Augmented reality-assisted training with selected Tai-Chi movements improves balance control and increases lower limb muscle strength in older adults: A prospective randomized trial.

BACKGROUND: Tai-Chi benefits older adults by enhancing balance control and increasing the muscle strength of the lower limbs. However, a complete set of traditional Tai-Chi exercises is sometimes too difficult for beginners. We investigated whether practicing augmented reality-assisted training with selected Tai-Chi movements tailored to the practitioner's ability (selected Tai-Chi, or sTC) is as effective as performing a complete set of Tai-Chi sequences (complete traditional Tai-Chi, or tTC). METHODS: In this prospective randomized trial carried out in the Beitou District of Taipei City, Taiwan, community-dwelling adults aged ≥65 and without any debilitating diseases (n = 28) were included. Participants were randomly assigned to the sTC group (n = 14) or the tTC group (n = 14). Participants in the sTC group practiced selected Tai-Chi movements using the augmented reality Tai-Chi training system. Participants of the tTC group were asked to complete the 24-form Yang-style Tai-Chi following the instructions of Tai-Chi masters. Each training session lasted 30 min, with 3 sessions per week for 8 weeks. Pre- and post-intervention evaluations included functional balance tests, comprising the Berg Balance Scale (BBS), Timed Up and Go test (TUG), and Functional Reach Test (FRT), as well as muscle strength measurements of the lower extremities. RESULTS: Pre-intervention evaluations showed significant differences in FRT (p = 0.034) and left hip abductor muscle strength (p = 0.046) between the sTC and tTC groups. After 8 weeks of training, the BBS, TUG, and FRT scores in the sTC group showed significant improvement overall. Although all three functional balance test scores improved in the tTC group, only the improvement in BBS was statistically significant (p = 0.001). After 8 weeks, all muscle strength measurements increased by an average of 3.1 ± 1.0 kgw in the sTC group and 1.6 ± 0.8 kgw in the tTC group. CONCLUSIONS: The augmented reality-assisted training with selected Tai-Chi movements, designed based on objective measurements of the practitioner's capability, improved balance control and muscle strength of lower limbs at least as effectively as the complete sequence of traditional Tai-Chi exercises. TRIAL REGISTRATION: This study was approved by the Institutional Review Board of National Yang-Ming University (IRB number: 1000087). Written informed consent was obtained from all participants.

Risk factors and prediction model for persistent breast-cancer-related lymphedema: a 5-year cohort study.

PURPOSE: Breast-cancer-related lymphedema (BCRL) can be a transient or persistent condition. The aims of this study were to (1) identify and weigh the risk factors for persistent lymphedema (PLE) among all patients with BCRL and (2) establish a prediction model for the occurrence of PLE. METHODS: A cohort of 342 patients with BCRL with a median follow-up of 5 years after the onset of swelling was analyzed. PLE was defined as a hardening of the subcutaneous tissue, the persistence of the circumferential difference (CD) between arms, or a flare-up of swelling during follow-up. Multiple logistic regression was used to identify risk factors for PLE, including tumors, treatments, and patient-related factors. The prediction accuracy of the model was assessed using the area under the receiver operating characteristic curve (AUC). RESULTS: Of the 342 patients with BCRL, 229 (67%) had PLE. Multiple logistic regression analysis revealed that the number of lymph node metastases (p = 0.012), the maximal CD between arms at the first occurrence of swelling (p < 0.001), and the largest difference during follow-up (p < 0.001) were significant predictors for PLE. The corresponding AUC was 0.908. Although inclusion of body weight gains (p = 0.008) and maximal CD at the latest follow-up (p = 0.002) increased the analytical accuracy (AUC = 0.920), the resulting AUC values (p = 0.113) were not significantly different. CONCLUSIONS: BCRL is persistent in two thirds of patients. Patients with more lymph node metastases, weight gain, and larger CD since the onset of swelling and during follow-up have an increased likelihood of developing PLE.

Effects of individualized Tai-Chi on balance and lower-limb strength in older adults.

