Robert F. Schaefer

Thromboembolism in patients undergoing thoracotomy

To determine the incidence of thromboembolism in relation to thoracotomy, 77 patients undergoing pulmonary resection were prospectively studied up to 30 days postoperatively for deep venous thrombosis and pulmonary embolism. Overall, 20 of 77 patients (26%) had thromboembolic events during their hospitalization. Four deep venous thromboses and 1 pulmonary embolism were detected in 5 of 77 patients preoperatively for an incidence of 6%. Postoperative thromboembolism was detected in 15 of 77 (19%): deep venous thrombosis in 11 (14%) and pulmonary embolism in 4 (5%). No postoperative thromboembolisms occurred in the 17 patients receiving preoperative aspirin or ibuprofen, whereas they did occur in 25% of the remainder (15/60). Thromboembolism after pulmonary resection was more frequent with bronchogenic carcinoma than with metastatic cancer or benign disease (15/59 [25%] versus 0/18 [0%]; p < 0.01), adenocarcinoma compared with other types of carcinoma (11/25 [44%] versus 4/34 [12%]; p < 0.0004), large primary lung cancer (> 3 cm in diameter) compared with smaller lesions (9/19 [47%] versus 6/40 [15%]; p < 0.0001), stage II compared with stage I (7/14 [50%] versus 7/34 [21%]; p < 0.04), and pneumonectomy or lobectomy compared with segmentectomy and wedge resection (14/49 [29%] versus 1/28 [4%]; p < 0.005). Three of 4 patients with thromboembolism detected preoperatively had operation within the previous year. Postoperative pulmonary embolism was fatal in 1 of 4 (25%) and accounted for the one death. These results suggest patients undergoing thoracotomy for lung cancer, especially adenocarcinoma, should be considered for thromboembolic prophylaxis.

Inhibitory effect of candesartan and rosuvastatin on CD40 and MMPs expression in Apo-E knockout mice: Novel insights into the role of RAS and dyslipidemia in atherogenesis

Background: There is increasing evidence of cross-talk between renin-angiotensin system (RAS) and dyslipidemia in atherogenesis mediated via activation of inflammatory cascade, involving CD40 and matrix metalloproteinases (MMPs). We postulated that inhibition of RAS with candesartan and dyslipidemia with rosuvastatin would have additive inhibitory effect on CD40 and MMPs expression and atherogenesis. Methods and Results: Apo-E knockout mice were fed high-cholesterol diet alone, or with candesartan or rosuvastatin or both. C57BL/6J mice on regular mice chow served as control. Twelve weeks later, apo-E knockout mice with high-cholesterol diet had extensive atherosclerosis, whereas C57BL/6J mice had no atherosclerosis. Candesartan and rosuvastatin alone decreased the extent of atherosclerosis. However, the combined feeding of candesartan and rosuvastatin reduced atherosclerosis in an additive fashion. The expression of CD40 and MMPs was found to be up-regulated in apo-E knockout mice. While candesartan and rosuvastatin each had a small inhibitory effect on the expression of CD40 and MMPs, the combination completely blocked the up-regulation of these inflammatory mediators. Conclusion: This study, for the first time, demonstrates that the combination of candesartan and rosuvastatin markedly affects the expression of CD40 and MMPs, resulting in a greater anti-atherosclerotic effect.

