Erdafitinib versus pembrolizumab in pretreated patients with advanced or metastatic urothelial cancer with select FGFR alterations: cohort 2 of the randomized phase III THOR trial.

BACKGROUND: Erdafitinib is an oral pan-fibroblast growth factor receptor (FGFR) tyrosine kinase inhibitor approved to treat locally advanced/metastatic urothelial carcinoma (mUC) in patients with susceptible FGFR3/2 alterations (FGFRalt) who progressed after platinum-containing chemotherapy. FGFR-altered tumours are enriched in luminal 1 subtype and may have limited clinical benefit from anti-programmed death-(ligand) 1 [PD-(L)1] treatment. This cohort in the randomized, open-label phase III THOR study assessed erdafitinib versus pembrolizumab in anti-PD-(L)1-naive patients with mUC. PATIENTS AND METHODS: Patients ≥18 years with unresectable advanced/mUC, with select FGFRalt, disease progression on one prior treatment, and who were anti-PD-(L)1-naive were randomized 1 : 1 to receive erdafitinib 8 mg once daily with pharmacodynamically guided uptitration to 9 mg or pembrolizumab 200 mg every 3 weeks. The primary endpoint was overall survival (OS). Secondary endpoints included progression-free survival (PFS), objective response rate (ORR), and safety. RESULTS: The intent-to-treat population (median follow-up 33 months) comprised 175 and 176 patients in the erdafitinib and pembrolizumab arms, respectively. There was no statistically significant difference in OS between erdafitinib and pembrolizumab [median 10.9 versus 11.1 months, respectively; hazard ratio (HR) 1.18; 95% confidence interval (CI) 0.92-1.51; P = 0.18]. Median PFS for erdafitinib and pembrolizumab was 4.4 and 2.7 months, respectively (HR 0.88; 95% CI 0.70-1.10). ORR was 40.0% and 21.6% (relative risk 1.85; 95% CI 1.32-2.59) and median duration of response was 4.3 and 14.4 months for erdafitinib and pembrolizumab, respectively. 64.7% and 50.9% of patients in the erdafitinib and pembrolizumab arms had ≥1 grade 3-4 adverse events (AEs); 5 (2.9%) and 12 (6.9%) patients, respectively, had AEs that led to death. CONCLUSIONS: Erdafitinib and pembrolizumab had similar median OS in this anti-PD-(L)1-naive, FGFR-altered mUC population. Outcomes with pembrolizumab were better than assumed and aligned with previous reports in non- FGFR-altered populations. Safety results were consistent with the known profiles for erdafitinib and pembrolizumab in this patient population.

Associations between KIR/KIR-ligand genotypes and clinical outcome for patients with advanced solid tumors receiving BEMPEG plus nivolumab combination therapy in the PIVOT-02 trial.

Bempegaldesleukin (BEMPEG), a CD122-preferential IL2 pathway agonist, has been shown to induce proliferation and activation of NK cells. NK activation is dependent on the balance of inhibitory and excitatory signals transmitted by NK receptors, including Fc-gamma receptors (FCγRs) and killer immunoglobulin-like receptors (KIRs) along with their KIR-ligands. The repertoire of KIRs/KIR-ligands an individual inherits and the single-nucleotide polymorphisms (SNPs) of FCγRs can influence NK function and affect responses to immunotherapies. In this retrospective analysis of the single-arm PIVOT-02 trial, 200 patients with advanced solid tumors were genotyped for KIR/KIR-ligand gene status and FCγR SNP status and evaluated for associations with clinical outcome. Patients with inhibitory KIR2DL2 and its ligand (HLA-C1) observed significantly greater tumor shrinkage (TS, median change -13.0 vs. 0%) and increased PFS (5.5 vs. 3.3 months) and a trend toward improved OR (31.2 vs. 19.5%) compared to patients with the complementary genotype. Furthermore, patients with KIR2DL2 and its ligand together with inhibitory KIR3DL1 and its ligand (HLA-Bw4) had improved OR (36.5 vs. 19.6%), greater TS (median change -16.1 vs. 0%), and a trend toward prolonged PFS (8.4 vs. 3.6 months) as compared to patients with the complementary genotype. FCγR polymorphisms did not influence OR/PFS/TS.These data show that clinical response to BEMPEG plus nivolumab treatment in the PIVOT-02 trial may be associated with the repertoire of KIR/KIR-ligands an individual inherits. Further investigation and validation of these results may enable KIR/KIR-ligand genotyping to be utilized prospectively for identifying patients likely to benefit from certain cancer immunotherapy regimens.

