Role of sample adequacy in fine needle aspiration biopsy of palpable breast lesions.

BACKGROUND: The role of fine needle aspiration biopsy (FNAB) in breast lesions remains uncertain because its accuracy has been questioned. We hypothesized that this is related to failure to define standards for adequacy of sample preparation. METHODS: We reviewed cytology and pathology reports from 351 patients undergoing FNAB at a 350-bed community, university-affiliated teaching hospital over a 2-year period. Patients were included if they had an open biopsy within 2 years of an FNAB of the same lesion. Cytology reports were reviewed by a cytopathologist unaware of the clinical setting or subsequent histology; surgeons unaware of the cytology reports reviewed histology reports. Cytological diagnoses were benign, likely benign, probable cancer, and definite cancer. Samples were characterized as satisfactory, less than optimal (few mammary epithelial clusters), or inadequate (no mammary epithelial clusters.) We assessed the proportion of inadequate samples, the accuracy of FNAB, and the influence of sample adequacy upon FNAB sensitivity. RESULTS: Ninety-nine (28%) FNABs were inadequate, 77 (22%) less than optimal, and 175 (50%) satisfactory. Ninety-five patients (27%) had a final diagnosis of malignancy. FNABs classified as satisfactory or less than optimal and characterized as benign (n = 102) had a negative predictive value (NPV) of 0.91; those termed definite cancer (n = 43) had a positive predictive value (PPV) of 0.98. Only 10% of all cancers were identified in the 28% of FNABs that were classified as inadequate (P <0.01). CONCLUSIONS: We concluded that too few FNABs are performed in a fashion that permits definitive cytological interpretation. Inadequate FNABs are less likely to detect malignancy. After excluding inadequate preparations, FNABs interpreted as definite cancer and as benign are highly accurate in identifying patients with and without cancer.

Laparoendoscopic approaches to occult gastrointestinal bleeding.

Identification of sites of small bowel hemorrhage remains a difficult problem. Endoscopy performed in association with surgery often proves successful when other attempts have failed. In attempts to minimize morbidity and even increase accuracy, surgeons have explored combining laparoscopic techniques with endoscopy. Although published experiences remain few, expectations remain high.

Variable expressivity of familial medullary thyroid carcinoma (FMTC) due to a RET V804M (GTG-->ATG) mutation.

BACKGROUND: Multiple endocrine neoplasia type 2 (MEN 2) and familial medullary thyroid carcinoma (FMTC) are autosomal dominantly inherited cancer syndromes that predispose to C-cell hyperplasia and MTC. MEN 2A and FMTC are caused by mutations in the RET proto-oncogene. METHODS: We used a multiplex polymerase chain reaction-based assay to screen exons 10, 11, 13, and 14 of RET for mutations in 2 families with FMTC. We correlated mutation status with calcitonin and pathologic studies to determine genotype-phenotype correlations. RESULTS: We identified a mutation in codon 804 in exon 14 (GTG-->ATG; V804M) in both families. An 86-year-old person who was a gene carrier and other individuals over age 70 who were suspected by pedigree analysis to be gene carriers had no overt clinical evidence of MTC. Four of 21 patients who underwent a thyroidectomy also had papillary thyroid cancer. One individual in each family had metastatic MTC at age 30 and 32 years, and all 26 people having thyroidectomies had either MTC or C-cell hyperplasia, leading us to continue to recommend prophylactic thyroidectomy for all identified patients who were gene carriers. CONCLUSIONS: Because of active MTC in younger members of these families, including metastases, we have continued to advocate thyroid surgery in mutation-positive individuals. While DNA diagnosis of gene carriers and subsequent genetic counseling was relatively straightforward, the acceptance of surgical recommendations was more difficult for some individuals. These families demonstrate that the search for RET mutations should include exons 13, 14, 15, and 16 in patients whose studies in exons 10 and 11 are negative.

Relationship between method of detection of breast cancer and stage of disease, method of treatment, and survival in women aged 40 to 49 years.

