Liver resection and ablation for squamous cell carcinoma liver metastases.

BACKGROUND: Limited evidence exists to guide the management of patients with liver metastases from squamous cell carcinoma (SCC). The aim of this retrospective multicentre cohort study was to describe patterns of disease recurrence after liver resection/ablation for SCC liver metastases and factors associated with recurrence-free survival (RFS) and overall survival (OS). METHOD: Members of the European-African Hepato-Pancreato-Biliary Association were invited to include all consecutive patients undergoing liver resection/ablation for SCC liver metastases between 2002 and 2019. Patient, tumour and perioperative characteristics were analysed with regard to RFS and OS. RESULTS: Among the 102 patients included from 24 European centres, 56 patients had anal cancer, and 46 patients had SCC from other origin. RFS in patients with anal cancer and non-anal cancer was 16 and 9 months, respectively (P = 0.134). A positive resection margin significantly influenced RFS for both anal cancer and non-anal cancer liver metastases (hazard ratio 6.82, 95 per cent c.i. 2.40 to 19.35, for the entire cohort). Median survival duration and 5-year OS rate among patients with anal cancer and non-anal cancer were 50 months and 45 per cent and 21 months and 25 per cent, respectively. For the entire cohort, only non-radical resection was associated with worse overall survival (hazard ratio 3.21, 95 per cent c.i. 1.24 to 8.30). CONCLUSION: Liver resection/ablation of liver metastases from SCC can result in long-term survival. Survival was superior in treated patients with liver metastases from anal versus non-anal cancer. A negative resection margin is paramount for acceptable outcome.

Can hypothermic oxygenated perfusion (HOPE) rescue futile DCD liver grafts?

BACKGROUND: The new UK-DCD-Risk-Score has been recently developed to predict graft loss in DCD liver transplantation. Donor-recipient combinations with a cumulative risk of >10 points were classified as futile and achieved an impaired one-year graft survival of <40%. The aim of this study was to show, if hypothermic oxygenated perfusion (HOPE) can rescue such extended DCD livers and improve outcomes. METHODS: "Futile"-classified donor-recipient combinations were selected from our HOPE-treated human DCD liver cohort (01/2012-5/2017), with a minimum follow-up of one year. Main risk factors, which contribute to the classification "futile" include: elderly donors>60years, prolonged functional donor warm ischemia time (fDWIT > 30min), long cold ischemia time>6hrs, donor BMI>25 kg/m2, advanced recipient age (>60years), MELD-score>25points and retransplantation status. Endpoints included all outcome measures during and after DCD LT. RESULTS: Twenty-one donor-recipient combinations were classified futile (median UK-DCD-Risk-Score:11 points). The median donor age and fDWIT were 62 years and 36 min, respectively. After cold storage, livers underwent routine HOPE-treatment for 120 min. All grafts showed immediate function. One-year and 5-year tumor death censored graft survival was 86%. CONCLUSION: HOPE-treatment achieved excellent outcomes, despite high-risk donor and recipient combinations. Such easy, endischemic perfusion approach may open the door for an increased utilization of futile DCD livers in other countries.

Risk Assessment in High- and Low-MELD Liver Transplantation.

Allocation of liver grafts triggers emotional debates, as those patients, not receiving an organ, are prone to death. We analyzed a high-Model of End-stage Liver Disease (MELD) cohort (laboratory MELD score ≥30, n = 100, median laboratory MELD score of 35; interquartile range 31-37) of liver transplant recipients at our center during the past 10 years and compared results with a low-MELD group, matched by propensity scoring for donor age, recipient age, and cold ischemia time. End points of our study were cumulative posttransplantation morbidity, cost, and survival. Six different prediction models, including donor age x recipient MELD (D-MELD), Difference between listing MELD and MELD at transplant (Delta MELD), donor-risk index (DRI), Survival Outcomes Following Liver Transplant (SOFT), balance-of-risk (BAR), and University of California Los Angeles-Futility Risk Score (UCLA-FRS), were applied in both cohorts to identify risk for poor outcome and high cost. All score models were compared with a clinical-oriented decision, based on the combination of hemofiltration plus ventilation. Median intensive care unit and hospital stays were 8 and 26 days, respectively, after liver transplantation of high-MELD patients, with a significantly increased morbidity compared with low-MELD patients (median comprehensive complication index 56 vs. 36 points [maximum points 100] and double cost [median US$179 631 vs. US$80 229]). Five-year survival, however, was only 8% less than that of low-MELD patients (70% vs. 78%). Most prediction scores showed disappointing low positive predictive values for posttransplantation mortality, such as mortality above thresholds, despite good specificity. The clinical observation of hemofiltration plus ventilation in high-MELD patients was even superior in this respect compared with D-MELD, DRI, Delta MELD, and UCLA-FRS but inferior to SOFT and BAR models. Of all models tested, only the BAR score was linearly associated with complications. In conclusion, the BAR score was most useful for risk classification in liver transplantation, based on expected posttransplantation mortality and morbidity. Difficult decisions to accept liver grafts in high-risk recipients may thus be guided by additional BAR score calculation, to increase the safe use of scarce organs.