Prevention of chronic radiation enteropathy by dietary glutamine

AbstractBackground: Nearly 50% of all cancer patients receive therapeutic radiation during the course of their disease. The risk of late complications is the main dose-limiting factor in the delivery of radiation therapy. The small intestine, the major site of chronic radiation enteropathy, is also the principal organ of glutamine consumption. We therefore hypothesized that the provision of supplemental glutamine may have a protective effect on the development of chronic radiation enteropathy. Methods: This study evaluated the effects of supplemental oral glutamine on the development of chronic radiation (XRT) enteropathy. After scrotalization of a loop of small intestine, rats were randomized to receive 1 g/kg/day glutamine (GLN) or glycine (GLY) by gavage. After 2 days of prefeeding, rats were randomized to 1 of 4 groups: GLN + XRT (n=10), GLY + XRT (n=10), GLN only (n=10), GLY only (n=10). Twenty Gy was delivered to the scrotalized bowel in the GLN + XRT and GLY + XRT groups via a collimated beam. Gavage was continued for 10 days. Animals were then pair-fed chow. Rats were killed at 2 months postirradiation. Chronic radiation injury was assessed microscopically. Results: Injury scores in GLN + XRT were similar to those of unirradiated bowel and significantly different from GLY + XRT (1.89 ± 0.48 in XRT + GLN vs. 6.42 ± 1.55 in the XRT + GLY,p<0.01). Elevated Injury Scores in the XRT + GLY group correlated with gross thickening and fibrosis, a 10-fold decrease in gut GLN extraction (1.40 ± 4.3% in GLY + XRT vs. 16.0 ± 5.1% in GLN + XRT,p<0.05), and a 30% decrease in glutathione content (2.46 ± 0.19 and GLY + XRT vs. 3.17 ± 0.17 GLN + XRT,p<0.05). Conclusions: Provision of GLN during abdominal/pelvic XRT may prevent XRT injury and decrease the long-term complications of radiation enteropathy.

Segmental pulmonary resection for cancer

Segmental pulmonary resection was employed in 61 patients with cancer whose ages ranged from 44 to 82 years (average 62 years). There were 39 patients in the curative group with disease staged T1N0M0, 9 patients in the limited group with residual thoracic disease, 8 patients in the palliative group with severe chronic obstructive pulmonary disease, and 5 patients in the metastatic group. Two patients died within 30 days after operation. Significant palliation was obtained in the limited and metastatic groups. Most patients in the palliative group died from emphysema within 1 to 2 years after resection. Early survival rates (64 percent after an average of 16 months) in the curative group were not as good as had been anticipated because small peripheral, asymptomatic, and predominantly scar adenocarcinoma spread systemically more than similar bronchogenic cancer. Furthermore, about half the deaths were related to the many other diseases of smoking. However, the local recurrence rate of 5 percent was low. Segmentectomy was well tolerated, even in patients with compromised pulmonary function.

INCREASED PROSTATIC LYSOPHOSPHATIDYLCHOLINE ACYLTRANSFERASE ACTIVITY IN HUMAN PROSTATE CANCER:: A MARKER FOR MALIGNANCY

PURPOSE Phospholipase A2 and lysophosphatidylcholine acyltransferase (LAT) constitute a deacylation-reacylation cycle that incorporates arachidonic acid into the lipid membrane. In a preliminary report we found increased LAT activity in malignant prostate tissue. We measured LAT activity in prostate tissue from a large number of patients undergoing prostatectomy. MATERIALS AND METHODS Prostate tissue from 93 patients undergoing radical prostatectomy for prostate carcinoma, 14 undergoing cystoprostatectomy for bladder cancer, 55 undergoing transurethral resection for benign prostatic hyperplasia and 11 with prostate cancer undergoing transurethral resection for relief of obstructive symptoms was analyzed for LAT activity. RESULTS In radical prostatectomy specimens using oleoyl coenzyme A as substrate mean increase in LAT activity between malignant and benign portions of the same specimen was 0.68 +/- 0.12 nmol./mg. protein per minute (p <0.00001). In all radical prostatectomy specimens analyzed LAT activity was 43% higher in the malignant than benign portions (2.25 +/- 0.15 versus 1.57 +/- 0.11 nmol./mg. protein per minute, p <0.001). In the 10 benign prostate specimens obtained from cystoprostatectomy mean LAT activity was 1.12 +/- 0.18 nmol./mg. protein per minute, which was significantly lower than that of benign portions of radical prostatectomy (p <0.05). LAT activity in benign cystoprostatectomy specimens was significantly higher than that in the 50 benign transurethral resection specimens (0.54 +/- 0.05, p <0.01), possibly due to heat damage in transurethral resection specimens during collection. However, LAT activity in transurethral resection specimens from patients with known prostate cancer was similarly increased. Similar results were obtained using arachidonoyl coenzyme A. CONCLUSIONS We demonstrated increased LAT activity in malignant tissue from patients with prostate cancer. Thus, the deacylation-acylation remodeling cycle may be enhanced to provide more arachidonic acid to meet the demand for prostaglandin E2 synthesis in malignant tissue.

