Utility of a multidisciplinary tumor board in the management of pancreatic and upper gastrointestinal diseases: an observational study

Background & objectives

Multidisciplinary tumor boards (MDTBs) are frequently employed in cancer centers but their value has been debated. We reviewed the decision-making process and resource utilization of our MDTB to assess its utility in the management of pancreatic and upper gastrointestinal tract conditions.

Optimal extent of surgical and pathologic lymph node evaluation for resected intrahepatic cholangiocarcinoma

Background

Lymph node (LN) status is an important predictor of overall survival for resected IHCC, yet guidelines for the extent of LN dissection are not evidence-based. We evaluated whether the number of LNs resected at the time of surgery is associated with overall survival for IHCC.

Changes in ventricular refractoriness after an extrastimulus: effects of prematurity, cycle length and procainamide

This study was performed to determine the ability of extrastimuli to change ventricular refractoriness. We prospectively evaluated the effects of stimulus prematurity and paced cycle length (PCL) in 30 patients and the effect of procainamide in 8 patients on changes in the ventricular effective refractory period (ERP) after a right ventricular extrastimulus (S2). An S2 was introduced at preselected coupling intervals at a PCL (S1-S1) of 600 and 400 ms. At each S1-S2 interval, a second extrastimulus (S3) was introduced in 5-ms decrements and the ERP of S2 measured. The decrease in the ERP after an S2 was directly related to prematurity and most of the shortening occurred over a narrow range of S1-S2 intervals. At a PCL of 600 ms, the ERP of S2 at S1-S2 intervals less than or equal to 400 ms was significantly shorter than the ERP of S1 (maximal shortening 23%). At a PCL of 400 ms, the ERP of S2 at S1-S2 intervals less than or equal to 350 ms was significantly shorter than the ERP of S1 (maximal shortening 25%). The ERP of S2 at the shortest S1-S2 interval was greater with a PCL of 600 ms than with 400 ms (200 +/- 31 versus 180 +/- 26 ms, p less than 0.001). However, the total shortening in ERP (ERPS1 - ERPS2 at shortest S1-S2 interval) was similar at both PCLs (55 +/- 14 versus 59 +/- 13 ms). Procainamide significantly prolonged the ERP of S2 at each S1-S2 interval.(ABSTRACT TRUNCATED AT 250 WORDS)     

Plasma MB creatine kinase after vigorous exercise in professional athletes

Plasma MB creatine kinase (CK) activity was quantitatively evaluated by several independent methods in 9 young professional athletes after vigorous exercise in competitive football games. Seven of the 9 had elevated total plasma CK activity. None had clinical findings of myocardial injury. However, 4 of the 7 with total CK elevations also had elevated MB-CK. MB-CK elevations occurred in players with the highest elevations of total CK activity. It is known that well-trained athletes liberate less conventionally measured muscle enzyme into the blood after exertion than do untrained individuals. These results indicate that a substantial fraction of professional athletes who engage in unusually vigorous exercise have elevations of plasma MB-CK that should not be interpreted as necessarily indicative of myocardial ischemic injury.     

Progressive nature of myocardial injury in selected patients with cardiogenic shock

To determine whether the extensive myocardial injury associated with cardiogenic shock in some patients results from a progressive rather than a discrete massive insult, a study was made of 15 selected patients who had cardiogenic shock within 48 hours of admission, 5 patients with hypovolemic shock without myocardial infarction and 11 patients with myocardial infarction without shock. Peak plasma MB creatine kinase (CK) activity was significantly higher in the seven patients with cardiogenic shock associated with initial infarction (213 international units [IU]/liter) than in patients with shock and previous infarction (98 IU/liter) and in patients with uncomplicated myocardial infarction (125 IU/liter). A prolonged time to peak MB CK activity (averaging 26 hours) and a plateau of elevated MB CK activity were seen in patients with shock associated with initial infarction. Because shock itself did not slow the rate of apparent MB CK disappearance, results obtained suggest that cardiogenic shock associated with initial infarction in selected patients results from progressive myocardial damage underlying continuing release of MB CK into the circulation. The findings are compatible with the concept that, in these patients, cardiogenic shock reflects a vicious cycle of spreading myocardial injury, progressive compromise of cardiac function, exacerbation of ischemia and perpetuation of myocardial damage.     