BACKGROUND: To investigate whether a simplified and personalized Tai-Chi program could be beneficial for practitioners. A prospective quasi-experimental observer-blinded controlled trial was done in Beitou District of Taipei City. METHODS: Community-dwelling adults aged 65 and older without debilitating disease (N = 50) participated the study. Those who were willing to participate in exercise program were assigned to individualized Tai-Chi (iTC) group (n = 20), receiving iTC training for 8 weeks, and traditional Tai-Chi (tTC) group (n = 15), receiving tTC training for 8 weeks. Those who were not willing to participate in exercise training were included in the control group (n = 15). Functional balance tests, the Berg Balance Scale (BBS), timed up-and-go (TUG) test, functional-reach test, and measurement of lower-extremity muscle strength were conducted before and 8 weeks after the intervention. RESULTS: Significant improvements were noted in all functional balance tests and strength assessments of 16 major lower-limb muscle groups in participants of the iTC group compared to the control group, whereas only BBS and muscle strength of hips and ankles were improved in the tTC group. Practitioners of iTC outperformed tTC in BBS and strength of two major muscles. CONCLUSIONS: Personalized Tai-Chi training designed based on an objective measurement and conducted according to graded intensity and complexity benefitted practitioners after a short period. TRIAL REGISTRATION: Trial registration number: ClinicalTrials.gov ID: NCT03659396 , Unique Protocol ID: 1000087 Date of registration: 03/28/2017 The trial was registered retrospectively.

Increased risk of dementia in patients with nasopharyngeal cancer treated with radiation therapy: A nationwide population-based cohort study.

PURPOSE: We evaluated the risk of dementia in patients with nasopharyngeal cancer (NPC) after undergoing radiation therapy (RT). METHODS: Between January 1, 2000, and December 31, 2015, 594 patients newly diagnosed with NPC and treated with RT (NPC cohort) were identified from the Longitudinal Health Insurance Database (LHID) for this nationwide population-based matched cohort study. LHID is a subset of the National Health Insurance Research Database of Taiwan. We selected 2376 controls (non-NPC comparison cohort) using a four-fold propensity score-matched by sex, age, comorbidities, education level, tobacco abuse, and index date (the date when the patient received first RT). After adjusting for confounding factors, Fine and Gray's competing risk analysis compared dementia development between the NPC study cohort and non-NPC comparison cohort over the observation period from 2000 to 2015. RESULTS: Dementia development was 6.57% (39 of 594) and 4.42% (105 of 2376) in the NPC study cohort and non-NPC comparison cohort, respectively. Patients with NPC receiving RT were more likely to develop dementia than the comparison cohort, with a crude hazard ratio (HR) of 1.63 [95% confidence interval (CI) = 1.25-2.13, P < 0.001]. After adjusting for age, sex, education level, tobacco abuse, comorbidity, geographic area, urbanization level of the residence, and care level, the adjusted HR was 1.91 (95% CI = 1.42-2.51, P < 0.001). CONCLUSIONS: Patients with NPC receiving RT had a 1.91-fold higher risk of dementia than the non-NPC comparison controls.

Bidirectional association between migraine and fibromyalgia: retrospective cohort analyses of two populations.

OBJECTIVE: Fibromyalgia (FM) and migraine are common pain disorders that tend to coexist. This study determined whether these two conditions exhibited any mutual influences. SETTING: Cohort study. PARTICIPANTS: A retrospective, longitudinal cohort study was conducted using data obtained from a nationwide healthcare database. This study had two arms. Arm 1 comprised 33 216 patients with FM and arm 2 consisted of 7420 patients with migraine; all of these patients were diagnosed between 2000 and 2010. Using the aforementioned database, control subjects who had neither FM nor migraine and were matched with the FM and migraine patients by sex, age and index date of diagnosis were recruited. Each control cohort was four times the size of the corresponding study cohort. Follow-up for the control and study cohorts was conducted until the end of 2011. RESULTS: The incidence rates of FM and migraine were calculated in arms 1 and 2, respectively. The overall incidence of migraine was greater in the FM cohort than in the corresponding control cohort (4.39 vs 2.07 per 1000 person-years (PY)); crude HR=2.12, 95% CI=1.96 to 2.30; adjusted HR (aHR)=1.89, 95% CI=1.75 to 2.05). After adjustment for sex, age and comorbidities, the overall incidence of FM in the migraine cohort was 1.57 times greater than that in the corresponding control cohort (7.01 vs 4.49 per 1000 PY; aHR=1.52, 95% CI=1.39 to 1.65). CONCLUSIONS: The present study revealed a bidirectional link between FM and migraine.

