Endothelial-monocyte activating polypeptide II, a novel antitumor cytokine that suppresses primary and metastatic tumor growth and induces apoptosis in growing endothelial cells.

Neovascularization is essential for growth and spread of primary and metastatic tumors. We have identified a novel cytokine, endothelial-monocyte activating polypeptide (EMAP) II, that potently inhibits tumor growth, and appears to have antiangiogenic activity. Mice implanted with Matrigel showed an intense local angiogenic response, which EMAP II blocked by 76% (P < 0.001). Neovascularization of the mouse cornea was similarly prevented by EMAP II (P < 0.003). Intraperitoneally administered EMAP II suppressed the growth of primary Lewis lung carcinomas, with a reduction in tumor volume of 65% versus controls (P < 0.003). Tumors from human breast carcinoma-derived MDA-MB 468 cells were suppressed by >80% in EMAP II-treated animals (P < 0.005). In a lung metastasis model, EMAP II blocked outgrowth of Lewis lung carcinoma macrometastases; total surface metastases were diminished by 65%, and of the 35% metastases present, approximately 80% were inhibited with maximum diameter <2 mm (P < 0.002 vs. controls). In growing capillary endothelial cultures, EMAP II induced apoptosis in a time- and dose-dependent manner, whereas other cell types were unaffected. These data suggest that EMAP II is a tumor-suppressive mediator with antiangiogenic properties allowing it to target growing endothelium and limit establishment of neovasculature.

Kaposi's sarcoma following chemotherapy for testicular cancer in a homosexual man: demonstration of cytomegalovirus RNA in sarcoma cells.

A 35-year-old white Jewish homosexual man who had undergone surgery and chemotherapy for an embryonal carcinoma of the testis subsequently developed Kaposi's sarcoma. The neoplasm involved the skin as well as visceral tissues. Tissue derived from a biopsy specimen of one of the skin lesions was used in the in situ hybridization technique for the detection of genetic material. Cytomegalovirus messenger RNA was identified in the neoplastic Kaposi cells in the skin. The significance of this finding is discussed.

Local/regional anesthesia for thyroidectomy: evaluation as an outpatient procedure.

BACKGROUND: The purpose of this paper was to review my evolving experience with local/regional anesthesia in an outpatient setting. METHODS: Two hundred three consecutive patients during a 9-year period who chose to undergo thyroid operation under regional/local anesthesia were reviewed. Early discharge was offered to patients who were observed for 6 hours without neck swelling and who had no surgical reasons for delaying discharge. RESULTS: In group A there were 2 patients who were given inhalation anesthesia during operation compared with none in groups B and C. The average length of stay in group A was 0.49 days, 0.55 days in group B, and 0.24 days in group C. Eighty-five percent of the patients whose operation began before 1300 hours were discharged within 6 hours versus only 50% of those operated on later in the day. Forty-seven percent of patients in group A, 65% of group B, and 77% of patients in group C were discharged within 6 hours of operation. On the basis of previous experience with general anesthesia, discharge time is not significantly influenced by the type of anesthesia chosen. There were no readmissions to the hospital, but 2 episodes of postoperative bleeding required reoperation. Survey showed that 95% of patients rated the level of pain equivalent or less severe than dental procedures under local anesthesia, and all patients would choose local again. CONCLUSIONS: These data suggest that thyroidectomy can be performed with the patient under local/regional anesthesia, with low morbidity and high patient satisfaction. Most patients can be discharged within 6 to 8 hours, and these discharges were not associated with readmissions.

Bilateral neck exploration for parathyroidectomy under local anesthesia: a viable technique for patients with coexisting thyroid disease with or without sestamibi scanning.

