(Pre)malignancies of the female anogenital tract in renal transplant recipients

This mini review describes human papillomavirus-related (pre)malignancies of the lower anogenital tract, for which female renal transplant recipients (RTRs) have a markedly increased risk. Until now, the implementation of intensified cervical cancer screening in RTRs is disappointing. We emphasize the need for improvement of cervical screening programs, combined with close inspection of the vulva and perianal area for potential lethal malignancies in RTRs.     

Reactivation of Latent HPV Infections After Renal Transplantation

Female renal transplant recipients (RTRs) have an increased risk for developing human papillomavirus (HPV)–related (pre)malignant lesions of the genital tract. This study aims to assess the genital prevalence of HPV before and after renal transplantation (RT). In female patients who were counseled for RT at the Radboud University Medical Center Nijmegen, the Netherlands, gynecological examination was performed at first visit, and 1 and 2 years later. HPV self‐sampling and questionnaires on sexual behavior were performed every 3 months. In 65 patients who underwent RT, the high‐risk human papillomavirus (hrHPV) prevalence as assessed with the highly sensitive SPF₁₀ ‐LiPA₂₅ test increased significantly from 19% before to 31% after RT (p = 0.045). Based upon the clinically validated Cobas 4800 HPV test, the hrHPV prevalence increased from 10% before to 14% after RT (p = 0.31). During follow‐up, no changes in sexual behavior were reported. Thirty‐three patients who did not undergo RT showed a hrHPV prevalence of 21% at study entry and of 27% after 12 months with the sensitive test, and a stable prevalence of 16% with the clinically validated test. The results of this study indicate that activation of latent HPV infections may contribute to the increased risk of HPV‐related (pre)malignant lesions in female RTRs.     

Multiple types of high-risk human papilloma virus in the lower genital tract of a female kidney recipient: a case report

We present a case of a female kidney recipient who was infected with 3 types of high-risk human papilloma viruses. An infection in the lower genital tract led to the development of both neoplastic cervical lesions and vulvar cancer.     

Human papillomavirus DNA in genital tract lesions histologically negative for condylomata. Analysis by in situ, Southern blot hybridization and the polymerase chain reaction

Koilocytotic atypia (nuclear atypia in conjunction with perinuclear halos) is diagnostic of condylomata of the lower female genital tract, over 90% of which contain human papillomavirus (HPV) DNA. Genital tract lesions may be clinically suggestive of condylomata but lack clear-cut koilocytotic atypia. Of 57 vulvar and 60 cervical lesions that lacked clear-cut koilocytotic atypia, four (7%) and two (3%), respectively, had HPV DNA detected by in situ analysis. Using Southern blot analysis, HPV DNA was detected in five of 27 (19%) and 20 of 55 (36%) vulvar and cervical lesions, respectively, that lacked koilocytotic atypia. When analyzed with the polymerase chain reaction (PCR), HPV DNA was detected in six of 22 (27%) and three of 18 (17%) vulvar and cervical lesions, respectively, that lacked koilocytotic atypia. These findings demonstrate that infection by HPV may be found in genital tract lesions that lack koilocytotic atypia. The lower detection rate of HPV in cervical lesions that lacked koilocytotic atypia with PCR as compared with Southern blot analysis may be related to the relatively high proportion of "novel" types (related to, but distinct from, the HPV types in the probe) in such lesions. The increase in the detection rate in vulvar lesions that lacked koilocytotic atypia with PCR compared with in situ hybridization suggests that about one third of such lesions are HPV related, but that in such cases the copy number of the virus is typically below the threshold of the in situ analysis.     

