Routine end-ischemic hypothermic machine perfusion in liver transplantation from donors after brain death: results of two-year follow-up of a randomized controlled trial.

BACKGROUND: Data on routine hypothermic machine perfusion of livers procured from donors after brain death (DBD) are scarce, and the benefits of the method have only been demonstrated in extended criteria grafts. The aim of this study was to assess if end-ischemic dual hypothermic oxygenated machine perfusion (dHOPE) is superior to static cold storage (SCS) in preservation of livers procured from DBD donors with respect to long-term outcomes. Existing data on short-term outcomes favours dHOPE in patients receiving high-risk grafts. METHODS: This prospective randomized controlled trial included 104 recipients of DBD livers randomly assigned to static cold storage arm (78 patients) and dHOPE arm (26 patients). Endpoints of interest were occurrence of biliary complications (biliary fistula, anastomotic, and nonanastomotic strictures) and overall patient (OS) and graft survival (GS) during two-year follow-up. RESULTS: A total of 36 patients developed biliary complications (at least one event) - 6 events in dHOPE arm and 30 in SCS arm. There was no significant difference in biliary complications between groups (23.7% vs. 43.4% [P=0.11]). No differences were found significant with respect to anastomotic (19.9% vs. 33.7% [P=0.20]) and non-anastomotic strictures (0% vs. 11.1% [P=0.10]) as well as biliary fistulas (11.7% vs. 12.2% [P=0.93]). Survival analysis did not show significantly different result in the study population - OS: 92.3% in dHOPE and 83.9% in SCS (P=0.35), and GS: 92.3% and 81.4% (P=0.23), respectively. However, significant difference in GS was noted in recipients of high-risk grafts - 100% in dHOPE and 73.1% in SCS, respectively (P=0.038). CONCLUSIONS: The long-term outcome data suggest that the routine use of dHOPE may be beneficial for recipients of high-risk grafts from DBD donors. The present study does not provide any evidence for benefits of dHOPE in low-risk grafts.

Routine End-ischemic Hypothermic Oxygenated Machine Perfusion in Liver Transplantation From Donors After Brain Death: A Randomized Controlled Trial.

OBJECTIVE: To assess whether end-ischemic hypothermic oxygenated machine perfusion (HOPE) is superior to static cold storage (SCS) in preserving livers procured from donors after brain death (DBD). BACKGROUND: There is increasing evidence of the benefits of HOPE in liver transplantation, but predominantly in the setting of high-risk donors. METHODS: In this randomized clinical trial, livers procured from DBDs were randomly assigned to either end-ischemic dual HOPE for at least 2 hours or SCS (1:3 allocation ratio). The Model for Early Allograft Function (MEAF) was the primary outcome measure. The secondary outcome measure was 90-day morbidity (ClinicalTrials. gov, NCT04812054). RESULTS: Of the 104 liver transplantations included in the study, 26 were assigned to HOPE and 78 to SCS. Mean MEAF was 4.94 and 5.49 in the HOPE and SCS groups ( P =0.24), respectively, with the corresponding rates of MEAF >8 of 3.8% (1/26) and 15.4% (12/78; P =0.18). Median Comprehensive Complication Index was 20.9 after transplantations with HOPE and 21.8 after transplantations with SCS ( P =0.19). Transaminase activity, bilirubin concentration, and international normalized ratio were similar in both groups. In the case of donor risk index >1.70, HOPE was associated with significantly lower mean MEAF (4.92 vs 6.31; P =0.037) and lower median Comprehensive Complication Index (4.35 vs 22.6; P =0.050). No significant differences between HOPE and SCS were observed for lower donor risk index values. CONCLUSION: Routine use of HOPE in DBD liver transplantations does not seem justified as the clinical benefits are limited to high-risk donors.

Neutrophil-to-lymphocyte ratio predicts nodal involvement in unfavourable, clinically nonmetastatic prostate cancer patients and overall survival in pN1 patients.