Speed and temporal adaptations during nonmotorized treadmill walking in Parkinson disease and nondisabled individuals.

Few studies have explored the potential of gait analysis and training in nonmotorized treadmill (NMT) in Parkinson's disease (PD) patients. We investigated (a) the walking strategy adopted by patients with PD on NMT and (b) how balance may influence spatiotemporal gait parameters. We enrolled 12 patients with PD of modified Hoehn and Yahr stage 2-3 and 13 nondisabled individuals as controls. All participants were evaluated using Tinetti's performance oriented mobility assessment scale, freezing of gait questionnaire, modified falls efficacy scale, and the timed up and go test. They were asked to ambulate with comfortable and maximal speeds on the NMT. The gait parameters acquired on the NMT included walking speed, cadence (CAD), step length, and vertical ground reaction force, which were calculated for intragroup and intergroup comparisons. The PD group took on with higher contribution of CAD and less contribution of step length to increase walking speed as compared with control group. The postural stability is correlated significantly positively to the CAD at the setting of maximal speed in the PD group. Moreover, a significantly lower ratio of vertical ground reaction force/body weight was noted in the PD group during both comfortable and maximal walking speeds compared with the nondisabled controls. Our study outcomes clearly support the perceived benefits of NMT to differentiate spatiotemporal gait parameters between PD and controls. NMT may potentially be useful to evaluate the recovery of physical activities in PD receiving medications and/or rehabilitation.

EMG changes during graded isometric exercise in pianists: comparison with non-musicians.

BACKGROUND: Long-term piano training might induce some biochemical and structural adaptations in the intrinsic muscles of the hand or change the motor strategy of the nervous system. The main purpose of this study was to analyze whether the intrinsic muscles of the hands of pianists and sedentary controls differ in electromyographic characteristics at different strengths. METHODS: Fifteen college piano students and 15 sedentary controls were asked to sit on an examination bench and perform first dorsal interosseous muscle contractions for 1 minute. The motor unit potentials were recorded during various percentages of maximal voluntary muscle contraction (MVC) by automatic decomposition electromyography. RESULTS: The pianists demonstrated a significantly higher firing rate, shorter duration, and higher amplitude of motor unit potentials during minimal muscle contractions than the sedentary controls. But when comparing all the parameters at other degrees of contractions, the pianists were found to have significantly higher firing rate only at 25% and 50% of MVC, and higher amplitude at maximal contraction than the control group. The amplitude at maximal control contraction was higher in pianists than in controls. CONCLUSION: These results imply that high-frequency and highly efficient muscle fibers are recruited in pianists when minimal muscle contractions are performed, which also indicate that by using smaller motor units, pianists may delicately control their fine motor performance.

Bypass surgery versus stenting for the treatment of multivessel disease in patients with unstable angina compared with stable angina.