Risk of genital warts in renal transplant recipients—A registry‐based,prospective cohort study

Genital warts (GWs) are a risk factor for subsequent human papillomavirus (HPV)–related anogenital cancers. In this register‐based, prospective cohort study, we estimated the risk of GWs in renal transplant recipients (RTRs) compared with a nontransplanted cohort. In a nationwide database, we identified first‐time RTRs in Denmark during 1996 to 2015. For each RTR, 50 age‐ and sex‐matched nontransplanted individuals were selected from the population registry. Information on GWs, sociodemographic characteristics, HPV vaccination, and other causes of immunosuppression was retrieved from registries. We estimated the cumulative incidence of GWs and used Cox regression to estimate hazard ratios (HR) of GWs in RTRs vs non‐RTRs. We included 3268 RTRs and 162 910 non‐RTRs without GWs 1 year before baseline. RTRs had higher hazard of GWs than non‐RTRs (HR = 3.30; 95% confidence interval, 2.76‐3.93, adjusted for sex, age, education, and income). The increased hazard of GWs compared with non‐RTRs was more pronounced in female than in male RTRs. Although not statistically significant, the hazard tended to be higher in RTRs with functioning grafts compared with RTRs on dialysis after graft failure. The hazard of GWs was increased <1 year after transplantation and remained increased during ≥10 years. In conclusion, RTRs had substantially higher risk of GWs than non‐RTRs.     

Colorectal and anal neoplasms following liver transplantation

Objective Liver transplantation (LT) is the treatment of choice for end‐stage liver disease. The required immunosuppression increases the risk for developing malignancies. Some viruses play a crucial role. Data on neoplasms of the colon, rectum and anus in LT are limited. Method A retrospective evaluation of the incidence and clinical course of colorectal and anal malignancies and colonic polyps in a series of 467 consecutive LTs in 402 individuals between 1998 and 2001 was performed. Standard immunosuppression included Tacrolimus, Mycophenolic acid and steroids. Results During a median follow up of 5.2 years, three colon adenocarcinomas, one EBV associated cecal post‐transplant lymphoproliferative tumour and two HPV associated anal tumours were identified. Pre‐LT colonoscopy was performed in 161 patients (40%), and of 153 evaluable individuals, 53 (34.9%) had polyps. Colonoscopy was performed in 186 patients (46.3%) median 14.8 (range 0.2–77.8) months post‐LT and 55 (29.3%) had polyps. Post‐LT adenomatous polyps were detected in 47.3% of patients with pre‐LT polyps vs 6.7% of patients without pre‐LT polyps (P < 0.001). Patients with alcoholic liver disease had a significantly higher rate of adenoma formation (50.0%vs 11.1%, P < 0.001). No patient died from colorectal/anal malignancy. Conclusion The incidence of metachronous and new polyp formation in our study is similar to people who are not immunocompromised, but subgroups are at increased risk. Viral‐associated malignancies, including post‐transplant lymphoproliferative disorders and anal cancer, are important entities in the LT population suggesting that complete screening of the colon, rectum and anus including pre‐LT and post‐LT colonoscopy should be utilized.     

Human papillomavirus--related diseases in the female patient.

Human papillomavirus (HPV) has been strongly associated with malignancy in the female lower genital tract. Because squamous-cell carcinoma of the cervix is preceded by a spectrum of easily detectable and treatable premalignant changes, it is very preventable. The management of the patient with an abnormal Papanicolaou smear and the treatment of cervical, vaginal, and vulvar disease are outlined.     

原发女性生殖道恶性黑色素瘤21例临床分析

目的探讨原发性女性生殖道恶性黑色素瘤的临床特点、治疗及预后。方法回顾分析本院1986年1月至2006年3月收治的原发性女性生殖道恶性黑色素瘤患者21例。其中外阴8例、阴道10例、阴道及宫颈1例、外阴及阴道1例、盆腔1例。结果患者中位年龄50(21~71)岁。临床表现主要为阴道流血、流液及发现外阴或阴道肿物。本资料阴道恶性黑色素瘤发病率高于外阴恶性黑色素瘤。按照国际妇产科联盟(FIGO)分期,期别和预后呈负相关。治疗以手术为主,手术方式由根治性切除逐渐衍变为扩大局部切除。随访:21例患者中随访率为67%(14/21),随访时间6~96个月,死亡7例,随访期间的死亡率为50%。结论女性生殖道恶性黑色素瘤发病率低,预后差。肿瘤厚度和淋巴结转移是其主要的危险因素。应采用手术基础上的综合治疗,治疗方案个体化。     

