Evaluation of the CT Scan as the First Examination for the Diagnosis and Therapeutic Strategy for Acute Cholecystitis.

BACKGROUND: The CT scan has supplanted the abdominal ultrasound for emergency examinations. A comparison of CT scan and ultrasound performance for the diagnosis and management of acute cholecystitis in acute care was proposed. The hypothesis is that the CT scan may be sufficient for the diagnosis of acute cholecystitis, which would allow faster progress to surgery. METHODS: The retrospective study of consecutive patients operated for acute cholecystitis or gallbladder distension with pre-operative imaging within 48 h in one centre. RESULTS: Between 2015 and 2017, a total of 341 cholecystectomies were performed in our centre. The analysis involved 120 patients. Ultrasound had better sensitivity than the CT scan, respectively, 79.4% [70.5-86.6] and 52.3% [42.5-62.1], but less specificity, with 61.5% [31.6-86.1] and 92.3% [64.0-99.8], respectively. However, there was a significant difference in favour of the CT scan for the diagnosis of complicated cholecystitis (p 0.004). The positive likelihood ratio of complicated cholecystitis is better at CT scan (7.8) [2.7-23.1] than in ultrasound (1.0) [0.1-9.7]. CT scan and ultrasound are equivalent for the diagnosis of acute cholecystitis, but CT scan is more efficient for the diagnosis of complicated cases (Youden index J 0.3 vs 0.001). CONCLUSION: It is possible to place the surgical indication of cholecystectomy on the only data of the CT scan. We propose a decision-making algorithm that uses the CT scan to make the diagnosis and decide on emergency treatment for complicated cases or that allows us to propose a delayed surgery for simple cholecystitis.

Preoperative evaluation of small bowel complications in Crohn's disease: comparison of diffusion-weighted and contrast-enhanced MR imaging.

PURPOSE: To compare the accuracy of MR enterography (MRE) using combined T2-weighted and contrast-enhanced (CE) sequences with that of combined T2- and diffusion-weighted (DW) sequences for the detection of complex enteric Crohn's disease (CD). MATERIALS: Thirty-eight patients who underwent surgery for CD complications and preoperative MRE from 2011 to 2016 were included. MRE examinations were blindly analyzed independently by one junior and one senior abdominal radiologist for the presence of fistula, stenosis and abscesses. During a first reading session, T2-weighted images (WI), steady-state sequences and DW-MRE were reviewed (set 1). During a separate distant session, T2-WI, True-FISP and CE-MRE were reviewed (set 2). Performance of each reader was evaluated by comparison with the standard of reference established using intraoperative and pathological findings. RESULTS: Forty-eight fistulas, 43 stenoses and 11 abscesses were found. For the senior radiologist, sensitivity for the detection of fistula, stenosis and abscess ranged from 80% to 100% for set 1 and 88% to 100% for set 2 and specificity ranged from 56% to 70% for set 1 and 53% to 93% for set 2, with no significant difference between the sets (p = 0.342-0.429). For the junior radiologist, sensitivity ranged from 53% to 63% for set 1 and 64% to 88% for set 2 and specificity ranged from 0% to 25% for set 1 and 17% to 40% for set 2 (p = 0.001 and 0.007, respectively). CONCLUSION: For a senior radiologist, DW-MRE has similar sensitivity as CE-MRE for the detection of CD complications. For a junior radiologist, CE-MRE yields the best results compared with DW-MRE. KEY POINTS: • For experienced readers, DWI has similar diagnostic capability as contrast-enhanced MR imaging for the diagnosis of Crohn's disease complications. • For senior radiologists, gadolinium chelate injection could be waived for the diagnosis of Crohn's disease complications. • The interpretation of DWI for Crohn's disease complications requires some experience.

What the radiologist should know about postoperative MDCT evaluation of a patient treated with cytoreductive surgery with or without hyperthermic intraperitoneal chemotherapy.

Cytoreductive surgery (CRS), often associated with hyperthermic intraperitoneal chemotherapy (HIPEC), is now a well-recognised treatment for most peritoneal malignancies in selected patients. As imaging is frequently performed postoperatively, radiologists are increasingly confronted with postoperative multidetector-row computed tomography (MDCT) examinations in these cases. In this article, after briefly describing the procedures that are currently being performed for the treatment of peritoneal metastases, the normal postoperative MDCT changes that may be encountered after these procedures are described. We then highlight complications that may arise after CRS, depending on the surgery performed, and those related to HIPEC, and illustrate their MDCT features.

