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PubMed1997

Beneficial effect of intracoronary verapamil on microvascular and myocardial salvage in patients with acute myocardial infarction.

OBJECTIVES: We assessed the acute effect of intracoronary injection of verapamil on microvascular function after primary percutaneous translumanal coronary angioplasty (PTCA) for acute myocardial infarction (AMI) with myocardial contrast echocardiography (MCE) in relation to functional outcomes. BACKGROUND: Recent clinical studies have documented the potential of verapamil for possible increase in coronary blood flow after primary PTCA. METHODS: Forty patients with a first AMI were randomly assigned to the verapamil group (n = 20) or the control group (n = 20). In the verapamil group, verapamil (0.5 mg) was injected into the infarct-related artery shortly after PTCA, followed by the oral administration. We performed MCE with an intracoronary injection of sonicated microbubbles before and after verapamil. To assess microvascular integrity, we determined the baseline-subtracted peak intensity in the risk area and the ratio of the no reflow zone plus the low reflow zone to the risk area (low reflow ratio). We determined the average wall motion score (dyskinesia/akinesia = 3; normal = 0) in the risk area on the day of AMI and a mean of 24 days later. RESULTS: The low reflow zone was observed shortly after PTCA in 14 verapamil group patients, and the low reflow ratio decreased after verapamil (0.39 +/- 0.23 vs. 0.29 +/- 0.17 [mean +/- SD], p < 0.05). Peak intensity significantly (p < 0.05) increased from 6 +/- 5 to 12 +/- 6 after verapamil. The reduction in wall motion score from the acute (day -1) to the late stage (day -24) was significantly greater in the verapamil group than in the control group (0.7 +/- 0.8 vs. 0.2 +/- 1.3, respectively, p < 0.05). CONCLUSIONS: Intracoronary administration of verapamil after primary PTCA can attenuate microvascular dysfunction and thereby augment myocardial blood flow in patients with AMI, leading to better functional outcome than with PTCA alone.

Adult↗

PubMed1998

Tissue-type plasminogen activator therapy versus primary coronary angioplasty: impact on myocardial tissue perfusion and regional function 1 month after uncomplicated myocardial infarction.

OBJECTIVES: This study sought to compare the impact of primary coronary angioplasty and thrombolytic therapy for acute myocardial infarction (AMI) on 1-month infarct size and microvascular perfusion. BACKGROUND: The effect of the reperfusion strategies of primary coronary angioplasty and thrombolytic therapy on microvascular integrity still remains to be determined. METHODS: Sixty-two consecutive patients with a first AMI, undergoing intravenous tissue-type plasminogen activator (t-PA) therapy (32 patients, Group I) or primary angioplasty (30 patients, Group II), were studied. Only patients with 1-month Thrombolysis in Myocardial Infarction (TIMI) flow grade 2 or 3 were selected for the study. Patients in whom primary angioplasty was unsuccessful or those with clinical evidence of failed reperfusion were excluded. Microvascular perfusion was assessed at 1 month by intracoronary injection of sonicated microbubbles. Contrast score index (CSI) and wall motion score index (WMSI) were derived using qualitative methods. RESULTS: At baseline there were no significant differences between groups for age, risk factors, time to hospital presentation, Killip class on admission, prevalence of multivessel disease or anterior infarct site, infarct area extension before reperfusion, peak creatine kinase levels and postinfarction treatment. Conversely, significant differences between groups were found at follow-up for percent residual infarct related-artery (IRA) stenosis (70 +/- 12 vs 36 +/- 14 [mean +/- SD], p = 0.0001), CSI (1.02 +/- 0.4 vs. 1.49 +/- 0.5, p = 0.0003) and WMSI (1.67 +/- 0.3 vs. 1.45 +/- 0.3, p = 0.015). In particular, in the subset of patients with TIMI grade 3 flow, a perfusion defect occurred in one or more segments subtended by the IRA in 72% of Group I versus 31% of Group II patients (p < 0.00001) and in 27% of Group I versus 8% of Group II segments (p < 0.00001). CONCLUSIONS: The present study shows, in a highly selected cohort with successful IRA recanalization, that primary angioplasty is more effective than thrombolysis in preserving microvascular flow and preventing extension of myocardial damage at 1-month after AMI.