Excellent cosmetic and functional result achieved by vulvar reconstruction using a V-Y myocutaneous flap after vulvectomy and lymphadenectomy in a young woman with stage II vulvar cancer

Vulvar carcinoma is currently accounting for 4% to 5% of all female genital tract malignancies. We report a 31-year-old woman with a 4-year history of vulvar pruritus and a progressively growing painless mass. The lesion was an invasive squamous cell carcinoma and contained oncogenic human papillomavirus (HPV) type 16. An excellent cosmetic and functional treatment result was achieved by radical vulvectomy with selective inguinal-femoral lymphadenectomy (using separate incisions) followed by immediate reconstructive surgery using a V-Y myocutaneous flap.     

Impact of pre-transplant dialysis modality on post-transplant diabetes mellitus after kidney transplantation

Courivaud C, Ladrière M, Toupance O, Caillard S, de Ligny BH, Ryckelynck J‐P, Moulin B, Rieu P, Frimat L, Chalopin J‐M, Chauvé S, Kazory A, Ducloux D. Impact of pre‐transplant dialysis modality on post‐transplant diabetes mellitus after kidney transplantation.
Clin Transplant 2011: 25: 794–799. © 2010 John Wiley & Sons A/S. Abstract: Post‐transplant diabetes mellitus (PTDM) is a well‐known complication in renal transplant recipients (RTRs). While a number of risk factors for PTDM have been identified, the potential impact of pre‐transplant dialysis modality on subsequent development of PTDM has not yet been explored. We performed a multicenter retrospective study on 2010 consecutive RTRs who did not have a history of diabetes prior to renal transplantation. PTDM was defined as a need for anti‐diabetic therapy in an RTR without a history of diabetes prior to transplantation. Analysis of the risk factors for development of PTDM was performed with respect to pre‐transplant dialysis modality. A total of 137 (6.8%) patients developed PTDM; 7% in the hemodialysis group and 6.5% in the peritoneal dialysis (PD) group (p = 0.85). In the multivariate analysis, age (p < 0.001), body mass index (BMI) (p < 0.001), use of tacrolimus (p = 0.002), and rejection episodes (p < 0.001) were identified as independent risk factors for development of PTDM. Patients in the PD group were younger (p = 0.004), had lower BMI (p = 0.07), and were less likely to have a history of hepatitis C (p = 0.007) and autosomal dominant polycystic kidney disease (p = 0.07). Adjustment for these variables did not modify the results. The results of this study suggest that pre‐transplant dialysis modality does not have an impact on the subsequent development of PTDM in RTRs.     

Angiogenesis in anal warts, anal intraepithelial neoplasia and anal squamous cell carcinoma

Introduction Most cases of anal carcinoma seem to develop from high grade anal intraepithelial neoplasia (AIN) caused by persistent anal warts. Similar pre‐invasive epithelial genital lesions (e.g. those of the cervix and vulva) have been shown to be associated with increased angiogenesis. In this study we examined biopsies of anal lesions ranging from warts to invasive anal carcinoma, with the aim of assessing the degree of angiogenesis in pre‐invasive anal lesions. Method Samples from 70 patients (51 male) who had undergone excision biopsy or resection of anal wart lesions (20), low grade AIN (12), high grade AIN (27) and anal squamous cell carcinoma (SCC) (11) were studied. Samples (6) from normal HIV‐anal skin were used as controls. The samples were stained for von Willebrand factor, a specific marker of endothelial cells. Angiogenesis was measured by microvessel density (MVD) analysis, quantifying the microvessels in the stroma adjacent to the epithelial lesion. Results There was a statistically significant (P < 0.001) progressive increase in MVD between low grade AIN, high grade AIN and anal SCC. The difference in MVD between normal skin, warts and low grade AIN was not statistically significant. Conclusion There are progressive abnormal patterns of angiogenesis in highly dysplastic lesions, similar to those found in cervical and vulvar pathology. These findings may have biological, prognostic and therapeutic implications.     

