Degree of differentiation of cutaneous squamous cell carcinoma: a comparison between a Swedish cohort of organ transplant recipients and immunocompetent patients.

BACKGROUND: Organ transplant recipients (OTRs) have a very high risk of developing cutaneous squamous cell carcinoma (cSCC). Immunosuppressed OTRs may have a higher proportion of poorly differentiated cSCC than non-OTRs. OBJECTIVES: The aim of this study was to investigate the degree of differentiation of cSCCs in OTRs compared with immunocompetent individuals. PATIENTS/METHODS: Data from the Swedish Cancer Registry were crosschecked with data from the Transplant registry of the Transplant Institute at Sahlgrenska University Hospital in Gothenburg, Sweden. All OTRs with a diagnosis of cSCC, basosquamous carcinoma, and/or cSCC in situ established at the Department of Dermatology, Sahlgrenska University Hospital, during 2002-2015 were included. The control group consisted of non-OTRs with the same diagnoses during the same time period. RESULTS: During 2002-2015, 82 OTRs diagnosed with 515 tumors and 883 non-OTRs with 1,247 tumors were included. OTRs developed 0.47 tumors/year vs 0.10 tumors/year for non-OTRs, but no significant differences were observed in the degree of tumor differentiation of invasive cSCCs between OTRs and non-OTRs (P = 0.4). The distribution of poorly, moderately, and well-differentiated invasive cSCCs among OTRs and non-OTRs were 8.5% vs 12.5%, 22.1% vs 29.9%, and 69.4% vs 57.6%, respectively. CONCLUSIONS: OTRs do not develop a higher proportion of poorly differentiated cSCCs than non-OTRs.

Platelet function recovery after ticagrelor withdrawal in patients awaiting urgent coronary surgery.

Objective: Dual antiplatelet therapy with ticagrelor and aspirin is associated with an increased risk of perioperative bleeding complications. Current guidelines recommend therefore discontinuation of ticagrelor 5 days before surgery to allow sufficient recovery of platelet function. It is not known how the time to recovery varies between individual patients after discontinuation of ticagrelor. Methods: Twenty-five patients accepted for urgent coronary artery bypass surgery and treated with ticagrelor and aspirin were included in a prospective observational study. Platelet aggregation was evaluated with impedance aggregometry at five timepoints 12-96 h after discontinuation of ticagrelor. In a subset of patients ( n = 15), we also tested the ex vivo efficacy of platelet concentrate supplementation on platelet aggregation. Results: There was a gradual increase in mean adenosine diphosphate-induced platelet aggregation after discontinuation of ticagrelor. After 72 h, mean aggregation was 38 ±23 aggregation units (U), which is above a previously suggested cut-off of 22 U, when patients can be operated without increased bleeding risk. However, there was a large interindividual variability (range 4‒88 U at 72 h) and 6/24 patients (25%) had <22 U after 72 h. Ex vivo administration of platelet concentrate did not improve adenosine diphosphate-induced aggregation at any timepoint after ticagrelor discontinuation. Conclusions: Adenosine diphosphate-induced aggregation was acceptable after 72 h in the majority of patients but with a large interindividual variability. Due to the large variability, platelet function testing may prove to be a valuable tool in timing of surgery in patients with ongoing or recently stopped ticagrelor treatment. Adenosine diphosphate-induced aggregation was not improved by addition of platelet concentrate.

Oral and lip cancer in solid organ transplant patients--a cohort study from a Swedish Transplant Centre.