When is polypectomy sufficient treatment for colorectal cancer in a polyp

Eighty-seven patients with a carcinoma in a polyp were reviewed over a 12-year period. Ten histologic criteria were analyzed for an association with the presence of residual carcinoma. Four factors were identified as having prognostic value: size greater than 1.5 cm, sessility, cancer of at least 50% of the adenoma volume, and invasive carcinoma. Polypectomy alone is adequate treatment unless the carcinoma invades deeper to the muscularis mucosa and is associated with one or more of these characteristics.

Neurotoxic Effects of Doxycycline Sclerotherapy

A patient experienced phrenic nerve paralysis after doxycycline sclerotherapy for treatment of chylous fistula at our institution. The purpose of this study is to use physiologic testing to determine whether doxycycline is capable of inducing defects in neural function. A nonrandomized, controlled trial was performed with nerve-conduction studies to determine possible deleterious effects of doxycycline sclerotherapy. Thirty-eight CD rats were used and separated into four groups. Doxycycline was applied to the sciatic nerves of rats by either topical application directly on the nerve or by intraneural injection. Nerve-conduction studies were done before surgery and at 1,7, and 21 days after surgery. The results showed a statistically significant decrement in nerve-conduction velocity and strength of transmitted impulse in those nerves injected with doxycycline solution. Complete nerve block was seen frequently. This effect was not seen with topical application of doxycycline or normal saline solution or with intraneural injection of normal saline solution. This study demonstrates that doxycycline can induce a marked decrement in neural function when applied to the subepineural layers of the sciatic nerve in the rat. Therefore doxycycline sclerotherapy should be used with great caution in situations in which it could become exposed to nerves that have sustained surgical trauma.

Severe colitis due to Strongyloides stercoralis in a patient with cutaneous Kaposi's sarcoma

Strongyloides stercoralis is an intestinal nematode endemic to the United States. Infection with Strongyloides is frequently asymptomatic or characterized by chronic mild gastrointestinal symptoms. 1 Hyperinfection syndrome and disseminated S. stercoralis are well described in immunocompromised patients.2-6 In addition to the ability to disseminate widely, Strongyloides is unique in that it may reside in the host and produce clinical illness for 30 or more years after exposure. The life cycle of Strongyloides is responsible for these characteristics.,9 We present a case of severe colitis secondary to Strongyloides occurring in a patient without evidence of dissemination. In addition, Strongyloides was shown to be present at the time of a major lower gastrointestinal hemorrhage in the same patient 10 months earlier.

Histologic effect of doxycycline sclerotheraphy on rat femoral nerve

This study stems from an encounter with a phrenic nerve paralysis in a patient following doxycycline sclerotherapy for treatment of chylous fistula. The purpose of this study is to identify possible histologic evidence of doxycycline‐induced nerve injury.

Urethral verumontanal polyp: Evidence of prostatic origin

A papillary adenomatous polyp of the verumontanum was studied morphologically and immunochemically. This rare polypoid neoplasm displayed rather typical prostatic acinar epithelium, and by immunoperoxidase method differentiation products of prostatic origin could be demonstrated easily. Findings support the concept that this type of lesion is prostatic in origin and probably arising from ectopic prostatic tissue in the prostatic urethra. The clinical symptoms of this lesion usually are hematospermia or hematuria, and this lesion can be effectively treated by transurethral excision.