Characteristics and outcomes of patients undergoing lumbar spine surgery for axial back pain in the Michigan Spine Surgery Improvement Collaborative

BACKGROUND CONTEXTThe indications for surgical intervention of axial back pain without leg pain for degenerative lumbar disorders have been limited in the literature, as most study designs allow some degree of leg symptoms in the inclusion criteria.PURPOSETo determine the outcome of surgery (decompression only vs. fusion) for pure axial back pain without leg pain.STUDY DESIGN/SETTINGProspectively collected data in the Michigan Spine Surgery Improvement Collaborative (MSSIC).PATIENT SAMPLEPatients with pure axial back pain without leg pain underwent lumbar spine surgery for primary diagnoses of lumbar disc herniation, lumbar stenosis, and isthmic or degenerative spondylolisthesis ≤ grade II.OUTCOME MEASURESMinimally clinically important difference (MCID) for back pain, Numeric Rating Scale of back pain, Patient-Reported Outcomes Measurement Information System Physical Function (PROMIS-PF), MCID of PROMIS-PF, and patient satisfaction on the North American Spine Surgery Patient Satisfaction Index were collected at 90 days, 1 year, and 2 years after surgery.METHODSLog-Poisson generalized estimating equation models were constructed with patient-reported outcomes as the independent variable, reporting adjusted risk ratios (RR_adj).RESULTSOf the 388 patients at 90 days, multi-level versus single level lumbar surgery decreased the likelihood of obtaining a MCID in back pain by 15% (RR_adj=0.85, p=.038). For every one-unit increase in preoperative back pain, the likelihood for a favorable outcome increased by 8% (RR_adj=1.08, p<.001). Of the 326 patients at 1 year, symptom duration > 1 year decreased the likelihood of a MCID in back pain by 16% (RR_adj=0.84, p=.041). The probability of obtaining a MCID in back pain increased by 9% (RR_adj=1.09, p<.001) for every 1-unit increase in baseline back pain score and by 14% for fusions versus decompression alone (RR_adj=1.14, p=.0362). Of the 283 patients at 2 years, the likelihood of obtaining MCID in back pain decreased by 30% for patients with depression (RR_adj=0.70, p<.001) and increased by 8% with every one-unit increase in baseline back pain score (RR_adj=1.08, p<.001).CONCLUSIONSOnly the severity of preoperative back pain was associated with improvement in MCID in back pain at all time points, suggesting that surgery should be considered for selected patients with severe axial pain without leg pain. Fusion surgery versus decompression alone was associated with improved patient-reported outcomes at 1 year only, but not at the other time points.     

Comparison of the characteristics of adult liver transplant recipients with prope (almost) tolerance and full immunosuppression regimen

BackgroundThe liver transplant recipients are often subjected to excessive therapy by immunosuppressive drugs which produce several complications. Consequently, the minimization or even withdrawal of immunosuppression in selected patients is an attractive alternative. We investigated the frequency and characteristics of these near (or prope from Latin) tolerance in liver transplant recipients in Shiraz Organ Transplant Center.Material and methodsWe reviewed the medical records of over 3800 adult liver transplant recipients to select a group treated with a low-dose tacrolimus monotherapy (n = 90) between 1994 and 2017 in our transplant center. The patients with the best liver function parameters were selected; then, the clinician arbitrarily decided to withdraw steroids first and then mycophenolate mofetil and maintain each patient on a low dose tacrolimus.We compared the characteristics of prope tolerant recipients on a low-dose tacrolimus with those on standard immunosuppression, namely full-dose tacrolimus plus steroids and mycophenolate mofetil (n = 233). Data were analyzed by t-test, chi-square test using SPSS software version 16.ResultsOut of over 3800 liver transplant patients, 90 (2.34%) recipients were treated with a minimum dose of tacrolimus monotherapy. These recipients were compared to a selected group of 233 (6.1%) recipients treated with full-dose tacrolimus plus steroids and mycophenolate mofetil. In a prope tolerant group, there were 55 males (61.1%) and 35 females (38.9%) recipients. Mean age at the time of transplant was 39.92 ± (SD = 13.40) years with an average time from the transplantation time to completed weaning from triple immunosuppression to low-dose monotherapy of 41.35 months (SD = 17.27). The most common etiology of liver disease among both groups was viral hepatitis.ConclusionThe achievement of prope (almost) immune tolerance was possible only in some liver transplant recipients with a relatively low risk of rejection. Our analysis suggests that there is a difference in the underlying diseases and recipients' age and the number of rejections between the two groups.     

