RESUMEN
Hepatocellular carcinoma (HCC) is predominantly known for its intrahepatic manifestations, yet extrahepatic dissemination, particularly intraperitoneal, remains rare. Herein, we present the very first case of successful transarterial chemoembolization (TACE) for an extrahepatic peritoneal HCC nodule. This intervention underscores the potential efficacy of TACE as a viable alternative to surgery in cases where arterial vessels supplying the lesion do not nourish vital parenchymal organs.
RESUMEN
BACKGROUND AND AIMS: Sarcopenia has been associated with poor outcomes in patients with cirrhosis and hepatocellular carcinoma. We investigated the impact of sarcopenia on survival in patients with advanced hepatocellular carcinoma treated with Sorafenib. METHODS: A total of 328 patients were retrospectively analyzed. All patients had an abdominal CT scan within 8 weeks prior to the start of treatment. Two cohorts of patients were analyzed: the "Training Group" (215 patients) and the "Validation Group" (113 patients). Sarcopenia was defined by reduced skeletal muscle index, calculated from an L3 section CT image. RESULTS: Sarcopenia was present in 48% of the training group and 50% of the validation group. At multivariate analysis, sarcopenia (HR: 1.47, p = 0.026 in training; HR 1.99, p = 0.033 in validation) and MELD > 9 (HR: 1.37, p = 0.037 in training; HR 1.78, p = 0.035 in validation) emerged as independent prognostic factors in both groups. We assembled a prognostic indicator named "SARCO-MELD" based on the two independent prognostic factors, creating three groups: group 1 (0 prognostic factors), group 2 (1 factor) and group 3 (2 factors), the latter with significantly worse survival and shorter time receiving treatment.
RESUMEN
The increased detection of pancreatic cysts in recent years has triggered extensive diagnostic investigations to clarify their potential risk of malignancy, resulting in a large number of patients undergoing numerous imaging follow-up studies for many years. Therefore, there is a growing need for optimization of the current surveillance protocol to reduce both healthcare costs and waiting lists, while still maintaining appropriate sensibility and specificity. Imaging is an essential tool for evaluating patients with intraductal papillary mucinous neoplasms (IPMNs) since it can assess several predictors for malignancy and thus guide further management recommendations. Although contrast-enhanced magnetic resonance imaging (MRI) with magnetic resonance cholangiopancreatography (MRCP) has been widely recommended by most international guidelines, recent results support the use of unenhanced abbreviated-MRI (A-MRI) protocols as a surveillance tool in patients with IPMN. In fact, A-MRI has shown high diagnostic performance in malignant detection, with high sensitivity and specificity as well as excellent interobserver agreement. The aim of this paper is, therefore, to discuss the current available evidence on whether the implementation of an abbreviated-MRI (A-MRI) protocol for cystic pancreatic lesion surveillance could improve healthcare economics and reduce waiting lists in clinical practice without significantly reducing diagnostic accuracy.
RESUMEN
RATIONALE AND OBJECTIVES: According to the 2019 update of the Bosniak classification, the main imaging features that need to be evaluated to achieve a correct characterization of renal cystic masses include the thickness of walls and septa, the number of septa, the appearance of walls and septa, the attenuation/intensity on non-contrast CT/MRI and the presence of unequivocally perceived or measurable enhancement of walls and septa. Despite the improvement deriving from a quantitative evaluation of imaging features, certain limitations seem to persist and some possible scenarios that can be encountered in clinical practice are still missing. MATERIALS AND METHODS: A deep analysis of the 2019 update of the Bosniak classification was performed. RESULTS: The most notable potential flaws concern: (1) the quantitative measurement of the walls and septa; (2) the fact that walls and septa > 2 mm are always referred to as "enhancing", not considering the alternative scenario; (3) the description of some class II masses partially overlaps with each other and with the definition of class I masses and (4) the morphological variations of cystic masses over time is not considered. CONCLUSION: The present paper analyzes in detail the limitations of the 2019 Bosniak classification to improve this important tool and facilitate its use in daily radiological practice.
