Micrometastasis to in-transit lymph nodes from extremity and truncal malignant melanoma.

BACKGROUND: The sentinel lymph node (SLN) is the first lymph node in the regional nodal basin to receive metastatic cells. In-transit nodes are found between the primary melanoma site and regional nodal basins. To date, this is one of the first reports on micrometastasis to in-transit nodes. METHODS: Retrospective database and medical records were reviewed from October 21, 1993, to November 19. 1999. At the UCSF Melanoma Center, patients with tumor thickness > 1 mm or < 1 mm with high-risk features are managed with preoperative lymphoscintigraphy, selective SLN dissection, and wide local excision. RESULTS: Thirty (5%) out of 557 extremity and truncal melanoma patients had in-transit SLNs. Three patients had positive in-transit SLNs and negative SLNs in the regional nodal basin. Two patients had positive in-transit and regional SLNs. Three patients had negative in-transit SLNs but positive regional SLNs. The remaining 22 patients were negative for in-transit and regional SLNs. CONCLUSIONS: In-transit SLNs may harbor micrometastasis. About 10% of the time, micrometastasis may involve the in-transit and not the regional SLN. Therefore, both in-transit and regional SLNs should be harvested.

Comparison between MR imaging and 99mTc MIBI scintigraphy in the evaluation of recurrent of persistent hyperparathyroidism.

PURPOSE: To compare the sensitivity and positive predictive value of magnetic resonance (MR) imaging and technetium 99m 2-methoxyisobutyl-isonitrile (MIBI) scintigraphy for the detection of hyperfunctioning parathyroid tissue when used alone and in combination in a large patient population with recurrent or persistent hyperparathyroidism (HPT). MATERIALS AND METHODS: In 98 consecutive patients with biochemically proved recurrent or persistent HPT after surgery, MR imaging and 99mTc MIBI study findings were retrospectively reviewed and compared with surgical and histopathologic findings. The sensitivity and positive predictive value of MR imaging and 99mTc MIBI scintigraphy were compared with each other and in combination. RESULTS: In these patients, 130 abnormal parathyroid glands were identified at surgery. The sensitivity and positive predictive value of MR imaging were 82% (95% CI: 75%, 89%) and 89%, respectively; those for (99m)Tc MIBI scintigraphy were 85% (95% CI: 79%, 91%) and 89%. No significant difference was found between MR imaging and 99mTc MIBI scintigraphy for sensitivity (P =.7). The sensitivity and positive predictive value for the detection of abnormal parathyroid tissue on a per-gland basis increased to 94% (95% CI: 90%, 98%) and 98%, respectively, when only one of the two tests was required to be positive. CONCLUSION: MR imaging and 99mTc MIBI scintigraphy have similarly good sensitivity and positive predictive value for the detection of hyperfunctioning parathyroid tissue in patients after surgery. The combination of the two tests provided a substantial increase in sensitivity and positive predictive value.

Evaluation of sentinel lymph node status in spindle cell melanomas.

BACKGROUND: The propensity for spindle cell melanoma to metastasize to the lymph node is relatively low despite its relative thick depth. To date, there are no published reports on the sentinel lymph node (SLN) status in patients diagnosed with spindle cell melanoma and desmoplastic malignant melanoma (DMM). OBJECTIVE: Our purpose was to report our experience on the SLN status in spindle cell melanoma and DMM. METHODS: We undertook a retrospective database and medical record review from Oct 21, 1993 to Sept 29, 1999. At the University of California at San Francisco Melanoma Center, patients with tumor thickness greater than 1 mm or less than 1 mm with high-risk features are managed with preoperative lymphoscintigraphy, selective SLN dissection, and wide excision. RESULTS: Of 29 patients diagnosed with spindle cell melanoma and DMM, 28 had negative SLNs and are free of disease except for one patient who experienced splenic, bony, and brain metastases. The mean follow-up in this population was 16.5 and 11 months, respectively. CONCLUSION: Our preliminary findings show that SLNs from patients diagnosed with spindle cell melanoma and DMM only rarely harbor micrometastasis despite their relative thickness. A larger number of cases from multicenter databases may further define the true biology of SLNs in this melanoma variant.

Multidisciplinary approach to selective sentinel lymph node mapping in breast cancer.