Polygenic risk score as a determinant of risk of non‐melanoma skin cancer in a European‐descent renal transplant cohort

Renal transplant recipients have an increased risk of non‐melanoma skin cancer (NMSC) compared to in the general population. Here, we show polygenic risk scores (PRS) calculated from genome‐wide association studies (GWAS) of NMSC in a general, nontransplant setting, can predict risk of, and time to posttransplant skin cancer. Genetic variants, reaching predefined P‐value thresholds were chosen from published squamous cell carcinoma (SCC) and basal cell carcinoma (BCC) nontransplant GWAS. Using these GWAS, BCC and SCC PRS were calculated for each sample across three European ancestry renal transplant cohorts (n = 889) and tested as predictors of case:control status and time to NMSC posttransplant. BCC PRS calculated at P‐value threshold 1 × 10^?5 was the most significant predictor of case:control status of NMSC posttransplant (OR = 1.61; adjusted P = .0022; AUC [full model adjusted for clinical predictors and PRS] = 0.81). SCC PRS at P‐value threshold 1 × 10^?5 was the most significant predictor of time to posttransplant NMSC (adjusted P = 9.39 × 10^?7; HR = 1.41, concordance [full model] = 0.74). PRS of nontransplant NMSC is predictive of case:control status and time to NMSC posttransplant. These results are relevant to how genomics can risk stratify patients to help develop personalized treatment regimens.     

Incidence and risk factors for nonmelanoma skin cancer after heart transplantation

Introduction

The incidence of skin cancer in heart transplant (HT) patients is higher than in the general population, reversing the proportion of cutaneous squamous cell carcinoma (SCC) and basal cell carcinoma (BCC) with a predominance of the former. The etiologic role of new immunosuppressants is not well known. We sought to ascertain the incidence of SCC and BCC in HT patients and the risk factors for its occurrence.

Patients and Methods

We report the incidence of all types of post-HT skin cancer, SCC, and BCC among adult HT patients in Spain (4089 subjects) as well as the influence of gender, age at heart transplant, immunosuppression, and sunlight exposure.

Results

The incidence rates of SCC and BCC, per 1000 persons/year, were 8.5 and 5.2, respectively. Males had a higher risk of SCC but not BCC. Induction therapy increased the risk of SCC and BCC. The relative risk of mycophenolate mofetil (MMF) was 0.3 (0.2-0.6; P < .0005) and azathioprine (AZA) 1.8 (1.2-2.7; P < .0032) for SCC, whereas tacrolimus and cyclosporine showed no difference. The relative risk of BCC was not affected by any immunosuppressant.

Conclusion

Age at transplantation >45 years, induction therapy use, and high sunshine zone were risk factors for both SCC and BCC. Different immunosuppressive agents have different risks of nonmelanoma skin cancer, as AZA increases the risk of SCC and MMF is a protective factor. The relative risk of BCC was not affected by any immunosuppressor.     

Efficacy and Safety of Switching to Azathioprine for Mycophenolate-Induced Diarrhea in Renal Transplant Recipients

BackgroundDiarrhea is a common adverse effect of mycophenolate treatment in renal transplant recipients. In patients with mycophenolate-induced diarrhea, one option is to switch to mycophenolate to azathioprine. In this study, we aimed to define the safety and efficacy of switching from mycophenolate to azathioprine for mycophenolate-related diarrhea in renal transplant recipients.MethodsA total of 177 patients, 59 of whom were switched to azathioprine because of diarrhea and 118 of whom comprised a matched control group without diarrhea and continued mycophenolate treatment participated in this study. We analyzed the effect of switching to azathioprine from mycophenolate on amelioration of diarrhea and graft survival.ResultsWe observed that 89.8% of patients who switched to azathioprine because of diarrhea had improved diarrhea complaints. Patients switched to azathioprine because of diarrhea had lower glomerular filtration rates (P < .001) and higher proteinuria (P < .001) compared with the control group before the switch. Patients switched to azathioprine compared with a subgroup of 59 control patients were matched to patients switched to azathioprine in terms of baseline renal function and proteinuria in addition to demographic parameters had higher 10-year graft loss compared with patients who continued mycophenolate (P = .03). Particularly in patients with a glomerular filtration rate <30 mL/min at the time of conversion, the risk of early graft loss was high.ConclusionsAlthough switching from mycophenolate to azathioprine was an effective approach to improve diarrhea, this approach is associated with increased risk of graft loss.     