The aim of our study was to determine the clinical utility of neutrophil-to-lymphocyte ratio (NLR) in predicting presence and prognosis of nodal involvement in patients treated with radical prostatectomy (RP) due to prostate cancer. This single-centre retrospective study included 205 patients treated with RP and lymphadenectomy between 2012 and 2018. Logistic regression and Kaplan-Meier analyses were performed to evaluate the prognostic value of preoperative NLR in terms of nodal spread and survival. Patients staged pN1 presented lower mean NLR (2.53 vs 3.86; p = 0.0025) compared to pN0 patients. On multivariable analysis of different haematological markers, only NLR exceeding the median (≥ 2.7) predicted pN1 (OR = 0.38; p = 0.0367) independently of biopsy grading and PSA. In internal validation (n = 31 pN1, n = 174 pN0) on the bootstrapped dataset using a spare cutoff of NLR ≥ 4.1 would allow sparing lymphadenectomy in 22.09% pN0 patients, missing 6.45% pN1 (NPV 92.66%; 95% CI 84.91-100%). Noticeably, in pN1 patients NLR ≥ 2.7 correlated with shorter overall survival (p = 0.0196), despite its association with reduced risk of pN1. High pre-prostatectomy NLR was negatively associated with pN1, yielding high NPV in internal validation. Simultaneously, high NLR in pN1 patients was associated with shorter survival.

The Clinical Utility of Systemic Immune-Inflammation Index Supporting Charlson Comorbidity Index and CAPRA-S Score in Determining Survival after Radical Prostatectomy-A Single Centre Study.

The selection of candidates for the curative treatment of PCa requires a careful assessment of life expectancy. Recently, blood-count inflammatory markers have been introduced as prognosticators of oncological and non-oncological outcomes in different settings. This retrospective, monocentric study included 421 patients treated with radical prostatectomy (RP) for nonmetastatic PCa and aimed at determining the utility of a preoperative SII (neutrophil count × platelet count/lymphocyte count) in predicting survival after RP. Patients with high SIIs (≥900) presented significantly shorter survival (p = 0.02) and high SIIs constituted an independent predictor of overall survival [HR 2.54 (95%CI 1.24−5.21); p = 0.01] when adjusted for high (≥6) age-adjusted CCI (ACCI) [HR 2.75 (95%CI 1.27−5.95); p = 0.01] and high (≥6) CAPRA-S [HR 2.65 (95%CI 1.32−5.31); p = 0.006]. Patients with high scores (ACCI and/or CAPRA-S) and high SIIs were at the highest risk of death (p < 0.0001) with approximately a one-year survival loss during the first seven years after surgery. In subgroup of high CAPRA-S (≥6), patients with high ACCIs and high SIIs were at the highest risk of death (p <0.0001). Our study introduces the SII as a straightforward marker of mortality after RP that can be helpful in pre- and postoperative decision-making.

E-Cadherin, Integrin Alpha2 (Cd49b), and Transferrin Receptor-1 (Tfr1) Are Promising Immunohistochemical Markers of Selected Adverse Pathological Features in Patients Treated with Radical Prostatectomy.

In patients treated for prostate cancer (PCa) with radical prostatectomy (RP), determining the risk of extraprostatic extension (EPE) and nodal involvement (NI) remains crucial for planning nerve-sparing and extended lymphadenectomy. The study aimed to determine proteins that could serve as immunohistochemical markers of locally advanced PCa. To select candidate proteins associated with adverse pathologic features (APF) reverse-phase protein array data of 498 patients was retrieved from The Cancer Genome Atlas. The analysis yielded 6 proteins which were then validated as predictors of APF utilizing immunohistochemistry in a randomly selected retrospective cohort of 53 patients. For univariate and multivariate analysis, logistic regression was used. Positive expression of TfR1 (OR 13.74; p = 0.015), reduced expression of CD49b (OR 10.15; p = 0.013), and PSA (OR 1.29; p = 0.013) constituted independent predictors of EPE, whereas reduced expression of e-cadherin (OR 10.22; p = 0.005), reduced expression of CD49b (OR 24.44; p = 0.017), and PSA (OR 1.18; p = 0.002) were independently associated with NI. Both models achieved high discrimination (AUROC 0.879 and 0.888, respectively). Immunohistochemistry constitutes a straightforward tool that might be easily utilized before RP. Expression of TfR1 and CD49b is associated with EPE, whereas expression of e-cadherin and CD49b is associated with NI. Since following immunohistochemical markers predicts respective APFs independently from PSA, in the future they might supplement existing preoperative nomograms or be implemented in novel tools.