Evaluation of the peritoneal carcinomatosis index with CT and MRI.

BACKGROUND: The aim was to determine the incremental value of MRI compared with CT in the preoperative estimation of the peritoneal carcinomatosis index (PCI). METHODS: CT and MRI examinations of patients with peritoneal carcinomatosis were evaluated. CT images were first analysed by two observers who determined a first PCI (PCICT ). Then, the two observers reviewed MRI examinations in combination with CT and determined a second PCI (PCICT+MRI ). The sensitivity and negative predictive value of the two imaging sets were determined using surgery as a reference standard (PCIRef ). RESULTS: CT plus MRI was more accurate in predicting the surgical PCI than CT alone. The absolute difference between PCICT+MRI and PCIRef was lower than that between PCICT and PCIRef (mean(s.d.) 3·96(4·10) versus 4·89(4·73); P = 0·010). The number of true-positive findings increased from 106 to 125 for reader 1 and from 117 to 132 for reader 2 with the adjunct of MRI. For both readers, an increased sensitivity was obtained when both MRI and CT were used (from 63 to 81 per cent for reader 1; from 44 to 81 per cent for reader 2). The increase in sensitivity was greater for patients with a moderate volume of disease. CONCLUSION: The combination of CT and MRI improved the preoperative estimation of PCI compared with CT alone.

Diagnosis and treatment of focal splenic lesions.

The spleen can be affected by many conditions, some of which are easily diagnosed by conventional imaging, mainly using computed tomography scans and magnetic resonance imaging. Despite the contribution of functional radiology techniques such as positron emission tomography, it is sometimes difficult to diagnose certain focal splenic lesions and definitive diagnosis sometimes requires histological confirmation by percutaneous biopsy or more rarely by diagnostic intervention. Once a diagnosis has been established, treatment is based mainly on surgery: total splenectomy for malignant lesions, or partial splenectomy whenever possible for benign lesions benign that are symptomatic and/or at risk of rupture.

[Stereotaxic radiotherapy of primary extracranial tumors]. / Radiothérapie stéréotaxique des tumeurs primitives extracrâniennes.

Stereotactic radiotherapy is a fundamental change from the conventional fractionated radiotherapy and represents a new therapeutic indication. Stereotactic radiotherapy is now a standard of care for inoperable patients or patients who refuse surgery. The results are encouraging with local control and survival rates very high in selected populations. The rate of late toxicity remains acceptable. Good tolerability makes it appropriate even for elderly and frail patients. In these fragile patients or in certain specific clinical situations, different surgical, radiotherapy or interventional radiology attitudes can be discussed on a case-by-case basis. These situations are considered in this article for the pulmonary, hepatic and prostatic localizations.

Computed tomography features of acinar cell carcinoma of the pancreas.

PURPOSE: To report the computed tomography (CT) features of pancreatic acinar cell carcinoma (ACC) and identify CT features that may help discriminate between pancreatic ACC and pancreatic ductal adenocarcinoma (PDA). MATERIALS AND METHODS: The CT examinations of 20 patients (13 men, 7 women; mean age, 66.5±10.7 [SD] years; range: 51-88 years) with 20 histopathologically proven pancreatic ACC were reviewed. CT images were analyzed qualitatively and quantitatively and compared to those obtained in 20 patients with PDA. Comparisons were performed using univariate analysis with a conditional logistic regression model. RESULTS: Pancreatic ACC presented as an enhancing (20/20; 100%), oval (15/20; 75%), well-delineated (14/20; 70%) and purely solid (13/20; 65%) pancreatic mass with a mean diameter of 52.6±28.0 (SD) mm (range: 24-120mm) in association with visible lymph nodes (14/20; 70%). At univariate analysis, well-defined margins (Odds ratio [OR], 7.00; P=0.005), nondilated bile ducts (OR, 9.00; P=0.007), visible lymph nodes (OR, 4.33; P=0.028) and adjacent organ involvement (OR, 5.67; P=0.02) were the most discriminating CT features to differentiate pancreatic ACC from PDA. When present, lymph nodes were larger in patients with pancreatic ACC (14±4.8 [SD]; range: 7-25mm) than in those with PDA (8.8±4.1 [SD]; range: 5-15mm) (P=0.039). CONCLUSION: On CT, pancreatic ACC presents as an enhancing, predominantly oval and purely solid pancreatic mass that most frequently present with no bile duct dilatation, no visible lymph nodes, no adjacent organ involvement and larger visible lymph nodes compared to PDA.