Risk Factors Associated With New-Onset Diabetes After Liver Transplant: A Case Control Study

BackgroundNew-onset diabetes after transplant is a severe complication that can present in liver transplant recipients, negatively impacting quality of life and graft survival. It also contributes to increased risk of infection, cardiovascular disease, and rejection, which are the main causes of death among liver transplant recipients. The aim of the present study was to assess the risk factors associated with new-onset diabetes after transplant.MethodThis was a case control study based on the data from 146 liver transplant patients at a reference hospital. The data from the charts were collected using a 2-part form: Part I (sociodemographic variables) and Part II (clinical variables).ResultsMultiple analysis showed that pre-existing systemic arterial hypertension (odds ratio [OR], 2.65; 95% CI, 1.12–6.28) and the use of sodium mycophenolate associated with tacrolimus (OR, 2.68; 95% CI, 1.02–7.06) increased the risk of new-onset diabetes after transplant. On comparing the anthropometric variables, lipid panel, and blood glucose levels of liver transplant patients with and without diabetes, higher glycemic levels were found in the group with diabetes (P < .001).ConclusionPre-existing systemic arterial hypertension and the associated use of sodium mycophenolate and tacrolimus increased the risk of new-onset diabetes after transplant.     

Yearly Burden of Skin Cancer in Non-Caucasian and Caucasian Solid-organ Transplant Recipients

Objective: To examine the skin cancer tumor accrual rates in non-Caucasian and Caucasian post-transplant recipients. Design/Setting/Participants: Retrospective chart review of solid-organ transplant patients who presented to the outpatient dermatology clinic at the University of Chicago and have had at least one skin biopsy to rule in/out skin cancer in the 10-year period from January 1, 2003, to December 31, 2012. One hundred fifty-two solid-organ transplant recipients were identified through a natural language search in CoPathPlus. Measurements: Each transplant patient’s skin cancer accrual rates, defined as the number of skin cancers per person per year, were examined. The average accrual rates for non-Caucasians and Caucasians were compared and analyzed. Results: Of the 152 post-transplant patients identified, 58 were non-Caucasian and 94 were Caucasian. Eight (13.8%) non-Caucasians developed skin cancer, compared to 61 (64.9%) Caucasians (P< 0.001). Non-Caucasian post-transplant patients had lower skin cancer accrual rates with an overall skin cancer accrual rate of 0.13, squamous cell carcinoma accrual rate of 0.10, and basal cell carcinoma accrual rate of 0.01 versus 1.13 (P< 0.001), 0.96 (P< 0.001), and 0.15 (P< 0.001), respectively, for Caucasian patients. Comparison of post-transplant non-Caucasian and Caucasian patients who developed skin cancer revealed lower overall (0.96 vs. 1.74; P=0.25), squamous cell carcinoma (0.75 vs. 1.49; P=0.16), and basal cell carcinoma (0.06 vs. 0.24; P=0.13) accrual rates in non-Caucasians. Conclusion: The authors’ findings highlight the importance of annual total body skin exams for post-transplant patients and the need to identify and further educate those transplant patients with a higher risk for skin cancer development.Skin cancer is the most common malignancy in organ transplant recipients, with squamous cell carcinoma (SCC) and basal cell carcinoma (BCC) accounting for more than 90 percent of the post-transplant skin cancer diagnoses.1,2 Compared to the general population, solid- organ transplant recipients have a higher risk of developing skin cancer.1-3 In the non-transplant population, BCC is the most common skin cancer, with the ratio of BCC to SCC diagnoses at 4:1. In contrast, in the organ transplant population, this ratio is reversed, with SCCs being the predominant skin cancer.1,2 Multifold increases in the incidence rates of various skin cancers when compared to the normal population have been described, ranging from a 65-fold increase in SCC to a ten-fold increase in BCC.1-4In general, skin cancer is less common in the non- Caucasian population than in Caucasians. Skin cancer accounts for 20 to 30 percent of all neoplasms in Caucasians, 2 to 4 percent in Asians, and 1 to 2 percent in African Americans and Asian Indians.5 Typically, the rates of skin cancer in non-Caucasian post-transplant patients are lower than the rates in Caucasian post-transplant recipients. Japanese studies have found that only around 2.5 percent of the malignancies in Japanese post-renal transplant patients were skin cancers.6,7 A Taiwanese study found no incidence of SCCs or BCCs post-renal transplant.8 Similar to these observations, South African studies showed no cases of nonmelanoma skin cancer in non-Caucasians.9,10 A recent American study found greater nonmelanoma skin cancer occurrences in renal transplants with skin types I to III than in types IV to VI.11 Likewise, a Switzerland study found a higher incidence of SCCs in light-skinned renal transplant patients compared to darker skinned transplant patients.12The primary goal of this study was to examine the distribution of biopsy-confirmed skin cancer diagnoses in Caucasian and non-Caucasian post-transplant recipients and compare the skin cancer tumor accrual rates (number of tumors per person per year) of non-Caucasian solid-organ transplant recipients to those of Caucasian solid-organ transplant recipients.     

