This study assessed the risk of malignancy (ROM) of nodules classified by five US risk stratification systems (US-RSSs) and evaluated the diagnostic performances of US-RSSs with biopsy criteria for diagnosing malignancy in focal [18F]fluorodeoxyglucose (FDG)-PET/CT thyroid incidentalomas (TIs). This retrospective cohort study included 216 patients with 236 [18F]FDG-PET/CT TIs, of whom 208 (96.3%) were oncology patients. The primary outcome included the diagnostic performances of five US-RSSs with biopsy criteria for diagnosing malignant tumors. Secondary outcomes included the ROM of nodules classified by US-RSSs and the diagnostic performance of US-RSS criteria combined with maximum standardized uptake value (SUVmax). The malignancy risk of intermediate-risk TIs was higher (33.8-48.2%) than the suggested ROM across all RSSs (p < 0.01). Low-risk category TIs had a significantly higher ROM (> 20%) only in Chinese-Thyroid Imaging Reporting and Data System (C-TIRADS; 35.0%, p < 0.01). The sensitivity for overall and aggressive malignancies was highest (97.3% and 100%, respectively) in the American Thyroid Association system and Korean-TIRADS, but lower (86.7-90.7% and 80.0-86.7%, respectively) in other RSSs for 189 TIs > 1 cm. American College of Radiology (ACR)-TIRADS showed the highest specificity (50.0%) and lowest unnecessary biopsy rate (30.2%, p < 0.01). Combined SUVmax-US-RSS criteria demonstrated increased sensitivity in ACR-TIRADS (96.0%, p = 0.02), but also showed greater unnecessary biopsy rates (p < 0.01). Intermediate-risk TIs had greater ROM across RSSs, while low-risk TIs showed a significant increase only in C-TIRADS. Although US-RSSs can reduce unnecessary biopsies, European-TIRADS, ACR-TIRADS, and C-TIRADS demonstrated relatively lower sensitivity for aggressive malignancies. Question The diagnostic performance of US risk stratification systems (US-RSS) from various professional societies remains unestablished in the assessment of focal [18F]fluorodeoxyglucose (FDG)-PET/CT thyroid incidentalomas. Findings While US-RSSs reduce unnecessary biopsies, European-, American College of Radiology-, and Chinese-thyroid imaging reporting and data systems (TIRADS) demonstrated relatively lower sensitivity for aggressive malignancies. Clinical relevance US-RSSs stratify malignancy risk in focal [18F]FDG-PET/CT incidentalomas, but lower biopsy size cutoffs may be needed for intermediate-risk nodules in European- and American College of Radiology-TIRADS and low-risk nodules in Chinese-TIRADS, based on oncology patients' clinical context.

Fine needle aspiration (FNA) is widely used in the examination of head and neck lesions and has been considered an important diagnostic tool in the evaluation of thyroid and parathyroid nodules. Thyroid nodules are frequent findings in the general population, although 90-95% of these nodules are benign. FNA plays a crucial role to determine which nodules are at greatest risk of malignancy and which nodules are benign and do not require surgical intervention. In the case of the parathyroid glands, the US-guided parathyroid FNA is an effective method for the identification of intrathyroidal or ectopic parathyroid tissue, and distinguish it from thyroid and other surrounding anatomical structures. In addition, the use of FNA can significantly increase the accuracy of parathyroid gland location in patients with hyperparathyroidism who are candidates for surgical treatment in cases where imaging techniques fail to identify the parathyroid. Widespread US guidance in FNA procedures, constellation of clearly defined, reproducible key diagno­stic cytopathological criteria for individual lesions in conjunction with images and clinical data as well as evolutions in FNA techniques and ancillary tests facilitate further diagnostic and clinical management. This paper aims to review the current state of the art in cytological evaluation of thyroid and parathyroid lesions.