OBJECTIVES: Previous large studies have shown that solid organ transplant (SOT) patients have an increased risk of developing malignancies. Few studies have compared the prognosis for SOT patients who develop cancer with that of non-transplanted cancer patients. In this study we have investigated the increased risk of oral and lip cancer in SOT patients and also compared the relative survival between SOT patients and non-SOT patients with oral and lip cancer. PATIENTS AND METHODS: From the patient registers at the Transplant Institute at Sahlgrenska University Hospital, records of 4604 SOT patients from 1965 to 2010 were collected. These patient records were linked to the nationwide Swedish Cancer Register and compared to those of the normal population regarding the risk of developing oral and lip cancer, and also to non-SOT patients with lip and oral cancer. A Poisson regression model was used to compare the relative survival between SOT and non-SOT patients with oral and lip cancer. RESULTS: We observed 17 oral cancers (expected 2.69) and 34 lip cancers (expected 0.78) in the cohort. The standardized incidence ratio (SIR) for oral cancer was 6.32 (95% CI, 3.7-10.1) and 43.7 (95% CI, 30.3-61.1) for lip cancer. Relative five-year survival for lip cancer was lower for SOT patients compared to non-SOT patients (p<0.001). CONCLUSION: This study shows that SOT patients have a higher risk of developing both oral and lip cancer, and in addition, that SOT patients with lip cancer have a worse prognosis.

Extracorporeal membrane oxygenation as a bridge to lung transplantation: a long-term study.

OBJECTIVES: We investigated early outcomes in patients with end-stage pulmonary disease bridged with extracorporeal membrane oxygenation (ECMO) with the intention to perform lung transplantation (LTx). METHODS: ECMO was used as a bridge to LTx in 20 patients between 2005 and 2013. Most patients suffered from rapid progress of disease and most failed to stabilize on mechanical ventilation. Sixteen patients (10 males, median age 42 years, range 25-59) underwent LTx after ECMO support for a median of 9 (range 1-229) days. Most patients were not on the waiting list while receiving ECMO, but after being assessed were on the waiting list for a median of 6 (range 1-72) days before LTx or death occurred. Median follow-up at 535 (range 36-3074) days was 100% complete, 9 patients have been followed for >1 year and 4 patients have been bridged during 2013. RESULTS: Four patients died on ECMO waiting for a donor and as intention-to-treat, the success for bridging was 80% (16/20) and 1-year survival was 62% (10/16, not including 4 with <1-year follow-up). For those who underwent LTx, 3 patients died in-hospital after LTx on Days 0, 16 and 82, respectively, and currently, 11/16 (69%) are alive and 1-year survival for transplanted patients was 9/12 (75%). Median ICU stay before and after LTx was 9 (range 2-229) days and 20 (range 0-53) days, respectively. At follow-up, lung function was evaluated, and mean forced expiratory volume at 1 s and forced vital capacity were 56±22% of predicted and 74±24% of predicted, respectively. CONCLUSIONS: ECMO used as a bridge to LTx results in acceptable survival in selected patients with end-stage pulmonary disease.

Coronary artery bypass grafting-related bleeding complications in real-life acute coronary syndrome patients treated with clopidogrel or ticagrelor.

OBJECTIVES: Ticagrelor reduces thrombotic events compared with clopidogrel in patients with acute coronary syndrome, but may also increase bleeding complications. Coronary artery bypass grafting (CABG)-related bleeding complications have not previously been compared in clopidogrel and ticagrelor-treated patients outside the controlled environment of clinical trials. METHODS: Four hundred and five consecutive CABG patients with acute coronary syndrome were included in a prospective observational study. The patients were treated with aspirin and ticagrelor (n = 173) or aspirin and clopidogrel (n = 232). Ticagrelor/clopidogrel was discontinued 5 days before surgery whenever deemed possible. Major bleeding complications according to modified blood conservation using antifibrinolytics in a randomized trial criteria (postoperative blood loss >1500 ml/12 h, re-exploration, red blood cell transfusion >10 units or death because of bleeding) were compared in all patients and when ticagrelor/clopidogrel was discontinued ≥5 days (n = 280), 2-4 days (n = 40) or 0-1 day before surgery (n = 85). RESULTS: Major bleeding complications did not differ significantly between ticagrelor- and clopidogrel-treated patients when all patients were compared (14.5 vs 13.8%, P = 0.89). Likewise, there were no significant differences between ticagrelor and clopidogrel when either drug was discontinued ≥5 days before surgery (6.8 vs 9.9%, P = 0.40) or 2-4 days before surgery (6.3 vs 25.0%, P = 0.21). When ticagrelor/clopidogrel was discontinued 0-1 day before surgery, there was a strong trend towards higher incidence of major bleeding in ticagrelor-treated patients (41.0 vs 21.7%, P = 0.063). CONCLUSIONS: There was no difference in major bleeding complications overall or when ticagrelor or clopidogrel was used in accordance with guidelines. In patients on dual antiplatelet medication up to 1 day before surgery, there tended to be more bleeding complications in ticagrelor-treated patients.