Although the role of axillary lymph node dissection is controversial with respect to survival benefits, its role as a staging procedure has been well established since nodal involvement is the most reliable prognostic indicator for patients with breast cancer. Selective sentinel lymph node (SLN) dissection is gaining acceptance as a useful staging procedure because it is minimally invasive and spares approximately 70-80% of the patients a more extensive axillary lymph node dissection. The evolving techniques for selective SLN dissection using blue dye and radiotracer methods are reviewed in this article. Based on the classic definition of the breast lymphatic drainage and recently published articles addressing the issue of peritumoral and intradermal injections, a possible new and simplified approach using intradermal injection may identify the axillary SLN more quickly and reliably. This article emphasizes the importance of a multidisciplinary approach in the identification of SLNs by preoperative lymphoscintigraphy performed by expert nuclear medicine physicians, the intraoperative mapping and harvesting of SLNs by well trained surgeons and the meticulous examination of SLNs by experienced pathologists. Therefore, to achieve the highest rate of accuracy regarding SLN status, it is imperative that a multidisciplinary team with close communication and cooperation be formed. The clinical significance of SLNs will be determined by results from follow-up and clinical trials.

Principles and controversies in lymphoscintigraphy with emphasis on breast cancer.

The concept of the sentinel node lay fallow until lymph node mapping was developed. This article provides a brief history of the sentinel lymph node concept, discusses reproducibility, radiopharmaceuticals, equipment, techniques, and radiation safety, and addresses metastasis in breast cancer and controversies in breast lymphoscintigraphy.

Sestamibi scanning is inadequate for directing unilateral neck exploration for first-time parathyroidectomy.

OBJECTIVE: To determine whether technetium Tc 99m sestamibi scanning is accurate enough to allow surgeons to perform unilateral neck exploration for first-time parathyroidectomy in patients with primary hyperparathyroidism. DESIGN: Retrospective review. SETTING: University tertiary care center. PATIENTS: Forty patients with primary hyperparathyroidism who underwent sestamibi scanning before first-time parathyroidectomy, of whom 28 had single adenomas, 9 had multiple adenomas, and 3 had hyperplasia. INTERVENTIONS: All 40 patients underwent bilateral neck exploration with identification of 4 parathyroid glands. MAIN OUTCOME MEASURES: We compared the results of preoperative sestamibi scanning with operative and histologic findings. We then used these data to calculate the projected success rates of parathyroidectomy if unilateral neck explorations had been performed based on the results of sestamibi scanning, instead of bilateral explorations. RESULTS: Sestamibi scanning was correct in 20 (71%) of 28 patients with single adenomas, 4 (44%) of 9 patients with multiple adenomas, and 0 (0%) of 3 patients with hyperplasia. If unilateral neck explorations had been performed on the basis of localization by sestamibi scanning, parathyroidectomy would have failed in 4 (10%) of 40 patients. CONCLUSIONS: Sestamibi scanning, although helpful, is inadequate for directing unilateral neck exploration for first-time parathyroidectomy. Surgeons who perform unilateral neck exploration based on the results of sestamibi scanning will record a higher failure rate and incur higher costs than those who perform bilateral neck exploration for first-time parathyroidectomy.

Optimal selective sentinel lymph node dissection in primary malignant melanoma.

OBJECTIVE: To determine the optimal approach of selective sentinel lymph node (SLN) dissection in primary malignant melanoma. DESIGN: Consecutive patient study. Prior to selective SLN dissection and wide local excision of the primary melanoma biopsy site, technetium Tc 99m sulfur colloid was injected intradermally around the primary melanoma or biopsy site to mark the SLN. Isosulfan blue (Lymphazurin, Hirsch Industries Inc, Richmond, Va) was injected at the primary biopsy site immediately before the surgical procedure. SETTING: Teaching hospital tertiary care referral center. MAIN OUTCOME MEASURES: Successful identification of SLNs being defined as positive for microscopic metastatic melanoma by blue dye staining, radioisotope uptake, or both. RESULTS: Selective intraoperative mapping by gamma probe and visualization of blue dye-stained SLN(s) resulted in a 98% (160/163) successful identification rate. Thirty patients (18.4%) had microscopic metastatic melanoma of the SLN(s), 22 of whom had subsequently completed lymphadenectomy. In 4 (18.2%) of these 22 patients, further microscopic metastatic disease was found in 1 of 8 nodes, 1 of 8 nodes, 1 of 28 nodes, and 1 of 9 nodes. No notable complications were encountered. Five recurrent cases from patients with SLNs without microscopic metastatic melanoma (3.8%) and 2 from patients with SLNs with microscopic metastatic melanoma (6%) were found during a median follow-up period of 463 days. A second primary melanoma developed in 2 patients; neither had no local recurrence. CONCLUSIONS: Sequential combination of preoperative lymphoscintigraphy and intraoperative mapping is a reliable way to identify regional SLN. The frequency of microscopic metastatic melanoma of the SLN(s) is 18.4%. Gamma-probe--guided resection minimizes the extent of lymph node dissection. Further follow-up is needed to assess the outcome of this group of patients for regional and systemic recurrences.