The optimal breast cancer screening program for women 40 to 49 years of age remains controversial. To help assess the value of screening mammography for this age group, we studied the relationship between the method of breast cancer detection and stage, therapy, and survival. Cases of breast cancer diagnosed at Sinai Hospital (Detroit, MI) between January 1985 and December 1994 were reviewed. A total of 181 cases involving 40- to 49-year-old women were available for analysis. The distribution of stage of disease significantly differed among the three methods of detection (P<0.0001). Breast-conserving surgery was more commonly performed in cases detected by screening mammography and clinical breast examination than in cases detected by breast self-examination (P = 0.001). Variation in the stage of disease resulted in improved survival for cases detected by screening mammography and clinical breast examination when compared with those detected by breast self-examination (P = 0.019). Women diagnosed with breast cancer between the ages of 40 and 49 years had earlier stage disease, were more likely to be treated with breast-conserving therapy, and had better survival if their disease was first recognized by screening mammography. Screening mammography has an important role for women of this age.

Effect of chronic vitamin D infusion upon in vivo glucose disposal.

We have previously demonstrated that parathyroid hormone (PTH) infusion decreases glucose disappearance rate (Kg) in vivo. Because in the rodent model used it was not possible to determine whether the PTH itself, the induced hypercalcemia, or both contributed to the glucose intolerance, we examined the effect of vitamin D infusion on insulin-mediated glucose disposal. In this model also hypercalcemia is induced but PTH levels are suppressed. Thirty male Sprague Dawley rats were continuously infused with vit D for 5 days using an Alzet miniosmotic pump, at a rate of 9.7 pmol/hour. Thirty controls were infused with the vehicle alone. On the 5th day, glucose 700 mg/kg and insulin 0.35 U/kg were given as a bolus through the left femoral vein and blood samples were obtained from the right femoral vein just prior to and at 2, 5, 10, and 20 minutes post-glucose/insulin infusion. At the end of 5 days, plasma calcium levels were higher in the vit D-infused rats than in the control rats (12.8 +/- 0.1 versus 10.0 +/- 0.1 mg/dL, P < 0.01) and rat PTH levels were suppressed (2.1 +/- 0.1 versus 62 +/- 12 pg/ml, P < 0. 01). Glucose levels were higher in the vit D animals only at 5 minutes following glucose/insulin bolus (375 +/- 7 versus 350 +/- 6 mg/dL, P < 0.01) but at no other time. There were no differences between serum insulin levels at any time. Unlike previous findings in PTH-infused rats, Kg (measured from 2 to 20 minutes following glucose/insulin bolus) was not different between groups (4.5 +/- 0.3 versus 4.7 +/- 0.2, P = 0.92.) A positive correlation between serum calcium and serum glucose was found only at 5 minutes (r = 0.55, P < 0.01) and only in the vit D animals. The areas under the glucose curves approached statistically significant differences (vit D-infused 5258 +/- 142 mg/dL/18 minutes versus control 4947 +/- 127, P = 0.06.) Analysis of serum glucose data by two-factor analysis of variance (ANOVA) suggests that the two groups differ slightly in glucose values (P = 0.03) but have parallel Kg. In order to define whether different effects of PTH (1-34) and vit D on intracellular calcium [Ca2+]i levels could partly explain the different effects of PTH and vit D infusion on glucose disposal, we investigated the effect of PTH and vit D infusions on basal and concanavalin A (con A)-stimulated changes in mononuclear [Ca+2]i levels. Following 5 days of PTH, vit D, or control infusion, peripheral mononuclear cells were incubated with 50 microgram/ml con A. Changes in [Ca+2]i over 5 minutes were calculated by flow cytometric measurement of the calcium sensitive fluo-3 AM dye. Despite achieving significant and comparable degrees of hypercalcemia in the PTH and vit D infused animals, there were no differences in basal or con A-stimulated [Ca+2]i levels from control. Consequently, we conclude that vit D-induced hypercalcemia associated with suppressed PTH levels has mild affects on glucose homeostasis but does not affect glucose disappearance rate in vivo (Kg) as does hypercalcemia induced by PTH infusion, and that neither chronic PTH infusion nor chronic vit D infusion are associated with long-standing changes in [Ca2+]i levels.