BACKGROUND: Earlier reports have shown that the outcome of balloon angioplasty or bypass surgery in unstable angina is less favorable than in stable angina. Recent improvements in percutaneous treatment (stent implantation) and bypass surgery (arterial grafts) warrant reevaluation of the relative merits of either technique in treatment of unstable angina. Methods and Results- Seven hundred fifty-five patients with stable angina were randomly assigned to coronary stenting (374) or bypass surgery (381), and 450 patients with unstable angina were randomly assigned to coronary stenting (226) or bypass surgery (224). All patients had multivessel disease considered to be equally treatable by either technique. Freedom from major adverse events, including death, myocardial infarction, and cerebrovascular events, at 1 year was not different in unstable patients (91.2% versus 88.9%) and stable patients (90.4% versus 92.6%) treated, respectively, with coronary stenting or bypass surgery. Freedom from repeat revascularization at 1 year was similar in unstable and stable angina treated with stenting (79.2% versus 78.9%) or bypass surgery (96.3% versus 96%) but was significantly higher in both unstable and stable patients treated with stenting (16.8% versus 16.9%) compared with bypass surgery (3.6% versus 3.5%). Neither the difference in costs between stented or bypassed stable or unstable angina ($2594 versus $3627) nor the cost-effectiveness was significantly different at 1 year. CONCLUSIONS: There was no difference in rates of death, myocardial infarction, and cerebrovascular event at 1 year in patients with unstable angina and multivessel disease treated with either stented angioplasty or bypass surgery compared with patients with stable angina. The rate of repeat revascularization of both unstable and stable angina was significantly higher in patients with stents.

Efficacy of coronary stenting versus balloon angioplasty in small coronary arteries. Stent Restenosis Study (STRESS) Investigators.

OBJECTIVES: The goal of this study was to compare the efficacy of elective stent implantation and balloon angioplasty for new lesions in small coronary arteries. BACKGROUND: Palmaz-Schatz stents have been designed and approved by the Food and Drug Administration for use in coronary arteries with diameters > or = 3.0 mm. The efficacy of elective stent placement in smaller vessels has not been determined. METHODS: By quantitative coronary angiography, 331 patients in the Stent Restenosis Study (STRESS) I-II were determined to have a reference vessel < 3.0 mm in diameter. Of these, 163 patients were randomly assigned to stenting (mean diameter 2.69 +/- 0.21 mm), and 168 patients were assigned to angioplasty (mean diameter 2.64 +/- 0.24 mm). The primary end point was restenosis, defined as > or = 50% diameter stenosis at 6-month follow-up angiography. Clinical event rates at 1 year were assessed. RESULTS: Baseline clinical and angiographic characteristics were similar in the two groups. Procedural success was achieved in 100% of patients assigned to stenting and in 92% of patients assigned to angioplasty (p < 0.001). Abrupt closure within 30 days occurred in 3.6% of patients in both groups. Compared with angioplasty, stenting conferred a significantly larger postprocedural lumen diameter (2.26 vs. 1.80 mm, p < 0.001) and a larger lumen at 6 months (1.54 vs. 1.27 mm, p < 0.001). Restenosis (> or = 50% diameter stenosis at follow-up) occurred in 34% of patients assigned to stenting and in 55% of patients assigned to angioplasty (p < 0.001). At 1 year, event-free survival was achieved in 78% of the stent group and in 67% of the angioplasty group (p = 0.019). CONCLUSIONS: These findings suggest that elective stent placement provides superior angiographic and clinical outcomes than balloon angioplasty in vessels slightly smaller than 3 mm.

First international new intravascular rigid-flex endovascular stent study (FINESS): clinical and angiographic results after elective and urgent stent implantation. The FINESS Trial Investigators.