Genetic and environmental determinants of unreduced gamete production in Brassica napus, Sinapis arvensis and their hybrids.

Unreduced gametes, sperm or egg cells with the somatic chromosome number, are an important mechanism of polyploid formation and gene flow between heteroploid plants. The meiotic processes leading to unreduced gamete formation are well documented, but the relative influence of environmental and genetic factors on the frequency of unreduced gametes remain largely untested. Furthermore, direct estimates of unreduced gametes based on DNA content are technically challenging and, hence, uncommon. Here, we use flow cytometry to measure the contribution of genetic (hybridization) and environmental (nutrient limitation, wounding) changes to unreduced male gamete production in Brassica napus, Sinapis arvensis and two hybrid lines. Treatments were applied to greenhouse grown plants in a random factorial design, with pollen sampled at two time intervals. Overall, the frequency of unreduced gametes averaged 0.59% (range 0.06-2.17%), plus a single outlier with 27%. Backcrossed hybrids had 39 to 75% higher unreduced gamete production than parental genotypes, averaged across all treatments, although the statistical significance of these differences depended on sampling period and wounding treatment. Unreduced gamete frequencies were higher for the second sampling period than the first. There were no direct effects of wounding or nutrient regime. Our results indicate that both genetic and environmental factors can induce increased unreduced gametes, highlighting the potential importance of environmental heterogeneity and genetic composition of populations in driving polyploid evolution.

Short Chemotherapy-Free Interval Improves Oncological Outcome in Patients Undergoing Two-Stage Hepatectomy for Colorectal Liver Metastases.

BACKGROUND: In patients undergoing two-stage hepatectomy (TSH) for colorectal liver metastases (CRLM), chemotherapy is discontinued before portal vein occlusion and restarted after curative resection. Long chemotherapy-free intervals (CFI) may lead to tumor progression and poor oncological outcomes. OBJECTIVE: The aim of this study was to investigate the impact of the length of CFI on oncological outcome in patients undergoing TSH for CRLM. PATIENTS AND METHODS: Overall, 74 patients suffering from bilobar CRLM who underwent ALPPS (associating liver partition with portal vein ligation for staged hepatectomy; n = 43) or conventional TSH (n = 31) at two tertiary centers were investigated. The impact of CFI on long-term outcomes was analyzed by univariable and multivariable analysis. RESULTS: Preoperative chemotherapy was administered in 91 % (67/74) of patients, and chemotherapy was resumed postoperatively in 69 % (44/64) of patients who completed TSH. The use of postoperative chemotherapy was significantly associated with improved mean overall survival (36 ± 3 vs. 13 ± 3 months; p < 0.001). Overall, the median CFI from surgery to postoperative chemotherapy was 16 weeks (interquartile range 11-31) and was significantly shorter in the ALPPS group when compared with the conventional TSH group (10 vs. 21 weeks; p < 0.001). Multivariable analysis revealed a CFI ≤ 10 weeks as an independent factor associated with improved overall survival (p = 0.006) and disease-free survival (p = 0.010). CONCLUSION: A short CFI is associated with improved oncological outcome in patients undergoing TSH for CRLM. Decreased interstage intervals after ALPPS may facilitate the timely resumption of chemotherapy.

Hypothermic Oxygenated Liver Perfusion: Basic Mechanisms and Clinical Application.

Dynamic preservation strategies such as hypothermic machine perfusion are increasingly discussed to improve liver graft quality before transplantation. This review summarizes current knowledge of this perfusion technique for liver preservation. We discuss optimization of perfusion conditions and current strategies to assess graft quality during cold perfusion. Next, we provide an overview of possible pathways of protection from ischemia-reperfusion injury. Finally, we report on recent clinical applications of human hypothermic machine liver perfusion.

Epidural analgesia and perioperative kidney function after major liver resection.

BACKGROUND: Epidural analgesia (EDA) is a common analgesia regimen in liver resection, and is accompanied by sympathicolysis, peripheral vasodilatation and hypotension in the context of deliberate intraoperative low central venous pressure. This associated fall in mean arterial pressure may compromise renal blood pressure autoregulation and lead to acute kidney injury (AKI). This study investigated whether EDA is a risk factor for postoperative AKI after liver surgery. METHODS: The incidence of AKI was investigated retrospectively in patients who underwent liver resection with or without EDA between 2002 and 2012. Univariable and multivariable analyses were performed including recognized preoperative and intraoperative predictors of posthepatectomy renal failure. RESULTS: A series of 1153 patients was investigated. AKI occurred in 8·2 per cent of patients and was associated with increased morbidity (71 versus 47·3 per cent; P = 0·003) and mortality (21 versus 0·3 per cent; P < 0·001) rates. The incidence of AKI was significantly higher in the EDA group (10·1 versus 3·7 per cent; P = 0·003). Although there was no significant difference in the incidence of AKI between patients undergoing minor hepatectomy with or without EDA (5·2 versus 2·7 per cent; P = 0·421), a substantial difference in AKI rates occurred in patients undergoing major hepatectomy (13·8 versus 5·0 per cent; P = 0·025). In multivariable analysis, EDA remained an independent risk factor for AKI after hepatectomy (P = 0·040). CONCLUSION: EDA may be a risk factor for postoperative AKI after major hepatectomy.