Upper tract urothelial carcinoma topical issue 2016: treatment of metastatic cancer.

PURPOSE: To review the management of metastatic upper tract urothelial carcinoma (UTUC) including recent advances in targeted and immune therapies as an update to the 2014 joint international consultation on UTUC, co-sponsored by the Société Internationale d'Urologie and International Consultation on Urological Diseases. METHODS: A PubMed database search was performed between January 2013 and May 2016 related to the treatment of metastatic UTUC, and 54 studies were selected for inclusion. RESULTS: The management of patients with metastatic UTUC is primarily an extrapolation from evidence guiding the management of metastatic urothelial carcinoma of the bladder. The first-line therapy for metastatic UTUC is platinum-based combination chemotherapy. Standard second-line therapies are limited and ineffective. Patients with UTUC who progress following platinum-based chemotherapy are encouraged to participate in clinical trials. Recent advances in genomic profiling present exciting opportunities to guide the use of targeted therapy. Immunotherapy with checkpoint inhibitors has demonstrated extremely promising results. Retrospective studies provide support for post-chemotherapy surgery in appropriately selected patients. CONCLUSIONS: The management of metastatic UTUC requires a multi-disciplinary approach. New insights from genomic profiling using targeted therapies, novel immunotherapies, and surgery represent promising avenues for further therapeutic exploration.

Portal Supply and Venous Drainage of the Caudate Lobe in the Healthy Human Liver: Virtual Three-Dimensional Computed Tomography Volume Study.

OBJECTIVE: The venous vascular anatomy of the caudate lobe is exceptional. The purpose of this study was to assess portal inflow and venous outflow volumes of the caudate lobe. METHODS: Extrahepatic (provided by the first-order branches) versus intrahepatic (provided by the second- to third-order branches) portal inflow, as well as direct (via Spieghel veins) versus indirect (via hepatic veins) venous drainage patterns were analyzed in virtual 3-D liver maps in 140 potential live liver donors. RESULTS: The caudate lobe has a greater intrahepatic than extrahepatic portal inflow volume (mean 55 ± 26 vs. 45 ± 26%: p = 0.0763), and a greater extrahepatic than intrahepatic venous drainage (mean 54-61 vs. 39-46%). Intrahepatic drainage based on mean estimated values showed the following distribution: middle > inferior (accessory) > right > left hepatic vein. CONCLUSIONS: Sacrifice of extrahepatic caudate portal branches can be compensated by the intrahepatic portal supply. The dominant outflow via Spieghel veins and the negligible role of left hepatic vein in caudate venous drainage may suggest reconstruction of caudate outflow via Spieghel veins in instances of extended left hemiliver live donation not inclusive of the middle hepatic vein. The anatomical data and the real implication for living donors must be further verified by clinical studies.

Mice selectively bred for high voluntary wheel running have larger midbrains: support for the mosaic model of brain evolution.