RESUMEN
Recent technical advances in liver imaging and surveillance for patients at high risk for developing hepatocellular carcinoma (HCC) have led to an increase in the detection of borderline hepatic nodules in the gray area of multistep carcinogenesis, particularly in those that are hypointense at the hepatobiliary phase (HBP) and do not show arterial phase hyperenhancement. Given their potential to transform and advance into hypervascular HCC, these nodules have progressively attracted the interest of the scientific community. To date, however, no shared guidelines have been established for the decision management of these borderline hepatic nodules. It is therefore extremely important to identify features that indicate the malignant potential of these nodules and the likelihood of vascularization. In fact, a more complete knowledge of their history and evolution would allow outlining shared guidelines for their clinical-surgical management, to implement early treatment programs and decide between a preventive curative treatment or a watchful follow-up. This review aims to summarize the current knowledge on hepatic borderline nodules, particularly focusing on those imaging features which are hypothetically correlated with their malignant evolution, and to discuss current guidelines and ongoing management in clinical practice.
RESUMEN
A man in his 40s presented to our Hospital with abdominal pain, jaundice, and pruritus. He had a history of Alagille Syndrome treated with cholecystojejunostomy in the neonatal period because of initial misdiagnosis of biliary atresia. Laboratory investigations showed hyperbilirubinemia (total bilirubin 1.76 mg/dL [<1.2 mg/dL]; conjugated 1.06 mg/dL [<0.3 mg/dL]) and cholestasis (GGT 78 U/L [<50 U/L]; ALP 200 U/L [<50 U/L]). Transabdominal ultrasound was limited by aerobilia due to the cholecystojejuno-anastomosis. Subsequent basal CT scan revealed an impacted stone within the patient's native common bile duct (CBD). Aerobilia in intrahepatic bile ducts and gallbladder was reported. Magnetic Resonance cholangiopancreatography confirmed the gallstone in the CBD compressing cystic duct and common hepatic duct, with dilation of the upstream bile ducts. Furthermore, the native CBD was obstructed by other gallstones. In Mirizzi syndrome, gallstones impacted in gallbladder's Hartmann's pouch or cystic duct extrinsically compress CBD. We suggest naming the present condition "Reverse Mirizzi Syndrome" (Renzulli Matteo Syndrome, RMS) because it is the exact opposite of Mirizzi syndrome.
RESUMEN
The present study aimed to evaluate the clinical and radiological 1-year outcomes of uterine artery embolization (UAE) performed in a selected population of women with symptomatic myomas and who do not wish to conceive. Between January 2004 and January 2018, a total of 62 patients with pre-menopausal status and with no wish to conceive in the future underwent UAE for the treatment of symptomatic fibroids. All the patients underwent magnetic resonance imaging (MRI) and/or transvaginal ultrasonography (TV-US) before and after the procedure at 1-year follow-up. Clinical and radiological parameters were recorded, stratifying the population into 3 groups according to the size of the dominant myoma (group 1: <50 mm; group 2: ≥50 and ≤80 mm; group 3: >80 mm). Mean fibroid diameter was significantly reduced (42.6% ± 21.6%) at 1-year follow-up, with excellent improvements in terms of both symptoms and quality of life. No significant difference was observed regarding baseline dimension and the number of myomas. No major complications were reported (2.5%). The present study confirms the safety and efficacy of UAE in the treatment of symptomatic fibroids in pre-menopausal women with no desire to conceive.
RESUMEN
Immunotherapy has remarkably revolutionized the management of advanced HCC and prompted clinical trials, with therapeutic agents being used to selectively target immune cells rather than cancer cells. Currently, there is great interest in the possibility of combining locoregional treatments with immunotherapy for HCC, as this combination is emerging as an effective and synergistic tool for enhancing immunity. On the one hand, immunotherapy could amplify and prolong the antitumoral immune response of locoregional treatments, improving patients' outcomes and reducing recurrence rates. On the other hand, locoregional therapies have been shown to positively alter the tumor immune microenvironment and could therefore enhance the efficacy of immunotherapy. Despite the encouraging results, many unanswered questions still remain, including which immunotherapy and locoregional treatment can guarantee the best survival and clinical outcomes; the most effective timing and sequence to obtain the most effective therapeutic response; and which biological and/or genetic biomarkers can be used to identify patients likely to benefit from this combined approach. Based on the current reported evidence and ongoing trials, the present review summarizes the current application of immunotherapy in combination with locoregional therapies for the treatment of HCC, and provides a critical evaluation of the current status and future directions.