Nadir CA-125 has prognostic value for recurrence, but not for survival in patients with ovarian cancer.

The objective of this study was to evaluate the nadir CA-125 in patients with epithelial ovarian cancer. A total of 168 patients who achieved complete remission (no clinical and radiological signs, CA-125 ≤ 35 U/ml) after first-line treatment were enrolled in the study. The relationship between CA-125 and survival was examined by applying generalized additive models to the Cox proportional hazards model. The median CA-125 concentration after the treatment was 10 U/ml (2.7-35 U/ml). The nadir CA-125 was related to progression-free survival but not to overall survival. The risk of recurrence in patients with 11-25 U/ml and 26-35 U/ml compared to patients with ≤ 10 U/ml was 1.87 (p < 0.0024) and 2.17 (p < 0.018), respectively. An increased risk of recurrence according to the nadir CA-125 (≤ 10 U/ml vs. 11-25 U/ml and ≤ 10 U/ml vs. 26-35 U/ml) was found in patients with high-grade tumours (hazard ratio, HR = 2.08 and 2.59, respectively), advanced disease (HR = 2.38 and 2.03, respectively), serous histology (HR = 2.08 and 2.43, respectively) and after complete cytoreduction (HR = 2.7 and 2.72, respectively). No correlation between the CA-125 nadir and recurrence risk was found in patients with early-stage disease or those receiving neoadjuvant chemotherapy or bevacizumab.

Incisional Surgical Site Infections After Mass and Layered Closure of Upper Abdominal Transverse Incisions: First Results of a Randomized Controlled Trial.

OBJECTIVE: To compare the early results of mass and layered closure of upper abdominal transverse incisions. SUMMARY OF BACKGROUND DATA: Contrary to midline incisions, data on closure of transverse abdominal incisions are lacking. METHODS: This is the first analysis of a randomized controlled trial primarily designed to compare mass with layered closure of transverse incisions with respect to incisional hernias. Patients undergoing laparotomy through upper abdominal transverse incisions were randomized to either mass or layered closure with continuous sutures. Incisional surgical site infection (incisional-SSI) was the primary end-point. Secondary end-points comprised suture-to-wound length ratio (SWLR), closure duration, and fascial dehiscence (clinicatrials.gov NCT03561727). RESULTS: A total of 268 patients were randomized to either mass (n=134) or layered (n=134) closure. Incisional-SSIs occurred in 24 (17.9%) and 8 (6.0%) patients after mass and layered closure, respectively (P =0.004), with crude odds ratio (OR) of 0.29 [95% confidence interval (95% CI) 0.13-0.67; P =0.004]. Layered technique was independently associated with fewer incisional-SSIs (OR: 0.29; 95% CI 0.12-0.69; P =0.005). The number needed to treat, absolute, and relative risk reduction for layered technique in reducing incisional-SSIs were 8.4 patients, 11.9%, and 66.5%, respectively. Dehiscence occurred in one (0.8%) patient after layered closure and in two (1.5%) patients after mass closure (P >0.999). Median SWLR were 8.1 and 5.6 (P <0.001) with median closure times of 27.5 and 25.0 minutes (P =0.044) for layered and mass closures, respectively. CONCLUSIONS: Layered closure of upper abdominal transverse incisions should be preferred due to lower risk of incisional-SSIs and higher SWLR, despite clinically irrelevant longer duration.

Rising serum CA-125 levels within the normal range is strongly associated recurrence risk and survival of ovarian cancer.