Increased brain size, relative to body mass, is a primary characteristic distinguishing the mammalian lineage. This greater encephalization has come with increased behavioral complexity and, accordingly, it has been suggested that selection on behavioral traits has been a significant factor leading to the evolution of larger whole-brain mass. In addition, brains may evolve in a mosaic fashion, with functional components having some freedom to evolve independently from other components, irrespective of, or in addition to, changes in size of the whole brain. We tested whether long-term selective breeding for high voluntary wheel running in laboratory house mice results in changes in brain size, and whether those changes have occurred in a concerted or mosaic fashion. We measured wet and dry brain mass via dissections and brain volume with ex vivo magnetic resonance imaging of brains that distinguished the caudate-putamen, hippocampus, midbrain, cerebellum and forebrain. Adjusting for body mass as a covariate, mice from the four replicate high-runner (HR) lines had statistically larger non-cerebellar wet and dry brain masses than those from four non-selected control lines, with no differences in cerebellum wet or dry mass or volume. Moreover, the midbrain volume in HR mice was ~13% larger (P<0.05), while volumes of the caudate-putamen, hippocampus, cerebellum and forebrain did not differ statistically between HR and control lines. We hypothesize that the enlarged midbrain of HR mice is related to altered neurophysiological function in their dopaminergic system. To our knowledge, this is the first example in which selection for a particular mammalian behavior has been shown to result in a change in size of a specific brain region.

Transhilar passage in right graft live donor liver transplantation: intrahilar anatomy and its impact on operative strategy.

The passage through the hilar plate during right graft live donor liver transplantation (LDLT) can have dangerous consequences for both donors and recipients. The purpose of our study was to delineate hilar transection and biliary reconstruction strategies in right graft LDLT, with special consideration of central and peripheral hilar anatomical variants. A total of 71 consecutive donors underwent preoperative three-dimensional (3D) CT reconstructions and virtual 3D hepatectomies. A three-modal hilar passage strategy was applied, and its impact on operative strategy analyzed. In 68.4% of cases, type I and II anatomical configurations allowed for an en block hilar transection with simple anastomotic reconstructions. In 23.6% of cases, donors had "difficult" type II and types III/IV hilar bile duct anatomy that required stepwise hilar transections and complex graft biliary reconstructions. Morbidity rates for our early (A) and recent (B) experience periods were 67% and 39%, respectively. (1) Our two-level classification and 3D imaging technique allowed for donor-individualized transhilar passage. (2) A stepwise transhilar passage was favored in types III and IV inside the right-sided hilar corridor. (3) Reconstruction techniques showed no ameliorating effect on early/late biliary morbidity rates.

Low rate of self-awareness and medical recognition of migraine in Germany.

OBJECTIVE: The study's objective was to assess self-awareness and medical recognition of migraine and their determinants in Germany. METHODS: We conducted a nationally representative study of the general population of Germany (N = 7341, aged ≥18 years) by means of computer-assisted telephone interviews. Migraine was diagnosed based on the International Classification of Headache Disorders, second edition (ICDH-II). RESULTS: Twelve-month prevalence of ICHD-II-migraine was 10.6% (women 15.6%, men 5.3%). Seventy percent of ICDH-II-migraineurs recognised their headaches as migraine (moderate agreement between ICDH-II and self-diagnosis, κ = 0.46). Only 42% of migraineurs consulted a physician in the previous 12 months. Of those, 63% reported a medical diagnosis of migraine (moderate agreement, κ = 0.40). Women were more likely to be self-aware (odds ratio [OR] 1.81, 95% confidence interval [CI] 1.27-2.60), but the difference was no longer significant when adjusting for migraine features. Physician recognition was more likely in patients with higher educational level (high vs. low education OR 3.90, 95% CI 1.43-10.61 after adjusting for migrainous features). Best predictors for self-awareness and medical recognition of migraine were typical migraine accompaniments and greater headache intensity. CONCLUSION: Self-awareness and physician recognition of migraine are low in Germany. Presence of typical migraine features and greater headache intensity facilitate medical recognition and awareness of migraine, especially in females.

Can clothing systems and human activity in operating rooms with mixed flow ventilation systems help achieve the ultraclean air requirement (≤10 CFU/m3) during orthopaedic surgeries?