Clinical utility of a microRNA classifier in cytologically indeterminate thyroid nodules with RAS mutations: A multi-institutional study

Introduction. Chemicals of various hazard classes are among the most common harmful production factors. We aimed to study conditions for the occurrence, prevalence and structure of occupational diseases from exposure to chemicals at enterprises in the Arctic in order to exclude cases of early restriction or complete termination of the labour activity of workers. The study design was to analyze data of social and hygienic monitoring “Working conditions and occupational morbidity of the population” in the Russian Federation in 2007-2020. Materials and methods. We studied the data of social and hygienic monitoring “Working conditions and occupational morbidity of the population of the Russian Federation” in 2007-2020. Results. In the Russian Arctic in 2007-2020, the share of chemicals in the structure of harmful production factors was 7.6%. They were the cause of 7.8% of occupational diseases, the number of which tended to decrease. Characteristic for this group of diseases is the predominant damage to the respiratory organs (74.6%) in workers in the nickel industry (68.3%). Also, a feature of the diseases was the formation in a shorter time (24.3±0.4 years); greater risk in women (relative risk (RR) = 3.48, confidence interval (CI) 2.91-4.16; p&lt;0.001); greater risk of malignancy (RR=3.55; CI 3.13-4.02; p&lt;0.001). Out of five hundred seventy one case of occupational pathology of nickel production workers, 355 (62.2%) were caused by water-insoluble nickel compounds. Other 188 (32.9%) and 28 (4.9%) cases were due to hydroaerosols of nickel salts and nickel tetracarbonyl, respectively. Out of 164 cases of intoxication, 138 (84.1%) had a chronic course and were mainly caused by nickel compounds (87.7%). The main cause of acute intoxication (n=26) was carbon monoxide (76.9%). Limitations. Methods for determining concentrations of chemicals in the air of work areas do not provide an accurate exposure assessment in workers who use personal protective equipment. Conclusion. To reduce the occupational health risks from chemicals, first of all, it is necessary, to decrease concentrations of nickel compounds in the air of the nickel enterprise working areas. In the prevention of certain forms of occupational pathology, priority should be given to respiratory diseases from exposure to water-insoluble nickel compounds, malignant neoplasms and acute carbon monoxide poisoning.

Predictive models of thyroid nodule cancer risk are presently based upon nodule composition, echogenicity, margins, and the presence of microcalcifications. Nodule shape has shown promise to be an additive factor helping determine the need for nodule biopsy. We sought to determine if calculation of a nodule's spherical shape independently associates with cancer risk. This prospective cohort study, conducted at a single large academic healthcare system in the United States, included patients with 1 or 2 clinically relevant thyroid nodules (predominantly solid and over 1 cm) presenting for diagnostic evaluation. Thyroid ultrasound, cytological evaluation with fine-needle biopsy, and/or histopathological examination on occasion of thyroid surgery were performed. We calculated the nodule's long to short ratio (spherical shape), and its association with tissue proven benign or malignant endpoints. The long to short nodule ratio was significantly lower in malignant compared to benign nodules indicating greater risk of malignancy in more spherical nodules (1.63 ± 0.38 for malignant nodules vs 1.74 ± 0.47 for benign, P < 0.0001). The risk of malignancy continually increased as the long to short ratio approached a purely spherical ratio of 1.0 (ratio > 2.00, 14.6% cancer; ratio 1.51-2.00, 19.7%; ratio 1.00-1.50, 25.5%, P < 0.0001). In multiple regression analysis, younger age, male sex, and nodule's spherical shape were each independently associated with cancer risk. The more a thyroid nodule is spherically shaped, as indicated by a long to short ratio approaching 1.0, the greater its risk of malignancy. This was independent of age, sex, and nodule size. Incorporating a nodule's sphericity in the risk stratification systems may improve individualized clinical decision making.