Does coronary artery bypass surgery improve survival?

OBJECTIVES: According to guide-lines, coronary bypass surgery improves survival in high risk patients. The evidence for this is more than 20 years old and may be questioned. Long waiting lists for coronary bypass surgery are detrimental but offer the possibility to compare the risk of death before and after surgery. We hypothesized that the risk of death is lower after bypass surgery than before the operation in high risk patients in a more recent cohort. DESIGN AND RESULTS: Death hazard functions were calculated by the use of Poisson regression scheduled for bypass surgery between 1 Jan 1995 and 31 July 2005. The analyses were performed in two states: 1) in the period after triage until admission for surgery during which optimal medication was intended and 2) after surgery and up to 11 years (corresponding to 57,548 patient years). The probability of death was calculated by entering individual risk profile data into the two multivariable functions. There were several significant differences between the hazard functions in the two states. All variables reflecting angiographic severity of coronary lesions indicated lower risk of death after bypass surgery. The risk associated with left ventricular impairment was lower after surgery (beta coefficients - 0.0546 vs. - 0.0234, p <0.001). Only one variable, age, indicated higher risk after surgery (which is also seen in a general population over time). The reduction of risk was dependent on preoperative risk with a large reduction when preoperative risk was high and vice versa. When preoperative risk was low, however, the risk increased due to surgical mortality. CONCLUSIONS: The risk of death is lower after bypass surgery than before the operation in high risk patients. This is most likely explained by a prognostic gain from bypass surgery. The gain is largest in high-risk patients but small or absent in low risk patients.

One single dose of histidine-tryptophan-ketoglutarate solution gives equally good myocardial protection in elective mitral valve surgery as repetitive cold blood cardioplegia: a prospective randomized study.

OBJECTIVES: Histidine-tryptophan-ketoglutarate (HTK-Custodiol) cardioplegic solution is administered as one single dose for more than 2 hours of ischemia. No prospective randomized clinical study has compared the effects of HTK and cold blood cardioplegia on myocardial damage in elective mitral valve surgery. Thus, the main aim of the present study was to examine whether one single dose of cold antegrade HTK gives as good myocardial protection as repetitive antegrade cold blood cardioplegia in mitral valve surgery. METHODS: Eighty consecutive patients undergoing elective isolated mitral valve surgery for mitral regurgitation, with or without ablation for atrial fibrillation, were included in the study and randomized to HTK or blood cardioplegia. Markers of myocardial injury (troponin-T and creatine kinase MB) were analyzed at baseline and 7 hours, 1 day, 2 days, and 3 days after surgery. RESULTS: No significant difference in creatine kinase MB and troponin-T between HTK and blood cardioplegia groups was found at any time point. There was a significant correlation between ischemic time and markers of myocardial injury in the HTK group only and significantly more spontaneous ventricular fibrillation after release of crossclamping in the HTK group. CONCLUSIONS: One single dose of antegrade cold HTK cardioplegic solution in elective mitral valve surgery protects the myocardium equally well as repetitive antegrade cold blood cardioplegia.

Incomplete revascularization reduces survival benefit of coronary artery bypass grafting: role of off-pump surgery.