Age Factors↗

PubMed1998

Administration of an intravenous perfluorocarbon contrast agent improves echocardiographic determination of left ventricular volumes and ejection fraction: comparison with cine magnetic resonance imaging.

OBJECTIVES: The purpose of this study was to determine whether contrast-enhanced transthoracic echocardiography improves the evaluation of left ventricular (LV) volumes and ejection fraction (EF). BACKGROUND: Echocardiographic assessment of LV volumes and EF is widely used but may be inaccurate when the endocardium is not completely visualized. Recently the intravenous (i.v.) administration of perfluorocarbon microbubbles has been shown to enhance opacification of the LV cavity, but the utility of these agents to improve the echocardiographic assessment of LV systolic function is unknown. METHODS: In 40 subjects (29 men and 11 women, aged 24 to 81 years) an assessment of LV volumes and EF was performed with a magnetic resonance imaging examination, followed immediately by a transthoracic echocardiogram before and after the intravenous administration of 2% dodecafluoropentane emulsion (EchoGen; Sonus Pharmaceuticals, Bothell, Washington). RESULTS: Contrast enhanced the echocardiographic assessment of LV end diastolic volume (p < 0.02), end systolic volume (p < 0.01) and LVEF (p < 0.03). The percentage of subjects in whom the correct echocardiographic classification EF was normal, mild to moderately depressed or severely reduced improved significantly after contrast enhancement (from 71% before contrast to 94% after, p < 0.03). These findings were most striking in the subjects with two or more adjacent endocardial segments not visualized at baseline. CONCLUSIONS: Administration of an intravenous contrast agent improves the ability to accurately assess LV volumes and EF in humans. Contrast enhancement is most useful in subjects with two or more adjacent endocardial segments not seen at baseline.

Adult↗

PubMed1999

Intravenous nicorandil can preserve microvascular integrity and myocardial viability in patients with reperfused anterior wall myocardial infarction.

OBJECTIVES: We assessed whether the intravenous administration of nicorandil, an adenosine triphosphate (ATP)-sensitive K+ channel opener, exerts beneficial effect on microvascular function and functional and clinical outcomes in patients with acute myocardial infarction (AMI). BACKGROUND: Experimental studies documented that ATP-sensitive K+ channel opener exerts cardioprotection after prolonged ischemia. METHODS: We randomly divided 81 patients with a first anterior AMI into two groups, nicorandil (n = 40) and control groups (n = 41). All patients received successful coronary angioplasty within 12 h after the symptom onset and underwent myocardial contrast echcardiography (MCE) with the intracoronary injection of sonicated microbubbles. In the nicorandil group, we injected 4 mg of nicorandil followed by the infusion at 6 mg/h for 24 h and by oral nicorandil (15 mg/day). RESULTS: The improvement in regional left ventricular function, wall motion score and regional wall motion was significantly better in the nicorandil group then in the control group. Intractable congestive heart failure, malignant ventricular arrhythmia and pericardial effusion were more frequently found in the control group than in the nicorandil group (15% vs. 37%, 5% vs. 20% and 8% vs. 37%, p < 0.05, respectively). The frequency of sizable MCE no reflow phenomenon was significantly lower in the nicorandil group than in the control group (15% vs. 33%, p < 0.05). CONCLUSIONS: Intravenous nicorandil in conjunction with coronary angioplasty is associated with better functional and clinical outcomes compared to angioplasty alone in patients with an anterior AMI. Myocardial contrast echocardiography findings imply that an improvement in microvascular function with nicorandil may be attributable to this better outcome.

Angioplasty, Balloon, Coronary↗

PubMed1995

[Effects of mechanical ventilation with PEEP on right to left intra-cardiac shunt caused by patent foramen ovale].