BACKGROUND: Bilateral neck exploration (BNE) with the patient under general anesthesia has been the standard for parathyroidectomy. In efforts to minimize invasiveness and recovery from the procedure, unilateral neck exploration with the patient under local anesthesia in combination with sestamibi scanning is being done. Patients with a nonlocalized adenoma, concurrent thyroid disease, and/or multiple parathyroid adenomas have been excluded from this minimally invasive procedure. METHODS: Two hundred thirty-six patients underwent BNE under local anesthesia for primary hyperparathyroidism that was performed by a single surgeon between 1988 and April 1999. RESULTS: The percentage of patients who underwent parathyroidectomy under local anesthesia increased from 3% in 1988 to 97% in 1999. Twenty-three percent of patients underwent a concurrent thyroid procedure, and 84% of patients had a single adenoma removed. Sixty-two percent of patients had a negative preoperative sestamibi scan or did not have a scan at all. The incidence of frozen section decreased in the initial 50 cases from 100% to 39% during the last 100 cases. Average operative time was 43 minutes without a thyroid procedure and 66 minutes with a thyroid procedure. Overall, 70% of patients were discharged within 6 hours of the surgical procedure; this percentage increased to 91% during the last 5 months. CONCLUSIONS: BNE with the patient under local anesthesia can be performed safely and effectively in patients with coexisting thyroid disease and a nonlocalized adenoma.

Incidence of cancer in surgically treated thyroid nodules based on method of selection.

A retrospective review of thyroidectomies to rule out cancer at Columbia Presbyterian Medical Center indicated that the maximum cancer incidence achievable in surgical specimens was only 57% if all microfollicular adenomas and thyroid cancers were removed. The size distribution of follicular cancer and microfollicular adenoma was similar and it does not appear to be useful in deciding which microfollicular lesions need to be surgically excised to exclude carcinoma. The incidence of thyroid cancer in patients undergoing thyroidectomy was not influenced by the introduction of fine-needle biopsy (FNB) at Columbia Presbyterian Medical Center. FNB did appear to increase the incidence of cancer at an affiliated community hospital. Coarse-needle biopsy definitely improved the incidence of cancer in patients undergoing thyroidectomy and was superior to FNB and clinical selection alone. A combination of FNB and coarse-needle biopsy when possible yielded a 41% incidence of cancer and appears to be the most useful technique for patient selection.

Comparison of fine-needle and coarse-needle biopsies in evaluating thyroid nodules.

The purpose of this study was to compare the results of fine-needle biopsy (FNB) and coarse-needle biopsy (CNB) in evaluating patients with dominant thyroid nodules. Five hundred twenty-six patients were seen because of solitary thyroid nodules. Three hundred of these underwent satisfactory CNB and FNB. Using the incidence of cancer found at operation as a guide to the specificity of the biopsy, CNB was better than FNB in determining underlying pathologic condition. The main difference between the two techniques was the inability of FNB to distinguish adenomatous hyperplasia from true adenoma. FNB, however, was as good as most older techniques in selecting patients for surgery. The main limitation of CNB was that it could only be applied on 69% of solid lesions.

Detection of circulating thyroid cells in peripheral blood.

BACKGROUND: Detection of circulating malignant thyroid cells may provide a method to identify postoperative patients at risk for metastatic thyroid cancer. METHODS: On the basis of tissue specificity of thyroglobulin gene expression and the sensitivity of the reverse transcriptase-polymerase chain reaction (RT-PCR) analysis, we performed RT-PCR using primers for thyroglobulin on blood samples from patients with thyroid disease to detect thyroglobulin RNA transcripts. Postoperative peripheral blood samples from 100 patients, including patients with known metastatic thyroid cancer (six papillary and three follicular), thyroid cancer and no evidence of current metastases (63 papillary, 10 follicular, and five patients with both papillary and follicular), benign thyroid disease (six nontoxic nodular goiters), and normal volunteers (seven). RESULTS: Thyroglobulin transcripts were detected in nine of nine patients with metastatic thyroid cancer, seven of 78 patients with thyroid cancer and no current metastases (although of these seven patients, five had a history of metastatic disease that had been previously treated by surgery, one had a coexisting parathyroid cancer, and one had both papillary and follicular thyroid cancers), zero of six patients with benign thyroid disease, and zero of seven normal volunteers. Identity of amplicons was confirmed by restriction enzyme digestion and by cloning and sequencing of RT-PCR amplified thyroglobulin fragment (the latter in a limited number of cases). CONCLUSIONS: These data indicate that RT-PCR can be used to detect thyroglobulin mRNA in peripheral blood. The presence of these transcripts correlates with the existence of extrathyroidal disease.

Surgical treatment of parathyroid disease: a review.

