The burden of cutaneous disease in solid organ transplant recipients of color

Organ transplant recipients (OTRs) are at increased risk of cutaneous malignancy. Skin disorders in OTRs of color (OTRoC) have rarely been systematically assessed. We aimed to ascertain the burden of skin disease encountered in OTRoC by prospectively collecting data from OTRs attending 2 posttransplant skin surveillance clinics: 1 in London, UK and 1 in Philadelphia, USA. Retrospective review of all dermatological diagnoses was performed. Data from 1766 OTRs were analyzed: 1024 (58%) white, 376 (21%) black, 261 (15%) Asian, 57 (3%) Middle Eastern/Mediterranean (ME/M), and 48 (2.7%) Hispanic; and 1128 (64%) male. Viral infections affected 45.1% of OTRs, and were more common in white and ME/M patients (P < .001). Fungal infections affected 28.1% and were more common in ME/M patients (P < .001). Inflammatory skin disease affected 24.5%, and was most common in black patients (P < .001). In addition, 26.4% of patients developed skin cancer. There was an increased risk of skin cancer in white vs nonwhite OTRs (HR 4.4, 95% CI 3.5-5.7, P < .001): keratinocyte cancers were more common in white OTRs (P < .001) and Kaposi sarcoma was more common in black OTRs (P < .001). These data support the need for programs that promote targeted dermatology surveillance for all OTRs, regardless of race/ethnicity or country of origin.     

Pretransplant solid organ malignancy and organ transplant candidacy: A consensus expert opinion statement

Patients undergoing evaluation for solid organ transplantation (SOT) often have a history of malignancy. Although the cancer has been treated in these patients, the benefits of transplantation need to be balanced against the risk of tumor recurrence, especially in the setting of immunosuppression. Prior guidelines of when to transplant patients with a prior treated malignancy do not take in to account current staging, disease biology, or advances in cancer treatments. To develop contemporary recommendations, the American Society of Transplantation held a consensus workshop to perform a comprehensive review of current literature regarding cancer therapies, cancer stage-specific prognosis, the kinetics of cancer recurrence, and the limited data on the effects of immunosuppression on cancer-specific outcomes. This document contains prognosis based on contemporary treatment and transplant recommendations for breast, colorectal, anal, urological, gynecological, and nonsmall cell lung cancers. This conference and consensus documents aim to provide recommendations to assist in the evaluation of patients for SOT given a history of a pretransplant malignancy.     

Immune checkpoint inhibitor therapy-associated graft intolerance syndrome in a failed kidney transplant recipient

Immune checkpoint inhibitors (ICPIs) are monoclonal antibodies against inhibitory receptors on T cells resulting in anticancer activity. In kidney transplant (KT) recipients, ICPI use has been associated with acute allograft rejection. In failed allografts, however, the effects of ICPIs are unknown. We present a case of a 66-year-old man with a history of diabetes, renal cell cancer, left native nephrectomy, and end-stage kidney disease. He received a deceased donor KT which failed after 6 years due to biopsy-proven recurrent diabetic nephrosclerosis. He was started on hemodialysis and his immunosuppression was gradually weaned off. A year later, he was diagnosed with renal cell cancer in his right native kidney requiring nephrectomy. He later developed metastasis and was started on combination ICPIs. He developed hematuria, allograft pain, and malaise consistent with graft intolerance syndrome 28 days after starting ICPIs. Urine culture and cystoscopy were normal. A computed tomography scan of his abdomen revealed an enlarged allograft with patchy enhancement. After a multidisciplinary discussion, he underwent transplant nephrectomy. Histopathology showed chronic active T cell–mediated rejection. As ICPI use becomes prevalent, practitioners need to be aware of its potential complications among KT recipients both with functioning and failed allografts.     

