, intervention and outcomes were analysed and compared to international literature. Results There were 130 patients with BSI identified (63.1% male), with a mean age of 11.3 ± 4.0 and a mean Injury Severity Score (ISS) of 21.6 ± 13.7. Bicycle accidents were the most common trauma mechanism (23.1%). Sixty-four percent were multi-trauma patients, 25% received blood transfusions, and 31% were haemodynamically unstable. Mean injury grade was 3.0, with 30% of patients having a high-grade injury. In total, 75% of patients underwent NOM with a 100% efficacy rate. Total splenectomy rate was 6.2%. Four patients died due to brain damage. Patients with a high-grade BSI (grades IV–V) had a significantly higher ISS and longer bedrest and more often presented with an active blush on computed tomography (CT) scans than patients with a low-grade BSI (grades I–III). Non-operative management was mainly the choice of treatment in both groups (76.6% and 79.5%, respectively). Haemodynamic instability was a predictor for operative management (OM) (p = 0.001). Predictors for a longer length of stay (LOS) included concomitant injuries, haemodynamic instability and OM (all p < 0.02). Interobserver agreement in the grading of BSI is moderate, with a Cohens Kappa coefficient of 0.493. Conclusion Non-operative management has proven to be a realistic management approach in both low- and high-grade splenic injuries. Consideration for operative management should be based on haemodynamic instability. Compared to the anticipated length of bedrest and hospital stay outlined in the APSA guidelines, the Netherlands can reduce the length of bedrest and hospital stay through their non-operative management. Level of evidence Therapeutic study, level III


Children ◽  
2021 ◽  
Vol 8 (5) ◽  
pp. 317
Author(s):  
Ling-Sai Chang ◽  
Ken-Pen Weng ◽  
Jia-Huei Yan ◽  
Wan-Shan Lo ◽  
Mindy Ming-Huey Guo ◽  
...  

(1) Background: Desquamation is a common characteristic of Kawasaki disease (KD). In this study, we analyzed patients’ varying desquamation levels in their hands or feet, in correlation with clinical presentation, to assess the relationship. (2) Methods: We retrospectively reviewed children with KD. We analyzed their age, laboratory data before intravenous immunoglobulin (IVIG) treatment and coronary artery abnormalities (CAA) based on the desquamation level of their hands and feet. We classified the desquamation level from 0 to 3 and defined high-grade desquamation as grade 2 and 3. (3) Results: We enrolled a total 112 patients in the study. We found the hands’ high-grade desquamation was positively associated with age and segmented neutrophil percentage (p = 0.047 and 0.029, respectively) but negatively associated with lymphocyte and monocyte percentage (p = 0.03 and 0.006, respectively). Meanwhile, the feet’s high-grade desquamation was positively associated with total white blood cell counts (p = 0.033). Furthermore, we found that high-grade hand desquamation had less probability of CAA formation compared with that of a low grade (7.1% vs. 40.8%, p = 0.016). (4) Conclusions: This report is the first to demonstrate that the desquamation level of hands or feet in KD is associated with different coronary artery abnormalities and laboratory findings.


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