Retrospective Evaluation of the Effect of Mycophenolate Mofetil Dosage on Survival of Kidney Grafts Based on Biopsy Results

IntroductionPlasma concentration monitoring is commonly used to adjust immunosuppressant dosage in transplant recipients, but adjustment is often based on clinical experience rather than rigorous quantitative indicators.MethodsWe examined the effect of mycophenolate mofetil (MMF) dosage on graft survival by pathologic and immunologic analysis of 88 kidney recipients who were given a postoperative immunosuppressive regimen of tacrolimus (FK506), MMF, and corticosteroids. Patients were given a conventional dosage (≥1.5 g/d; n = 40) or a reduced dosage (n = 48) of MMF owing to postoperative adverse side effects.ResultsThe reduced-dose group included patients given low doses (≤1.0 g/d; n = 27), ultra-low doses (≤0.5 g/d; n = 15), and those who discontinued MMF (n = 6). The dose reduction group had increased acute rejection, chronic rejection, and graft dysfunction, poorer pathologic scores, and increased cell infiltration of graft tissue (CD4, CD8, CD68, and CD138 positivity) and expression of interleukin-2R and HLA-DR. Finally, hazard analysis indicated that patients given low doses and ultra-low doses of MMF had poorer long-term kidney grafts survival (hazard ratios of 1.52 and 1.78, respectively).ConclusionsThese results indicate the importance of using an appropriate dosage of MMF in kidney transplant recipients.     

Skin cancer following transplantation: the Israel Penn International Transplant Tumor Registry experience

The purpose of this study was to analyze a large series of skin cancers in solid organ transplant recipients to determine their biologic behavior. METHODS: A retrospective review of all US transplant recipients with skin cancer reported to the Israel Penn International Transplant Tumor Registry was performed. RESULTS: Transplant recipients from the United States with skin malignancies were identified (n = 2018) and assigned to 1 of 3 groups: squamous cell cancer (SCC), basal cell cancer (BCC), or combined malignancies (BCC/SCC). Squamous cell to basal cell cancer ratio was found to be 1.9 to 1. The ratio of extrarenal to renal allograft recipients was identical for all 3 groups (3:1). The median interval from transplant to skin cancer diagnosis was greater than 4 years in each group and longest in those with isolated SCC lesions. In the SCC group, there was a 9% incidence of nodal or secondary site involvement affecting the cervix, perineum, or lung. The highest recurrence rate was demonstrated in the combined malignancy group. Cancer-specific deaths were significantly higher in the SCC (8%) and BCC/SCC (6.8%) groups compared to the BCC (3.6%) group. CONCLUSIONS: This large experience indicates that SCC is more common than BCC in transplant recipients. SCC alone or in combination with BCC appears aggressive and is associated with significant mortality.     