OBJECTIVES: The level of airborne microbial contamination in operating rooms (ORs) is an important indicator of indoor air quality and ensures a clean surgical environment. The main objective of this study was to clarify the possibility of achieving the requirement for an ultraclean operating room (≤ 10 CFU/m3) with mixed flow ventilation based on clothing and human activity. METHODS: Experimental measurements during mock surgeries were conducted in an actual OR with mixed flow ventilation in the Emergency, Heart and Lung Centre at St. Olavs Hospital in Trondheim. The bacterial concentration close to the surgical site was measured during five mock-up surgeries. All five mock-up surgeries followed real surgical procedures which could represent similar conditions in the OR. RESULTS: The experiment results verified that the average CFU/m3 of three of the five mock-up surgeries was 8.5, which was below or equal to the ultraclean requirement, while the other two mock-up surgeries did not meet the ultraclean requirement. Surgical activity together with the type of clothing worn by surgical staff in ORs seem to be the most significant reason for the high CFU level during surgery. CONCLUSIONS: It is possible to achieve the ultraclean air requirement (≤ 10 CFU/m3) during a surgical process with proper clothing and low surgical activity in ORs. This study clarifies the effect of clothing and human activity on the CFU level in the surgical micro-environment in ORs, and contributes to developing new products for the surgical team.

Ventilation design conditions associated with airborne bacteria levels within the wound area during surgical procedures: a systematic review.

BACKGROUND: Without confirmation of the ventilation design conditions (typology and airflow rate), the common practice of identifying unidirectional airflow (UDAF) systems as equivalent to ultra-clean air ventilation systems may be misleading, but also any claims about the ineffectiveness of UDAF systems should be doubted. The aim of this review was to assess and compare ventilation system design conditions for which ultra-clean air (mean <10 cfu/m3) within 50 cm from the wound has been reported. Six medical databases were systematically searched to identify and select studies reporting intraoperative airborne levels expressed as cfu/m3 close to the wound site, and ventilation system design conditions. Available data on confounding factors such as the number of persons present in the operating room, number of door openings, and clothing material were also included. Predictors for achieving mean airborne bacteria levels within <10 cfu/m3 were identified using a penalized multivariate logistic regression model. Twelve studies met the eligibility criteria and were included for analysis. UDAF systems considered had significantly higher air volume flows compared with turbulent ventilation (TV) systems considered. Ultra-clean environments were reported in all UDAF-ventilated (N = 7) rooms compared with four of 11 operating rooms equipped with TV. On multivariate analysis, the total number of air exchange rates (P=0.019; odds ratio (OR) 95% confidence interval (CI): 0.66-0.96) and type of clothing material (P=0.031; OR 95% CI: 0.01-0.71) were significantly associated with achieving mean levels of airborne bacteria <10 cfu/m3. High-volume UDAF systems complying with DIN 1946-4:2008 standards for the airflow rate and ceiling diffuser size unconditionally achieve ultra-clean air close to the wound site. In conclusion, the studied articles demonstrate that high-volume UDAF systems perform as ultra-clean air systems and are superior to TV systems in reducing airborne bacteria levels close to the wound site.

Intra-articular anaesthesia of the equine stifle improves foot lameness.

BACKGROUND: Equine diagnostic anaesthesia can be a useful tool in challenging lameness examinations. However, anaesthetics diffuse over time leading to nonspecific desensitisation of periarticular structures. Nerves that convey sensation from the distal limb to the central nervous system pass in close proximity to the caudal stifle joint capsule. Therefore, diffusion of intra-articular (IA) anaesthetics could cause inadvertent desensitisation of the distal limb resulting in a false diagnosis of stifle lameness. OBJECTIVES: To determine if IA stifle anaesthesia can alleviate lameness originating in the distal limb. STUDY DESIGN: Crossover experiment. METHODS: Nine horses were fitted with a circumferential hoof clamp to induce a moderate unilateral hindlimb lameness. Intra-articular stifle anaesthesia was performed and gait was evaluated every 10 min during the 90-min trial using an inertial sensor system. Push-off and landing components of the lameness were assessed by measuring the mean inter-stride difference between the maximum and minimum heights of the pelvis respectively. Differences were compared using a Wilcoxon signed-rank test. RESULTS: Overall, horses with hoof clamp-induced foot pain had a reduction in push-off lameness after IA stifle anaesthesia. The mean change in diffmax at 90 min was -4.3 mm (P = 0.005) for the experimental group vs. -2.3 mm (P = 0.2) for the control group. Lameness decreased over time, with an average improvement of 23% at 30 min, 33% at 60 min and 38% at 90 min. There was high inter-horse variability; 3/9 horses improved by ~50% within 30 min, while 2/9 improved by ~30% and 4/9 had minimal (<10%) or no improvement in lameness. Improvement after IA stifle anaesthesia was not related to the severity of baseline lameness (P = 0.3-0.7). MAIN LIMITATIONS: Limited clinical applicability of our lameness induction model. CONCLUSIONS: Intra-articular stifle anaesthesia reduces foot lameness in a third of horses by up to 50% within 30 min. Clinically, the results of IA stifle anaesthesia should be considered in the light of these findings before treatment recommendations are made, as additional diagnostics may be required to rule out pain originating in the distal limb.