OBJECTIVE: We sought to analyze the influence, if any, of incomplete revascularization and on/off-pump techniques on long-term mortality after coronary artery bypass grafting. METHODS: A total of 9408 patients undergoing coronary artery bypass grafting, 8461 on pump and 947 off pump, operated on between 1995 and 2004 were included in the study. Adjusted hazard function for long-term mortality was estimated with Poisson regression analysis in a model that included variables reflecting completeness of revascularization, operative method (on/off pump), and background risk factors for death. RESULTS: Mean follow-up after surgical intervention for survivors was 5.0 +/- 2.8 years (range, 0.5-10.5 years), with a total follow-up of 45,076 patient years. Leaving 1 diseased vascular segment without a bypass graft in 2- or 3-vessel disease did not increase the hazard ratio for death in comparison with complete revascularization (hazard ratio, 1.05; 95% confidence interval, 0.87-1.27; P = .60). In contrast, leaving 2 vascular segments without a bypass graft in 3-vessel disease was associated with an increased hazard ratio for death (hazard ratio, 1.82; 95% confidence interval, 1.15-2.85; P = .01). Incomplete revascularization was more common in the off-pump group (P < .001) in our study. If adjusting for incomplete revascularization, there was no significant influence of the use of on/off-pump techniques on the hazard ratio for death (hazard ratio, 1.08; 95% confidence interval, 0.82-1.40; P = .57). CONCLUSIONS: Incomplete revascularization of patients with 3-vessel disease is an independent risk factor for increased long-term mortality after coronary artery bypass grafting. In contrast, the use of on- or off-pump techniques had no significant effect on survival after adjusting for incomplete revascularization.

A simple score to assess mortality risk in patients waiting for coronary artery bypass grafting.

BACKGROUND: Independent risk factors for death in patients waiting for elective coronary artery bypass surgery have previously been identified. A prioritization where these factors are considered may potentially reduce waiting list mortality. A simple score based on the risk factors was constructed and validated. METHODS: A scoring system based on risk factors in 5,864 consecutive patients operated from 1995 to 1999 was constructed. The following factors were included in the score: unstable angina (3 points [p]), left main stenosis (2p), concomitant aortic valve disease (2p), operative risk (0-2p), left ventricular ejection fraction (0-2p), and male gender (1p). The score was retrospectively validated in 5,167 new patients operated from 1999 to 2003. Based on the sum of risk score points, the patients were divided into three risk groups: low risk (0-2p), intermediate risk (3-5p) and high risk (> or = 6p). The risk groups were related to waiting list mortality and clinical priority (imperative, urgent, and routine). RESULTS: Median waiting time was 33 days. Forty-two patients (0.8%) died while waiting for surgery (5.2 deaths/100 waiting years). Of the patients, 2,406 (47%) were low risk, 1,990 (38%) intermediate risk, and 771 (15%) high risk. Mortality incidence in the high-risk group was fivefold higher than in the intermediate group and 25-fold higher than in the low-risk group (32, 7, and 1.3 deaths/100 waiting years, respectively, p < 0.001 between all groups). Twenty-three percent of the patients in the high-risk group had not been given imperative clinical priority. CONCLUSIONS: The score system identifies patients with increased risk of death while waiting for coronary artery bypass grafting. The score may be used to facilitate and improve the prioritization process.

Waiting time and mortality after elective coronary artery bypass grafting.

BACKGROUND: Limited resources for coronary artery bypass grafting (CABG) results in waiting times, prioritization between patients, and to mortality among the patients on the waiting list. Waiting time is an independent predictor for mortality on the waiting list, but it is not clear if the waiting time also influences outcome after CABG. METHODS: The study population was 5453 consecutive CABG patients who were prioritized at acceptance into three groups: imperative (CABG intended within 2 weeks), urgent (within 12 weeks), and routine (within 6 months). Postoperative mortality was compared between patients operated on within or after the intended waiting time in their respective groups. A multivariate Poisson regression model was used to further determine the effect of waiting time on postoperative mortality. Mean follow up was 24 +/- 15 months. RESULTS: Median waiting time was 55 days. Fifty-five percent of the patients were operated on within the intended waiting time. Postoperative mortality during follow-up was higher in patients operated on after the intended time (8.0 vs 6.2%, p = 0.014), but after correction for age, gender, operative risk, and angina symptoms, waiting time was not an independent predictor for postoperative death (risk ratio, 0.98 per waiting month; 95% confidence interval, 0.97 to 1.00; p = 0.44). CONCLUSIONS: The results suggest that mortality after CABG is not influenced by prolonged waiting time. The result does not exclude subgroups of patients that might benefit from a shorter waiting time.