Preemptive Second Kidney Transplant Outcomes by Induction Type in the United States

BackgroundThe role of induction in preemptive second kidney recipients is unclear. We examined the association between induction therapy and the long-term graft and recipient survival in the settings of tacrolimus and mycophenolate maintenance.MethodsWe identified all preemptive second kidney transplant recipients between 2000 and 2020 in the Scientific Registry of Transplant Recipients. We excluded those with missing or mixed induction regimens and positive crossmatch. We grouped recipients by induction type into 3 groups: anti-thymocyte globulin (n = 1442), alemtuzumab (n = 362), and interleukin-2 receptor antagonist (IL-2RA; n = 481). We generated Kaplan-Meier curves of the recipient and death-censored graft survival (DCGS) with follow-up censored at 10 years. We used multivariable Cox proportional hazards models to examine the association between induction and the above outcomes. We adjusted the models for recipient and donor variables.ResultsRates of delayed graft function, rejection, hospitalization, and post-transplant lymphoproliferative disorder at one year were not statistically different. Recipient survival did not vary by induction type in the Kaplan-Meier analysis (log-rank P = .189) or in the multivariable model. However, DCGS was the lowest in the Alemtuzumab group (log-rank P = .01). In the multivariable models, alemtuzumab was associated with a 57% increased risk of graft loss (1.57, 95% confidence interval (1.08, 2.30), P = .019) compared to anti-thymocyte. Live-donor kidneys were associated with significantly better recipient survival and DCGS.ConclusionsCompared to anti-thymocyte induction, alemtuzumab, but not IL-2RA, was associated with inferior graft survival in preemptive second transplant recipients discharged on tacrolimus and mycophenolate.     

Association between preoperative administration of gabapentinoids and 30-day hospital readmission: A retrospective hospital registry study.

Study objectiveTo evaluate the effectiveness of preoperative gabapentinoid administration.DesignRetrospective hospital registry study.SettingTertiary referral center (Boston, MA).Patients111,008 adult non-emergency, non-cardiac surgical patients between 2014 and 2018.InterventionsPreoperative administration of gabapentinoids (gabapentin or pregabalin).MeasurementsWe tested the primary hypothesis that preoperative gabapentinoid use was associated with lower odds of hospital readmission within 30 days. Contingent on this hypothesis, we examined whether lower intraoperative opioid utilization mediated this effect. Secondary outcome was postoperative respiratory complications.Main resultsGabapentinoid administration was associated with lower odds of readmission (adjusted odds ratio [OR_adj] 0.80 [95% CI, 0.75–0.85]; p < 0.001). This effect was in part mediated by lower intraoperative opioid utilization in patients receiving gabapentinoids (8.2% [2.4–11.5%]; p = 0.012). Readmissions for gastrointestinal disorders (OR_adj 0.74 [0.60–0.90]; p = 0.003), neuro-psychiatric complications (OR_adj 0.66 [0.49–0.87]; p = 0.004), non-surgical site infections (OR_adj 0.68 [0.52–0.88; p = 0.004) and trauma or poisoning (OR_adj 0.25 [0.16–0.41]; p < 0.001) occurred less frequently in patients receiving gabapentinoids. The risk of postoperative respiratory complications was lower in patients receiving gabapentinoids (OR_adj 0.77 [0.70–0.85]; p < 0.001). Lower doses of pregabalin (< 75 mg) and gabapentin (< 300 mg) compared to both, no and high-dose administration of gabapentinoids, were associated with a lower risk of postoperative respiratory complications (OR_adj 0.61 [0.50–0.75]; p < 0.001 and OR_adj 0.70 [0.53–0.92]; p = 0.012, respectively). These lower gabapentinoid doses prevented 30-day readmission (OR_adj 0.74 [0.65–0.85]; p < 0.001). The results were robust in several sensitivity analyses including surgical procedure defined subgroups and patients undergoing ambulatory surgery.ConclusionsThe preoperative use of pregabalin and gabapentin, up to doses of 75 and 300 mg respectively, mitigates the risks of hospital readmission and postoperative respiratory complications which can in part be explained by lower intraoperative opioid use. Further research is warranted to elucidate mechanisms of the preventive action.     