Prevalence of mammary carcinoma in patients with gynaecologic cancer

Six hundred and forty-four patients with primary malignant tumours of the female genital tract were subject to a two-stage screening program on admission, with clinical examination in all and mammography in 380. Clinical examination alone revealed 4 cancers, while supplementary mammography screening of 369 patients with normal clinical examination revealed an additional 6 tumours, of which 5 were invasive. The prevalence rate was about three times that found in two mass-screening programs in different parts of Sweden. Thus, it could be concluded that there is an increased risk for mammary carcinoma in patients with gynaecologic malignancies. It seems reasonable therefore, to recommend mammography routinely in this group of patients.     

Cervical human papillomavirus infection in the early postoperative period after liver transplantation: Prevalence,risk factors,and concordance with anal infections

Solid organ transplant recipients are at increased risk of developing several human papillomavirus (HPV)‐related malignancies, including cervical and anal cancers. The purpose of this prospective study was to assess the initial prevalence and risk factors for high‐risk HPV (HR‐HPV) cervical infections in liver transplant recipients, as well as their concordance with anal infections. A total of 50 female patients were enrolled in the Department of General, Transplant and Liver Surgery at the Medical University of Warsaw (center with >1600 liver transplantations). The initial prevalence of cervical HR‐HPV infection was 10.0% (5/50). The only significant risk factor for cervical HR‐HPV infection was ≥4 lifetime sexual partners (P=.037). Statistical tendencies toward higher prevalence of cervical HR‐HPV infections were found for patients with hepatitis B virus (HBV, P=.082) and with model for end‐stage liver disease (MELD) score ≤8 (P=.064). Cervical cytology was abnormal in 10 patients, including three with HR‐HPV. Out of 12 patients with available data on anal HR‐HPV, one had concordant HPV 16 infection. In conclusion, the initial prevalence of high‐risk HPV infection is relatively low, except for patients with ≥4 previous sexual partners and potentially in those with HBV and/or low MELD score.     

High plasma hemopexin activity is an independent risk factor for late graft failure in renal transplant recipients

Chronic low‐grade inflammation is involved in late renal transplant dysfunction. Recent studies suggest a role for hemopexin, an acute phase protein, in kidney damage. We investigated whether hemopexin activity (Hx) predicts graft failure in renal transplant recipients (RTRs). In 557 RTRs with functioning grafts for ≥1 year, Hx was measured in citrate‐plasma. RTRs were divided according to Hx into two groups; A: sextile 1–5 (464 RTRs, 83%) and B: sextile 6 (92 RTRs, 17%). Hx [median (IQR) 11.1 (3.3–19.1) arbitrary units] was measured at 6.0 (2.6–11.5) years post‐transplant. RTRs with high Hx (group B) had significantly higher urinary protein excretion (UP) and diastolic blood pressure than group A, despite significantly more prevalent use of renin‐angiotensin‐aldosterone system inhibitors. After follow‐up  [4.6 (3.8–5.2) years], incidence of graft failure in group A was 25 (5%) and in group B 14 (15%,P = 0.0009) After adjustment for high‐sensitivity C‐reactive protein (hsCRP), UP and other potential confounders, Hx remained an independent predictor of graft failure [HR = 2.5 (95% CI 1.2–5.3), P = 0.01]. In conclusion, elevated Hx predicts late graft failure in RTRs, independent of hsCRP and UP. This suggests that Hx measurement, next to measurement of creatinine clearance and UP, could be of value for the identification of RTRs at risk for graft failure.     

