Lewis, Bradley

Abstract Background: Anemia is an extremely prevalent disease and contributes to a substantial percentage of worldwide years lived with disability. Clinicians generally agree that investigation of the gastrointestinal (GI) tract with colonoscopy and/or endoscopy is warranted in the presence of either overt clinical evidence of GI bleeding or in the presence of documented iron deficiency. However, little is known about the appropriateness of these procedures in the evaluation of patients without either overt GI bleeding or iron deficiency. Additionally, while a large number of colonoscopies and endoscopies are performed each year, the proportion of such procedures performed in the absence of suspect history or findings has not been characterized. Methods: We performed a retrospective review of all patients at Mayo Clinic Rochester who underwent endoscopy, colonoscopy, or both procedures between July 1, 2014 and June 30, 2015 for an indication of either "anemia" or "iron deficiency anemia." Sources of data included provider notes, laboratory values, procedure notes, and pathology reports. Information including patient demographic characteristics, medical comorbidities, laboratory values related to anemia, findings at the time of gastrointestinal procedure, and procedure-related complications was collected. Data was entered into an electronic database and data analysis was performed using Microsoft Excel. Results: 999 procedures were included, including 224 colonoscopies, 306 endoscopies, and 469 combined colonoscopy/endoscopies. Of the 999 total procedures, 78 (8%) had no documented pre-procedure hemoglobin value, 666 (67%) were performed after documented anemia (defined as hemoglobin ≤12 g/dL), and 255 (26%) were performed after a documented hemoglobin of >12 g/dL. Of the 675 procedures performed for "iron deficiency anemia," 462 (68%) patients had documented anemia and documented ferritin prior to the procedure, including only 237 (35%) with both hemoglobin ≤12 and ferritin ≤ 20. 388 (39%) had a documented pre-procedure patient and/or provider report of blood in the stool, and 111 (11%) had a documented pre-procedure positive hemoccult test. 365 (37%) of the 999 procedures identified a probable benign source of bleeding, 54 (5.4%) identified a probable malignant source, and 580 (58%) had no findings consistent with a bleeding source. Patients with documented anemia were more likely to have a probable bleeding source identified than those without documented anemia [46% versus 34%, p<.001]. Of the 83 patients with hemoglobin >12 and ferritin >20, only 1 procedure in 83 demonstrated a malignant finding, and this patient did have blood in the stool at the time of the procedure. There were 46 patients who underwent a procedure without any "warning signs" (either anemia and/or blood in the stool and/or positive hemoccult). Of these patients, 0 had a malignant finding. Conclusions: A large number of procedures performed for either "anemia" or "iron deficiency anemia" were done without pre-procedure documentation of anemia and/or iron deficiency. Documentation of anemia is associated with an increased chance of finding a source of bleeding during the procedure. There were no missed diagnoses of malignancy among patients undergoing procedures without anemia, blood in the stool, and/or positive hemoccult. Careful attention to documentation should be encouraged, and quality improvement initiatives requiring appropriate documentation prior to performing these procedures may be helpful. Disclosures No relevant conflicts of interest to declare.

PURPOSE: We have completed a phase I study, followed by three phase I/II studies, in patients with metastatic melanoma, renal cell carcinoma (RCC), and sarcoma in order to evaluate the safety, toxicity, and antitumor activity of Leuvectin (Vical Inc, San Diego, CA), a gene transfer product containing a plasmid encoding human interleukin (IL)-2 formulated with the cationic lipid 1,2-dimyristyloxypropyl-3-dimethyl-hydroxyethyl ammonium bromide/dioleyl-phosphatidyl-ethanolamine (DMRIE/DOPE) and administered intratumorally. PATIENTS AND METHODS: Twenty-four patients were treated in the phase I study. Leuvectin doses were 10 μg, 30 μg, or 300 μg weekly for 6 weeks. In three subsequent phase I/II studies, a total of 52 patients (18 with melanoma, 17 with RCC, and 17 with sarcoma) were treated with further escalating doses of Leuvectin: 300 μg twice a week for 3 weeks, 750 μg weekly for 6 weeks, and 1,500 μg weekly for 6 weeks. RESULTS: There were no drug-related grade 4 toxicities and only one grade 3 toxicity, but the majority ofpatients experienced mild constitutional symptoms after treatment. In the phase I/II studies, 45 patients were assessable for response (14 with RCC, 16 with melanoma, and 15 with sarcoma). Two patients with RCC and one with melanoma have achieved partial responses lasting from 16 to 19 months and continuing. In addition, two RCC, three melanoma, and six sarcoma patients had stable disease lasting from 3 to 18 months and continuing. The plasmid was detected by polymerase chain reaction assay in the posttreatment samples of 29 of 46 evaluated patients. Immunohistochemistry studies on serial biopsy specimens showed increased IL-2 expression and CD8+ infiltration after treatment in the tumor samples of several patients (12 and 16, respectively). CONCLUSION: Direct intratumoral injection of Leuvectin is a safe and possibly effective immunotherapeutic approach in the treatment of certain tumor types.