Relationship of plasma leucine and α-ketoisocaproate during a L-[1-13C]leucine infusion in man: A method for measuring human intracellular leucine tracer enrichment

The keto analog of leucine, α-ketoisocaproate (KIC), is formed intracellularly from leucine and is released, in part, into the systemic circulation. Therefore, KIC can be used to estimate intracellular leucine tracer enrichment in man during labeled-leucine tracer experiments without requiring tissue biopsy samples. This approach was studied in young, healthy, male adults maintained on different dietary protein intakes from generous (1.5 g kg^?1d^?1) to deficient (0.0 g kg^?1d^?1) for 5–7 day periods. At the end of each dietary period, the volunteers were given a primed, continuous infusion of L-[1-¹³C]leucine either after an overnight fast (postabsorptive state) or while being fed hourly aliquots of the same diet. The plasma concentrations of all 3 branched-chain amino and keto acid pairs were measured from early morning blood samples taken from 4 subjects at 4 different levels of protein intake. Leucine concentration showed a weak correlation, and valine concentration showed a strong correlation with protein intake; isoleucine and the 3 keto acids did not. However, each branched-chain amino acid concentration was strongly correlated with its corresponding keto acid concentration. In plasma samples obtained during the L-[1-¹³C]leucine infusions, the ratio of [1-¹³C]KIC to [1-¹³C]leucine enrichment ratio remained relatively constant (77 ± 1% over the wide range of dietary protein intakes and for both the fed and postabsorptive states. For the tissues from which the plasma KIC originates, the rate of plasma leucine into cells will account for approximately 77% of the intracellular leucine flux with the remaining 23% coming primarily from leucine release via protein breakdown. The constant nature of the plasma KIC to leucine ¹³C enrichment ratio implies that relative changes in leucine kinetics will appear the same under many dietary circumstances regardless of whether plasma leucine or KIC enrichments are used for the calculations.     

Increased congestive heart failure after myocardial infarction of modest extent in patients with diabetes mellitus

To elucidate the factors involved in the reduced survival rate of diabetic patients after acute myocardial infarction (AMI), we prospectively evaluated 100 patients with well-documented diabetes and 426 control patients. We characterized infarct size and analyzed the incidence and severity of congestive heart failure (CHF) and subsequent death with respect to infarct size. The extent of the index infarct was less in diabetic compared to nondiabetic patients, 16.2 ± 2.2 CK-gm-eq/m² compared with 19.2 ± 0.9 (p < 0.02). However, CHF was more prevalent in diabetic patients (31.2% of the diabetic patients compared to 15.7%). The difference was most prominent in diabetic patients who had sustained prior infarction (50% compared to 16%), but was evident also in diabetic patients with initial infarction (26% compared to 16%). The mortality rate was greater in diabetic patients (p < 0.04). When diabetic and nondiabetic patients were stratified with respect to the presence or absence of CHF, survival curves were comparable. The increased incidence of CHF despite a smaller infarct size suggests that additional factors must contribute to myocardial dysfunction and the resultant excess in mortality.     

Interferon-based chemoradiation followed by gemcitabine for resected pancreatic adenocarcinoma: long-term follow-up

To report long-term follow up of a phase II, single-arm trial of resectable pancreatic ductal adenocarcinoma (PDAC) treated with adjuvant interferon-based chemoradiation followed by gemcitabine to determine survival, recurrence, and complications.

Gated cardiac blood pool imaging and thallium-201 myocardial scintigraphy for detection of remote myocardial infarction

The primary goal of this study was to assess the frequency of persistent regional wall motion abnormalities and myocardial perfusion defects detectable late after myocardial infarction with radionuclide ventriculography and thallium-201 imaging, respectively. The study was performed prospectively in 32 patients in whom infarct size was estimated enzymatically at the time of the acute episode and in 10 patients without infarction. Thallium-201 imaging and radionuclide ventriculography were performed with the patient at rest an average of 11 months after infarction (range 6 to 20 months) and analyzed independently by two observers who were unaware of results of other clinical and laboratory data. Perfusion defects were detected in 94 percent (30 of 32) by observer I and in 91 percent (29 of 32) by observer II. Wall motion abnormalities were detected in 78 percent (25 of 32) and 75 percent (24 of 32) by observers I and II, respectively, but in 10 of the patients with an infarct size less than 20 creatine kinase-gram-equivalents (CK-g-eq), wall motion abnormalities were found in only 50 and 40 percent, respectively, by these observers (p <0.04). Electrocardiographic changes of infarction (Q waves) were present in only 56 percent (18 of 32) of patients. Sixty-eight percent of patients with an infarct size greater than 20 CK-g-eq had persistent Q waves but these were present in only 30 percent with an infarct size less than 20 CK-g-eq (p <0.04). The sites of perfusion defects and of wall motion abnormalities corresponded closely and were concordant with electrocardiographic localization. Thus, thallium-201 imaging and radionuclide ventriculography are sensitive noninvasive techniques for identifying prior myocardial infarction, and are particularly helpful in patients with conduction abnormalities or equivocal electrocardiographic findings.     