Prediction of tumor grade and lymphovascular space invasion in endometrial adenocarcinoma with MR imaging-based radiomic analysis.

PURPOSE: To evaluate the capabilities of two-dimensional magnetic resonance imaging (MRI)-based texture analysis features, tumor volume, tumor short axis and apparent diffusion coefficient (ADC) in predicting histopathological high-grade and lymphovascular space invasion (LVSI) in endometrial adenocarcinoma. MATERIALS AND METHODS: Seventy-three women (mean age: 66±11.5 [SD] years; range: 45-88 years) with endometrial adenocarcinoma who underwent MRI of the pelvis at 1.5-T before hysterectomy were retrospectively included. Texture analysis was performed using TexRAD® software on T2-weighted images and ADC maps. Primary outcomes were high-grade and LVSI prediction using histopathological analysis as standard of reference. After data reduction using ascending hierarchical classification analysis, a predictive model was obtained by stepwise multivariate logistic regression and performances were assessed using cross-validated receiver operator curve (ROC). RESULTS: A total of 72 texture features per tumor were computed. Texture model yielded 52% sensitivity and 75% specificity for the diagnosis of high-grade tumor (areas under ROC curve [AUC]=0.64) and 71% sensitivity and 59% specificity for the diagnosis of LVSI (AUC=0.59). Volumes and tumor short axis were greater for high-grade tumors (P=0.0002 and P=0.004, respectively) and for patients with LVSI (P=0.004 and P=0.0279, respectively). No differences in ADC values were found between high-grade and low-grade tumors and for LVSI. A tumor short axis≥20mm yielded 95% sensitivity and 75% specificity for the diagnosis of high-grade tumor (AUC=0.86). CONCLUSION: MRI-based texture analysis is of limited value to predict high grade and LVSI of endometrial adenocarcinoma. A tumor short axis≥20mm is the best predictor of high grade and LVSI.

MR imaging features of pancreatic acinar cell carcinoma.

PURPOSE: This study aimed to report the magnetic resonance imaging (MRI) features of acinar cell carcinoma (ACC) of the pancreas including diffusion-weighted MRI findings. MATERIALS AND METHODS: The MRI examinations of five patients (3 men, 2 women; median age, 61years) with histopathologically proven ACC of the pancreas were retrospectively reviewed. MR images were analyzed qualitatively (location, shape, homogeneity, signal intensity, vascular involvement and extrapancreatic extent of ACC) and quantitatively (tumor size, apparent diffusion coefficient [ADC] and normalized ADC of ACC). RESULTS: All ACC were visible on MRI, presenting as an oval pancreatic mass (5/5; 100%), with moderate and heterogeneous enhancement (5/5; 100%), with a median transverse diameter of 43mm (Q1, 35; Q3, 82mm; range: 30-91mm). Tumor capsule was visible in 4/5 ACC (80%) and Wirsung duct enlargement in 2/5 ACC (40%). On diffusion-weighted MRI, all ACC (5/5; 100%) were hyperintense on the 3 b value images. Median ADC value of ACC was 1.061×10-3mm2/s (Q1, 0.870×10-3mm2/s; Q3, 1.138×10-3mm2/s; range: 0.834-1.195×10-3mm2/s). Median normalized ADC ratio of ACC was 1.127 (Q1, 1.071; Q3, 1.237; range: 1.054-1.244). CONCLUSIONS: On MRI, ACC of the pancreas presents as a large, oval pancreatic mass with moderate and heterogeneous enhancement after intravenous administration of a gadolinium chelate, with restricted diffusion and a median ADC value of 1.061×10-3mm2/s on diffusion-weighted MRI. Further studies however are needed to confirm our findings obtained in a limited number of patients.

How to differentiate uterine leiomyosarcoma from leiomyoma with imaging.