OBJECTIVES: The purpose of this study was to determine the feasibility, safety and efficacy of elective and urgent deployment of the new intravascular rigid-flex (NIR) stent in patients with coronary artery disease. BACKGROUND: Stent implantation has been shown to be effective in the treatment of focal, new coronary stenoses and in restoring coronary flow after coronary dissection and abrupt vessel closure. However, currently available stents either lack flexibility, hindering navigation through tortuous arteries, or lack axial strength, resulting in suboptimal scaffolding of the vessel. The unique transforming multicellular design of the NIR stent appears to provide both longitudinal flexibility and radial strength. METHODS: NIR stent implantation was attempted in 255 patients (341 lesions) enrolled prospectively in a multicenter international registry from December 1995 through March 1996. Nine-, 16- and 32-mm long NIR stents were manually crimped onto coronary balloons and deployed in native coronary (94%) and saphenous vein graft (6%) lesions. Seventy-four percent of patients underwent elective stenting for primary or restenotic lesions, 21% for a suboptimal angioplasty result and 5% for threatened or abrupt vessel closure. Fifty-two percent of patients presented with unstable angina, 48% had a previous myocardial infarction, and 45% had multivessel disease. Coronary lesions were frequently complex, occurring in relatively small arteries (mean [+/-SD] reference diameter 2.8 +/- 0.6 mm). Patients were followed up for 6 months for the occurrence of major adverse cardiovascular events. RESULTS: Stent deployment was accomplished in 98% of lesions. Mean minimal lumen diameter increased by 1.51 +/- 0.51 mm (from 1.09 +/- 0.43 mm before to 2.60 +/- 0.50 mm after the procedure). Mean percent diameter stenosis decreased from 61 +/- 13% before to 17 +/- 7% after intervention. A successful interventional procedure with < 50% diameter stenosis of all treatment site lesions and no major adverse cardiac events within 30 days occurred in 95% of patients. Event-free survival at 6 months was 82%. Ninety-four percent of surviving patients were either asymptomatic or had mild stable angina at 6 month follow-up. CONCLUSIONS: Despite unfavorable clinical and angiographic characteristics of the majority of patients enrolled, the acute angiographic results and early clinical outcome after NIR stent deployment were very promising. A prospective, randomized trial comparing the NIR stent with other currently available stents appears warranted.

Does ticlopidine reduce reocclusion and other adverse events after successful balloon angioplasty of occluded coronary arteries? Results from the Total Occlusion Study of Canada (TOSCA).

OBJECTIVES: Ticlopidine reduces stent thrombosis and other adverse events among patients receiving coronary stents. Whether ticlopidine is beneficial after balloon angioplasty is unknown. Our purpose was to compare the clinical outcome of patients undergoing balloon angioplasty treated with both aspirin and ticlopidine versus aspirin alone. METHODS AND RESULTS: We performed a databank analysis of the Total Occlusion Study of Canada (TOSCA), a randomized trial with angiographic follow-up comparing the frequency of reocclusion after angioplasty of a subtotal or total coronary occlusion in patients receiving >/=1 heparin-coated Palmaz-Schatz stent versus balloon angioplasty alone. In TOSCA, 102 patients undergoing balloon angioplasty were treated with both aspirin and ticlopidine (generally for 15-30 days) and 94 were treated with aspirin alone, by physician preference. After 6 months, failure to sustain patency (less than Thrombolysis in Myocardial Infarction [TIMI] grade 3 flow on follow-up angiography) occurred in 23% of patients on ticlopidine and aspirin versus 16% of patients on aspirin alone (P =.21); the frequency of target vessel revascularization was also similar in the 2 groups (32% vs 25%, P =.27). Myocardial infarction was infrequent in both groups (2.0% vs 1.1%, respectively, P not significant). Patients treated with aspirin and ticlopidine had more adverse angiographic and procedural characteristics, including longer lesions and treatment lengths. Multivariate analysis to adjust for these and other differences failed to reveal a benefit of ticlopidine in maintaining patency and reducing adverse clinical events. CONCLUSIONS: After balloon angioplasty of a subtotal or total coronary occlusion, no reduction in adverse events was observed among patients in whom ticlopidine was added to aspirin, even after adjustment for clinical and lesion characteristics.

Kaposi's sarcoma in organ transplant recipients: report of 20 cases.

There is an increased incidence of Kaposi's sarcoma (KS) in organ transplant recipients in whom it comprises more than 3% of all de novo neoplasms. Any such patient who develops reddish blue macules or plaques in the skin or oropharyngeal mucosa, or has apparently infected granulomas that fail to heal, should be suspected of having KS. In 45% of the patients, the internal viscera are involved. This variety has a bad prognosis. Apart from conventional treatment with surgical excision, radiotherapy or chemotherapy, cessation, reduction, or modification of immunosuppressive therapy produces gratifying results in a significant number of patients.

Malignant melanoma in organ allograft recipients.