BACKGROUND: In clinical practice alterations in CA-125 concentration within normal range in patients with ovarian cancer after first-line treatment are common. Even minor increase in CA-125 concentration is associated with patients' anxiety and difficult interpretation and counselling for clinicians. The aim of this study was to evaluate the significance of CA-125 fluctuations within reference level in patients who suffered from ovarian cancer with complete response after first-line treatment. RESULTS: 168 patients with epithelial ovarian cancer, who achieved complete remission after first line treatment were enrolled in the study. CA-125 concentration assessment was carried out during follow up visits. The recurrence of the disease was diagnosed on the first appearance of symptoms: clinical, radiological or histopathological/cytological. PFS and 5-year survival rate was calculated with Kaplan-Meier plots. Statistical analysis was performed with SAS / STAT® 9.4 / 14.4, SAS Institute Inc., Cary, NC, USA, 2017. Median concentration of CA-125 after first-line therapy was 10 U/ml. Increasing CA-125 concentration by > 5 U/ml, 3 and 6 months after the treatment was associated with higher risk of relapse (HR = 7.6, p < 0.0001 and HR = 5.29, p < 0.0001 respectively). 5-year survival rate was significantly lower in patients with increased CA-125 by 5 U/ml, 3 and 6 months after therapy (56.79% vs 0 and 50.62% vs 15.55%). CONCLUSIONS: Increased concentration of CA-125 by > 5 U/ml within normal range, 3 and 6 months after treatment was unfavorable prognostic factor in ovarian cancer patients with complete response to primary therapy.

Effect of Smoking Cessation on the Pharmacokinetics and Pharmacodynamics of Clopidogrel after PCI: The Smoking Cessation Paradox Study.

BACKGROUND: Cigarette smoking is associated with enhanced clopidogrel effect and platelet inhibition. However, the effect of smoking cessation on clopidogrel pharmacokinetics (PK) and pharmacodynamics (PD) is unknown. We aimed to determine the effect of smoking cessation, confirmed by cotinine measurement, on clopidogrel PK and PD after percutaneous coronary intervention (PCI). METHODS AND RESULTS: Following successful PCI, patients treated with 75 mg/day clopidogrel who reported smoking ≥10 cigarettes/day with NicAlert urine cotinine level 6 were enrolled. Clopidogrel and its metabolite concentrations, VerifyNow P2Y12 reaction units (PRUs), and NicAlert levels were measured in the study group before and at 30 days after smoking cessation and in a control group. CYP1A2 and CYP2C19 genotypes were determined. At 30-day visit (n = 87), 45 patients continued smoking, whereas 42 patients stopped smoking. Baseline PRUs were similar between groups. At 30 days, the smoking cessation group had higher PRUs (150.5 ± 68.6 vs. 118.4 ± 65.9, p = 0.03), greater absolute PRU change (27.7 ± 39.8 vs. -12.9 ± 55.4, p = 0.0002), greater change of PRUs adjusted for baseline platelet reactivity (38.6 ± 10.0, p < 0.01), greater risk of high platelet reactivity (HPR) (odds ratio: 10.14 [1.52-67.5], p = 0.017), and a trend towards decreased H3 clopidogrel metabolite levels (-3.41 ng/mL [-11.00 to 0.54 ng/mL], p = 0.072). CYP2C19 LoF carriers who stopped smoking had the highest PRUs, whereas those with the wild type who continued smoking had the lowest PRUs (p < 0.008). CONCLUSION: Smoking cessation in clopidogrel-treated patients after PCI is associated with increased platelet reactivity and greater risk of HPR. Alternative P2Y12 inhibitors may be considered in selected patients who stop smoking after PCI.

Shadows Behind Using Simple Risk Models in Selection of Hepatocellular Carcinoma Patients for Liver Transplantation.

OBJECTIVE: To assess the potential influence of replacing Milan criteria with simple risk scores on outcomes of hepatocellular carcinoma (HCC) patients undergoing liver transplantation. SUMMARY BACKGROUND DATA: Several risk scores combining morphological and biological features were recently proposed for precise selection of HCC patients for transplantation. METHODS: This retrospective study included 282 HCC liver transplant recipients. Recurrence-free survival (RFS), the primary outcome measure, was evaluated according to Metroticket 2.0 model and French AFP model with Milan criteria serving as benchmark. RESULTS: Patients were well stratified with respect to RFS by Milan criteria, Metroticket 2.0 criteria, and AFP model cut-off ≤2 points (all P < 0.001) with c-statistics of 0.680, 0.695, and 0.681, respectively. Neither Metroticket 2.0 criteria (0.014, Z = 0.023; P = 0.509) nor AFP model (-0.014, Z = -0.021; P = 0.492) provided significant net reclassification improvement. Both patients within the Metroticket 2.0 criteria and AFP model ≤2 points exhibited heterogeneous recurrence risk, dependent upon alpha-fetoprotein (P = 0.026) and tumor number (P = 0.024), respectively. RFS of patients beyond Milan but within Metroticket 2.0 criteria (75.3%) or with AFP model ≤2 points (74.1%) was inferior to that observed for patients within Milan criteria (87.1%; P = 0.067 and P = 0.045, respectively). Corresponding microvascular invasion rates were 37.2% and 50.0%, compared with 13.6% in patients within Milan criteria (both P < 0.001). Moreover, Milan-out status was associated with significantly higher recurrence risk in subgroups within Metroticket 2.0 criteria (P = 0.021) or AFP model ≤2 points (P = 0.014). CONCLUSION: Utilization of simple risk scores for liver transplant eligibility assessment leads to selection of patients at higher risk of posttransplant HCC recurrence.