Transitional cell carcinoma of the urinary tract associated with vulvar Paget's disease: a report of two cases

Two cases of the urothelial cancers associated with extramammary Paget's disease are reported. In one patient, vulvar Paget's disease was discovered 6 years after complete resection of a ureteral tumor. In another patient, vulvar and vaginal Paget's disease developed during a period of repeated transurethral surgery leading up to the final total cystectomy for recurrent bladder carcinoma. Since genital Paget's disease is frequently accompanied by internal malignancies, a skin biopsy is mandatory when an eczematous lesion has been persistent in the genital region of patients with genitourinary cancers.     

Usefulness of a program of neoplasia surveillance in liver transplantation. A preliminary report

Abstract:  De novo malignancies are frequent complications after liver transplantation. Aim of the study is to evaluate whether a surveillance program for malignancy may improve patient survival. We have compared the survival after the diagnosis of malignancy (excluding cutaneous and hepatobiliary carcinomas and lymphoproliferative disease) of patients with symptomatic or incidental malignancies with patients with neoplasia diagnosed on screening. Two hundred and eighty patients with a follow-up greater than three months were followed for a median of 77.5 months (total follow-up: 1515 patient-yr). Thirty-three patients developed 41 malignancies. When compared with general population, the entire cohort of liver transplant recipients had a significantly higher risk of malignancy (relative risk: 2.34), gastrointestinal tract (relative risk: 2.52), urological tract (relative risk: 2.94) and head and neck cancer (relative risk: 4.14), and cancer-related death (relative risk: 2.35). All nine patients diagnosed with cancer with active screening are currently alive and free of malignancy after a median follow-up of 25 months. By contrast, 18/24 patients with diagnosis of cancer prompted by symptoms or incidentally diagnosed died as a consequence of the cancer (median survival: 13.5 months). The difference in survival between both groups was significant (p = 0.002). In conclusion, a close surveillance protocol for the diagnosis of malignancy could be life-saving in liver transplant recipients.     

Accurate detection of male subclinical genital tract infection via cervical culture and DNA hybridization assay of the female partner

The accuracy of the PACE2 DNA hybridization assay of the cervix and cervical culture in female partners for the diagnosis of male subclinical genital tract infection were assessed in a male infertility population. A total of 184 men were screened for the presence of Chlamydia trachomatis, Ureaplasma urealyticum and Mycoplasma hominis. Seventy-one men were identified with a positive test for one or more of the above mentioned micro-organisms. The overall prevalence of bacterial infection was 39%. Female partners of all men were tested with the PACE2 DNA hybridization assay to detect a C. trachomatis infection. Sensitivity was 100% and specificity was 100%. In 67 female partners (94%) of men who tested positive for U. urealyticum and/or M. hominis, a cervical swab culture was performed. The sensitivity of the cervical swab culture was 100%. In view of the high prevalence of U. urealyticum and M. hominis in the male genital tract and the role these sexually transmitted pathogens may play in infertility, one might question whether all couples should be screened for the presence of these pathogens. Transurethral swab culture after digital prostatic massage is disincentive to men. The cervical culture in their female partner, performed as part of the routine fertility work-up, is a suitable alternative to detect the presence of these micro-organisms in the male genital tract.     