Laparoscopic repair of abdominal hernias using an ePTFE patch--a modification of a previously described technique.

BACKGROUND: A variety of laparoscopic procedures for the repair of abdominal wall hernias have been described. The repair described in this paper represents a modification and improvement of one approach. METHODS: Our technique employs an Origin Tacker (Origin Medsystems, Inc, Menlo Park, CA) and a Gore suture passer (W. L. Gore, Flagstaff, AZ) to secure an expanded polytetrafluoroethylene (ePTFE) patch, (DualMesh, W. L. Gore, Flagstaff, AZ) to the anterior abdominal wall. RESULTS: This approach simplifies the repair by minimizing the number of steps required to secure the ePTFE graft to the anterior abdominal. CONCLUSIONS: We have found this to be a safe and reliable technique that may be used in the laparoscopic repair of ventral, umbilical, or inguinal hernias.

Cholecystogastrocolonic fistula with intrahepatic abscess: a rare complication of biliary stone disease.

A 52-year-old woman exhibited both a cholecystogastrocolonic fistula and intrahepatic abscess. Biliary-enteric fistulas are unusual complications of gallstone disease, and multiple, complex fistulas are extremely uncommon. Hepatic abscesses are also unusual complications of gallstone disease. The combination of a complex biliary-enteric fistula and hepatic abscess arising from gallstone disease has not been reported. In our patient, surgery was prompted by the hepatic abscesses; the fistula was not recognized preoperatively. We elected to resect gallbladder, gastric antrum, and transverse colon en bloc with primary closure of the gastric defect and, because the colon had not been "prepped," we created a right transverse colostomy and left mucus fistula. Under ideal circumstances, the anatomy of biliary fistulas is characterized preoperatively and managed definitively with a single procedure.

Parathyroid hormone and parathyroid hormone-related peptide in venous umbilical cord blood of healthy neonates.

Objective of this study was to assess the role umbilical cord serum parathyroid hormone (PTH), and parathyroid hormone-related peptide (PTH-RP) may play in maintaining the maternal-fetal calcium (Ca) gradient. PTH and PTH-RP and total and ionized Ca levels were measured in blood samples of 20 neonates immediately after birth. Maternal peripheral blood total Ca was measured simultaneously. Mothers were free of hypertension, diabetes or Ca disorders. Neonates were healthy term babies with Apgar scores of eight or greater at one and at five minutes post delivery. PTH was measured using an immunoradiometric double antibody assay that recognizes intact PTH (1-84). PTH-RP was measured by an immunoradiometric double antibody assay that recognizes only PTH-RP (1-74). There was no overlap between the two assays. Ca levels in the neonates were higher than those in their mothers (p < 0.01), confirming a maternal-fetal Ca gradient. However in 18 out of 20 neonates PTH levels in cord blood were below the detection limit (3 pg/ml) and PTH-RP levels also were below detection limit (0.2 pmol/L). PTH-RP and PTH levels in the other two neonates were 0.5 and 0.6 pmol/L (PTH-RP) and 3 pg/ml (PTH) which are in the low normal range for normal adults. We conclude that these data do not support a role for either PTH or PTH-RP in venous cord blood in maintaining the maternal-fetal Ca gradient. They are, however, compatible with a paracrine role for these hormones.

Effect of patient position upon success in placing central venous catheters.

BACKGROUND: There is little consensus regarding the most efficient or the safest method by which to place a central venous catheter (CVC). METHODS: A single house officer prospectively evaluated 140 patients for whom he was requested to place CVCs. One hundred and eight patients participated in a randomized study of positioning. Of the 140 patients, 7 had emergency line placement; 105 randomized patients undergoing elective CVC placement form the basis for this report (power > 80% to detect change of one needle pass between groups). Patient positions were termed "bump" (head turned to the contralateral side and a rolled towel placed vertically between the scapulas) and "no bump" (head facing forward and no towel placed in the back.) RESULTS: Ninety-three of 105 patients had successful catheter placement. Catheters were more often successfully introduced in the bump group than no bump group (98% versus 83%, P < 0.04). For patients with difficult CVC placement (those > 160 pounds, those with a weight-to-height ratio > 29, those with previous unsuccessful catheterization), the bump position was superior with respect to increased likelihood of venous blood return, decreased likelihood of arterial blood return, and increased likelihood of successful catheterization, although differences did not reach statistical significance (P < 0.05) in individual analyses. Of patients with successful catheterization, 97% had three or fewer needle passes. Those with more than three needle passes were less likely to have successful catheter placement (P < 0.01), were more likely to have arterial blood return (P < 0.01) and pneumothorax (P = 0.12). CONCLUSIONS: The bump position improves the likelihood of successful central venous catheter placement. No more than three needle passes ought to be attempted.