Territorial belonging of the middle hepatic vein in living liver donor candidates evaluated by three-dimensional computed tomographic reconstruction and virtual liver resection.

BACKGROUND: Postoperative venous congestion can lead to graft and remnant liver failure in living donor liver transplantation. This study was designed to delineate 'territorial belonging' of the middle hepatic vein (MHV) and to identify hepatic venous anatomy at high risk of outflow congestion. METHODS: MHV belonging patterns for right (RHL) and left (LHL) hemilivers were evaluated by three-dimensional computed tomographic reconstruction and virtual hepatectomy in 138 consecutive living liver donor candidates. RESULTS: The right hepatic vein (RHV) was dominant in 84.1 per cent and an accessory inferior hepatic vein (IHV) was present in 47.1 per cent of livers. Three MHV belonging types were identified for the RHL. Strong and complex MHV types A and C were associated with large RHL venous congestion. The MHV belonged to the LHL in 65.9 per cent, draining 37 per cent of this hemiliver. In virtual liver resections, left MHV type D was a risk category for small left liver remnants. CONCLUSION: MHV territorial belonging types A and C were identified as high risk for RHL venous congestion. Their presence should prompt consideration of either inclusion of the MHV with the right graft or reconstruction of its tributaries, and preservation of IHV territory.

Major liver resections for primary liver malignancies in the elderly.

PURPOSE: The aim of our prospective study was to assess the results of major hepatic resections for primary liver tumours in patients 75 years of age or older. METHODS: From 10/1999 to 04/2006, 23 patients with non-cirrhotic livers > or = 75 years presented to our department to undergo curative resection for primary liver malignancies. Data were collected prospectively. Patients were assigned to two groups. Group A included those with resectable tumours, while Group B was made up of those with unresectable lesions. RESULTS: Fourteen patients had intrahepatic cholangiocarcinoma while 9 had hepatocellular carcinoma. Comorbidities were present in every case. Morbidity and hospital mortality rates for group A patients were 25% and 8%, respectively. The corresponding rates for group B patients were 9% and 9%. The 1-, 2-, and 3-year cumulative group A survival was 71%, 51% and 26% for cholangiocarcinoma and 80%, 60% and 60% for hepatocellular carcinoma, respectively. The corresponding group B survival was 45%, 18% and 0%. CONCLUSION: Advanced age does not seem to negatively affect the outcome of liver resections for malignancies. Hepatic resections in patients 75 years of age or older may be carried out with relative safety as long as patients are appropriately selected.

[Myofibroblastic sarcoma of the larynx : a case report and review]. / Myofibroblastische Sarkome des Larynx : Fallbericht und Ubersicht.