Since the first parathyroidectomy was performed by Mandl in 1925, there have been many advances in our understanding of the parathyroid gland and its related disorders of calcium homeostasis. Our ability to establish the diagnosis of parathyroid neoplasia and locate the source of autonomous parathormone production has also dramatically improved. Nevertheless, it was the advent of the routine calcium and phosphate screening done on the sequential multiple analyzer (SMA-12) that has caused a tremendous increase in the number of patients who are diagnosed to have hyperparathyroidism and who therefore present for surgical treatment. Essential for successful and uncomplicated treatment of this disorder is a thorough understanding of the anatomy, physiology, and pathology of the parathyroid glands. This review will consider the parathyroid glands in their normal state, as well as the diagnosis and management of the various disorders associated with them.

Twenty-five year experience with primary hyperparathyroidism at Columbia Presbyterian Medical Center.

A retrospective review of 500 patients with primary hyperparathyroidism seen from 1951 to 1975 was conducted; the effect of routine screening of calcium and phosphate levels (initiated in 1968) on the incidence and spectrum of the disease was analyzed. The majority of the patients (77%) were diagnosed in the eight-year period after routine biochemical screening was instituted. Comparing the group of patients diagnosed before the advent of biochemical screening and those diagnosed since screening was instituted, we found: (1) a small but significant increase in the number of asymptomatic patients diagnosed (from 2% to 12%); (2) no change in the incidence of related medical disorders, i.e., nephrocalcinosis and hypertension; (3) no change in the incidence of primary hyperplasia and adenoma; and (4) no change in the mean serum calcium level, the mean age at diagnosis, or the number or location of the involved parathyroid glands. Although routine calcium screening has identified significantly more cases of primary hyperparathyroidism, screening apparently does not enable diagnosis at an earlier stage.

Thyroid surgery using monitored anesthesia care: an alternative to general anesthesia.

Forty consecutive patients undergoing thyroid surgery under local anesthesia (LA) by a single surgeon over a 5-year period were included in this retrospective review. In all cases, the indication for LA was patient request. The study included 29 females and 11 males with an average age of 44 years (range 22-66 years). Body habitus was thin in 12.5%, average in 67.5%, and obese in 20%. Operations consisted of 21 unilateral thyroid lobectomies, 3 partial thyroidectomies, 3 subtotal thyroidectomies, and 13 total thyroidectomies. The pathology revealed benign disease in 45% and malignant disease in 55%. All procedures were performed using lidocaine and/or bupivacaine to administer a deep cervical plexus block as well as a field block. Mild additional intraoperative intravenous sedation was provided in most cases. Two patients were converted emergently to general endotracheal anesthesia because of inability to tolerate LA in one and a seizure secondary to intraarterial injection of lidocaine in the other patient. There were no instances of wound infection hemorrhage, recurrent laryngeal nerve injury, or hypoparathyroidism. In conclusion, thyroid surgery in selected patients can be performed safely using LA by experienced surgeons. If patients are carefully prepared preoperatively, LA offers a simple and reasonable alternative to general anesthesia.

Method for biopsy of the wall of a thyroid cyst.

Cystic thyroid lesions can arise from benign and malignant or potentially malignant thyroid tumors that have undergone cystic degeneration. In this paper we described a method for biopsing the wall of these cystic lesions to help determine the underlying pathologic abnormality that leads to cyst formation. Initial results have shown that most cysts arise from benign thyroid disease. Twenty five percent of the cysts, however, did arise from degeneration of thyroid adenomas.

Parathyroid surgery using monitored anesthesia care as an alternative to general anesthesia.

BACKGROUND: Although there have been several reports in the literature describing a renewed interest in performing thyroid surgery under local anesthesia (LA), there has been little information regarding parathyroid surgery under local anesthesia. METHODS: We retrospectively reviewed our experience of 49 LA parathyroid patients over a 9-year period at a single institution. A bilateral cervical block (C2-C3) was administered by a single surgeon using lidocaine and bupivacaine. RESULTS: The study included 39 females and 10 males with an average age of 62 years (range, 35-89 years). Every surgery was curative and the final pathology revealed 46 parathyroid adenomas and 3 cases of parathyroid hyperplasia. Forty-seven percent of the patients were discharged within 6 hours of operation and the remaining patients had a 1.4-day average length of hospital stay. A group of age- and sex-matched controls who underwent parathyroid surgery using general anesthesia (GA) served as a control group with 27% of operations performed as outpatients and an average length of stay of 1.6 days. Return to work averaged 6 days for the LA group versus 8 days for the GA. In the LA group, there was one instance of postoperative hemorrhage requiring reoperation and one instance of conversion to GA secondary to an inability to tolerate LA. There were no instances of recurrent laryngeal nerve injury or permanent hypoparathyroidism in either group. CONCLUSIONS: These data suggest that experienced surgeons can perform parathyroid surgery safely and effectively using LA as an alternative to GA.