It was previously shown in three subpopulations that subjects not identified with colorectal cancer (CRC) at bowel endoscopy, but with increased serological cancer-associated protein biomarker levels had an increased risk of being diagnosed with subsequent malignant diseases. The aim of the present study was to perform a pooled analysis of subjects from the three subpopulations and subsequently validate the results in an independent study. The study population denoted the training set includes N = 4,076 subjects with symptoms attributable to CRC and the independent validation set N = 3,774 similar subjects. Levels of CEA, CA19-9, TIMP-1 and YKL-40 were determined in blood samples collected prior to diagnostic bowel endoscopy. Follow-up of subjects not diagnosed with CRC at endoscopy, was ten years and identified subjects diagnosed with primary intra- or extra-colonic malignant diseases. The primary analysis was time to a newly diagnosed malignant disease and was analyzed with death as a competing risk in the training set. Subjects with HNPCC or FAP were excluded. The cumulated incidence was estimated for each biomarker and in a multivariate model. The resulting model was then validated on the second study population. In the training set primary malignancies were identified in 515 (12.6%) of the 4,076 subjects, who had a colorectal endoscopy with non-malignant findings. In detail, 33 subjects were subsequently diagnosed with CRC and 482 subjects with various extra-colonic cancers. Multivariate additive analysis of the dichotomized biomarkers demonstrated that CEA (HR = 1.50, 95% CI:1.21-1.86, p < 0.001), CA19-9 (HR = 1.41, 95% CI:1.10-1.81, p = 0.007) and TIMP-1 (HR = 1.25 95% CI: 1.01-1.54, p = 0.041) were significant predictors of subsequent malignancy. The cumulated incidence at 5 years landmark time was 17% for those subjects with elevated CEA, CA19-9 and TIMP-1 versus 6.7% for those with low levels of all. When the model was applied to the validation set the cumulated 5-year incidence was 10.5% for subjects with elevated CEA, CA19-9 and TIMP-1 and 5.6% for subjects with low levels of all biomarkers. Further analysis demonstrated a significant interaction between TIMP-1 and age in the training set. The age dependency of TIMP-1 indicated a greater risk of malignancy in younger subjects if the biomarker was elevated. This observation was validated in the second set. Elevated cancer-associated protein biomarker levels in subjects with non-malignant findings at large bowel endoscopy identifies subjects at increased risk of being diagnosed with subsequent primary malignancy. CEA, CA19-9 and TIMP-1 were significant predictors of malignant disease in this analysis. TIMP-1 was found dependent on age. The results were validated in an independent symptomatic population.

Aims & Objectives of the study: This is a prospective study to evaluate the incidence of hypocalcemia (both transient and permanent) following total thyroidectomy. About 120 patients were included over a period of 3 years from January 2018 to December 2021 admitted in department of general surgery, Trichy SRM Medical College and Research centre. Observation and Conclusion: Postoperative hypocalcemia is the most common and sometimes the most severe and potentially debilitating complication observed after Near total thyroidectomy and Total thyroidectomy. Regarding the sex distribution in this study, there were 23 males (19.2%) and 117 females (81.8%), thus we can infer that thyroid disorders are overwhelmingly more common in the fairer sex. But malignancy of thyroid gland was more common in male gender (60% of cases), probably male gender being in a greater risk for malignancy as per the AGES/AMES Criteria for thyroid malignancies. But the benign disorders of thyroid were more common among females in age group of 20-50 yrs (60%). Malignant disorders of thyroid were more common after 50 yrs of age. The incidence of hypocalcemia (transient) in our study is 21.6% and permanent hypocalcemia requiring lifelong calcium and/or vitamin D3 supplementation is 7.5%.