Persistent/recurrent hyperparathyroidism: a comparison of sestamibi scintigraphy, MRI, and ultrasonography.

For patients with persistent or recurrent hyperparathyroidism, parathyroid imaging is indicated to confirm the presence of abnormal parathyroid gland(s) and identify their location. These imaging techniques are being modified constantly and newer methods have been developed. Sestamibi scintigraphy, MRI and sonography were compared in 23 patients with persistent or recurrent hyperparathyroidism. Preoperative 99m-Technetium Sestamibi (MIBI), MRI and ultrasonographic (US) studies of 23 patients with 25 histopathologically confirmed abnormal parathyroid glands were compared, using independent prospective interpretations. All patients had been operated upon previously for hyperparthytroidism. Accuracy of various combinations of MRI, MIBI, and US also were calculated. The results are shown for all abnormal glands (n =25); sensitivities and accuracies were 88 and 84% for MRI, 80 and 80% for MIBI, and 58 and 44% for US. For only parathyroid adenomas (n = 18), sensitivities and accuracies were 89 and 89% for MRI, 94 and 94% for MIBI, and 58 and 39% for US. Finally, for parathyroid hyperplasia (n = 7 glands in five patients), sensitivities and accuracies were 83 and 71% for MRI, 43 and 43% for MIBI, and 57 and 57% for US. Either MIBI or MRI results were significantly better for detecting abnormal parathyroid glands than US (P < 0.01), but MRI and MIBI were not statistically different. Combining MRI and MIBI produced a combined accuracy of 92%, whereas combining either of these tests with US did not improve on the accuracy of either test alone. In conclusion, for patients with persistent or recurrent hyperparathyroidism, MRI and MIBI are equally accurate for detecting abnormal parathyroid glands, and the combination of both tests may be more accurate than either test alone.

Effects of a novel cholecystokinin (CCK) receptor antagonist, MK-329, on gallbladder contraction and gastric emptying in humans. Implications for the physiology of CCK.

To explore the physiology of cholecystokinin (CCK) in humans, we investigated the effect on gallbladder contraction and gastric emptying of a recently developed CCK receptor antagonist, MK-329. In a double-blind, four-period crossover study eight subjects received single doses of 0.5, 2, or 10 mg MK-329, or placebo, followed by an intravenous infusion of CCK-8 (30 pmol/kg.h). In placebo-treated subjects gallbladder volumes decreased on average to 43% of initial volumes after 2 h of CCK infusion. MK-329 caused a dose-dependent inhibition of CCK-stimulated gallbladder contraction with 10 mg producing complete blockade (P less than 0.01, cf. placebo). Gallbladder contraction and gastric emptying rates after a mixed meal were then measured in a two-period crossover study. Subjects received placebo or 10 mg of MK-329 2 h before eating. Gastric emptying of both solids and liquids was measured simultaneously by gamma scintigraphy. In placebo-treated subjects plasma CCK levels increased postprandially to 2.3 pM, gallbladder volumes decreased 68.4 +/- 3.8% (SE), and the times for 50% emptying of liquids and solids from the stomach were 58 +/- 10 and 128 +/- 8 min, respectively. In MK-329-treated subjects there was a marked elevation in peak CCK levels to 13.8 pM (P less than 0.01, cf. placebo), and gallbladder contraction was completely inhibited. Solid and liquid emptying rates were unaffected. These findings demonstrate that (a) MK-329 is a potent, orally active antagonist of CCK in humans, and (b) CCK is the major regulator of postprandial gallbladder contraction. These data also support the concept of negative feedback regulation of CCK secretion and suggest that mechanisms other than CCK play a dominant role in the regulation of postprandial gastric emptying rates.

Physiological role for cholecystokinin in reducing postprandial hyperglycemia in humans.