Three groups of tumors were studied. The first group was melanomas inadvertently transmitted from donors. Brain metastases from melanoma were often misdiagnosed in the donors as primary brain tumors or cerebral hemorrhage. Eleven donors provided organs to 20 recipients of whom 3 never manifested evidence of melanoma, 1 showed local spread of tumor beyond the allograft, and 16 had metastases. Of the last group 11 died from melanoma, but 4 patients had complete remissions following transplant nephrectomy and discontinuation of immunosuppressive therapy. The second group was Melanomas treated pretransplantation. Thirty patients had cutaneous melanomas and one an ocular melanoma. Six patients (19%) had recurrences posttransplantation. Three were treated < 2 years pretransplantation, 2 between 2-5 years pretransplantation, and one 120 months pretransplantation. The third group was De novo melanomas. Cutaneous melanomas occurred in 164 patients, melanomas of unknown origin in 8, and ocular melanomas in 5. Melanomas constituted 5.2% of posttransplant skin cancers compared with 2.7% in the general population. Unusual features of cutaneous melanomas were that 6 (4%) occurred in children, and 9 (5%) occurred in bone marrow recipients who were treated for leukemia. Forty-four patients (27%) who had cutaneous melanomas also had other skin cancers. Forty-seven of 68 patients (69%) had thick skin lesions (Clark's level III or greater or > 0.76 mm by Breslow's technique). Lymph node metastases occurred in 32 patients (20%) with cutaneous melanomas. Fifty patients (30%) with cutaneous melanomas died of their malignancies, as did 5 with melanomas of unknown origin, and 1 with ocular melanoma. The risks of melanoma may be reduced by stringent selection of donors; by waiting at least 5 years between treatment of melanoma and undertaking transplantation; and, perhaps, by reducing sunlight exposure and by early excision of suspicious dysplastic lesions.

The effect of immunosuppression on pre-existing cancers.

This study of 939 pre-existing malignancies that occurred in 913 renal transplant recipients showed that in 823 patients the tumors were treated prior to or at transplantation, in 78 after transplantation, at an unspecified time in 20, while 18 received no treatment. Of patients treated pretransplantation 185 (22%) developed recurrences posttransplantation. Low recurrence rates (0-10%) occurred with incidentally discovered renal tumors; lymphomas; and testicular, uterine cervical, and thyroid carcinomas. Intermediate recurrence rates (11-25%) occurred with carcinomas of the uterine body; Wilms' tumors; and carcinomas of the colon, prostate, and breast. High recurrence rates (> or = 26%) occurred with carcinomas of the bladder, sarcomas, malignant melanomas, symptomatic renal carcinomas, nonmelanomatous skin cancers, and myelomas. Overall 53% of 185 recurrences occurred in patients treated 0-24 months pretransplantation, 34% in patients treated 25-60 months pretransplantation, and 13% in patients treated > 60 months pretransplantation. Of 78 patients whose cancers were first treated after transplantation, 27% developed recurrences. However, 63% did not do so in follow-ups averaging 53 months. A two-year waiting period between treatment of cancer and transplantation is justified for most neoplasms except for incidentally discovered renal carcinomas, in situ carcinomas, and possibly focal neoplasms (a small single focus), low-grade bladder cancers, and basal cell skin cancers. In these cases no waiting period is necessary. On the other hand, a waiting period > 2 years is necessary for most malignant melanomas, breast carcinomas, and colorectal carcinomas. Conflicting data are presented as to whether immunosuppression affects growth of existing tumor cells but most of the evidence suggests acceleration of neoplastic growth.

Transplantation in patients with primary renal malignancies.

Seventy-three patients with primary renal neoplasms underwent kidney transplantation. Three distinct groups were identified. Thirty-four patients (group 1), who underwent antineoplastic therapy 1 year or less before transplantation, developed metastases or recurrences in 53% of the cases. In contrast, none of 15 patients in group 2 had this problem. All of these patients had a waiting period of at least 15 months between nephrectomy and transplantation. These findings emphasize the value of a lengthy waiting period between treatment of the neoplasm and performance of transplantation with its associated immunosuppressive therapy. Group 3 also had a favorable outcome. All had incidentally discovered renal malignancies, in 18 patients during the work-up of chronic renal failure or after bilateral nephrectomy in preparation for renal transplantation, and in 6 several months after transplantation when the recipient's own kidneys were removed or autopsy examination was performed. None of these 24 patients developed recurrences or metastases.