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Somatic and germline mutations of PTEN tumor suppressor gene are associated with follicular-pattern thyroid tumors and PTEN Hamartoma Tumor Syndrome (PHTS). The incidence of cancer in thyroid nodules positive for PTEN mutations on fine-needle aspiration (FNA) is not well defined. The aim of this study was to characterize diagnostic and phenotypic features of thyroid nodules with preoperatively detected PTEN mutations and their impact on management. Thyroid nodules with PTEN mutations on ThyroSeq v3 GC testing of FNA and core needle biopsy specimens from November 2017 to July 2020 were identified from the ThyroSeq Molecular Database. Demographic and clinicopathologic data were obtained through retrospective chart review. We identified 49 PTEN mutation-positive nodules from 48 patients. Patients were 57 years old on average (range 14-88) and 80% female. Cytology was predominantly indeterminate (73% atypia of undermined significance, 18% follicular neoplasm). There were 18 (29%) frameshift, 6 (10%) splice site, and 39 (62%) single nucleotide variant PTEN mutations. Fourteen (29%) nodules had two PTEN mutations, 5 (10%) had copy number alterations, and single cases had concurrent BRAF K601N, EZH1, and NRAS mutations. Surveillance was pursued for 27 (56%) and surgery for 21 (44%) patients (16 lobectomies, 5 total thyroidectomies). There were 14 follicular adenomas (FA), 4 oncocytic FA’s, 1 oncocytic hyperplastic nodule, and 1 encapsulated follicular variant papillary thyroid carcinoma (EFVPTC). The EFVPTC had two low-frequency PTEN mutations, PTEN locus loss, an NRAS mutation, and was a low-risk tumor with capsular but no angiolymphatic invasion. Four (8.3%) patients had confirmed or suspected PHTS, all with multiple nodules. Two had surgery finding no malignancies (2 FA). One PHTS patient had a prior thyroidectomy for a MET mutation-positive nodule that was follicular carcinoma. On US, the mean nodule size of patients who had surgery was larger than the surveillance group (3.2 cm vs. 2.3 cm, p=0.02) but there was no difference in TI-RADS level (p=0.54). There was no difference in mean nodule size (3.5 cm vs. 2.6 cm, p=0.35) or TI-RADS level (p=0.81) between PHTS and non-PHTS patients. Among surveillance patients, follow-up US was done at 1 year in 13/19 (68%) and 2 years in 3/6 (50%) of eligible cases. Only 1/19 (5%) underwent repeat FNA for increased nodule size. No thyroid malignancy was found with a mean of 1.75 years of follow-up (range 1.00-2.78). The EFVPTC patient had no recurrence after 1.05 years of follow-up. In summary, thyroid nodules with isolated somatic PTEN mutations are primarily benign and can be safely followed with serial imaging. Nodules with multiple PTEN mutations were only associated with malignancy when accompanied by an additional NRAS mutation. About 8% of patients with PTEN mutations may be PHTS patients who may be at greater risk for malignancy.

Background and ObjectivesCancer services are under increasing pressure to deliver waiting time targets. Our service has seen referral numbers increase to over 3000 per annum, with more than 80% coming from secondary care. In order to deliver a responsive service, the department has introduced a daily diagnostic multidisciplinary meeting (DMDT) with the aim being stratification of resources by directing rapid access to clinics and diagnostics to those felt to be at greatest risk of malignancy at the start of the pathway. It also aimed to improve communication with patients and referrers, consistency in decision making and deliver improved diagnostic turn-around times in a sustainable manner. An evaluation was undertaken to assess whether the introduction of the DMDT has improved the pathway, the primary endpoint being a reduction in time to definitive diagnosis (TTDD). Secondary endpoints included measurements of efficiency and whether there has been a reduction in variation in practice.MethodsRetrospective access to a prospective database over a 1-month period before (2015) and after (2018) the intervention.ResultsThe introduction of the DMDT has led to a reduction in TTDD (7 days). The service also has an added benefit in reducing average total patient miles travelled over the course of diagnosis by 22.68 miles.ConclusionThe introduction of a diagnostic MDT at the start of the pathway does lead to an improvement in service efficiency and a reduction in TTDD.

A single-center, retrospective record review of malignancy prevalence in patients with dermatomyositis with anti-transcription intermediary factor 1γ antibodies via line immunoassay versus immunoprecipitation

Mo1675 COLONOSCOPIC SURVEILLANCE AMONG INDIVIDUALS WITH LARGE TUBULAR ADENOMAS

Ultrasonography (US) is the main imaging method to assess thyroid nodules. In the pediatric population, thyroid nodules are less prevalently seen than those in adults. However, approximately 25% of the nodules can be malignant. Validation of Thyroid Image Reporting and Data System (TI-RADS) classification has been mostly tested in adults, and information on pediatric cases is limited. In the current study, we aim to define the diagnostic power of the TI-RADS risk stratification method in pediatric thyroid nodules.The study population consists of 68 nodules of 64 patients (20 malignant, 48 benign). We have included patients at least 18 years and with a pathological diagnosis. The researchers evaluated the US images of the patients, if available. If US images cannot be found, US reports of the patients were evaluated to define TI-RADS points and category.Mean age of the population is 15.15 ± 2.66 years. There were 10 (17.7%) male patients and 58 (85.3%) female patients. Median nodule size was 8 mm. Final diagnosis was benign in 48 nodules (70.6%) and malignant in 20 nodules (29.4%). There were 5 follicular carcinoma cases and 15 papillary carcinoma cases. The area under the curve estimate was 0.89 (95% confidence interval, 0.80-0.98), and the area under the curve value confirmed the diagnostic efficacy of TI-RADS categorization in pediatric thyroid nodules. A TI-RADS category of 4 or 5 seemed to be a good cutoff point to predict malignancy.To conclude, TI-RADS categorization can be effectively used to assess pediatric thyroid nodules. Nodules with TI-RADS categories of 4 and 5 have the greatest risk of malignancy, and they should be evaluated pathologically.