Asunto(s)
Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/patología , Neoplasias Hepáticas/patología , Inmunoterapia/métodos , Terapia Combinada , Microambiente TumoralRESUMEN
Biliary anatomic variations are usually asymptomatic, but they may cause problems in diagnostic investigations and interventional and surgical procedures, increasing both their technical difficulty and their postoperative complication rates. The aim of the present study was to evaluate the prevalence of anatomic variations in the intrahepatic biliary ducts (IHBD) in relation to demographical and clinical characteristics in a large study population requiring magnetic resonance cholangiopancreatography (MRCP) for various clinical conditions. The possible association between IHBD and extrahepatic biliary ducts (EHBD) variants was then explored. From January 2017 to May 2019, 1004 patients underwent MRCP. Demographical and clinical data were collected. IHBD and EHBD anatomy were recorded and the EHBD anatomy was classified using both qualitative and quantitative classifications. The presence of a type 3 EHBD variant (an abnormal proximal cystic duct [CD] insertion) in both qualitative and quantitative classifications and an intrapancreatic CD were associated with the presence of IHBD variants at univariate analysis (p = 0.008, p = 0.019, and p = 0.001, respectively). The presence of a posterior or medial insertion of the CD into the EHBD was a strong predictive factor of the presence of IHBD variants both at uni- and multivariate analysis (p = 0.002 and p = 0.003 for posterior insertion and p = 0.002 and p = 0.002 for medial insertion, respectively). The presence of gallstones on MRCP resulted in a strong predictor of the presence of an anatomical variant of the IHBD both at uni- and multivariate analysis (p = 0.027 and p = 0.046, respectively). In conclusion, the presence of a type 3 variant of the EHBD, an intrapancreatic CD and, especially, a posterior/medial CD insertion into the EHBD represent predictive factors of the concomitant presence of IHBD variants, thus radiologists must be vigilant when encountering these EHBD configurations and always remember to "look up" at the IHBD. Finally, the presence of an IHBD variant is a strong predictive factor of gallstones.
Asunto(s)
Conductos Biliares Extrahepáticos , Conductos Biliares Intrahepáticos , Humanos , Conductos Biliares Extrahepáticos/anatomía & histología , Conductos Biliares Extrahepáticos/diagnóstico por imagen , Conductos Biliares Intrahepáticos/anatomía & histología , Conductos Biliares Intrahepáticos/diagnóstico por imagen , Pancreatocolangiografía por Resonancia Magnética , Cálculos Biliares/diagnóstico por imagen , Masculino , Femenino , Persona de Mediana Edad , AncianoRESUMEN
The liver is a secondary and often collateral target of COVID-19 disease but can lead to important consequences. COVID-19 might directly cause a high number of complications in patients with pre-existing chronic liver disease, increasing their risk of hepatic decompensation. Moreover, it also determines indirect consequences in the management of patients with liver disease, especially in those suffering from decompensated cirrhosis and HCC, as well as in the execution of their follow-up and the availability of all therapeutic possibilities. Liver imaging in COVID-19 patients proved to be highly nonspecific, but it can still be useful for identifying the complications that derive from the infection. Moreover, the recent implementation of telemedicine constitutes a possible solution to both the physical distancing and the re-organizational difficulties arising from the pandemic. The present review aims to encompass the currently hypothesized pathophysiological mechanisms of liver injury in patients with COVID-19 mediated by both the direct invasion of the virus and its indirect effects and analyze the consequence of the pandemic in patients with chronic liver disease and liver tumors, with particular regard to the management strategies that have been implemented to face this worldwide emergency and that can be further improved.