A world-wide survey on kidney transplantation practices in breast cancer survivors: The need for new management guidelines

Kidney transplantation reduces mortality in patients with end stage renal disease (ESRD). Decisions about performing kidney transplantation in the setting of a prior cancer are challenging, as cancer recurrence in the setting of immunosuppression can result in poor outcomes. For cancer of the breast, rapid advances in molecular characterization have allowed improved prognostication, which is not reflected in current guidelines. We developed a 19-question survey to determine transplant surgeons’ knowledge, practice, and attitudes regarding guidelines for kidney transplantation in women with breast cancer. Of the 129 respondents from 32 states and 14 countries, 74.8% felt that current guidelines are inadequate. Surgeons outside the United States (US) were more likely to consider transplantation in a breast cancer patient without a waiting period (p = .017). Within the US, 29.2% of surgeons in the Western region would consider transplantation without a waiting period, versus 3.6% of surgeons in the East (p = .004). Encouragingly, 90.4% of providers surveyed would consider eliminating wait-times for women with a low risk of cancer recurrence based on the accurate prediction of molecular assays. These findings support the need for new guidelines incorporating individualized recurrence risk to improve care of ESRD patients with breast cancer.     

Changes in retinoblastoma gene expression during cervical cancer progression

The role of tumour suppressor genes in the development of human cancers has been studied extensively. In viral carcinogenesis, the inactivation of suppressor proteins such as retinoblastoma (pRb) and p53, and cellular oncogenes overexpression, such as c-myc, has been the subject of a number of investigations. In uterine-cervix carcinomas, where high-risk human papillomavirus (HPV) plays an important role, pRb and p53 are inactivated by E7 and E6 viral oncoproteins, respectively. However, little is known about the in situ expression of some of these proteins in pre-malignant and malignant cervical tissues. On the other hand, it has also been demonstrated that c-myc is involved in cervical carcinogenesis, and that pRb participates in the control of c-myc gene expression. By using immunostaining techniques, we investigated pRb immunodetection pattern in normal tissues, squamous intraepithelial lesions (SILs) and invasive carcinomas from the uterine cervix. Our data show low pRb detection in both normal cervical tissue and invasive lesions, but a higher expression in SILs. C-Myc protein was observed in most of the cellular nuclei of the invasive lesions, while in SILs was low. These findings indicate a heterogeneous pRb immunostaining during the different stages of cervical carcinogenesis, and suggest that this staining pattern could be a common feature implicated in the pathogenesis of uterine-cervix carcinoma.     

HLA-D Antigen Expression and Langerhans' Cell Infiltrates in Thyroid Tumors

Papillary carcinomas (PCs) of thyroid are among the most common but least aggressive human malignancies. The factors explaining the indolence of these tumors are unknown but host-tumor immune interactions may play a role. This study was designed to determine if there is morphologic evidence of these. Frozen tissues collected from 21 PCs, 4 follicular adenomas (FAs), 4 follicular carcinomas (FCs), and 11 nodular hyperplasias (NHs) were stained immunohistochemically for HLA-D antigens, lymphocyte and macrophage markers; results were graded numerically. Paraffin-embedded tumors (35 PCs, 10 FAs, and 10 FCs) were stained for S-100 protein to detect Langerhans' cells (LCs). Diffuse staining for HLA-D antigens and heavy mononuclear infiltrates were found more commonly in PCs compared to follicular neoplasms (FNs) or NHs. No consistent relationship was found between lymphocyte/macrophage infiltrates and expression of HLA-D antigens. The largest number of LCs was in PCs (median 11.8 cells/standard microscopic field [c/smf]), fewer cells were found in FA (3.7 c/smf), and the least in FC (0.05 c/smf). Features of host-tumor interaction including HLA-D expression and infiltrates with lymphocyte macrophages and LC are more strongly expressed in PC than other tumors. This may play a role in explaining their biological behavior.     