Gender and mortality risk on the waiting list for coronary artery bypass grafting.

OBJECTIVE: There are gender differences in clinical presentation, treatment and outcome of patients with coronary artery disease. We investigated whether there is also a gender difference in terms of mortality risk on the waiting list in patients accepted for coronary artery bypass grafting (CABG). METHODS: All our patients accepted for elective CABG 1995-1999 (1303 women and 4561 men) were included. Prospectively registered preoperative characteristics and mortality were compared between men and women. Hazard functions for death on the waiting list were calculated using Poisson regression. RESULTS: At acceptance, women were older (68+/-9 vs 65+/-9 years, P<0.001), had a higher Cleveland risk score (2.4+/-1.8 vs 1.8+/-1.8, P<0.001) and a better left ventricular ejection fraction (60+/-14 vs 57+/-14%, P<0.001). More women had unstable angina pectoris (33 vs 20%, P<0.001), diabetes mellitus (23 vs 17%, P<0.001), chronic obstructive pulmonary disease (8 vs 5%, P<0.001), hypertension (47 vs 37%, P<0.001) and planned concomitant aortic valve surgery (13 vs 4%, P<0.001) while more men had three vessel disease (70 vs 66%, P=0.001). Median waiting time (55 vs 54 days, P=0.19) and unadjusted mortality (1.4 vs 1.0%, P=0.25) on the waiting list did not differ significantly between men and women but in a multivariate hazard analysis, female gender was associated with a lower risk than men of death on the waiting list (risk ratio 0.42, 95% confidence interval 0.19-0.93, P=0.032). CONCLUSIONS: Women have a lower risk of death on the waiting list for CABG, in spite of more advanced age, more co-morbidity, and a higher percentage of unstable angina pectoris.

Mortality on the waiting list for coronary artery bypass grafting: incidence and risk factors.

BACKGROUND: Insufficient capacity for coronary artery bypass grafting results in waiting times before operation, prioritization of patients and, ultimately, death on the waiting list. We aimed to calculate waiting list mortality and to identify risk factors for death on the waiting list. METHODS: The study included 5,864 consecutive patients accepted for elective coronary artery bypass grafting (78% male; mean age, 66 +/- 9 years). The patients were categorized at acceptance into three priority groups: imperative (39%), urgent (36%), or routine (25%). Waiting list mortality was calculated and compared between groups, and risk factors were identified by Poisson regression. RESULTS: Median waiting time for the whole population was 55 days. Seventy-seven patients (1.3%) died, corresponding to a mortality rate of 5.8 deaths per 100 patient-years. The mortality rate per 100 patient-years was highest for those in the imperative group, 15.1 deaths, compared with 5.3 deaths in the urgent group and 3.2 in the routine group (p < 0.001). Independent risk factors were male sex (p = 0.032), Cleveland Clinic risk score (p = 0.005), impaired left ventricular ejection fraction (p = 0.007), unstable angina pectoris (p = 0.001), concomitant aortic valve disease (p = 0.002), priority group (p < 0.001), and time after acceptance (p = 0.019). The mortality risk increased with time after acceptance by 11% a month. CONCLUSIONS: Long waiting lists for coronary artery bypass grafting are associated with considerable mortality. The risk of death increases significantly with waiting time. Sex, unstable angina, perioperative risk, impaired left ventricular function, and concomitant aortic valve disease are independent risk factors and should be considered at triage.

On the allocation of cardiac allografts from blood group-O donors.

An organ allocation policy, in which hearts from blood group-O donors are used to transplant recipients with other blood groups (ABO-compatible, non-identical transplantations), may affect blood group-O patients on the waiting list. We investigated how blood group affiliation influences potential recipients on the waiting list. In the case of patients with blood group O, fewer patients were transplanted, waiting list mortality was higher and waiting time to transplantation was longer. Patients with blood group O awaiting cardiac transplantation are affected considerably by an organ allocation policy in which ABO-compatible, non-identical transplantations are performed.