Uterine leiomyomas, the most frequent benign myomatous tumors of the uterus, often cannot be distinguished from malignant uterine leiomyosarcomas using clinical criteria. Furthermore, imaging differentiation between both entities is frequently challenging due to their potential overlapping features. Because a suspected leiomyoma is often managed conservatively or with minimally invasive treatments, the misdiagnosis of leiomyosarcoma for a benign leiomyoma could potentially result in significant treatment delays, therefore increasing morbidity and mortality. In this review, we provide an overview of the differences between leiomyoma and leiomyosarcoma, mainly focusing on imaging characteristics, but also briefly touching upon their demographic, histopathological and clinical differences. The main indications and limitations of available cross-sectional imaging techniques are discussed, including ultrasound, computed tomography, magnetic resonance imaging (MRI) and positron emission tomography/computed tomography. A particular emphasis is placed on the review of specific MRI features that may allow distinction between leiomyomas and leiomyosarcomas according to the most recent evidence in the literature. The potential contribution of texture analysis is also discussed. In order to help guide-imaging diagnosis, we provide an MRI-based diagnostic algorithm which takes into account morphological and functional features, both individually and in combination, in an attempt to optimize radiologic differentiation of leiomyomas from leiomyosarcomas.

[Ductal adenocarcinoma, four years follow-up]. / Adénocarcinome ductal de la prostate, quatre ans de suivi.

Ductal adenocarcinoma of the prostate (DAP) is an unusual form of prostatic cancer rising in the light of the acini and prostatic ducts with preservation of their architecture. We report the case of a 78-year-old patient presenting a pure ductal adenocarcinoma of the prostate locally advanced, with a four years' follow-up. With this case, we report the principal aspects of the literature.

Preoperative assessment of peritoneal carcinomatosis of colorectal origin.

The goal of preoperative assessment of patients with peritoneal carcinomatosis (PC) from colorectal origin is to select candidates for curative surgery by evaluating the possibility of complete resection, and to plan the surgical procedure. Quantitative and qualitative evaluation of lesional localization remains difficult even with current technical progress in imaging. Computed tomography (CT), the reference imaging technique, allows detection of both peritoneal and extra-peritoneal lesions. Sensitivity and specificity for detecting PC are 83% (95%CI: 79-86%) and 86% (95%CI: 82-89%), respectively. Functional imaging, with diffusion-weighted magnetic resonance imaging (MRI) and positron emission tomography PET-CT allows efficient exploration of peritoneal lesions. MRI is operator-dependent, with a long learning curve, and is, at present, essentially used only in expert centers. A standardized protocol provided by the radiologists working with the French National Center for rare peritoneal tumors RENA-RAD (http://www.renape-online.fr/fr/espace-professionnel/rena-rad.html) is however available on line. PET-CT is particularly useful for identifying and defining extra-peritoneal disease. Combining imaging techniques, particular CT with MRI, seems to improve the calculation of the Peritoneal Cancer Index compared to CT alone. Surgical exploration is the reference technique to evaluate PC. Currently, the literature cannot confirm whether laparoscopy performs as well as laparotomy, but laparoscopy is, de facto, the fundamental tool to decrease the number of unnecessary laparotomies in these patients. To optimize the pre-, intra- and postoperative reporting of the extent of PC, the French National Network for management of PC (RENAPE and BIG-RENAPE: http://www.e-promise.org/) has offered on-line a free-of-charge, standardized, multidisciplinary and transversal software.

Measurement variability of liver metastases from neuroendocrine tumors on different magnetic resonance imaging sequences.

PURPOSE: To assess dimension measurement variability of liver metastases from neuroendocrine tumors (LMNET) on different magnetic resonance imaging (MRI) sequences. MATERIAL AND METHODS: In this institutional review board-approved retrospective study from January 2011 to December 2012, all liver MRI examinations performed at our department in patients with at least one measurable LMNET according to response evaluation criteria in solid tumors (RECIST1.1) were included. Up to two lesions were selected on T2-weighted MR images. Three reviewers independently measured long axes of 135 hepatic metastases in 30 patients (16 men, 14 women, mean age 61±11.4 (SD) years; range 28-78 years), during two separate reading sessions, on T2-weighted, diffusion-weighted MRI (DWI) (b; 50, 400, 800 s/mm2) and arterial, portal and late phases after intravenous administration of a gadolinium chelate. Intraclass-correlation coefficients and Bland-Altman plots were used to assess intra-and interobserver variability. RESULTS: Intra- and interobserver agreements ranged between 0.87-0.98, and 0.88-0.97, respectively. Intersequence agreements ranged between 0.92 [95%CI: 0.82-0.98] and 0.98 [95%CI: 0.93-0.99]. 95% limits of agreement for measurements were -10.2%,+8.9% for DWI (b=50s/mm2) versus -21.9%,+24.2% and -15.8,+17.2% for arterial and portal phases, respectively. CONCLUSION: An increase<9% in measurement and a decrease of -10% on DWI should not be considered as true changes, with 95% confidence, versus 24% and -22% on arterial and 17%, -16% on portal phases, respectively. DWI might thus be the most reliable MR sequence for monitoring size variations of LMNETs.