Prognostic Relevance of a Complete Pathologic Response in Liver Transplantation for Hepatocellular Carcinoma.

BACKGROUND: A complete pathologic response (CPR) after neoadjuvant treatment is reported to be associated with an exceptionally low risk of recurrence after liver transplantation for hepatocellular carcinoma (HCC). This study aimed to evaluate the prognostic role of CPR in liver transplantation for HCC. METHODS: This retrospective cohort study was based on 222 HCC transplant recipients. Incidence of recurrence and survival at 5 years were the primary and secondary outcome measures, respectively. Competing risk analyses were applied to evaluate recurrence incidence and its predictors. Propensity score matching was performed to compare the outcomes for patients after neoadjuvant treatment with and without CPR. RESULTS: Neoadjuvant treatment was performed for 127 patients, 32 of whom achieved CPR (25.2%). Comparison of baseline characteristics showed that the patients with CPR were at lowest baseline recurrence risk, followed by treatment-naïve patients and patients without CPR. Adjusted for potential confounders, CPR did not have any significant effects on tumor recurrence. No significant net reclassification improvement was noted after addition of CPR to existing criteria. Neoadjuvant treatment without CPR was associated with increased risk of recurrence in subgroups within the Milan criteria (p = 0.016), with alpha-fetoprotein concentration (AFP) model not exceeding 2 points (p = 0.021) and within the Warsaw criteria (p = 0.007) compared with treatment-naïve patients who were at risk similar to those with CPR. The 5-year incidences of recurrence in propensity score-matched patients with and without CPR were respectively 14.0% and 15.9% (p = 0.661), with corresponding survival rates of 73.2% and 67.4%, respectively (p = 0.329). CONCLUSIONS: The findings showed that CPR is not independently associated with long-term outcomes after liver transplantation for HCC.

Extremes of Liver Transplantation for Hepatocellular Carcinoma.

The aim of this retrospective observational study was to evaluate outcomes of patients with extremely advanced hepatocellular carcinoma (HCC) after liver transplantation. A total of 285 HCC patients after liver transplantation were screened for eligibility based on either intrahepatic dissemination (≥10 tumors) or macrovascular invasion. Tumor recurrence was the primary end-point. The study cohort comprised 26 patients. Median recurrence-free survival was 23.2 months with hepatitis B virus (HBV) infection (p = 0.038), higher AFP model score (p = 0.001), prolonged graft ischemia (p = 0.004), and younger donor age (p = 0.016) being significant risk factors. Median recurrence-free survival of HBV-negative and HBV-positive patients was 29.8 and 9.3 months, respectively (p = 0.053). In patients with macrovascular invasion, recurrence-free survival at 3 years was 46.3% with no specific predictors. Tumor size (p = 0.044), higher AFP model score (p = 0.019), prolonged graft ischemia (p = 0.016), and younger donor age (p = 0.041) were significant risk factors in patients with intrahepatic dissemination. Superior 3-year outcomes were observed in patients with intrahepatic dissemination and tumor size <3.5 cm (83.3%, p = 0.027) and HBV-negative patients with ischemia <9.7 h (85.7%, p = 0.028). In conclusion, patients with extremely advanced HCCs are remarkably heterogeneous with respect to their profile of tumor recurrence risk. This heterogeneity is largely driven by factors other than standard predictors of post-transplant HCC recurrence.

Predicting side-specific prostate cancer extracapsular extension: a simple decision rule of PSA, biopsy, and MRI parameters.