Asunto(s)
COVID-19 , Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Neoplasias Hepáticas/epidemiología , Neoplasias Hepáticas/etiología , Neoplasias Hepáticas/terapia , Carcinoma Hepatocelular/epidemiología , Carcinoma Hepatocelular/etiología , Carcinoma Hepatocelular/terapia , COVID-19/complicaciones , Cirrosis Hepática/etiologíaRESUMEN
BACKGROUND: The role of sarcopenia in predicting decompensation other than hepatic encephalopathy is unclear. We aimed to evaluate the prognostic role of sarcopenia, assessed by computed tomography (CT), in the development of ascites and mortality in patients with advanced chronic liver disease (ACLD) outside the liver transplantation (LT) setting. MATERIAL AND METHODS: We retrospectively evaluated ACLD patients with liver stiffness measurement (LSM) >10 kPa and an available CT scan within 6 months. Sarcopenia was defined as skeletal muscle index (SMI) <50 and <39 cm2/m2, respectively, in men and women. Competing risk regression models were used to assess the variables associated with the main outcomes. RESULTS: 209 patients were included in the final analysis and sarcopenia was present in 134 (64.1%). During a median follow-up of 37 (20-63) months, 52 patients developed ascites, 24 underwent LT, and 30 died. Sarcopenia was found a predictive factor of decompensation with ascites (SHR 2.083, 95%-CI: 1.091-3.978), independently from the features of clinically significant portal hypertension (LSM≥21 kPa or portosystemic shunts). Sarcopenia (SHR: 2.744, 95%-CI: 1.105-6.816) and LSM≥21 kPa (SHR: 3.973, 95%-CI: 1.548-10.197) were independent risk factors for increased mortality. CONCLUSIONS: Sarcopenia and portal hypertension are two major and independent risk factors for decompensation with ascites and mortality in cirrhotic patients outside the LT context.
Asunto(s)
Hipertensión Portal , Sarcopenia , Masculino , Humanos , Femenino , Sarcopenia/complicaciones , Sarcopenia/diagnóstico por imagen , Ascitis/complicaciones , Estudios Retrospectivos , Cirrosis Hepática/complicaciones , Hipertensión Portal/etiologíaRESUMEN
Background: The aim of the present study is to determine the feasibility of biopsy for atypical liver nodules in patients under surveillance for hepatocellular carcinoma (HCC), assessing which factors influence the decision to perform it. Methods: A total of 128 atypical liver nodules in 108 patients under surveillance for HCC, who underwent CT between September 2018 and September 2019, were included. All the images were saved digitally (on CD-ROM) and the two most representative images in the arterial and delayed phases were selected for each lesion and inserted into a digital atlas (on PDF). Two experienced radiologists (Readers 1 and 2) reviewed both the CD-ROM and the PDF to define the feasibility of biopsy in both scenarios, specifying the reasons for the unfeasibility of biopsy. The intra-observer variability and inter-observer variability were assessed. Results: When reviewing the PDF, 76 (59.4%) and 68 (53.1%) nodules were deemed unfeasible for biopsy by the less experienced radiologist (Reader 1) and the more experienced radiologist (Reader 2), respectively (p = 0.604). When reviewing the entire CT study, both percentages decreased slightly (Reader 1 = 70/128 (54.7%); Reader 2 = 61/128 (47.6%); p = 0.591). The intra-reader agreement on the PDF was substantial (k = 0.648 (95% CI = 0.513-0.783)). The inter-reader agreement on the PDF was slight (k = 0.185 (95% CI = 0.021-0.348)) and moderate on the entire CT study (k = 0.424 (95% CI = 0.269-0.579)). When assessing the PDF, the nodule size (10-20 mm) and location in segments six and eight were negatively and positively associated with the feasibility of liver biopsy, respectively. When assessing the CD-ROM, only the nodule dimension was associated with the unfeasibility of liver biopsy. Conclusions: The unfeasibility of liver biopsy is mainly due to the small size of the lesions and their location.