It is known that the ingestion of glucose alone causes a greater increase in plasma glucose levels than ingestion of the same amount of glucose given with other nutrients. Since physiological plasma concentrations of cholecystokinin (CCK) prolong gastric emptying, it is proposed that after a meal, CCK may modify plasma glucose levels by delaying glucose delivery to the duodenum. To evaluate the effect of CCK on oral glucose tolerance, plasma CCK, insulin, and glucose levels and gastric emptying rates were measured in eight normal males before and after the ingestion of 60 g glucose with the simultaneous infusion of either saline or one of two doses of CCK-8 (12 or 24 pmol/kg per h). Gastric emptying rates were measured by gamma camera scintigraphy of technetium 99m sulfur colloid and plasma CCK levels were measured by a sensitive and specific bioassay. Basal CCK levels averaged 1.0 +/- 0.1 pM (mean +/- SEM, n = 8) and increased to 7.1 +/- 1.1 pM after a mixed liquid meal. After glucose ingestion, but without CCK infusion, CCK levels did not change from basal, and the gastric emptying t1/2 was 68 +/- 3 min. Plasma glucose levels increased from basal levels of 91 +/- 3.9 mg/dl to peak levels of 162 +/- 11 mg/dl and insulin levels increased from 10.7 +/- 1.8 microU/ml to peak levels of 58 +/- 11 microU/ml. After glucose ingestion, with CCK infused at 24 pmol/kg per h, plasma CCK levels increased to 8 pM and the gastric emptying t1/2 increased to 148 +/- 16 min. In concert with this delay in gastric emptying, peak glucose levels rose to only 129 +/- 17 mg% and peak insulin levels rose to only 24.2 +/- 4.2 microU/ml. With CCK at 12 pmol/kg per h, similar but less dramatic changes were seen. To demonstrate that endogenous CCK could modify the plasma glucose and insulin responses to oral glucose, oral glucose was given with 50 g of lipid containing long-chain triglycerides. This lipid increased peak CCK levels to 3.7 +/- 0.9 pM. Concomitant with this rise in CCK was a delay in gastric emptying and a lowering of plasma glucose and insulin values. To confirm that CCK reduced hyperglycemia by its effect on gastric motility, 36 g glucose was perfused directly into the duodenum through a nasal-duodenal feeding tube in four subjects. With duodenal perfusion of glucose, there was no change in plasma CCK levels, but plasma glucose levels increased from basal levels of 93+/-5 to 148+/-6 mg/dl and insulin levels rose from 10.6+/-3.5 to 29.5+/-5.2 microU/ml. When CCK was infused at 24 pmol/kg per h, neither the plasma glucose nor insulin responses to the duodenal administration of glucose were modified. Thus we conclude that CCK, in physiological concentrations, delays gastric emptying, slows the delivery of glucose to the duodenum, and reduces postprandial hyperglycemia. These data indicate, therefore, that CCK has a significant role in regulating glucose homeostasis in human.

Regulation of gastric emptying in humans by cholecystokinin.

In the present study we used a bioassay system for measuring plasma cholecystokinin (CCK) to evaluate whether CCK has a physiologic role in regulating gastric emptying in humans. Plasma CCK levels and gastric emptying after ingestion of a mixed liquid meal were determined in five normal male volunteers. Fasting CCK levels averaged 0.8 +/- 0.1 pM and increased to 6.5 +/- 1.0 pM within 10 min of drinking the mixed meal. CCK levels remained elevated for up to 90 min. Gastric emptying after a meal was slow; at the end of the 90 min 68% of the original volume remained in the stomach. The rate of gastric emptying of water was then measured in the same individuals with a simultaneous infusion of either saline, or one of two doses of CCK (12 pmol/kg per h and 24 pmol/kg per h). With the saline infusion, plasma CCK levels did not increase above basal and gastric contents emptied rapidly. At the end of 90 min only 7% of the original volume remained in the stomach. The lower dose of CCK resulted in a plasma level of 3.4 pM which both reproduced the average postprandial plasma level and caused a significant delay in gastric emptying. The higher dose of CCK achieved plasma levels of 8 pM and resulted in a delay in gastric emptying that was similar to that seen with the mixed meal. Since exogenous CCK at concentrations which occur postprandially delays gastric emptying, we conclude that CCK is a physiologic regulator of gastric emptying.

Hepatic scan defects following radiotherapy for lymphoma.

Twenty-one patients with lymphoma were evaluated for the presence of hepatic scan defects following radiotherapy to fields which included the left lobe of the liver. Two distinct patterns of hepatic scan defects were noted: (a) a radiation port defect (Type I), and (b) attenuation of the left lobe (Type II). Five of seven patients evaluated within six weeks after radiotherapy demonstrated Type I defects but all seven subsequently developed Type II defects. Seventeen of the 21 patients developed Type II defects which have persisted (follow-up, up to 66 months). These characteristic defects should not be confused with other causes of hepatic scan defects in evaluating patients with lymphoma. The defects occur in a high percentage of patients and may persist for long periods.