Incidence of skin cancer after renal transplantation in The Netherlands

The incidence of squamous cell carcinoma (SCC) and basal cell carcinoma (BCC) was analyzed separately in all 764 patients who received a renal allograft between 1966 and 1988 at the Leiden University Hospital. The mean follow-up period was 8.7 posttransplant years (range 1-21 years). During this time period 176 skin cancers were diagnosed in 47 patients. The overall risk to develop a first tumor increased from 10% after 10 years to 40% after 20 years of graft survival. The overall incidence of SCC was 250 times higher and that of BCC 10 times higher when compared with the general Dutch population. Moreover the localization of SCCs and BCCs differed considerably. Solar radiation is thought to be an important risk factor for the development of skin cancer. However, the occurrence of skin cancer in long-term graft survivors forms also a major problem in a country with a higher geographical latitude and a moderate amount of sun-exposure, such as the Netherlands.     

Incomplete excision of non-melanoma skin cancer of the head and neck: can we predict failure?

Background

Reported incomplete excision rates vary widely. This study described a single center's treatment of basal cell carcinoma (BCC) and squamous cell carcinomas (SCC) of the head and neck and investigated possible causes of incomplete excision.

Methods

All excised BCCs and SCCs in 2011 were included into the study. Patients were identified by the diagnostic (diagnosis-related group (DRG)) codes from DC44.0 to DC44.4. A total of 437 patients were treated for 516 skin lesions.

Results

Mean age was 71.4 years and the male–female ratio was 1.29. Incomplete tumor removal was found in 11 % of all cases. Four significant factors were identified to predict incomplete excision, including age >75 years (relative risk (RR)?=?14.8 % (95 %-CI: 5.8–24.7 %)), BCC tumor size above 1.5 cm (RR?=?17.1 % (95 %-CI: 3.7–28.7 %)), lack of sufficient excision margin in SCC (<6 mm) (RR?=?17.1 % (95 %-CI: 0.1–36.9 %)) and lack of frozen sectioning in high-risk areas (RR?=?16.9 % (95 %-CI: 7.5–27.2 %)). Neither gender, tumor type, histological subtype, biopsy prior to surgery, tumor location nor surgeon grade predicted incomplete excision.

Conclusions

Head and neck BCCs, and SCCs are difficult to treat, and the need for complete tumor excision is mandatory prior to reconstruction. Our findings showed that causes of incomplete excision could be identified. With this knowledge, we are able to optimize our quality of treatment, patient satisfaction, and finally, the cost/effectiveness of our department. Level of Evidence: Level III, prognostic/risk study.     

Second Kidney Transplant Outcomes in Dialysis Dependent Recipients by Induction Type in the United States

BackgroundWe examined the association between induction type for a second kidney transplant in dialysis-dependent recipients and the long-term outcomes.MethodsUsing the Scientific Registry of Transplant Recipients, we identified all second kidney transplant recipients who returned to dialysis before re-transplantation. Exclusion criteria included: missing, unusual, or no-induction regimens, maintenance regimens other than tacrolimus and mycophenolate, and positive crossmatch status. We grouped recipients by induction type into 3 groups: the anti-thymocyte group (N = 9899), the alemtuzumab group (N = 1982), and the interleukin 2 receptor antagonist group (N = 1904). We analyzed recipient and death-censored graft survival (DCGS) using the Kaplan-Meier survival function with follow-up censored at 10 years post-transplant. We used Cox proportional hazard models to examine the association between induction and the outcomes of interest. To account for the center-specific effect, we included the center as a random effect. We adjusted the models for the pertinent recipient and organ variables.ResultsIn the Kaplan-Meier analyses, induction type did not alter recipient survival (log-rank P = .419) or DCGS (log-rank P = .146). Similarly, in the adjusted models, induction type was not a predictor of recipient or graft survival. Live-donor kidneys were associated with better recipient survival (HR 0.73, 95% CI [0.65, 0.83], P < .001) and graft survival (HR 0.72, 95% CI [0.64, 0.82], P < .001). Publicly insured recipients had worse recipient and allograft outcomes.ConclusionIn this large cohort of average immunologic-risk dialysis-dependent second kidney transplant recipients, who were discharged on tacrolimus and mycophenolate maintenance, induction type did not influence the long-term outcomes of recipient or graft survival. Live-donor kidneys improved recipient and graft survival.     