OBJECTIVE: To develop an easy-to-use side-specific tool for the prediction of prostate cancer extracapsular extension (ECE) using clinical, biopsy, and MRI parameters. MATERIALS AND METHODS: Retrospective analysis of patients who underwent radical prostatectomy preceded by staging multiparametric MRI of the prostate was performed. Multivariate logistic regression analysis was used to choose independent predictors of ECE. Continuous variables were transformed to categorical ones by choosing threshold values using spline knots or testing thresholds used in previously described models. Internal validation of the rule was carried out as well as validation of other algorithms on our group was performed. RESULTS: In the analyzed period of time, 88 out of 164 patients who underwent radical prostatectomy met inclusion criteria. ECE was evidenced at radical prostatectomy in 41 patients (46.6%) and in 53 lobes (30.1%). In the multivariate analysis PSA, total percentage of cancerous tissue in cores (%PCa) and maximum tumour diameter (MTD) of Likert 3-5 lesions on MRI were independent predictors of ECE. The following rule for predicting side-specific ECE was proposed: %PCa ≥ 15% OR MTD ≥ 15 mm OR PSA ≥ 20 ng/mL. Internal validation of the algorithm revealed safe lower confidence limits for sensitivity and NPV, proving that model offers accurate risk grouping that can be safely used in decision-making. CONCLUSION: The rule developed in this study makes ECE prediction fast, intuitive, and side-specific. However, until validated externally it should be used with caution.

Pain reduction after lumbar epidural injections using particulate versus non-particulate steroids: intensity of the baseline pain matters.

OBJECTIVES: To compare pain relief after CT-guided lumbar epidural steroid injections (ESI) using particulate (triamcinolone) and non-particulate (dexamethasone) steroids, and to explore factors affecting the effectiveness of both steroid types. METHODS: This retrospective observational study included 806 patients with lumbar radiculopathy and corresponding MRI or CT abnormalities of the lumbar spine, who were matched using the propensity score method, yielding two cohorts of 209 patients each. Pain intensity was evaluated prior to the procedure using a pain numerical rating scale (NRS) with range 0-10. Reevaluation took place 1 day and 4 weeks post-injection. Logistic regression analysis and cubic splines applied to generalized additive models were implemented to assess the differences in pain reduction after ESI in the analyzed patient groups. RESULTS: Four weeks post-injection, the overall chance of ≥ 50% pain reduction was lower in the dexamethasone group than that in the triamcinolone group (odds ratio [OR] = 0.55; p < 0.012). In the dexamethasone cohort, the intensity of baseline pain and the presence of a herniated intervertebral disc in the infiltrated segment were both significant and independent predictors of ≥ 50% pain relief. Patients with baseline NRS score ≥ 7 points had markedly less chance of ≥ 50% pain relief than patients with NRS score < 7 (OR = 0.53; p < 0.032), whereas disc herniation increased the chances more than twofold (OR = 2.29; p < 0.044). There was no significant correlation between the effectiveness of triamcinolone and any analyzed concomitant variables. CONCLUSIONS: Triamcinolone was superior for lumbar radiculopathy of severe intensity. For mild to moderate pain, no benefit of using triamcinolone over dexamethasone was found. The effectiveness of dexamethasone was lower for stenotic spinal lesions than for disc herniation. KEY POINTS: • Triamcinolone is superior to dexamethasone for epidural treatment of severe lumbar radiculopathy. • For mild to moderate pain, dexamethasone could be equally effective. • Dexamethasone reduces pain caused by disc herniation much better than it does to pain caused by fixed stenotic spinal lesions.

Ischemia-reperfusion injury and the risk of hepatocellular carcinoma recurrence after deceased donor liver transplantation.