阴道镜下常规活检诊断宫颈上皮内瘤样病变108例分析

目的：通过阴道镜下常规活检，探讨宫颈上皮内瘤样癌变（CIN）的检查率、镜图像特征及诊断价值。方法：回顾分析5年来阴道镜检查834例中108例CIN的阴道镜检结果。结果：834例中CIN发现108例，占12．8％，CIN的异常阴道镜像主要为血管异常及腺口白环、白腺。结论：阴道镜是辅助诊断CIN的重要方法，初次阴道镜检可疑时应进行常规活检。     

宫颈癌组织中环氧合酶-2和诱生型一氧化氮合酶的表达及其意义

目的 :研究环氧合酶 2 (COX 2 )和诱生型一氧化氮合酶(iNOS)在宫颈癌发生发展中的作用。方法 :用免疫组化方法检测 80例宫颈癌患者COX 2和iNOS的表达水平 ,并以 3 1例宫颈上皮内瘤样病变(CIN)、3 0例慢性宫颈炎症患者和 3 0例正常宫颈上皮为对照组。结果 :(1 )宫颈癌患者COX 2和iNOS表达阳性率分别为 5 8.75 %和 86.2 5 % ,高于CIN、慢性宫颈炎症患者和正常宫颈上皮组 ;(2 )宫颈癌患者COX 2和iNOS的表达水平与临床分期、组织学分型及细胞分化程度无关 (P >0 .0 5 ) ;(3 )伴淋巴结转移的宫颈癌患者COX 2的表达水平略高于不伴淋巴结转移者 ,但差异无显著性 (P >0 .0 5 ) ,而iNOS的表达水平明显高于不伴淋巴结转移者 (P <0 .0 5 ) ;(4 )肿瘤直径≥ 5cm的宫颈癌患者COX 2的阳性表达率明显高于肿瘤直径 <5cm者 (P <0 .0 5 ) ,而iNOS的阳性表达率高于肿瘤直径 <5cm者 ,但差异无显著性 (P >0 .0 5 ) ;(5 )伴宫旁浸润或脉管浸润的宫颈癌患者COX 2和iNOS表达水平明显高于不伴宫旁浸润或脉管浸润者 (P <0 .0 1 ) ;(6)宫颈癌患者COX 2和iNOS的表达之间无相关性 ,而慢性宫颈炎症患者COX 2和iNOS的表达之间有相关性。结论 :宫颈癌患者COX 2和iNOS的表达水平明显上调 ,其表达与宫颈癌的发生发展有关     

宫颈细胞学和电子阴道镜在宫颈病变早期诊断中的应用研究

目的进一步评价细胞学和电子阴道镜在宫颈病变的早期诊断中的价值.方法回顾性分析431例宫颈涂片和阴道镜检的结果,与活检组织病理学的结果进行对比研究.结果 431例中检出宫颈上皮内瘤变(CIN)Ⅰ 39例、CIN Ⅱ 36例、CIN Ⅲ 32例、宫颈鳞癌11例和宫颈湿疣27例,其余286例为慢性宫颈炎.宫颈涂片检出了93.5%宫颈病变,阴道镜检出了95.9%宫颈病变,细胞学与阴道镜下活检联合应用无漏诊.结论细胞学与阴道镜下活检联合应用能提高宫颈病变的检出率,阴道镜检查能明显提高宫颈湿疣的检出率.     

B(a)P诱导小鼠前胃癌过程中组织病理学变化

目的：探讨B(a)P诱导小鼠前胃癌过程中胃组织形态学的动态改变。方法：小鼠用5mg／ml的B(a)P灌胃，每周两次，共4周。以后每隔4周处死一部分小鼠，对胃组织进行病理组织学观察。结果：从第17周开始小鼠前胃开始出现肉眼可见的肿瘤，前胃组织由局部腺体增生、排列紊乱逐步发展为腺体普遍异常增生，形成早期胃癌，进一步发展出现进展期胃癌。结论：B(a)P诱导的小鼠前胃癌的潜伏期大约3个月左右，前胃组织病理学动态变化过程是萎缩性胃炎、不典型增生、胃癌。