Previous results following subfascial endoscopic perforator vein surgery were reported to be worse in post-thrombotic syndrome than in limbs with primary valvular incompetence. This report comprises a larger patient cohort with longer follow-up. The goal of this study was to determine if subfascial endoscopic perforator vein surgery is justified in patients with postthrombotic venous insufficiency. The clinical data of 91 consecutive patients who underwent subfascial endoscopic perforator vein surgery with or without superficial reflux ablation over a 7-year period from May 1993 to June 2000 were retrospectively analyzed. Fifty-four females and 37 males (median age, 53 years; range, 20-77) underwent 103 subfascial endoscopic perforator vein surgery procedures. Forty-two limbs were classified as C6 (active ulcer), 34 as C5 (healed ulcer), and 24 as C4 (lipodermatosclerosis). Thirty procedures were performed in post-thrombotic limbs. Concomitant superficial reflux ablation was performed in 74 limbs (72%); saphenous vein stripping had been previously performed in 29 (28%). Deep venous incompetence was present in 89% of limbs; 13% had venous outflow obstruction on plethysmography. Cumulative ulcer healing in post-thrombotic limbs was not significantly different from limbs with primary valvular incompetence; 30-, 60-, and 90-day healing rates were 44%, 72%, and 72% vs 39%, 70%, and 87%, respectively (p = 0.35). On univariate analysis, the presence of ulcer greater than 2 cm in diameter was associated with delayed ulcer healing (p = 0.02). Cumulative ulcer recurrence in all limbs was 4%, 20%, and 27% at 1, 3, and 5 years, respectively. Ulcer recurrence in post-thrombotic limbs was higher than in limbs with primary valvular incompetence at 1, 3, and 5 years; 16%, 47%, and 56% vs 0%, 8%, and 15%, respectively (p = 0.001). Recurrent ulcers were small, superficial, and easier to heal. Clinical improvement was significant even in post-thrombotic limbs; median clinical score decreased from 9.5 to 3 (p=0.001), and median outcome score was +2 (mean 1.9; range, -I to 3). Median clinical score in patients with primary valvular incompetence improved from 6 to 1.5 (p = 0.0001). Subfascial endoscopic perforator vein surgery with superficial reflux ablation promoted ulcer healing, improved clinical outcome, and resulted in a low long-term ulcer recurrence rate in limbs with primary valvular incompetence. Despite good clinical outcome in post-thrombotic limbs, ulcer recurrence was high. These results imply that the role of subfascial endoscopic perforator vein surgery with superficial reflux ablation in patients with post-thrombotic limbs continues to be controversial.

The purpose of this study was to examine the technical aspects of intraoperative duplex ultrasound (DUS) following carotid endarterectomy (CEA), suggest criteria to differentiate significant lesions requiring immediate surgical revision from normal or benign defects, and evaluate how frequently intraoperative DUS provides useful or unsuspected information. A retrospective study was performed on all patients who had both CEA and intraoperative carotid DUS between January 1,1990. and January 1,1995. A total of 155 DUS examinations were performed in 149 patients. Findings were grouped into three categories: normal; minor/insignificant lesions; and hemodynamically significant lesions based on the presence or absence of elevated peak systolic velocities, visible stenosis/thrombus, or intimal flap/dissection. Postoperative status was correlated with intraoperative DUS findings. Ninety-one (59%) examinations performed on 87 patients produced normal findings. Forty-seven (30%) examinations performed on 45 patients showed minor abnormalities consisting of insignificant residual plaque, residual external carotid artery stenoses, small intimal flaps, elevated velocities with no associated anatomic lesion, or an arterial kink. Fourteen patients (9%) had significant findings requiring immediate surgical revision. These consisted of large intimal flaps or dissection in six patients, marked residual plaque and significant stenosis in five patients, thrombus in two patients, and a kink in one patient. Three additional patients ( 2 %) had significant findings but were not revised for various reasons. No significant difference was identified in morbidity or mortality rates between those patients with normal findings, those patients with minor technical defects, and those patients with significant abnormalities undergoing immediate surgical revision. However, two of three patients who had significant abnormalities within the common carotid artery that were not revised suffered perioperative ipsilateral strokes. Intraoperative DUS is a safe and accurate method to assess the technical adequacy of CEA. Intraoperative DUS showed significant lesions in 11% of patients. Identification and immediate repair of significant technical defects may decrease perioperative complication rate and long-term restenosis rate.