Lymphocytic Infiltrates and Subclinical Epithelial Tumor Extension in Patients With Chronic Leukemia and Solid-Organ Transplantation

BACKGROUND: Dense infiltrates in association with squamous cell carcinoma (SCC) or basal cell carcinoma (BCC) in patients with underlying chronic lymphocytic leukemia (CLL) may complicate pathologic interpretation of histologic margins. OBJECTIVE: The study was conducted to determine the frequency of identifying dense inflammatory infiltrates in frozen histologic sections during Mohs operation for BCC or SCC in patients with CLL and organ-transplant recipients, to characterize the infiltrate (reactive versus leukemic) in CLL, and to estimate the subclinical tumor extension in patients with CLL, transplant recipients, and control subjects undergoing Mohs procedure. METHODS: Frozen sections of head and neck BCC and SCC obtained during Mohs procedures in patients with CLL, organ transplant recipients, and a control group were reviewed retrospectively. Biopsy specimens of CLL with dense infiltrates were assessed with immunohistochemical stains. Subclinical tumor extension (postoperative defect size minus preoperative tumor size) was evaluated in each group. RESULTS: Dense infiltrates were found in tumors of 20 of 55 patients with CLL (36%), 1 of 8 transplant recipients (13%), and 1 of 105 controls (1%). In patients with CLL, 75% of the dense infiltrates were B-cell leukemic. Compared with controls, the mean subclinical tumor extension was larger in patients with CLL (P=0.029) and in transplant recipients (P=0.55). CONCLUSION: Dense leukemic infiltrates associated with BCC or SCC in CLL may complicate pathologic interpretation of Mohs surgical histologic margins and may be associated with larger postoperative defects relative to preoperative clinical tumor appearance. In patients with CLL, as in transplant recipients, SCC seems more likely to develop than BCC.     

Gastrointestinal Disorders After Renal Transplantation

BackgroundGastrointestinal disorders (GDs) are common in renal transplant recipients. The main cause of GDs seems to be the use of immunosuppressive medications, especially mycophenolic acid in the form of mycophenolate mofetil (MMF).ObjectiveThe aim of this study was to estimate the frequency and severity of GDs in renal allograft recipients with the use of the Gastrointestinal Symptom Rating Scale (GSRS).MethodsEighty-five renal allograft recipients, 50 ± 12 years old, treated with methylprednisolone, calcineurin inhibitor (cyclosporine [CsA], n = 42; tacrolimus (TAC), n = 43), and MMF were studied.ResultsAt the time of completion of the GSRS questionnaire, 38 of the 85 patients (45%) already had their MMF dose reduced because of GDs. Only 15 patients (18%) were totally free from GDs. The most frequent and severe GDs recorded were indigestion and diarrhea who were significantly more frequent in women (P = .045). GDs were recorded in patients receiving both standard and reduced dose of MMF. MMF dose was significantly associated only with diarrhea. Although TAC-treated patients had the highest mean GSRS scores, no statistically significant differences were observed compared with CsA-treated patients. In 31 patients, MMF was replaced by enteric-coated mycophenolate sodium (EC-MPS) and new questionnaires were completed 1 month later. Significant improvement in total and all subscores of GSRS was demonstrated (P < .001). Although EC-MPS dose tolerated by the patients was higher than MMF dose, the difference was not statistically significant.ConclusionsFemale sex and the use of MMF, especially in combination with TAC, are related to the occurrence of severe gastrointestinal symptoms. Substitution of MMF with EC-MPS significantly reduces the severity of symptoms and permits the use of higher doses.     