This study aimed to evaluate the effects of ischemia-reperfusion injury (IRI) on the risk of hepatocellular carcinoma (HCC) recurrence after liver transplantation. Data of 195 patients were retrospectively analysed. Post-reperfusion aspartate (AST), alanine transaminase, and lactate dehydrogenase (LDH) levels were the primary measures of IRI. Tumour recurrence was the primary endpoint. Post-reperfusion AST was a continuous risk factor for tumour recurrence in patients within Milan criteria (p = 0.035), with an optimal cut-off of 1896 U/L. Recurrence-free survival of patients within Milan criteria and post-reperfusion AST of <1896 and ≥1896 U/L was 96.6% and 71.9% at 5 and 3.7 years, respectively (p = 0.006). Additionally, post-reperfusion AST and LDH exceeding the upper quartile significantly increased the risk of HCC recurrence in patients within Milan criteria (p = 0.039, hazard ratio [HR] = 5.99 and p = 0.040, HR = 6.08, respectively) and to a lesser extent, in patients within Up-to-7 criteria (p = 0.028, HR = 3.58 and p = 0.039, HR = 3.33, respectively). No other significant IRI effects were found in patients beyond the Up-to-7 criteria and in analyses stratified for independent risk factors for recurrence: tumour number and differentiation, alpha-fetoprotein, and microvascular invasion. Thus, IRI exerts major negative effects on the risk of HCC recurrence after liver transplantation in patients within standard and extended criteria.

Autologous peripheral blood stem cell transplantation in dialysis-dependent multiple myeloma patients-DAUTOS Study of the Polish Myeloma Study Group.

INTRODUCTION: Dialysis-dependent (DD) multiple myeloma patients (MM) have a poor prognosis and high tumour burden, thus may benefit from autologous peripheral blood stem cell transplantation (auto-PBSCT), however, these patients have an increased risk of toxicity. AIMS: To evaluate the outcomes (toxicity, PFS, OS) of high dose therapy followed by auto-PBSCT during an observational study and after propensity score matching. PATIENTS AND METHODS: Between 2004-2015, 24 DD patients, (aged 38-67 years), ISS 3, treated with auto-PBSCT, requiring dialysis at diagnosis and auto-PBSCT were evaluated, matched and compared to 55 normal renal function MM patients (NRF) with ISS 3 for outcomes of interest. RESULTS: In DD patients compared to NRF patients risk of mucositis (88% vs 55%), infection (79% vs 51%), parenteral nutrition (50% vs 24%), diarrhoea (71% vs 38%), prolonged duration of hospitalisation (medians: 30 vs 21 days), requirement for RBC transfusion (83% vs 36%) were significantly higher, while no significant differences were found in post-transplant response (ORR; 75% vs 87%), 5-year PFS (36% vs 20%) and OS (39% vs 50%). Subgroup analyses based on toxicity supported these results. CONCLUSIONS: Despite the increased risk of toxicity in DD patients these events do not significantly affect both the PFS and OS.

Symptomatic medulla compression by vertebral artery.

OBJECTIVE: Vertebral artery medulla compression syndrome (VAMCS) is a very rare condition manifesting as different neurological focal deficits. The case of a 36-year-old male with symptomatic brainstem compression by vertebral artery (VA) treated by means of microvascular decompression (MVD) and a review of the literature is presented. CASE REPORT: On admission, a 36-year-old patient presented with hypoalgesia, hypothermesthesia and hemiparesis on the left side. Magnetic resonance imaging (MRI) of the head disclosed the right VA loop compressing the ventrolateral medulla and excluded other entities such as brain tumor, stroke and multiple sclerosis. Since displacement and significant compression of the right pyramidal tract was confirmed by diffusion tensor imaging (DTI), neurovascular compression syndrome was diagnosed. The patient underwent MVD of the medulla using a Gore-Tex implant as a separating material via the right far-lateral approach. The left hemiparesis and hemisensory loss remitted rapidly after the procedure. The post-procedural neurological improvement was maintained at one year follow-up. Based on a review of the literature, a total of 33 cases of surgically treated VAMCS has been reported so far. CONCLUSION: VAMCS should be considered as the cause of neurological deficits when other pathological entities are ruled out. In symptomatic conflict of the VA with the medulla, microvascular decompression using a Gore-Tex implant can be an effective method of treatment. Nevertheless, a statistical analysis on all reported cases showed favorable results using the VA repositioning technique when compared with MVD (success rate 91% vs. 58%, p<0.05).

Heart infarct as the major cause of death of hematological patients as identified by autopsy.