Comparative pharmacology of calcium antagonists: Nifedipine,verapamil and diltiazem

Calcium antagonists (slow channel Mocking agents) are a very heterogeneous group of agents with dissimilar structural, electrophysiologic and pharmacologic properties. Nifedipine is a potent, long-acting vasodilator that has proved highly efficacious in relieving anginal symptoms caused by coronary vasospasm. In vivo, it exerts no myocardial depressant effects and has no antiarrhythmic properties. Treatment with nifedipine can safely be combined with administration of a beta receptor blocking agent. Verapamil prolongs atrioventricular (A-V) conduction (A-H interval) in a dose-dependent manner. It is the drug of choice for the treatment of reentrant supraventricular arrhythmias, irrespective of whether reentry occurs within the A-V node or through an accessory pathway (the Wolff-Parkinson-White syndrome). Verapamil is only moderately effective as an antianginal agent. Diltiazem is efficacious for the treatment of angiospastic angina, but its value as an antiarrhythmic agent remains to be delineated.     

Abnormal technetium-99m pyrophosphate images in unstable angina: Ischemia versus infarction?

There is controversy concerning the specificity of myocardial infarct imaging with technetium-99m pyrophosphate due to the high frequency of false positive images, especially in patients with unstable angina. In this study technetium-99m pyrophosphate images were compared with frequent determinations of plasma creatine kinase, MB isoenzyme (MB CK) activity in 116 patients admitted with the diagnosis of unstable angina. It was hypothesized that frequent measurement of MB CK activity, a sensitive and specific marker for myocardial necrosis, using sensitive assay techniques would detect small amounts of myocardial necrosis which might have been unrecognized by conventional clinical methods. The scintigraphic results and isoenzyme determinations agreed in 88 percent of patients; both tests were normal in 69 percent and both were abnormal, indicating acute myocardial infarcation, in 19 percent of patients. In the remaining 14 patients (12 percent), the scans were abnormal, but MB CK activity was normal. In five of these patients (4 percent), abnormal scintigrams presumably reflected persistent scan positivity after previous myocardial infarction. Only the remaining nine patients (8 percent) could be classified as having unexplained false positive scans, a frequency substantially less than that reported by other investigators who based the diagnosis of myocardial infarction on conventional clinical criteria. These results suggest that abnormal technetium-99m pyrophosphate images in patients with unstable angina generally indicate myocardial necrosis.     

Detection of ischemic myocardium in vivo through the chest wall by quantitative ultrasonic tissue characterization

Quantitative analysis of ultrasound offers a potentially valuable method for noninvasive differentiation of specific types of cardiac disease and for assessment of their severity. Clinical application necessitates quantitative measurement of the ultrasonic properties of myocardium through the chest wall. This study was designed to determine whether such measurements could be made noninvasively with the aid of conventional M mode echocardiographic guidance and to characterize the quantitative effects of intervening tissue (chest wall) on the ultrasonic signals backscattered by ischemic and normal myocardium. Frequency-dependent ultrasonic backscatter (2 to 7 MHz) from normal myocardium was measured in dogs in vivo through the closed chest with the use of M mode guidance and with the chest open, directly from the myocardium. Closed-chest and open-chest measurements were repeated after ligation of the left anterior descending coronary artery in the same animals. Closed-chest data were compensated by correcting for the average value for the slope of the attenuation-frequency function of chest wall, which was determined from measurements obtained by analysis on excised tissue. Compensated closed-chest measurements correlated with measurements obtained from the epicardial surface of the heart. The differentiation of normal from ischemic myocardium with both the closed- and open-chest measurements was consistent (p < 0.005). The successful differentiation of normal from ischemic myocardium by determination of quantitative backscatter through the intervening chest wall supports the concept that tissue characterization by quantitative analysis of backscattered ultrasound is a potentially useful, clinically applicable approach to noninvasive detection and differentiation of intrinsic properties of normal and diseased myocardium.     