Human Papillomaviruses in Transplant-Associated Skin Cancers

Background. Human papillomavirus (HPV) infection has been suggested to be involved in the development of nonmelanoma skin cancer, the most common malignancy after solid-organ transplantation.
Objective. The objective of this study was to analyze the prevalence of different HPV types in squamous cell carcinomas (SCC) and basal cell carcinomas (BCC) of transplant recipients and nonimmunosuppressed patients.
Methods. To include the complete spectrum of HPV types in skin lesions, a comprehensive polymerase chain reaction assay with five different primer combinations was used.
Results. For SCC, HPV DNA was detected more frequently in tumors of transplant recipients (12/16, 75%) than of nonimmunosuppressed patients (7/19, 37%). In contrast, the HPV detection rate was similar in BCC specimens (4/8 or 50% in transplanted patients; 27/56 or 48% in nonimmunosupressed patients). Overall, 22 different HPV types were identified. HPV types 5 and 8 were detected predominately in SCC from transplant recipients. The amount of viral DNA was slightly higher in SCC of transplanted than in nonimmunosuppressed patients, but much lower than in both cutaneous and genital warts.
Conclusions. Cutaneous infections with HPV5 and HPV8 may represent an increased risk for SCC development in transplant recipients. The mechanisms by which these viruses may contribute to skin cancer development still remain unclear.     

Cutaneous manifestations in Italian kidney transplant recipients

Several cutaneous disorders may occur in organ transplant recipients. We examined the incidence and the clinical spectrum of cutaneous manifestations among kidney transplant recipients. One hundred nine patients (70 males and 39 females), aged 19 to 69 years (mean: 42.5 years), were consecutively examined as outpatients between June 2000 and August 2004. The mean interval after kidney transplantation was 61 months (range: 2 to 120 months). The immunosuppressive regimen consisted of combinations including cyclosporine, systemic corticosteroids, azathioprine, tacrolimus, mycophenolate mofetil, antivirals, and antibiotics. Ninety-one cutaneous manifestations were identified in 60 of 109 (55.0%) kidney transplant patients over a 4-year period. Sixteen (17.5%) cutaneous viral infections identified in 11 patients (10.0%) included verruca vulgaris (n = 9), herpes zoster (n = 5) and herpes simplex (n = 2). Thirteen (11.9%) patients showed 19 (20.8%) superficial fungal infections, consisting of dermatophytosis (n = 6), onycomycosis (n = 6), pityriasis versicolor (n = 5) and mucocutaneous candidiasis (n = 2). Twenty (22%) nonmelanoma skin cancers were identified in seven (6.4%) patients, six basal cell carcinomas (BCC) in four patients, two squamous cell carcinomas (SCC) in two patients, and 11 BCCs in addition to one SCC in one patient. Twenty-six (23.8%) patients developed 32 (35.4%) drug-related manifestations, including acneiform eruption (n = 14), gingival hypertrophy (n = 6), hypertrichosis (n = 6), ecchymosis (n = 3), and plantar hyperkeratosis (n = 3). In addition, psoriasis and seborrheic dermatitis, which had been diagnosed before kidney transplantation, were observed in five and three patients, respectively. Our results emphasize the importance of dermatologic examinations and monitoring kidney transplant recipients to obtain an early diagnosis and treatment of cutaneous manifestations.     

Polygenic risk score of non-melanoma skin cancer predicts post-transplant skin cancer across multiple organ types

Polygenic risk scores (PRSs) calculated from genome-wide association studies (GWASs) of non-melanoma skin cancer (NMSC) in a general, non-transplant setting have recently been shown to predict risk of and time to post-renal transplant skin cancer. In this study, we set out to test these findings in a cohort of heart, lung, and liver transplant patients to see whether these scores could be applied across different organ transplant types. Using the PRS from Stapleton et al (2018), PRS was calculated for each sample across a European ancestry heart, lung, and liver transplant cohorts (n = 523) and tested as predictor of time to NMSC post-transplant. The top PRS, squamous cell carcinoma (SCC) pT1 x 10⁻⁵, (n SNPs = 1953), SCC pT1 x 10⁻⁶, and SCC pT1 x 10⁻⁶ (n SNPs = 1061) were significantly predictive in the time to NMSC, SCC, and basal cell carcinoma (BCC) analysis across organ (P = .006, .02, and .02, respectively). We observed here a similar direction of effect and effect size [NMSC HR = 1.31(1.08-1.59)] to that in the original discovery study with increased polygenic burden leading to a faster time to developing NMSC. In summary, we found that PRS of NMSC calculated from GWAS of NMSC in non-transplant populations independently replicated in this cohort of heart, lung, and liver transplant.