Abstract Objective: Review and analyze serum values of Risk of Ovarian Malignancy Algorithm (ROMA) and Multivariate Index Assay (MIA) in subgroups of women who underwent surgery for adnexal masses to determine sensitivity in different ethnic populations. Methods: Serum samples from 179 women diagnosed with ovarian malignancy were analyzed for ROMA and MIA results. Biomarker data was obtained from previous prospective studies that validated the MIA test. Of these, 167 women were Caucasian (C) and 12 African-American (AA) in the MIA testing. Sample for ROMA included 161 C and 11 AA. Sensitivity (true positive rate) for preoperative test results were calculated using DTCompair package of the R programming language. In premenopausal women, a risk of ovarian malignancy algorithm (ROMA) value equal to or greater than 1.14 indicates a high risk of finding epithelial ovarian cancer. In premenopausal women, MIA values of greater than 5.0 are associated with greater risk of malignancy. In postmenopausal women, a ROMA value equal to or greater than 2.99 indicates a high risk of finding epithelial ovarian cancer. In postmenopausal women, MIA values of greater than 4.4 are associated with greater risk of malignancy. Results: Primary ovarian malignancy was diagnosed in 179 cases (167 C/12 AA). Sensitivity testing results are seen for each subgroup and for MIA levels and CA125 results: Primary Ovarian Malignancy: Caucasian MIA 97.0%, ROMA 89.4%, AA MIA 75.0% ROMA 45.5%. Sensitivity of ROMA in AA premenopausal women was 50% and in postmenopausal women 33.3 %. Conclusion: Our results demonstrate that ROMA in both C andAA women with adnexal masses have lower sensitivity for detection of malignancy than does MIA. It is more pronounced in AA women. Implementation of MIA in evaluation of adnexal masses will increase sensitivity of detection of malignancy compared to CA125 testing, with most marked results in AA women. Key Words: Ethnicity, CA125, and Multivariate Index Assay Sensitivity of MIA vs. ROMA Ovarian MalignancyRaceTestStatusMenopauseNumberSensitivityCaucasianMIAAll16797.0CaucasianMIAPre4395.3CaucasianMIAPost12497.6CaucasianROMAAll16189.4CaucasianROMAPre4092.5CaucasianROMAPost12188.4African AmericaMIAAll1275African AmericaMIAPre977.8African AmericaMIAPost366.7African AmericaROMAAll1145.5African AmericaROMAPre850.0African AmericaROMAPost333.3 Citation Format: Charles Dunton, Herbert Fritsche, Rowan Bullock. Ethnic disparity in ovarian malignancy tumor markers: MIA and ROMA [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 3339.

Risk of malignancy in the categories of the Papanicolaou Society of Cytopathology system for reporting pancreaticobiliary cytology

Barrett's esophagus (BE) is a controversial condition. The significance of this condition lies in its premalignant potential, so it is important that clinically applicable biomarkers be identified for early detection and targeted prevention. Dysplasia is currently used as main biomarker, but others most recently surveyed in cancer also include microRNAs. Classically, BE was considered to be an acquired disease related to pathological gastroesophageal acid and bile reflux. However, some cases are associated with genetic predisposition, representing an inherited, familial form of BE. The actual gene, or genes, involved in this condition have not yet been identified. Main therapeutic options include medical treatment and antireflux surgery. Both types of treatment are equally efficient in controlling symptoms and neither is able to cause the metaplastic segment to disappear, which is why the risk of malignancy remains. However, we may use endoscopic radiofrequency to eradicate BE and replace it by the typical squamous epithelium of the esophagus. The currently accepted indications of radiofrequency in BE include low- and high-grade dysplasia, but not Barrett's esophagus without dysplasia. In conclusion, BE may have two different presentations: environmental ("human", reflux) or sporadic BE, which is the most common form, and genetic ("divine", inherited) or familiar BE, less common but with a greater risk for malignancy. As they might be two different diseases, surveillance programs and treatments should also be different.