OBJECTIVE: To assess the presence of a patent foramen ovale (PFO) using colloid contrast transoesophageal echocardiography in mechanically ventilated patient with and without PEEP and it repercussion on PaO2. STUDY DESIGN: Prospective open before-after trial. PATIENTS: Forty-nine mechanically ventilated patients with respiratory failure (PaO2/FiO2 < 250). METHODS: PEEP assessment before and after adding a PEEP = 10 cmH2O. At each level of PEEP, semi-quantification of PFO was performed and arterial blood gases were withdrawn at FiO2 = 1, with 15 min at each level. Semi-quantification of the right-to-left intra cardiac shunt through a patent foramen ovale was obtained using the quantity of microbubbles in the left atrium on a basal short axis view. RESULTS: A PFO was detected in 11 out of 49 patients (22%). A right-to-left shunt developed in one and worsen in three patients when PEEP was added. In patients without a PFO, PaO2 increased significantly (from 119 +/- 10 mmHg to 145 +/- 10 mmHg, P < 0.001). In patients with a PFO, non significant changes occurred (118 +/- 15 mmHg to 120 +/- 17 mmHg). After adding PEEP, the difference between the two groups was significant (ANOVA, P < 0.05). Moreover, a PFO was present during the whole respiratory cycle in two out of 11 patients. These 2 patients exhibited a PaO2 < 100 mmHg with or without PEEP. CONCLUSION: This study suggests that mechanical ventilation with PEEP enhances an intracardiac right-to-left shunt through a PFO. This condition is responsible for the lack of improvement in blood oxygenation when PEEP is added. When a PFO is present all over the respiratory cycle, or when the oxygenation is worsened with PEEP, this positive pressure ventilation should be avoided. The deleterious consequences of mechanical ventilation on venous return may be minimized by partial ventilation and weaning from ventilator.

Echocardiography, Transesophageal↗

PubMed1998

Effect of gas-containing microspheres and echo contrast agents on free radical formation by ultrasound.

Stabilized microbubbles (microspheres) are widely used to enhance the contrast of ultrasound imaging. Our data provide direct evidence that the contrast agents, Levovist, PVC-AN (polyvinylidene chloride-acrylonitryl copolymer), and Albunex (compared to 5% human albumin), at concentrations comparable to those used for ultrasound imaging, enhance H2O2 production (through the superoxide-dependent pathway) in air-saturated aqueous solutions exposed to 47 kHz ultrasound above the cavitation threshold. These agents also act as scavengers of .H atoms and .OH radicals, thus lowering H2O2 formation (by recombination of .OH radicals) in argon-saturated solutions. EPR spin trapping also reveals that secondary radicals derived from the contrast agents are produced by reactions with .H and .OH which are formed by pyrolysis of water inside cavitation bubbles. In addition, the contrast agents themselves undergo pyrolysis reactions in the cavitation bubbles as demonstrated by formation of methyl radicals. Possible deleterious consequences of the formation of sonochemical intermediates may have to be assessed, particularly since some of the echo contrast agents have been shown to lower the cavitation threshold of diagnostic ultrasound. Unlike the microspheres formed from organic molecules, inorganic microspheres, Eccospheres, because of their stability and inert nature with respect to participation in free radical processes, appear to be suitable tools for enhancing the yields of aqueous sonochemical reactions.

Acrylic Resins↗

PubMed2003

Contrast echocardiography using intravenous octafluoropropane and real-time perfusion imaging predicts functional recovery after acute myocardial infarction.

Akinesia after acute myocardial infarction (MI) may be reversible, secondary to stunning, or irreversible, as a result of extensive myocyte necrosis. Distinguishing these 2 entities soon after MI is difficult, but has important clinical implications. The current study assessed the use of intravenous myocardial contrast echocardiography (MCE) in this setting. A total of 35 patients were studied 2 (+/- 1) days after an acute MI. Of these, 31 (91%) underwent myocardial revascularization. Perfusion was assessed using real-time MCE and an intravenous infusion of octafluoropropane microbubbles. Repeated echocardiograms were obtained 56 (+/- 29) days later. Normal perfusion predicted functional recovery with a positive predictive value of 66% and a negative predictive value of 81%. The accuracy of the technique was superior in myocardial segments supplied by the left anterior descending coronary artery (positive and negative predictive value: 70% and 90%, respectively). In multivariable analysis, the mean MCE perfusion score in akinetic segments was the most powerful independent predictor of functional recovery (odds ratio 8.6, P =.02). These data suggest that real-time intravenous MCE is a useful predictor of functional recovery of akinetic myocardium after acute MI.

Aged↗

PubMedDate not supplied

Multifold sonicated dilutions of albumin with fifty percent dextrose improve left ventricular contrast videointensity after intravenous injection in human beings.