Muco‐cutaneous manifestations in 178 renal transplant recipients

Khosravi M, Golchai J, Mokhtari G. Muco‐cutaneous manifestations in 178 renal transplant recipients.
Clin Transplant 2011: 25: 395–400. © 2010 John Wiley & Sons A/S. Abstract: Introduction: Mucosal membrane and skin can be affected by immunosuppressive drug(s) and immunosuppression itself. The spectrum of muco‐cutaneous lesions can range from malignancy at one end to infection, iatrogenic lesions, and esthetic effects on the other end. Method: In Razi Hospital of Guilan University of Medical Sciences, a cross‐sectional study for the detection of muco‐cutaneous lesions in 178 renal transplant recipients (RTRs) was conducted from the years 2001 to 2006. Biopsy and skin scraping according to the type of skin lesions were performed. Results: A total of 31 RTRs (25%) had normal skin. Iatrogenic lesions were the most common (70%) followed by infectious lesions (57%), and miscellaneous skin lesions were exhibited by 26% of the patients. Among the iatrogenic skin lesions, gingival hyperplasia was the most common lesion (48%), followed by hypertrichosis and acne. Malignant lesions (biopsy proven) were recorded in seven patients (5%). Four patients were found to have Kaposi’s sarcoma, and three patients were identified with basal cell carcinoma. Conclusion: Our results showed that muco‐cutaneous lesions are crucial problems with RTRs. Attending physicians must pay close attention to skin care regularly and consider reduction of immunosuppression to a safe level, and patient must have self‐checkups.     

Analysis of sexual functions in male nondiabetic hemodialysis patients and renal transplant recipients

Disturbance of sexual functions among hemodialysis patients and renal transplant recipients (RTRs) is controversial. Diabetes mellitus (DM) is known to have a significant negative impact on sexual functions. Most previous studies concerning the issue of disturbance of sexual functions among hemodialysis patients and renal transplant recipients have included diabetic patients also, which might have influenced their results. The aim of this study was to evaluate sexual functions of nondiabetic male (NDM) dialysis patients and RTRs, and to compare our findings with those of the others. Twenty‐five nondiabetic male RTRs, 25 age‐matched NDM hemodialysis patients, and 25 age‐matched NDM controls were the subjects of this study. Sexual functions of all subjects were assessed using the International Index of Erectile Function (IIEF) questionnaire. Statistical analysis was performed using appropriate statistical tests with the level of significance set at P < 0.05. Data were described using mean, standard deviation (SD), median and interquartile range (IQR). Renal transplant recipients (RTRs) and hemodialysis patients had depressed erectile function (EF) and Intercourse satisfaction (IS) function, but normal orgasmic (OF) function. Sexual desire (SxD) function of RTRs group, although subnormal, was better than that of hemodialysis patients. Overall satisfaction (OS) of RTRs, unlike that of hemodialysis patients, was normal. Sexual dysfunction is prevalent even in NDM hemodialysis patients and RTRs. Although ED is equally prevalent among these two groups, it is more profound among the former one. OF is spared in these patients. Renal transplantation seems to normalize OS and improve SxD function of nondiabetic male renal transplant recipients (NDM RTRs).     

Surgery of female genital tract tumour lung metastases

IntroductionLung metastases originating from tumors of the female genital tract are rare. Due to this rarity and their variable histology, it has been difficult to compare different patient series.Material and methodsA retrospective study of patients who underwent resection of lung metastases of female genital tract tumors (uterine, fallopian and cervical cancer) during the period from 01/01/1989 to 12/31/2006. Epidemiological, diagnostic and treatment data were collected. Non-parametric tests and the survival analysis were performed using the Kaplan-Meier curves and the log-rank test.ResultsDuring the study period, 27 underwent resection. Mean disease-free interval (DFI) from initial diagnosis to the diagnosis of metastasis was 58 months (1–195 months). Mean survival from the diagnosis of metastasis was 94 months. The overall 5-year survival after diagnosis of metastasis was 84.1%. A second surgery for metastasis was performed on 5 patients (18.5%). Survival after second surgery of metastases was 80.5 months. Five-year survivals from diagnosis of metastasis were: endometrial carcinoma 100%; cervical cancer 62.5%; uterine sarcoma 60%. Adjuvant hormone therapy was prescribed in15 out of 16 patients with endometrial carcinoma. There was a statistically significant difference in survival depending on the histological type and disease free interval.ConclusionSurgical treatment of lung metastases originating from female genital tract tumors (mainly endometrial carcinoma) is associated with a high long-term survival.