Reliable anticoagulation with enoxaparin in patients undergoing percutaneous coronary intervention: The pharmacokinetics of enoxaparin in PCI (PEPCI) study.

The objective of this study was to evaluate the pharmacokinetic response to intravenous (IV) enoxaparin given 8-12 hr after subcutaneous (SC) dosing in patients undergoing percutaneous coronary intervention (PCI). Fifty-five patients received SC enoxaparin (1 mg/kg every 12 hr) followed by an IV bolus (0.3 mg/kg) 8-12 hr after the last SC dose, at the start of PCI or during catheterization. Anti-Xa levels were within the target range in 98% of patients 2-8 hr after the last SC dose, in 96% of patients following the IV bolus, and in 91% of patients for a further 2 hr. Subcutaneous enoxaparin (1 mg/kg every 12 hr) provides sufficient anti-Xa levels for PCI 2-8 hr after the last dose. An additional 0.3 mg/kg enoxaparin dose given IV 8-12 hr after the last SC dose reliably maintains anti-Xa levels within the target for at least 2 additional hr.     

Accuracy of transrectal ultrasound in predicting pathologic stage of rectal cancer before and after preoperative radiation therapy

Transrectal ultrasound (TRUS) and CT scan staging of rectal cancers before, and TRUS staging after, 45 Gy of irradiation were compared with the pathologic stage of the resected specimen in 19 patients. Accuracy of TRUS before and after irradiation, and of CT scan before irradiation, was 32 percent, 63 percent, and 53 percent, respectively. CT scan before and TRUS after irradiation predicted lymph node involvement in 79 percent and 68 percent of cases, respectively. Positive predictive value for lymph node involvement before irradiation was 60 percent for CT scan and 37.5 percent for TRUS; after irradiation, it was 50 percent for TRUS. Negative predictive value was 100 percent for CT scan and TRUS before radiation and 88 percent for TRUS after irradiation. Preoperative radiation therapy makes TRUS and CT scan less effective as staging techniques. The absence of lymph nodes on TRUS and CT scan before and after irradiation is reliable.Read in part at the Tripartitate Meeting, Birmingham, England, June 19 to 22, 1989.     

Risk of Second Cancers in Patients with Colorectal Carcinoids

INTRODUCTION: It is often stated that patients with colorectal carcinoid tumors have an increased risk of developing other malignancies. However, this risk has not been conclusively documented. A comprehensive evaluation is needed to more thoroughly assess the risk of second cancers in patients with colorectal carcinoids. METHODS: A search of the National Cancer Institute Surveillance, Epidemiology, and End Result database from 1973 to 1996 revealed 2,086 patients with colorectal carcinoids. This subset of patients was examined for occurrence of second cancers. The observed incidence of cancer for each site was compared with the expected incidence based on the gender-adjusted and age-adjusted cancer rates in the remaining Surveillance, Epidemiology, and End Result file. A Poisson distribution probability was used to determine the significance of these comparisons. RESULTS: Patients with colorectal carcinoids had an increased rate of cancer in the colon and rectum (P < 0.001), small bowel (P < 0.001), esophagus/stomach (P = 0.02), lung/bronchus (P < 0.001), urinary tract (P = 0.005), and prostate (P < 0.001), when compared with a control population. Most of the gastrointestinal tract cancers were synchronous cancers, whereas lesions outside the gastrointestinal tract were most commonly metachronous tumors. CONCLUSIONS: A significantly increased risk of synchronous colorectal, small-bowel, gastric, and esophageal cancers and metachronous lung, prostate, and urinary tract neoplasms is clearly demonstrated. After the diagnosis of colorectal carcinoid tumors, patients should undergo appropriate screening and surveillance for cancer at these sites.     