Objective:To review and analyze the serum values of risk of ovarian malignancy algorithm (ROMA) and multivariate index assay (MIA) in subgroups of women who underwent surgery for adnexal masses to determine sensitivity, specificity, and positive and negative predictive values for the detection of malignancy in different ethnic populations.Methods:Serum samples from 2 prospective trials of 1029 women in which 274 women diagnosed with malignancy were analyzed for ROMA scores and MIA results. Biomarker data were obtained from the previous prospective studies that validated the MIA test. Of these, 250 women were Caucasian (C) and 24 were African-American (AA). Sensitivity, specificity, positive and negative predictive values, and confidence intervals for preoperative test results were calculated using DTComPair package of the R programming language. In premenopausal women, a ROMA value equal to or greater than 1.14 indicates a high risk of finding epithelial ovarian cancer. In premenopausal women, MIA values greater than 5.0 are associated with a greater risk of malignancy. In postmenopausal women, a ROMA value equal to or greater than 2.99 indicates a high risk of finding epithelial ovarian cancer. In postmenopausal women, MIA values greater than 4.4 are associated with a greater risk of malignancy.Results:Primary ovarian malignancy was diagnosed in 179 cases (167 C/12 AA) and metastatic disease to the ovary in an additional 27 cases (22 C/5 AA). Overall results are shown below.Conclusions:Our results demonstrate that ROMA in AA women with adnexal masses have lower sensitivity for the detection of malignancy than does MIA. Implementation of MIA in the evaluation of adnexal masses will increase the sensitivity of the detection of malignancy compared with ROMA, with the most marked results in AA women.

This study aimed to assess the presence of pancreatic hyperenzymemia in patients with pancreatic cystic lesions as compared to other chronic diseases of the pancreas. Ninety-one patients were studied: 32 had mucinous cystic lesions, 35 had chronic pancreatitis (CP), and 24 had pancreatic ductal adenocarcinoma (PDAC). Surgery was carried out in 10 of the 32 patients with mucinous cystic lesion (7 of them had severe dysplasia), in 5 patients with CP, and in 9 patients with PDAC. Abnormally high serum pancreatic isoamylase activity was present in 11 (34.4%) patients with mucinous cystic lesions, in 14 (40.0%) patients with CP, and none in patients with PDAC (P = 0.002); whereas serum lipase activity was abnormally high in 8 (25.0%) patients with mucinous cystic lesion, in 17 (48.6%) patients with CP, and in 3 (12.5%) patients with PDAC (P = 0.009). In 7 patients with mucinous cystic lesions and histologically confirmed severe dysplasia, abnormally high levels of both serum pancreatic amylase and lipase were present in 3 (42.9%) patients. High serum concentrations of pancreatic amylase and lipase were found in no more than half of the patients with mucinous cystic lesions. High levels of pancreatic enzymes were not associated with a greater risk of malignancy.

An Analysis of Weight Gains and Body Mass Index in Patients with Barrett’s Esophagus

From the early days of transplantation onwards, increased cancer development in transplant recipients, who require immunosuppression to avoid graft rejection, has been recognized. Registry data indicate that approximately 10-30% of deaths are attributed to post-transplant malignancy, with an upward trend in this incidence as more patients have been exposed to chronic lifelong immunosuppression. In this Review, the overall incidence and most frequent types of cancer encountered are summarized, along with information about which transplant recipients are at the greatest risk of malignancy. Reasons for why differences exist in susceptibility to cancer in this patient population are examined, and approaches that might improve our understanding of the options available for reducing the incidence of this adverse effect of immunosuppression are described. Whether anti-rejection drugs have been successful in diminishing overall immunosuppressive burden, and consequently show any promise for decreasing post-transplant malignancies is also discussed. The topic shifts to one class of conventional anti-rejection drugs, the mammalian target of rapamycin (mTOR) inhibitors, which paradoxically have both immunosuppressive and anti-neoplastic properties. The complex activities of mTOR are reviewed in order to provide context for how these seemingly opposing effects are possible, and the latest clinical data on use of mTOR inhibitors in the clinic are discussed. The current and future perspectives on how best to normalize these unacceptably high rates of post-transplantation malignancies are highlighted.