Parathyroid hormone decreases in vivo insulin effect on glucose utilization.

Hyperparathyroidism is associated with impaired glucose tolerance, and parathyroidectomy may improve carbohydrate homeostasis. It has been suggested that parathyroid hormone (PTH) suppresses insulin secretion but it is unclear whether it also interferes with the peripheral action of insulin. To evaluate in vivo effects of PTH on insulin-mediated glucose utilization, 15 male Sprague Dawley rats were continuously infused with rat PTH (1-34) using an Alzet miniosmotic pump at a rate of 0.03 nm/hour. Controls were infused with the vehicle alone. Following 5 days of PTH infusion, plasma calcium (Ca) levels were higher in the PTH-infused rats (12.3 +/- 0.2 versus 9.9 +/- 0.1 mg/dl, P < 0.01). On the 5th day, glucose (700 mg/kg) and insulin (0.175 U/kg) were given as a bolus infusion through the left femoral vein, blood samples were obtained from the right femoral vein, and plasma glucose and insulin were measured at basal (0 minutes) and at 2, 5, 10, and 20 minutes postinfusion. Basal, nonfasting glucose levels were higher (166 +/- 4 versus 155 +/- 4 mg/dL, P < 0.04) in the PTH-infused rats but their insulin levels were similar to those of controls (6.5 +/- 0.6 versus 5.6 +/- 0.5 ng/ml). Postinfusions and maximal (2 minutes) glucose and insulin levels were similar in both groups. However, although insulin levels were similar in both groups at all measured time points, glucose levels at 20 minutes were higher in the PTH-treated rats (205 +/- 13 versus 173 +/- 9; P < 0.03).(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of long-term lithium infusion on normal parathyroid tissue.

BACKGROUND: Approximately 10% of patients taking lithium for manic-depressive disorders become hypercalcemic. It remains unclear whether lithium initiates disease or promotes underlying hyperparathyroidism. We have previously demonstrated that at therapeutic concentrations lithium stimulates in vitro incorporation of both tritiated thymidine and bromodeoxyuridine into abnormal human parathyroid tissue, reflecting growth-promoting properties. Whether lithium has similar growth-promoting properties in normal parathyroid tissue remains unresolved. METHODS: We infused lithium (0 mmol/L, 3 mmol/L, or 10 mmol/L) through implantable subcutaneous pumps into normal rats for 3 months and measured levels of serum lithium, serum calcium, and serum parathyroid hormone (PTH) (with a radioimmunoassay specific for rat PTH 1-34.) On completion of the infusion, bromodeoxyuridine (30 mg/kg) was administered intraperitoneally. The parathyroid glands were removed and measured in two dimensions to calculate gland volume [V = (pi/6) x (d1) x (d2)2.] Parathyroid incorporation of bromodeoxyuridine was assessed by using immunocytochemistry. RESULTS: Serum lithium level was significantly (p < 0.05) different between groups and constant within groups. Levels of serum calcium and PTH were inversely related to each other; however, no significant differences were noted between groups with respect to level of serum calcium or serum PTH at any measurement. Similarly, no significant differences were noted between groups with respect to gland size or number of bromodeoxyuridine-positive cells. CONCLUSIONS: Long-term lithium infusion in rats for a period representing approximately 15% of their life span failed to evoke changes in parathyroid gland size or function. These data are consistent with (1) lithium as a promoter of hyperparathyroidism and (2) resection of abnormal parathyroid tissue and resumption of lithium for patients requiring long-term therapy.