BACKGROUND: Myofibroblastic sarcomas or myofibrosarcoma, are extremely rare malignant neoplasms of myofibroblasts. They are characterized by the pattern of cells and special immunohistochemical markers such as vimentin, desmin and alpha-smooth-muscle actin. PATIENT AND METHOD: The case of a patient with a history of frequently relapsing papillomas of the larynx is reported. Chronic laryngitis with focal low-grade dysplasia of the squamous epithelium was diagnosed approximately 1 year after the first treatment of the papillomas. After approximately 2 years the pathologist diagnosed the rare myofibroblastic sarcoma of the larynx. The patient underwent laryngectomy due to the spread of the tumor with a bilateral selective neck dissection. The patient is at present still free of recurrence and metastases. RESULTS AND CONCLUSIONS: There is a great danger of misjudging a myofibroblastic sarcoma as an inflammatory myofibroblastic tumor and consequently to delay the urgently needed treatment. Therefore, an overview of the present state of knowledge about diagnosis and treatment of myofibroblastic sarcomas will be given based on this case report.

Expression of miRNA-371a-3p in seminal plasma and ejaculate is associated with sperm concentration.

BACKGROUND: The microRNAs of the miR-371-3 cluster are novel serum markers for testicular germ cell tumors. Sporadic reports suggested the expression of this miRNA in semen. OBJECTIVES: To verify the expression of miR-371a-3p in seminal plasma and unprocessed ejaculate; to compare seminal plasma miRNA levels in germ cell tumors patients with those of controls; to look for an association of miRNA levels with semen quality. MATERIALS AND METHODS: The miR-371a-3p expression was analyzed with qPCR. The study population consisted of 100 participants: seminal plasma samples from 20 germ cell tumors patients and 30 controls, serum samples from 12 healthy men, ejaculate samples from 38 men undergoing fertility testing. RESULTS: The seminal plasma miR-371a-3p levels of germ cell tumors patients were not different from controls. The miRNA expression was very low in serum but much higher in seminal plasma. In ejaculate samples, the miRNA expression significantly correlated with sperm concentration and the total sperm count. DISCUSSION: miR-371-a-3p is present in sperm-containing fluids. Seminal plasma levels cannot be used to distinguish germ cell tumors from controls. The correlation with sperm concentration in ejaculate samples suggests the spermatozoa as possible source of miR-371a-3p production. CONCLUSION: The miR-371a-3p levels in ejaculate could represent a novel biomarker for the non-invasive evaluation of male infertility.

Median liver lobe of woodchuck as a model to study hepatic outflow obstruction: a pilot study.

BACKGROUND: Hepatic vein outflow obstruction represents an important clinical problem in living-liver transplantation. An animal model is required to study the influence of outflow obstruction on the intrahepatic regulation of liver perfusion and the subsequent effects on liver injury and recovery during liver regeneration. The size of woodchucks enables the use of standard clinical imaging procedures. AIM: This study aims at describing hepatic vascular and territorial anatomy of the woodchuck liver based on a virtual three-dimensional (3D) visualization of the hepatic vascular tree. METHODS: Woodchucks (n=6) were subjected to an all-in-one computed tomography (CT) after contrasting the vascular and the biliary tree. CT-images were used for 3D-reconstruction of hepatic and portal veins and calculation of the corresponding portal and hepatic vein territories and their respective volume using hepavision (MeVisLab). A virtual resection was performed following the Cantlie-line and territories at risk were calculated. RESULTS: The median lobe of the woodchuck liver has a similar vascular supply and drainage as the human liver with two portal (right and left median portal vein) and three hepatic veins (left, middle and right median hepatic vein). The corresponding portal and hepatic vein subterritories are of a similar relative size compared with the human liver. Virtual splitting of the median lobe of the woodchuck liver revealed areas at risk of focal outflow obstruction, as observed clinically. CONCLUSION: The median liver lobe of the woodchuck represents, to a small extent, the hepatic vascular anatomy of the human liver and is therefore a suitable potential model to correlate repeated imaging of impaired liver perfusion with histomorphological findings of liver damage and regeneration.

Preoperative volume prediction in adult live donor liver transplantation: 3-D CT volumetry approach to prevent miscalculations.