Experimental bacteremia and hepatic nutrient blood flow

To study altered hepatic nutrient blood flow during the early phases of bacteremia, Sprague-Dawley rats (250-350 gm) underwent carotid cannulation; 24 hr later, they received an intravascular infusion of 2.5 X 10(8) Escherichia coli (LD70) over 45 min. Controls were anesthetized and cannulated only. Experimental and control animals then received a flow-dependent dose of indocyanine green (5 mg/kg) via the cannula, and arterial blood was sampled at 3, 4, 5, 6, 7, and 8 min after. Separate groups of animals were studied at 3 and 6 hr after bacteremia. The half-life (t1/2) of indocyanine green clearance was then determined at each time period, with t1/2 representing an estimation of total hepatic nutrient blood flow. Results indicated a prolonged t1/2 at both time periods in the bacteremic rats. Hepatic histology from plastic-embedded sections appeared to reveal fibrin, platelets, and leukocyte fragments within the sinusoids. From these data, we conclude that reduced nutrient blood flow occurs during experimental bacteremia prior to systemic changes of arterial pressure.     

Longer Time Interval Between Completion of Neoadjuvant Chemoradiation and Surgical Resection Does Not Improve Downstaging of Rectal Carcinoma

PURPOSE: An interval of six to eight weeks between completion of preoperative chemoradiation therapy and surgical resection of advanced rectal cancer has been described. Our purpose was to determine whether a longer time interval between completion of therapy and resection increases tumor downstaging and affects perioperative morbidity. METHODS: Forty patients with advanced adenocarcinoma of the rectum underwent preoperative chemoradiation on a prospective trial with irinotecan (50 mg/m2), 5-fluorouracil (225 mg/m2), and concomitant external-beam radiation (45-54 Gy) followed by complete surgical resection of the tumor with total mesorectal excision. The time interval between completion of chemoradiation and surgical resection ranged from 28 to 97 days. The patients were divided into two groups with 33 eligible patients: Group A (4-week to 8-week time interval; 28-56 days) and Group B (10-week to 14-week interval; 67-97 days). Tumor downstaging was compared between these two groups. The number of patients downstaged by at least one T stage, those downstaged by at least one N stage, those with pathologic complete responses, and those with only residual microscopic tumor foci were compared. Postoperative length of stay, estimated blood loss, perioperative morbidity, and sphincter-sparing procedures were also compared. Chi-squared tests and Student's t-test were calculated. RESULTS: Group A had 19 patients, and Group B had 14 patients. Patient demographics were comparable. Mean age was 52 years, and 70 percent of patients were male. There were no deaths. There were no statistical differences in perioperative morbidity, with three anastomotic leaks in Group A. Tumors were downstaged in 58 percent of patients in Group A and 43 percent of those in Group B (P = 0.61). Nodal downstaging occurred in 78 percent of Group A and 67 percent of Group B (P = 0.9). The pathologic complete response rate was 21 percent in Group A and 14 percent in Group B (P = 0.97), and a residual microfocus of tumor was found in 33 percent of patients in Group A and 42 percent of those in Group B (P = 0.90). These differences were not statistically significant. CONCLUSIONS: Perioperative morbidity is not affected by longer intervals. A longer interval between completion of neoadjuvant chemoradiation and surgical resection may not increase the tumor response rate of advanced rectal cancer in this cohort.     

IMMUNOGLOBULINS IN THE SKIN IN DERMATITIS HERPETIFORMIS AND CŒLIAC DISEASE

The unaffected skin of eighteen patients with dermatitis herpetiformis (D.H.), twenty-two patients with cœliac disease (C.D.), and eight controls were examined using direct immunofluorescence and class-specific fluorescein-conjugated anti-human IgA, IgM, and IgG antisera. All eighteen patients with D.H. showed IgA deposits in the skin: in seventeen the deposits were only found in the dermal papillæ, whilst in one it was found in a continuous line below the basement membrane, confirmed by immuno-electronmicroscopy. IgM deposits were also found in the dermal papillæ in three patients with D.H. and IgG deposits below the basement membrane in one patient. In cœliac disease, however, only one of the twenty-two patients showed papillary IgA deposits and one had continuous IgM deposits. These immunoglobulin deposits in D.H. and C.D. seem to be on the reticulin of the dermal papillæ. It is suggested that in D.H. there is a fault of the reticulin in the skin and small intestine, whilst in cœliac disease it is present in the small intestine but not in the skin. The reticulin cross-reacts with gluten complexes to give rise to an immunological reaction. In support of this hypothesis we have demonstrated cross-reactivity between gluten and reticulin.