Primary kidney tumors before and after renal transplantation.

Three groups of patients were reviewed. Primary carcinomas were found in donors kidneys of 47 recipients. In 30 instances a tumor was present at harvesting. When a neoplasm was removed immediately pretransplantation or early posttransplantation there were no recurrences in 14 recipients. In another two instances, a tumor was not removed or was incompletely excised pretransplantation and both recipients died of metastases. Fourteen other patients received kidneys from donors in whom the opposite kidney had a malignancy. Thirteen remained tumor-free and one had allograft nephrectomy for rejection 3 months posttransplantation when a carcinoma was found. In 17 recipients an allograft neoplasm was not recognized at harvesting. In 9 it was discovered at graft nephrectomy an average of 3 months posttransplantation. In a tenth patient a hypoechogenic area, found on routine posttransplant ultrasonography, progressively increased in size and proved to be malignant. Another 7 patients developed metastases from renal carcinomas an average of 12 months posttransplantation. Preexisting carcinomas were found in 350 recipients. Seventy-one patients with incidentally discovered tumors had no recurrences no matter when nephrectomy was performed in relationship to transplantation. Of 279 patients with symptomatic renal tumors, 70 (25%) had recurrences, 63% of which occurred in patients treated < or = 2 years pretransplantation. De novo cancers were found posttransplantation in 256 recipients. Renal carcinomas were 4.6% of posttransplant cancers compared with 3% of tumors in the general population. In 222 patients their own diseased kidneys were involved, in 24 tumors occurred in the allograft, and in 10 cases the site was not stated. Development of neoplasia seemed to be related not to the immunosuppressive therapy but to the underlying cause of renal failure, especially analgesic nephropathy. A disproportionate number of carcinomas (15%) involved the renal pelvis, most likely because of prior analgesic abuse.

Cancers following cyclosporine therapy.

Malignancies developed in 141 organ transplant recipients treated with cyclosporine. The cancers showed important differences from those seen following conventional immunosuppressive therapy (CIT). They appeared an average of 20 months after cyclosporine and 60 months after CIT. Non-Hodgkin's lymphomas (NHLs) were the most common tumors, being 41% compared with 12% in CIT patients. They appeared an average of 11 months after transplantation compared with an average of 42 months after CIT. Unlike CIT patients they more often involved lymph nodes, more frequently involved the small intestine, rarely involved the brain, and were more likely to regress after reduction of immunosuppressive therapy. Skin cancers (15% of cancers) were much less common than in CIT patients (40%). Kaposi's sarcomas were more common (8% vs. 3%). In this small series there was a surprising frequency of endocrine-related cancers and renal cell carcinomas. Only 8 patients (6%) were treated with cyclosporine exclusively. The neoplasms probably are not specific to cyclosporine therapy but appear to be a complication of immunosuppression per se.

Sarcomas in organ allograft recipients.