Volvulus of the sigmoid colon is associated with hypotrophy of the left lateral segment of the liver and the absence of sigmoid diverticulum.

PURPOSE: To investigate the possible relationships between sigmoid diverticula, the volume of the left lateral segment of the liver and sigmoid colon volvulus. MATERIAL AND METHODS: The presence of sigmoid diverticula was analyzed in 36 patients (24 men, 12 women; mean age, 70.77±19.86 [SD] years) with sigmoid volvulus (group 1). The volumes of left lateral segment of the liver (i.e., segments 2 and 3 and further referred to as liver 1), liver 2 (i.e., segments 1, 4, 5, 6, 7 and 8), total liver volume and liver volume ratio (LVR) (i.e., [liver 1/liver 2]×100) were calculated from abdominal CT performed distantly from the acute episode of sigmoid volvulus. Results of volumetric measurements in group 1 were compared with those of two groups of age and gender-matched control patients without hepatopathy: one patient group with sigmoid diverticula (group 2) and one group without sigmoid diverticula (group 3). RESULTS: No patients with sigmoid volvulus had diverticulum. Liver 1 volume was lower in group 1 (193.8cm3) than in group 2 (273.75cm3) (P=0.0003). Mean LVR was greater in group 2 (24.18%) than in group 1 (14.46%) (P=1×10-7) and group 3 (18.36%) (P=0.003). Mean LVR was greater in group 3 than in group 1 (P=0.01). No significant differences in liver 2 volume and total liver volumes were found between the 3 groups. CONCLUSION: Elasticity of colon wall associated with relative hypotrophy of left lateral segment of the liver are significantly associated with sigmoid volvulus. Further studies are needed to elucidate the pathophysiological mechanisms behind this association.

Diagnosis of hepatocellular carcinoma: An update on international guidelines.

Imaging is essential for the successful management of patients with or at risk of developing hepatocellular carcinoma (HCC). If ultrasound remains the key screening modality, computed tomography and magnetic resonance imaging (MRI) can play a major role in the characterization and noninvasive diagnosis of nodules in patients at risk of developing HCC. Each technique has succeeded in adapting to the wide histological spectrum of focal liver lesions. In this review, we discuss recent advancements in imaging techniques and evaluation - notably diffusion-weighted imaging, contrast-enhanced ultrasound, and liver-specific MRI contrast agents - as well as their addition to international guidelines and reporting systems such as the Liver imaging reporting and data system (LI-RADS).

Mass-forming lesions of the duodenum: A pictorial review.

Recent advances in imaging have resulted in marked changes in the investigation of the duodenum, which still remains primarily evaluated with videoendoscopy. However, improvements in computed tomography (CT) and magnetic resonance (MR) imaging have made detection and characterization of duodenal mass-forming abnormalities easier. The goal of this pictorial review was to illustrate the most common conditions of the duodenum that present as mass-forming lesions with a specific emphasis on CT and MR imaging. MR imaging used in conjunction with duodenal distension appears as a second line imaging modality for the characterization of duodenal mass-forming lesions. CT remains the first line imaging modality for the detection and characterization of a wide range of duodenal mass-forming lesions.

Diagnosis of acute overt gastrointestinal bleeding with CT-angiography: Comparison of the diagnostic performance of individual acquisition phases.