An intravenous injection of a onefold dilution of sonicated albumin with 50% dextrose improves echocardiographic left ventricular cavitary opacification in dogs compared with sonicated albumin. The objective of this study was to determine whether sonicated dilutions of albumin with dextrose would improve left ventricular videointensity after intravenous injection in humans and to delineate what ratio of albumin with dextrose results in optimal left ventricular cavitary opacification. We gave intravenous injections (randomized) of sonicated albumin and three different dilutions of albumin with 50% dextrose sonicated at different time intervals (onefold, threefold, and sevenfold dilutions sonicated albumin for 40 seconds and threefold and sevenfold dilutions sonicated albumin for 80 to 100 seconds) to 10 healthy human volunteers. End-diastolic and end-systolic videointensity and mean transit time from the mid-left ventricular cavity were compared after an 8.0 ml intravenous injection of all six samples. The threefold and sevenfold dilutions sonicated for 80 to 100 seconds produced microbubble concentrations similar to those of sonicated albumin but with significantly larger (5.6 microns versus 4.7 microns for sonicated albumin) size. These dilutions produced significantly higher end-diastolic and end-systolic videointensity, area under the time-intensity curve, and mean transit time compared with sonicated albumin or any of the dilutions sonicated for 40 seconds (p < or = 0.005). These data suggest that multifold dilutions of albumin with dextrose produce improved ultrasound contrast.

Adult↗

PubMedDate not supplied

Acquired coronary-to-left ventricle fistula: evidence by myocardial contrast echocardiography.

The case report subject is a patient with an old anteroseptal myocardial infarction and postinfarction angina who developed, over the years, a small left coronary-to-left ventricle fistula. The first coronary angiogram, performed 4 months after the infarction, was negative for coronary fistula. The diagnosis was made 3 years later, at repeat cardiac catheterization with myocardial contrast echocardiography. Left and right coronary injections of 0.2 cc of sonicated 5% human albumin microbubbles generated a bright cloud of contrast entering the left ventricular cavity at the level of the distal third of the interventricular septum. Conversely, cineangiography failed to show on-line the fistulous communication that was evident only after careful cineangiographic reviewing. This case demonstrates the high efficacy of myocardial contrast echocardiography in identifying very small coronary fistulae.

Cardiomyopathies↗

PubMedDate not supplied

Quantitative myocardial ultrasonic integrated backscatter measurements during contrast injections.

We and others have shown that normal myocardium exhibits 4 to 5 dB diastolic-to-systolic cyclic variation (CV) of integrated backscatter. To investigate the effect of intramyocardial contrast on integrated backscatter, we injected 5% sonicated albumin, containing microbubbles in the range of 5 microns in diameter, into the left atrium in nine open-chest dogs. The dogs were anesthetized and placed in the right lateral decubitus position on a specially designed table with a cutout allowing ultrasound imaging from below. Ultrasonic data was obtained from the right precordium by use of a prototype M-mode integrated backscatter system implemented in a commercially available two-dimensional system. Usable data were obtained in eight of nine dogs. Integrated backscatter increased up to 13 dB after contrast injections. There was a significantly decreased CV of integrated backscatter during myocardial contrast in all eight dogs. The mean level of CV of integrated backscatter for the eight dogs decreased from 4.7 dB (530 beats analyzed) without contrast to 2.8 dB during contrast (436 beats analyzed). There was a trend to greater CV at higher levels of contrast. Septal excursion, as measured by M-mode echocardiography simultaneously with integrated backscatter by the same ultrasound beam, was similar with and without contrast (mean 8.2 vs 8.3 mm). Thus left atrium contrast injection produces quantitatively measurable integrated backscatter effects. Cyclic variation of integrated backscatter decreases with contrast. However, at higher contrast levels the decrease tends to be smaller. These effects should be considered during quantitative tissue characterization and myocardial contrast studies.

Albumins↗

PubMedDate not supplied

Myocardial perfusion studies by contrast echocardiography.

Determination of regional myocardial blood flow may provide clinically valuable information about ischemia, risk area, and the effect of angioplastic, surgical, and pharmacologic interventions. Contrast echocardiography, with use of prepared microbubbles of 4 to 8 microns size, graphically demonstrates perfusion characteristics in the catheterization laboratory. Analysis and interpretation of this data and the creation of contrast materials that will demonstrate myocardial perfusion after intravenous injection are some of the next challenges in these techniques.