“Redistribution” of myocardial thallium-201 without reperfusion: Implications regarding absolute quantification of perfusion

Thallium-201 scintigraphy is often used clinically to detect regions of ischemia. In clinical and experimental studies, such regions exhibit defects (cold spots) in initial scintigrams that resolve with time, even when normal flow is not reestablished. To characterize the basis for this apparent redistribution, 29 isolated hearts were perfused retrograde with erythrocyte-enriched modified Krebs-Henseleit buffer solution. Myocardial tracer time-activity curves were obtained after bolus injections of thallium-201 with the use of a pair of scintillation probes, from which the residual fraction (the fraction of tracer remaining in the heart after a bolus injection) and the biologic half time (the time at which 50 percent of initially extracted tracer is lost) were calculated. Under control conditions, the residual fraction was 81 ± 7 percent (mean ± standard deviation) and half-time 22 ± 2 minutes. When hearts were subjected to low flow (with flow decreased from a control value of 1.4 to 0.6 ml/g per min) the residual fraction increased and half-time was prolonged (94 ± 4 percent and 44 ± 17 minutes, respectively; probability [p] < 0.05 for each). Conversely, when hearts were subjected to high flow (2.3 ml/g per min), both residual fraction and half-time diminished (68 ± 6 percent and 15 ± 5 minutes, respectively; p < 0.05). Alterations in oxygen consumption Induced with pacing and increased preload at constant flow did not alter these measurements from control values. Hypoxia caused prolongation of biologic half-time. Because both extraction and myocardlal clearance of thallium-201 by the heart were greatly dependent on flow rate, even under conditions in which recirculation was excluded, and because Initial uptake of tracer is related to flow, at any interval subsequent to exposure to tracer, myocardial activity is a complex function of both extraction and clearance resulting in underestimation of the intensity of ischemia.     

Nifedipine blockade of ergonovine-lnduced coronary arterial spasm: Angiographic documentations

To determine whether calcium-flux blockade with nifedipine blunts coronary vasospasm, four patients with angiographically demonstrable coronary arterial spasm in the absence of Significant fixed coronary arterial stenosis were evaluated with coronary arteriography before and after treatment with nifedipine. After initial coronary arteriography, ergonovine was administered in successive doses of 0.05, 0.1 and (when necessary) 0.2 mg intravenously at 3 minute intervals. Three patients had symptomatic high grade focal coronary arterial spasm with electrocardiographic changes, and the fourth exhibited asymptomatic 60 percent constriction of the left anterior descending coronary artery. A maximal ergonovine challenge was repeated 30 minutes later after each patient had been pretreated with a 20 mg sublingual dose of nifedipine. Under these conditions, no patient had chest pain or electrocardiographic changes. Furthermore, neither focal nor diffuse coronary arterial spasm was demonstrable angiographically after the second challenge. Thus, in each case, a single dose of nifedipine precluded the angiographie expression of ergonovine-provoked coronary arterial spasm.     

Norepinephrine and epinephrine secretion from a clinically epinephrine-secreting pheochromocytoma

A 46 year old woman suffered five episodes characterized by hypotension, pulmonary edema, ventricular arrhythmias and cardiopulmonary arrest. She was found to have increased urinary total metanephrine and vanillylmandelic acid excretion and a mass in the left adrenal gland was detected on computed tomographic scanning. Because of the clinical picture of an epinephrine-secreting pheochromocytoma, she was prepared for adrenalectomy only with a beta-adrenergic blocking agent. Hypertension did not develop preoperatively. Surgery was complicated by severe hypertension, with blood pressure levels as high as $\text{240}\text{130}$ mm Hg, requiring the intravenous administration of alpha-adrenergic blocking agents. Plasma epinephrine and norepinephrine values, determined preoperatively but reported postoperatively, confirmed the presence of markedly elevated plasma epinephrine levels (1,210 and 1,840 pg/ml). Notably, however, plasma norepinephrine concentrations were also increased (1,980 and 3,000 pg/ml) and the tumor contained large amounts of norepinephrine as well as epinephrine. Thus, combined norepinephrine secretion was documented in a patient with the clinical picture of an epinephrine-secreting pheochromocytoma. In our judgement, such patients should be prepared for surgery with both beta- and alpha-adrenergic blocking agents.This patient exemplified the utility of isotope derivative measurements of plasma norepinephrine and epinephrine concentrations in the diagnosis of pheochromocytoma. Of 15 patients with surgically proved pheochromocytomas studied in our laboratory, plasma catecholamine concentrations were increased in all 14 with clinical manifestations compatible with catecholamine excess. Plasma catecholamine concentrations were not distinguishable from normal in one patient studied only because of a family history of pheochromocytoma.