BACKGROUND: Despite progress in diagnostic procedures, clinical diagnosis is not always confirmed by an autopsy. An autopsy is a valuable tool in evaluating diagnostic accuracy. OBJECTIVES: The aim of the study was to compare clinical diagnoses of immediate causes of death with autopsy findings in patients with hematological malignancies or aplastic anemia. MATERIAL AND METHODS: In this study, the results of 154 autopsies (1993-2004) of patients with hematological diseases were reviewed and compared with clinical data. The most probable causes of death in the case of particular hematological diseases as well as the discordances between clinical and autopsy diagnoses and their relation to the clinical characteristic were identified in the studied cohort, which primarily included patients whose death at that particular time was not explained by the clinical course, and in 50% of cases was sudden. RESULTS: Although various combined infections have been found to be responsible for the largest number of deaths (26.6%), the most common single cause was myocardial infarction (29 patients, 18.8%). The discordance between clinical and post-mortem diagnoses of immediate causes of death was found in 55 patients (35.7%; 95% CI 28.2-42.8%), with 50.9% of cases considered class I discrepancies according to Goldman's criteria. The myocardial infarction was found to be clinically undiagnosed in 69% of cases. In 41% of cases, it was a class I discrepant diagnosis. CONCLUSIONS: This data suggests that hematological patients require special attention and probably preventive measures concerning coronary heart disease, particularly during the initiation of antineoplastic therapy.

Challenging the principle of utility as a barrier for wider use of liver transplantation for hepatocellular cancer.

BACKGROUND: Although transplant benefit appears superior for patients with advanced hepatocellular cancer (HCC), liver transplantation remains limited to selected low-risk HCC patients to keep their outcomes similar to heterogeneous group of non-HCC patients. The purpose of this study was to assess the rationale for current policy of restricting access to liver transplantation to minority of HCC patients based on utility principle. METHODS: This retrospective cohort study comprised 1246 liver transplant recipients, including 206 HCC and 1040 non-HCC patients. Patient survival was the primary outcome measure. Patients with HCC and benign diseases were divided into low-, moderate-, and high-risk subgroups basing on independent risk factors for disease-free survival and model for end-stage liver disease (MELD) score (<30, 30-40, >40), respectively. RESULTS: MELD (p < 0.001) and presence of HCC (p = 0.008) were independent risk factors for early and late mortality, respectively. Total tumor volume (p = 0.008) and alpha-fetoprotein (p = 0.013) were independent predictors of recurrence and mortality used for division of HCC patients into low-, moderate-, and high-risk subgroups, with disease-free survival rates of 74.9% (5 years), 51.7% (5 years), and 8.0% (3 years), respectively (p < 0.001). There were no differences in 5-year overall survival between low-risk HCC (74.9%) and non-HCC (81.9%) patients (p = 0.210), moderate-risk HCC (63.3%) and non-HCC (68.0%) patients (p = 0.372), and high-risk HCC (55.0%) and non-HCC (56.0%) patients (p = 0.559). CONCLUSIONS: The principle of utility is unequally applied for restriction of access to liver transplantation for HCC patients. The results provide rationale for discussion on reinitiation of liver transplantation for advanced HCCs.

Limitations of predicting microvascular invasion in patients with hepatocellular cancer prior to liver transplantation.

Microvascular invasion (MVI) is well known to negatively influence outcomes following surgical treatment of hepatocellular cancer (HCC) patients. The aim of this study was to evaluate the rationale for prediction of MVI before liver transplantation (LT). Data of 200 HCC patients after LT were subject to retrospective analysis. MVI was present in 57 patients (28.5%). Tumor number (p = 0.001) and size (p = 0.009), and alpha-fetoprotein (p = 0.049) were independent predictors of MVI used to create a prediction model, defined as: 0.293x(tumor number) + 0.283x(tumor size in cm) + 0.164xloge(alpha-fetoprotein in ng/ml) (c statistic = 0.743). The established cut-off (≥2.24) was associated with sensitivity and specificity of 72%. MVI was not an independent risk factor for recurrence (p = 0.307), in contrast to tumor number (p = 0.047) and size (p < 0.001), alpha-fetoprotein (p < 0.001) and poor differentiation (p = 0.039). Recurrence-free survival at 5 years for patients without MVI was 85.9% as compared to 83.3% (p = 0.546) and 55.3% (p = 0.001) for patients with false negative and true positive prediction of MVI, respectively. The use of both morphological and biological tumor features enables effective pre-transplant prediction of high-risk MVI. Provided that these parameters are combined in selection of HCC patients for LT, pre-transplant identification of all patients with MVI does not appear necessary.