Contrast Media↗

PubMedDate not supplied

Left ventricular volume determination using Albunex.

The aim of this study was to assess the ability of intravenous injection of Albunex to improve left ventricular volume determination in patients with various cardiac diseases. It is conceivable that the intravenous injection of microbubbles could improve echocardiographic left ventricular border delineation leading to improved interobserver variability. Echocardiograms were obtained during simultaneous intravenous injection of 0.08 and 0.12 ml/kg Albunex (four-chamber view). Within 6 hours after the recording of the contrast echocardiograms routine left heart angiography was performed. Volumes were measured using the slice method in native and contrast echocardiograms as well as in the angiograms by two independent investigators. The mean differences of angiographic-native echocardiographic and angiographic-contrast echocardiographic volumes (ml) as well as the calculated ejection fraction and their confidence intervals were tabulated and significance was anticipated if the confidence interval did not include zero. Significant changes to angiographic values could be observed concerning end-diastolic, echocardiographic, and contrast echocardiographic volumes at end diastole and end systole, while ejection fractions were similar. Differences between observers were significantly smaller in the contrast echocardiographic images than in the native echocardiographic images. Albunex led to a significantly decreased interobserver variability.

Adult↗

PubMed1997

Safety and efficacy of QW7437, a new fluorocarbon-based echocardiographic contrast agent.

The aim of this study was to evaluate the safety and efficacy of QW7437, a new fluorocarbon-based transpulmonary myocardial echocardiographic contrast agent. QW7437 is an anionically charged 2% dodecafluoropentane emulsion molecule, similar to EchoGen, a contrast agent previously shown to be efficacious in providing myocardial opacification by means of venous injection. This new agent has theoretical potential to provide greater safety and efficacy as a result of (1) reduced adherence to the negatively charged vascular endothelium and (2) reduced microbubble coalescence. Myocardial contrast echocardiography was performed in 10 dogs to evaluate the safety and efficacy of this agent. QW7437 (0.05 ml/kg) was injected as an intravenous bolus during intermittent harmonic epicardial imaging. Hemodynamic variables including heart rate, blood pressure, pulmonary artery pressure, pulmonary capillary wedge pressure, cardiac output, and arterial blood gases were determined at baseline and serially after contrast administration. Left ventricular fractional area shortening the regional myocardial blood flow at rest and during hyperemia (adenosine 140 micrograms/kg/min) were measured before and after contrast echocardiography. QW7437 provided dense myocardial opacification which persisted for more than 2 minutes in all subjects. This prolonged contrast effect did not result in significant changes in any hemodynamic variables, left ventricular function, or myocardial blood flow. Future studies should address the potential of this agent for human use.

Animals↗

PubMedDate not supplied

Massive air embolus to the left ventricle: diagnosis and monitoring by serial echocardiography.

Air embolization is an unusual but potentially dangerous complication in left heart catheterization. Microbubbles can be detected with two-dimensional echocardiography, which is often used for this purpose during open heart and bypass surgeries. Permanent neurologic sequelae and hemodynamic collapse can result from embolization of air bubbles to the cerebral and coronary circulations, respectively. Hyperbaric oxygen is the treatment of choice for cerebral air embolization. We present a 39-year-old man who had air embolization during left ventriculography in the form of a large pocket of "pooled" air. The patient was treated with conservative therapy successfully. Two-dimensional transthoracic echocardiography was used to document the presence of the air and follow its dissolution.

Adult↗

PubMed1998

Tissue harmonic imaging: why does it work?

The recent utilization of harmonic frequencies in the imaging of both tissue and contrast agents has dramatically improved echocardiographic image quality. In contrast harmonics, the harmonic frequency energy is generated on reflection from the microbubble contrast agent. In tissue harmonics, the harmonic frequency energy is generated gradually as the ultrasonic wave propagates through the tissue. Critical to the utility of tissue-generated harmonic frequencies is their origin beyond the chest wall and their nonlinear relation to the fundamental frequency energy strength. These two characteristics of tissue-generated harmonics ensure that the echoes most likely to produce artifact are least likely to produce harmonic waves. Armed with an understanding of how these images are produced and with data emerging as to their clinical utility, we anticipate that harmonic imaging will become the standard for assessing regional and global left ventricular function in technically difficult studies.