Laparoendoscopy (laparoscopy assisted enteroscopy) and partial resection of small bowel.

We investigated laparoendoscopy (laparoscopy-assisted small bowel enteroscopy) as an aid in managing the challenging diagnostic problem of occult small bowel hemorrhage. We performed laparoendoscopy on five nonconditioned dogs and five conditioned dogs. In each case, we laparoscopically inspected the small bowel from the ligament of Treitz to the ileocecal valve. Small bowel was exteriorized, an enterotomy was performed, and an Olympus CL-100L colonoscope was inserted and advanced proximally to the stomach and distally to the ileocecal valve. A segment of small bowel was arbitrarily designated as the site of bleeding, was exteriorized, and was resected. Bowel continuity was restored with a stapled anastomosis. The animals were euthanized and autopsied immediately after the procedure (n = 5) or a week following the procedure (n = 5), at which time the anastomoses were tested for leakage and patency. The entire small bowel was visualized in all animals. There were no anastomotic leaks. Laparoendoscopy may be of value in identifying and treating hemorrhagic origin of small bowel. Clinical trials are warranted.

A two-person, two-handed technique for laparoscopic cholecystectomy.

This manuscript describes a technique of laparoscopic cholecystectomy which permits the surgeon to use both hands. The technique can be modified to accommodate both right- and left-handed surgeons. Advantages we have appreciated in performing over 100 procedures in this manner include a less crowded operating environment, a less costly operating team, and a resident assistant closer to the patient with two hands available so that he or she can better develop the co-ordination necessary to assume increasing responsibility for the procedure.

Effect of lithium on incorporation of bromodeoxyuridine and tritiated thymidine into human parathyroid cells.

OBJECTIVE: To measure lithium chloride-stimulated incorporation of tritiated thymidine (3H-TdR) and bromodeoxyuridine (BrdU) by human parathyroid cells as an indicator of lithium's growth-promoting properties. DESIGN: Cell suspensions derived from abnormal human parathyroid tissue were incubated for 5 days with graded concentrations of lithium and pulsed with either 0.074 MBq of 3H-TdR or 0.6 microgram of BrdU. The 3H-TdR incorporation was measured by counting cell filtrates in a beta counter, and nuclear BrdU incorporation was determined by counting nuclei positively stained by an antibody to BrdU. Counts of BrdU-positive cells by two observers unaware of incubation conditions were correlated with 3H-TdR counts. RESULTS: Cell suspensions derived from adenomatous and hyperplastic parathyroid glands demonstrated a dose-related increase in 3H-TdR incorporation. There was close correlation between the two observers' counts of BrdU-positive cells (r = 0.70, P = .01) and between each observer's counts and 3H-TdR counts (r = 0.70, P = .02, and r = 0.90, P = .01, respectively). CONCLUSIONS: Lithium stimulates in vitro incorporation of 3H-TdR and BrdU by abnormal human parathyroid cells, consistent with a growth-promoting effect.

Laparoscopic cholecystectomy in patients aged 65 or older.

Laparoscopic cholecystectomy is replacing open cholecystectomy in the surgical management of gallstone disease in healthy individuals. However, the role of laparoscopic cholecystectomy in patients thought to be at higher risk for surgical morbidity is still being defined. The course of patients aged 65 or greater who underwent attempted and successful laparoscopic cholecystectomies were reviewed. Eleven patients (12%) were converted from laparoscopic to open cholecystectomy. For the 83 patients completing laparoscopic cholecystectomy, the median time of surgery was 115 min and the median length of postoperative stay was 1 day. Two patients required parenteral analgesia longer than 48 h. Seven patients were admitted and monitored postoperatively, although five of these were preoperatively planned. Five patients were readmitted within 30 days. One patient was admitted with a myocardial infarction, one a subphrenic abscess, one an incarcerated hernia, one with pyrexia and leukocytosis (for which no source was identified), and one for an elective urinary tract procedure. Laparoscopic cholecystectomy provides patients aged 65 or older the same benefits of shorter hospital stay and less pain than it provides younger patients. Age alone should not be a contraindication to attempted laparoscopic cholecystectomy.