BACKGROUND: The precise preoperative calculation of functional liver volumes for both donor and recipient is a crucial part of the evaluation process in adult living donor liver transplantation. The purpose of this study was to describe and validate our modus 3-D CT volumetry. PATIENTS AND METHODS: Native (unenhanced), arterial, and venous phase CT images from 62 consecutive live liver donors were subjected to 3-D CT liver volume calculations and virtual 3-D liver partitioning. Graft-volume estimates based on our modus 3-D volumetry, which subtracted intrahepatic vascular volume from the "smallest" (native) unenhanced CT phase, were subsequently compared to the intraoperative graft-weights obtained in all 62 cases. Calculated (preoperative) liver-volume-body-weight-ratios and measured (intraoperative) liver-weight-body-weight-ratios of liver grafts were analyzed. RESULTS: Preoperative calculations of graft-volume according to our modus 3-D CT volumetry did not yield statistically significant over- or under-estimations when compared to the intraoperative findings independent of their age or gender. CONCLUSION: Our modus 3-D volumetry, when based on the "smallest" (native) unenhanced CT phase, accurately accounted for intrahepatic vascular volumes and offered a precise virtual model of individualized operative conditions for each potential live liver donor.

Intensive care unit management of liver transplant patients: a formidable challenge for the intensivist.

Patients with end-stage liver disease, particular following liver transplantation, are a major challenge for the intensivist. The recipient is at risk for cardiac decompensation, respiratory failure following reperfusion, and kidney failure. This review will focus on these topics to provide useful information concerning pathophysiology and treatment. Intensivists, who are involved in the postoperative care of liver transplant patients, have to be aware of these problems.

Liver transplantation for hepatocellular carcinoma with intrahepatic lymphatic invasion: case reports.

Multiple studies addressing liver transplantation (OLT) for hepatocellular carcinoma (HCC) have identified various prognostic determinants of tumor recurrence and decreased patient survival. However, little information is available on the impact of intrahepatic lymphatic invasion on tumor recurrence and survival after OLT for HCC. Intrahepatic lymphatic invasion was observed in 1.4% (n = 2) of liver explants with HCC in our series. Both recipients are alive without tumor recurrence at 16 and 39 months post-OLT, respectively. Intrahepatic lymphatic invasion may not be an absolute adverse prognostic factor in cases of HCC with no hilar lymph node involvement at the time of OLT.

Liver "compliance": a previously unrecognized preoperative predictor of small-for-size syndrome in adult living donor liver transplantation.

BACKGROUND: The purpose of this study was to investigate the effect of liver compliance on computed tomography (CT) volumetry and to determine its association with postoperative small-for-size syndrome (SFSS). PATIENTS AND METHODS: Unenhanced, arterial, and venous phase CT images of 83 consecutive living liver donors who underwent graft hepatectomy for adult-to-adult living donor liver transplantation (ALDLT) were prospectively subjected to three-dimensional (3-D) CT liver volume calculations and virtual 3-D liver partitioning. Graft volume estimates based on 3-D volumetry, which subtracted intrahepatic vascular volume from the "smallest" (native) unenhanced and the "largest" (venous) CT phases, were subsequently compared with the intraoperative graft weights. Calculated (preoperative) graft volume-to-body weight ratios (GVBWR) and intraoperative measured graft weight-to-body weight ratios (GWBWR) were analyzed for postoperative SFSS. RESULTS: Significant differences in minimum versus maximum total liver volumes, graft volumes, and GVBWR calculations were observed among the largest (venous) and the smallest (unenhanced) CT phases. SFSS occurred in 6% (5/83) of recipients, with a mortality rate of 80% (4/5). In four cases with postoperative SFSS (n = 3 lethal, n = 1 reversible), we had transplanted a small-for-size graft (real GWBWR < 0.8). The three SFS grafts with lethal SFSS showed a nonsignificant volume "compliance" with a maximum GVBWR < 0.83. This observation contrasts with the seven recipients with small-for-size grafts and reversible versus no SFSS who showed a "safe" maximum GVBWR of 0.92 to 1.16. CONCLUSION: The recognition and precise assessment of each individual's liver compliance displayed by the minimum and maximum GVBWR values is critical for the accurate prediction of functional liver mass and prevention of SFSS in ALDLT.