RESUMEN
BACKGROUND: The widespread use of ultrasonography has led to an increased number of incidentally detected small non-palpable lesions, with Leydig cell tumours representing the majority of them. OBJECTIVES: The ultrasonography, real-time elastography and contrast-enhanced ultrasonography features of a large series of non-palpable testicular lesions were evaluated, focusing on the differences between Leydig cell tumours and other testicular masses. MATERIALS AND METHODS: Of the 4679 testicular ultrasonography examinations performed at the Authors' Institution between January 2009 and December 2018, 78 patients (1.7%) were incidentally diagnosed with at least one non-palpable lesion and were enrolled. Thirteen patients (16.6%) declined surgery and were thus excluded. The remaining 65 underwent surgical resection with frozen section analysis. The conventional ultrasonography, colour Doppler, real-time elastography and contrast-enhanced ultrasonography were performed by a radiologist having more than 10 years of experience. Demographic and clinical data were collected. RESULTS: Leydig cell tumours were detected in 32 patients, being the most frequent benign tumours (49.2%); of the non-Leydig cell tumours, 25 patients had malignant tumours, five non-neoplastic lesions and three other benign tumours. The Leydig cell tumour group had mostly infertility problems whereas the non-Leydig cell tumour group frequently experienced pain (p < 0.001). Leydig cell tumours were all hypoechoic (32/32, 100%; p = 0.002), more frequently presented with well-defined margins compared to non-Leydig cell tumours (30/32, 93.8% vs. 19/33, 57.6%; p = 0.001) and tended to be smaller than non-Leydig cell tumours (5.3 mm [standard deviation 2.7 mm] vs. 10.6 mm [standard deviation 3.8 mm], respectively; p < 0.001). The vascular pattern characterised by the rapid wash-in followed by the delayed wash-out observed during contrast-enhanced ultrasonography was significantly associated with the Leydig cell tumour histological diagnosis, even at multivariate analysis (odds ratio 480.5, p < 0.001), and yielded a high diagnostic accuracy (area under the receiver operating characteristic curve 0.954, 95% confidence interval 0.903-1). DISCUSSION: Contrast-enhanced ultrasonography demonstrated high diagnostic accuracy in identifying benign testicular lesions, such as Leydig cell tumours; they are the most common non-palpable tumours detected in infertile men and may benefit from enucleation.
Asunto(s)
Diagnóstico por Imagen de Elasticidad , Tumor de Células de Leydig , Neoplasias Testiculares , Humanos , Tumor de Células de Leydig/diagnóstico por imagen , Tumor de Células de Leydig/patología , Masculino , Neoplasias Testiculares/patología , UltrasonografíaRESUMEN
Background: Bacterial and fungal co-infections and superinfections have a critical role in the outcome of the COVID-19 patients admitted to the Intensive Care Unit (ICU). Methods: The present study is a retrospective analysis of 95 patients admitted to the ICU for COVID-19-related ARDS during the first (February−May 2020) and second waves of the pandemic (October 2020−January 2021). Demographic and clinical data, CT imaging features, and pulmonary and extra-pulmonary complications were recorded, as well as the temporal evolution of CT findings when more than one scan was available. The presence of co-infections and superinfections was registered, reporting the culprit pathogens and the specimen type for culture. A comparison between patients with and without bacterial and/or co-infections/superinfections was performed. Results: Sixty-three patients (66.3%) developed at least one confirmed co-infection/superinfection, with 52 (82.5%) developing pneumonia and 43 (68.3%) bloodstream infection. Gram-negative bacteria were the most common co-pathogens identified and Aspergillus spp. was the most frequent pulmonary microorganism. Consolidations, cavitations, and bronchiectasis were significantly associated with the presence of co-infections/superinfections (p = 0.009, p = 0.010 and p = 0.009, respectively); when considering only patients with pulmonary co-pathogens, only consolidations remained statistically significative (p = 0.004). Invasive pulmonary aspergillosis was significantly associated with the presence of cavitations and bronchiectasis (p < 0.001). Patients with co-infections/superinfections presented a significantly higher mortality rate compared to patients with COVID-19 only (52.4% vs. 25%, p = 0.016). Conclusions: Bacterial and fungal co-infections and superinfections are frequent in COVID-19 patients admitted to ICU and are associated with worse outcomes. Imaging plays an important role in monitoring critically ill COVID-19 patients and may help detect these complications, suggesting further laboratory investigations.