PURPOSE: To compare the respective values of arterial phase, portal venous phase and combination of phases using 64-section multidetector computed tomography (MDCT) for diagnosing acute overt gastrointestinal bleeding (AOGIB). PATIENTS AND METHODS: Forty-nine patients with AOGIB were included. There were 30 men and 19 women, with a mean age of 65.4±15.6 (SD) years [range, 34-91years]. Two observers reviewed MDCT examinations in consensus for presence of active bleeding, location of bleeding site and nature of causative lesion. The different acquisition phases were reviewed independently. RESULTS: AOGIB was identified in 28/49 patients (57%) with the multiphasic set, in 26/49 patients (53%) with arterial phase and in 25/49 patients (51%) with portal venous phase. Multiphasic set helped locate the bleeding site in 40/49 patients (82%). The cause was elucidated in 23/49 patients (47%) with multiphasic set. The differences between set performances were not statistically significant. Sensitivity for depicting AOGIB with the multiphasic set was 92% and specificity was 76%. CONCLUSION: Multiphasic 64-section MDCT has high diagnostic performances in patients with AOGIB. Further studies with a larger population are needed to reach statistical significance and demonstrate better diagnostic performance of multiphasic MDCT in comparison with the arterial or portal phase alone.

Prediction of clinical outcome using blood flow volume in the superior mesenteric artery in patients with pseudomyxoma peritonei treated by cytoreductive surgery.

BACKGROUND: Pseudomyxoma peritonei (PMP) is a rare carcinomatosis limited to the peritoneal cavity, mainly supplied by the superior mesenteric artery (SMA). The only curative treatment is cytoreductive surgery (CRS) associated with hyperthermic intraperitoneal chemotherapy. This study aimed to evaluate the ability of blood flow volume (BFV) recorded in the SMA using Doppler ultrasonography pre-operatively to predict the extent and resectability of the disease and post-operatively to assess clinical outcome. METHODS: BFV was measured in the SMA of forty-nine patients before and the year following CRS. Patients were categorized in 3 groups according to clinical and surgical outcomes: group-1 (n = 22): patient with completed CRS, group-2 (n = 16): incomplete resection with slowly progressive disease (alive at 2 years without severe clinical symptoms), group-3 (n = 11): incomplete resection and with severe clinical symptoms or dead within two years. RESULTS: Pre-operative mean SMA BFV was higher in group-2 (510 mL/min, p = 0.027) and in group-3 (572 mL/min, p = 0.004) than in group-1 (378 mL/min). After surgery, BFV dropped to normal values (203 mL/min, p = 0.001) in group-1, and to 423 mL/min (p = 0.047) in group-2. It remained elevated in group-3 (626 mL/min, p = 0.566). BFV allowed stratification of 1) resectability before CRS (group-2 and -3 vs group-1, area under the ROC curve: 0.794 [0.650-0.939]), and 2) non progression after incomplete CRS (group-3 vs group-2, area under the ROC curve: 0.827 [0.565-1.00]. CONCLUSIONS: Pre-operative BFV in the SMA correlates with extent and resectability of PMP. After incomplete surgery, post-operative BFV might aid in identifying patients who may benefit of post-operative therapy.

Abdominopelvic ultrasonographic findings after uncomplicated delivery.

PURPOSE: To prospectively determine the range of abdominopelvic ultrasonographic findings, including Doppler resistance index (RI) of uterine arteries, 2 and 24 hours after uncomplicated delivery. METHOD: Women who delivered vaginally or after cesarean section without complication from January 2012 to April 2012 in a tertiary care hospital were prospectively included. Abdominopelvic ultrasonography, including uterine artery resistance index (RI) at duplex Doppler ultrasonography, was performed 2 hours and 24 hours after delivery. RESULTS: Ninety-two women (mean age, 32.7 years) were included. Sixty-one (66%) delivered vaginally and 31 (34%) had cesarean section. Twenty-four hours after vaginal delivery, endometrial and anterior wall thicknesses dropped and uterine width increased (P<0.001). No changes in uterine length and posterior wall thickness were observed between 2 and 24 hours after delivery. Transient pelvic free-fluid effusion was observed in 1/92 woman (1%). Uterine artery RI increased significantly from 2 to 24 hours (0.50 vs 0.57, respectively; P<0.001). CONCLUSION: Pelvic free-fluid effusion is exceedingly rare in the early course of uncomplicated delivery. A significant increase in uterine artery RI during the 24 hours following uncomplicated delivery is a normal finding. It can be anticipated that familiarity with these findings would result in more confident diagnosis of complications.