Artifacts↗

PubMed1998

Detection of perfusion defects during coronary occlusion and myocardial reperfusion after thrombolysis by intravenous administration of the echo-enhancing agent BR1.

The purpose of this study was to detect myocardial perfusion defects as a result of coronary occlusion and myocardial reperfusion after thrombolysis with intravenous (i.v.) administration of the echo contrast agent BR1 (Bracco Research, Switzerland), which consists of microbubbles (median diameter 2.5 microm) containing sulfur exafluoride in a phospholipidic shell. To generate a coronary thrombosis, a copper coil was advanced into the left circumflex coronary artery in eight anesthetized dogs with opened chest cavities. Coronary occlusion occurred 18 +/- 10 minutes after the insertion of the coil and was documented both by an electromagnetic flow meter (as zero blood flow) and by radiolabeled microspheres (as myocardial perfusion defect). After 2 hours of occlusion, streptokinase was infused i.v.; reperfusion was documented by both the flow-meter and microspheres. Left ventricular cavity enhancement was apparent after all contrast injections. Peak cavity intensity did not increase with dose and was not affected by signal processing (suggesting signal saturation), whereas the duration of contrast effect significantly increased with the dose (from 26 +/- 16 to 147 +/- 74 seconds). Myocardial contrast intensity also increased after contrast (from 15 +/- 12 to 21 +/- 18 gray level/pixel, p < 0.001). Contrast echo detected myocardial perfusion defects (corresponding to 17% +/- 11% of LV cross-sectional area) in all the injections performed during coronary occlusion and detected myocardial reperfusion with a sensitivity of 50% versus microspheres. The extent of perfusion defects by contrast echo showed a good correlation with microspheres (r = 0.73). Myocardial reperfusion was not detected by changes in heart rate, aortic pressure, pulmonary arterial pressure, cardiac output, left ventricular fractional area change, or wall-motion score index. Hemodynamic parameters were not affected by contrast injections. Thus, the i.v. administration of BR1 allows us to accurately detect myocardial perfusion defects during coronary occlusion and, to a lesser extent, myocardial reperfusion after thrombolysis.

Animals↗

PubMed1999

Potential advantage of flash echocardiography for digital subtraction of B-mode images acquired during myocardial contrast echocardiography.

Optimal assessment of myocardial perfusion with contrast echocardiography by using B-mode imaging often requires image alignment and background subtraction, which are time consuming and need extensive expertise. Flash echocardiography is a new technique in which primary images are gated to the electrocardiogram and secondary images are obtained by transmitting ultrasound pulses in rapid succession after each primary image. Myocardial opacification is seen in the primary image and not in the secondary images because of ultrasound-induced bubble destruction. Because the interval between the primary and first few secondary images is very short, cardiac motion between these images should be minimal. Therefore we hypothesized that 1 or more secondary images could be subtracted from the primary image without the need for image alignment. The ability of ultrasound to destroy microbubbles was assessed by varying the sampling rate, line density, and mechanical index in 6 open-chest dogs. The degree of translation between images was quantified in the x and y directions with the use of computer cross-correlation. At sampling rates of 158 Hz or less and a mechanical index of more than 0.6, videointensity rapidly declined to baseline levels by 25 ms. Significant translation between images was noted only at intervals of more than 112 ms. It is concluded that flash echocardiography can be used for digital subtraction of baseline from contrast-enhanced B-mode images without image alignment. Background subtraction is therefore feasible on-line, potentially eliminating the need for off-line image processing in the future.

Animals↗

PubMedDate not supplied

Contrast-enhanced power Doppler US: is it useful in the differentiation of gallbladder disease?

Thirteen patients with gallbladder disease underwent power Doppler ultrasound (PDUS) before and after microbubble contrast agent injection. Lesion and liver bed vascularity was evaluated. Pathological diagnoses in nine patients were two acute cholecystitis, four chronic inflammation, one adenoma and two adenocarcinoma. Two cases of cancer were included on clinical and radiological findings. Two cases were excluded because no pathologic diagnosis was available. Liver bed hyperemia was noted only in acute cholecystitis. Contrast-enhanced PDUS was superior to nonenhanced PDUS in the demonstration of vascularity of gallbladder diseases. However, contrast-enhanced PDUS has limited value in the differentiation.

Adenocarcinoma↗