RESUMEN
Hepatocellular carcinoma (HCC) has become the second greatest cause of cancer-related mortality worldwide and the newest advancements in liver imaging have improved the diagnosis of both overt malignancies and premalignant lesions, such as cirrhotic or dysplastic nodules, which is crucial to improve overall patient survival rate and to choose the best treatment options. The role of Computed Tomography (CT) and Magnetic Resonance Imaging (MRI) has grown in the last 20 years. In particular, the introduction of hepatospecific contrast agents has strongly increased the definition of precursor nodules and detection of high-grade dysplastic nodules and early HCCs. Nevertheless, the diagnosis of liver tumours in cirrhotic patients sometimes remains challenging for radiologists, thus, in doubtful cases, biopsy and histological analysis become critical in clinical practice. This current review briefly summarizes the history of imaging and histology for HCC, covering the newest techniques and their limits. Then, the article discusses the links between radiological and pathological characteristics of liver lesions in cirrhotic patients, by describing the multistep process of hepatocarcinogenesis. Explaining the evolution of pathologic change from cirrhotic nodules to malignancy, the list of analyzed lesions provides regenerative nodules, low-grade and high-grade dysplastic nodules, small HCC and progressed HCC, including common subtypes (steatohepatitic HCC, scirrhous HCC, macrotrabecular massive HCC) and more rare forms (clear cell HCC, chromophobe HCC, neutrophil-rich HCC, lymphocyte-rich HCC, fibrolamellar HCC). The last chapter covers the importance of the new integrated morphological-molecular classification and its association with radiological features.
Asunto(s)
Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/diagnóstico , Neoplasias Hepáticas/diagnóstico , Cirrosis Hepática/diagnóstico , Imagen por Resonancia Magnética/efectos adversos , Imagen por Resonancia Magnética/métodos , Espectroscopía de Resonancia Magnética/efectos adversosRESUMEN
Background: To evaluate the segmental distribution of hepatocellular carcinoma (HCC) according to Couinaud's anatomical division in cirrhotic patients. Methods: Between 2020 and 2021, a total of 322 HCC nodules were diagnosed in 217 cirrhotic patients who underwent computed tomography (CT) or magnetic resonance imaging (MRI) for the evaluation of suspicious nodules (>1 cm) detected during ultrasound surveillance. For each patient, the segmental position of the HCC nodule was recorded according to Couinaud's description. The clinical data and nodule characteristics were collected. Results: A total of 234 (72.7%) HCC nodules were situated in the right lobe whereas 79 (24.5%) were detected in the left lobe (p < 0.0001) and only 9 nodules were in the caudate lobe (2.8%). HCC was most common in segment 8 (n = 88, 27.4%) and least common in segment 1 (n = 9, 2.8%). No significant differences were found in the frequencies of segmental or lobar involvement considering patient demographic and clinical characteristics, nodule dimension, or disease appearance. Conclusions: The intrahepatic distribution of HCC differs among Couinaud's segments, with segment 8 being the most common location and segment 1 being the least common. The segmental distribution of tumour location was similar to the normal liver volume distribution, supporting a possible correlation between HCC location and the volume of hepatic segments and/or the volumetric distribution of the portal blood flow.
RESUMEN
A significant proportion of patients with COVID-19 pneumonia could develop acute respiratory distress syndrome (ARDS), thus requiring mechanical ventilation, and resulting in a high rate of intensive care unit (ICU) admission. Several complications can arise during an ICU stay, from both COVID-19 infection and the respiratory supporting system, including barotraumas (pneumothorax and pneumomediastinum), superimposed pneumonia, coagulation disorders (pulmonary embolism, venous thromboembolism, hemorrhages and acute ischemic stroke), abdominal involvement (acute mesenteric ischemia, pancreatitis and acute kidney injury) and sarcopenia. Imaging plays a pivotal role in the detection and monitoring of ICU complications and is expanding even to prognosis prediction. The present pictorial review describes the clinicopathological and radiological findings of COVID-19 ARDS in ICU patients and discusses the imaging features of complications related to invasive ventilation support, as well as those of COVID-19 itself in this particularly fragile population. Radiologists need to be familiar with COVID-19's possible extra-pulmonary complications and, through reliable and constant monitoring, guide therapeutic decisions. Moreover, as more research is pursued and the pathophysiology of COVID-19 is increasingly understood, the role of imaging must evolve accordingly, expanding from the diagnosis and subsequent management of patients to prognosis prediction.
RESUMEN
During the coronavirus disease 19 (COVID-19) pandemic, extracorporeal membrane oxygenation (ECMO) has been proposed as a possible therapy for COVID-19 patients with acute respiratory distress syndrome. This pictorial review is intended to provide radiologists with up-to-date information regarding different types of ECMO devices, correct placement of ECMO cannulae, and imaging features of potential complications and disease evolution in COVID-19 patients treated with ECMO, which is essential for a correct interpretation of diagnostic imaging, so as to guide proper patient management.