In a review of 8724 de novo malignancies that occurred in 8191 organ allograft recipients sarcomas were 7.4% of cancers. Kaposi's sarcoma (KS) made up 5.7%, and other sarcomas (OS) 1.7% a much higher proportion than in the general population. KS was most common in Arab, black, Italian, Jewish, or Greek patients. In 60% of patients with KS the lesions were confined to the skin and/or oropharynx while 40% involved internal organs and/or lymph nodes. Complete remissions following various treatments occurred in 53% of the former group and 27% of the latter. In both groups 32% and 60% of remissions, respectively, occurred when the only treatment was reduction or cessation of immunosuppressive therapy. However, this treatment caused impaired function or allograft loss from rejection in 22 of 34 kidney recipients. Recurrent KS occurred in 5% of patients in remission when immunosuppressive therapy was resumed. Nine of 114 patients (8%) tested for human immunodeficiency virus were positive. Most OS arose in internal organs or soft tissues. The major types were fibrous histiocytoma (20 patients), leiomyosarcoma (15), fibrosarcoma (12), rhabdomyosarcoma (9), hemangiosarcoma (8), undifferentiated sarcoma (7) and mesothelioma (6). Several unusual features were noted. Remarkably, 10 of 105 (10%) sarcomas occurred adjacent to or in a renal (6) or hepatic (4) allograft. Leiomyosarcomas are rare in children, yet 5 of 15 (33%) occurred in pediatric patients. Three hemangiosarcomas occurred in forearms at sites of arteriovenous fistulas used for pretransplant hemodialysis access. One leiomyosarcoma and one fibrosarcoma occurred in previously irradiated areas. One patient with mesothelioma had a history of asbestos exposure and two others had possible exposure.

Central nervous system lymphomas in organ allograft recipients.

Central nervous system (CNS) involvement occurred in 289 of 1332 patients (22%) with posttransplant non-Hodgkins lymphomas. The average time of appearance was 33 months (range 3 weeks to 248.5 months) posttransplantation. Lesions were confined to the CNS in 159 patients (55%), while 130 (45%) had involvement of other organs. Lesions involved the brain in 254 patients (88%), the brain and spinal cord in 5 (2%), the spinal cord in 2 (1%), unspecified locations in the CNS in 13 (4%), the meninges in 8 (3%), and the cerebrospinal fluid (CSF) in 7 (2%). All patients whose only involvement of the CNS was of the meninges or CSF had lymphomas involving multiple organs. Many tumors (48%) appeared within one year after transplantation. Brain lesions were frequently multicentric in distribution. Ninety-one (31%) of the 289 patients had no treatment and died, 70 (77%) of their malignancies and 21 (23%) from other causes. Of 198 patients who received treatment 124 (63%) died of their malignancies; 40 (20%) died of other causes, including 17 patients who had had complete remissions following treatment; 22 (11%) are currently alive and in complete remission; and 12 (6%) are alive and still undergoing therapy. The treatment of choice is local radiotherapy to the brain, which either alone (18 patients) or in combination with other modalities (14 patients) caused 32 of the 39 (82%) complete remissions. Ten of 30 patients with disease localized to the CNS survived more than 5 years, including 6 who survived more than 10 years. CNS lymphomas should be suspected whenever a transplant patient has neurologic symptoms however minor, and prompt work-up is essential to eliminate other possible causes. The dismal prognosis can be improved only by early diagnosis and prompt therapy.

Merkel's cell carcinoma in organ recipients: report of 41 cases.

In the general population Merkel's cell carcinoma (MCC) is an aggressive neuroendocrine skin cancer. More than 600 cases have been reported. MCC seems to be common in transplant recipients, with 41 cases being reported to the Cincinnati Transplant Tumor Registry, and another 11 in the transplant literature. In the general population, it is a disease of older adults, with only 51% of cases occurring below the age of 50 years. In transplant patients, the mean age at diagnosis was 53 (range 33-78) years, and 29% of recipients were <50 years old. The tumor appeared from 5 to 286 (mean 91.5) months after the transplant. Of 44 lesions that occurred in 41 patients, the distribution was similar to that seen in the general population, with 36% occurring on the head and neck, 32% on the upper extremities, 16% on the trunk, 9% at unknown sites, and 7% on the lower extremities. Twenty of the patients (49%) had 22 other malignancies, the great majority of which (91%) were other skin cancers. Treatment depended on the stage of the disease and included wide surgical excision, radical lymph node dissection, radiation therapy, and chemotherapy. In transplant patients, MCC probably proved to be more aggressive than in the general population in that 68% of patients developed lymph node metastases and 56% died of their malignancies. Furthermore, one third of surviving patients still have active cancers from which they may die. Also, follow-up of survivors has been relatively short, with a mean of only 18 (range 0-135) months.