Reversal of severe fatty hepatic infiltration after intestinal bypass for morbid obesity by calorie-free amino acid infusion.

Hepatic fatty infiltration complicating jejunoileal bypass can be massive and may require restoration of gastrointestinal continuity. This fatty infiltration appears to be caused by protein depletion associated with adequate or high carbohydrate intake. The present study has shown that calorie-free amino acid alimentation can reverse these changes. In three of thirteen patients who underwent 12 inch to 6 inch jejunoileal bypass procedures, symptomatic hepatomegaly developed with near total replacement of hepatocytes by massive fatty infiltration. After undergoing liver scan, liver biopsy, and liver function tests, the patients were started on a peripheral infusion of 2L per day of a 4.25 per cent crystalline amino acid solution, allowing for fat mobilization while preserving body protein stores. All oral intake was withheld except for water. At the end of a fourteen to twenty-one day infusion period, serum albumin levels increased by 1 gm in all patients. Decreases in liver volume of 83, 45, and 40 per cent occurred. During the infusion period ketonuria was 4 plus in all patients indicating active lipolysis. Weight loss was impressive (17, 19, and 40 pounds). All patients showed marked symptomatic improvement, and postinfusion liver biopsy specimens showed a return to near normal architecture. Maintenance of normal liver size by a high-protein, low-carbohydrate diet was observed in a five to seven month follow-up period. In contrast to previous studies using standard hyperalimentation solutions, the use of calorie-free amino acid solutions reverses the hepatic fatty infiltration seen after intestinal bypass by mobilization of fat. This fat mobilization does not occur as readily in the presence of large amounts of glucose.

The value of coarse needle biopsy in evaluating thyroid nodules.

At Columbia Presbyterian Medical Center, CPMC, the incidence of thyroid cancer found at surgery (CI) has recently changed. CI prior to 1950 was 3-4%. The CI gradually increased to 29% in 1975 without the use of needle biopsy. Fine needle biopsy (FNB) was introduced in 1976. The CI did not change during the next 7 years but remained stable at 27% in patients who did not undergo coarse needle biopsy (CNB). The overall CI using both FNB and CNB in 1982 was 42% and with CNB alone, 47%. Since that time, extensive experience using both CNB and FNB has led to a CI of 51%. The CI in patients who only received FNB remains at 28%. The increase in CI seen in patients undergoing CNB are a result of better distinction between hyperplastic lesions and microfollicular neoplasms. 78 patients, referred for surgery because of suspicion of a follicular neoplasm determined on FNB alone, underwent CNB. 35 of these patients were shown to have benign macro-micro follicular lesions (hyperplastic). In a review of 1,625 patients who have undergone CNB there were 3 complications which required surgical intervention (.018%). All of these were for bleeding 6-72 hours after CNB. These 3 patients underwent total thyroidectomy for follicular cancer without complications. There were no other significant complications. These experiences demonstrate that CNB is extremely useful in evaluating thyroid nodules. The complication rate is low and is offset by a large decrease (40%) in the number of patients referred for operation. The primary value of CNB is in differentiating between true microfollicular neoplasms and hyperplastic ones.

Carcinoembryonic antigen and prognosis in patients with colon cancer.

One-hundred and fifty patients with non-metastatic colo-rectal cancer were followed for a period of 24 to 36 months postoperatively. Preoperative CEA values have been shown to correlate with the extent of the disease and the patient's prognosis. The prognosis for recurrences is greater in patients with elevated pre-operative CEA values regardless of the stage of their disease. This tendency to have recurrences is 1.8 times higher in individuals with increased pre-operative CEA levels. This same relationship occurs to a greater or lesser extent at each stage of the disease.