[Patient classification and analysis of risk profiles for type 2 diabetics as the main focus point in practice. Results of the TEMPO study]. / Patientenklassifikation und Risikoprofilanalysen bei Typ-2-Diabetikern in der Schwerpunktpraxis. Ergebnisse der TEMPO-Studie.

BACKGROUND AND OBJECTIVE: Disease management programs (DMP) e. g. for diabetes mellitus, should be the clinical and economic basis for a structured treatment. This article shows results of specialized outpatient treatment using a risk factor depending patient classification. PATIENTS AND METHODS: Diabetes associated co-morbidities, micro- and macrovascular complications, the results and findings of blood pressure and metabolism of glucose and lipids, as well as all treatment-associated costs of 5245 type 2 diabetics were collected for a period of 12 months, accompanied by different measures of quality control. For documentation in the centres, all available original data were used as local data sources. RESULTS: The patient classification system, on which diabetic risk profiles are based, covered 74.3 % of all type 2 diabetic patients. Daily direct costs for all treatment measures ranged between EUR 4.79 (primary prevention) and EUR 8.96 for patients suffering from advanced diabetic foot syndrome. Most of the treatment costs arose from prescriptions of pharmaceuticals, other remedies and aids. Specific strategies of therapy were both related to the severity of co-morbidities and the time since manifestation of diabetes (r = 0.486; p < 0.01, two-sided). The share of patients receiving diet and exercise only decreased from 22.8 % (primary prevention) to below 10 % of patients suffering from microvascular complications. Simultaneously, the share of patients receiving insulin increased up to 81.8 % of patients suffering from advanced diabetic retinopathy. CONCLUSION: The risk profile specific variation in the results clearly shows the need of a risk factor depending classification system for type 2 diabetes, which could be useful to reform and focus the system of compensating payments between health insurance companies more and more on morbidity, or on risk profiles.

[Pseudotumor focal xanthogranulomatous pyelonephritis in adults. Role of imaging technics in the diagnosis]. / Pyélonéphrite xanthogranulomateuse focale pseudotumorale de l'adulte. Place de l'imagerie dans le diagnostic.

Based on 8 personal cases, pseudo-tumoral xanthogranulomatous pyelonephritis is reviewed with emphasis on diagnosis. The condition is a particular form of chronic renal suppuration of histologic definition (combined lesions of chronic pyelonephritis and xanthogranulomatous foam cells). Two forms are recognized: one diffuse, fairly frequent form corresponding to a pyonephrosis, and a pseudo tumoral focal form, the only type discussed in this report, which raises the problem of diagnosis of a renal mass that requires the application of all currently available exploration means to define its true nature. Intravenous urography, ultrasound and CT scan imaging show a non-specific mass of variable character. Selective renal arteriography sometimes shows inflammatory type vascularization, a valuable aid but again non-specific. Puncture biopsy has been used by few authors. However, the presence of a renal mass associated with a chronic pyelonephritis, lithiasis and recurrent episodes of urinary infection should suggest the diagnosis and make use of imaging techniques to detect the affection and adapt therapy, major oncologic surgery being of no utility. Perhaps NMR imaging will provide a step forward in tissue characterization, but it is too early to say.

[Calcified masses of the kidney. Apropos of 58 cases]. / Masses calcifiées du rein. A propos de 58 dossiers.

Case reports were analyzed of patients with calcified renal masses observed in the department since 1968. Of the 65 radiologic reports reviewed, 7 were rejected since the course since diagnosis was unknown. Of the 58 case reports studied, 34 were of masses of certain diagnosis, 12 undetermined, 7 of masses in polycystic kidneys, 3 in tuberculous kidneys and 3 probably calcified hematomas. Analysis involved only those masses of proven diagnosis. Results confirmed the absence of specificity in favor of the cyst of peripheral character of calcifications: 33% of these masses were cancers. The existence of tissue calcification is synonymous of a solid mass, nearly always malignant (92% of cases). For peripherally calcified masses, arteriography was not sufficient to affirm benign nature of lesions, most of these masses having a particularly poorly vascularized or even avascular appearance. In these cases angiotensin was of special interest. Ultrasound imaging proved to be a reliable and perfectly sensitive examination. The presence of calcifications rarely interfered with study of tumoral contents. CT scan imaging and puncture biopsy were also perfectly sensitive and reliable examinations. Because of the high frequency of cancers in masses with peripheral calcification, all these masses should be surgically explored or at least punctured. Although a "benign" CT scan image appears sufficient to affirm the benign nature, this still requires more ample confirmation.

The radiological appearances of telangiectatic osteosarcoma. A study of 14 cases.

Fourteen telangiectatic osteosarcomas are reported. They are rare, clinically and radiologically aggressive lesions, involving mainly the femurs of young patients, often misdiagnosed as aneurysmal bone cysts. An explanation for a characteristic early radiological appearance consisting of regular parallel striations of the shaft is suggested.