Contribution of inert mass to experimental cancer cachexia in rats.

An inert artificial tumor (AFT) was inflated in male F344 rats to simulate, experimentally, the growth in mass of large transplantable tumors that produce cachexia. The AFT depressed host weight gain and skeletal muscle mass up to 30% and food intake up to 20% of the depression induced by tumors of comparable size. When the growth rate of the AFT was low, there was no depression of food intake. Work-induced hypertrophy of skeletal muscles, as assessed by a gastrocnemius tenotomy model, was approximately equal to that of normal, tumor-bearing, and AFT-bearing animals. The AFT elevated host total energy expenditure by 12.5% and compartment-of-energy expenditure attributable to motor activity by 10.5%. The elevation of energy expenditure accounted for most of the depression of weight gain of AFT-bearing animals below that of intact animals. The large mass of most transplantable tumors leads to an overestimate of the malignant tissue-depletive effects of tumor and an under-estimate of the asthenic effects.

Insulin reversal of cancer cachexia in rats.

The anabolic effects of exogenous neutral protamine hagedorn insulin on tumor-bearing (TB) and non-tumor-bearing (NTB) rats were examined. Exogenous insulin (2 units/100 g/day) produced similar hypoglycemia in TB and NTB rats. Food intake and body weight gain were significantly increased by insulin in NTB rats. In TB rats in an early stage of cachexia, insulin increased food intake and host weight (total body weight minus tumor weight). In TB rats with severe cachexia, insulin increased food intake and stabilized host weight when untreated TB controls were not eating and were losing weight. When daily insulin administration was started at an early stage of tumor growth and continued until death, there was again significant enhancement of host weight and food intake. Heart and adrenal weights were significantly reduced in insulin-treated TB animals. Tumor growth was not stimulated by insulin treatment. Survival time was slightly reduced in TB rats treated with long-term insulin. Survival time in TB rats randomized to insulin during late cachectic decline was not different from untreated TB controls. Insulin did not have any measurable effect on energy expenditure or the motor activity compartment of energy expenditure in either TB or NTB rats. Insulin treatment can reverse experimental cancer cachexia. It is a nutritional therapy which preferentially feeds the host over the tumor. As yet, its beneficial effects have not prolonged survival of tumor-bearing animals.

Body composition changes in rats with experimental cancer cachexia: improvement with exogenous insulin.

Exogenous insulin treatment has been shown to improve food intake and host weight of cachectic tumor-bearing (TB) rats, but the composition of the host weight gain has not been quantitated. Sixty-six Fischer 344 rats were randomized to seven groups: early nontumor-bearing (NTB) (n = 10) who underwent compositional analysis (CA) on the day the methylcholanthrene sarcoma was implanted in TB rats; pretreatment-NTB (n = 10) and pretreatment-TB (n = 10) who underwent CA 25 days later when rats began treatment with saline or insulin; and finally saline-treated NTB (n = 9), saline-treated TB (n = 9), insulin-treated NTB (n = 9), and insulin-treated TB (n = 9), who underwent CA following 5 days of treatment with daily saline or neutral protamine hagedorn insulin 2 units/100 g. Body weight and food intake were measured daily. For compositional analysis, the tumor was separated from the host in TB rats and the entire rat in NTB animals was homogenized, lyophilized and analyzed for fat, water, protein, potassium, chloride, and sodium. The tumor was processed in a similar fashion. In response to insulin, NTB rats ate significantly more food, and had an increase in body weight gain. Compositional analysis of insulin-treated NTB rats indicated a slight, but insignificant, increase in body fat and a similar insignificant decrease in body protein. TB rats ate significantly less than NTB rats during the 5-day experimental period, and insulin treatment significantly increased food intake to levels similar to NTB animals. Compositional analysis indicated that the tumor-bearing state resulted in a significant decrease in total host water, protein, fat, potassium, sodium, and chloride. Insulin administration resulted in preservation of host nitrogen, fat, potassium, sodium, and chloride in cachectic tumor-bearing rats. Insulin treatment did not affect tumor dry weight or composition. The results suggest that exogenous insulin, can preserve normal host composition of TB rats during cachectic decline.

Parabiotic transfer of cancer anorexia/cachexia in male rats.

To demonstrate that the anorexia and depletion of cachexia reverses on tumor removal, F344 rats underwent sarcoma resection when their food intake fell to 0 g/day. In survivors of surgery, reversal in food intake was apparent within 3 days postoperatively, followed after 2 days by gain in host weight. To detect whether the transmission of anorexia/cachexia in these tumor-bearing (TB) rats was via the circulation, four groups were studied: single non-tumor bearing (NTB); single TB; parabiotic NTB; and parabiotic TB. The measured blood exchange rate between parabiotic halves was 1.2-1.5%/min. No cachectic effect was detected in either half of the NTB parabionts. There was no evidence of sarcoma metastases in the tumor-free half of the parabiotic TB pair. All the rats associated with the presence of tumor showed cachectic effects but the degree and timing of effect varied among the three conditions, single TB, parabiotic TB half, and parabiotic tumor-free half. In all variables examined (fall in food intake, time of first fall in food intake, host weight loss, elevation of blood urea nitrogen) the severities were always in the same sequence: single TB greater than parabiotic TB half greater than parabiotic tumor-free half greater than NTB. In addition, the TB parabiotic pair had a significantly longer survival time and grew a significantly larger tumor than did the single TB animal. The parabiotic tumor had a slower initial growth rate and a slower deceleration rate than the singlet tumor. These results provide evidence for the humoral mediation of cancer-associated cachexia.

Low frequency of ras gene mutations in neuroblastomas, pheochromocytomas, and medullary thyroid cancers.

Little is known about the prevalence and significance of ras gene activation in neural crest tumors such as neuroblastomas, pheochromocytomas, and medullary thyroid cancers (MTCs). Therefore, we analyzed DNA from 10 human neuroblastoma cell lines and 10 primary human pheochromocytomas for activating mutations in N-ras, H-ras, and K-ras. We also studied DNA from 24 primary neuroblastomas and 10 MTCs for N-ras mutations. ras genes were analyzed by direct sequencing of specific DNA fragments amplified by the polymerase chain reaction. With the exception of the SK-N-SH cell line, the examined ras gene sequences were normal in all the neuroblastomas, pheochromocytomas, and MTCs tested. A single point mutation was identified at codon 59 (GCT(ala)----ACT(thr)) in one N-ras allele in an SK-N-SH subline. Interestingly, this mutation is different from the activating codon 61 mutation which resulted in the initial identification of N-ras from SK-N-SH DNA. Therefore, we analyzed the sequences of earlier passages and sublines of the SK-N-SH cell line, but mutations at codon 59 or 61 were not detected, suggesting that neither mutation was present in the primary tumor. Our results indicate that N-ras mutations may occur spontaneously during in vitro passage of cell lines but rarely, if ever, occur in primary neuroblastomas, pheochromocytomas, and MTCs. In addition, we have not found H-ras or K-ras mutations in any neuroblastoma cell line or primary pheochromocytoma.

Consistent association of 1p loss of heterozygosity with pheochromocytomas from patients with multiple endocrine neoplasia type 2 syndromes.

Pheochromocytomas and medullary thyroid cancers (MTCs) are neuroendocrine tumors which arise sporadically or as part of the multiple endocrine neoplasia type 2 (MEN-2) hereditary syndromes. The most consistent molecular genetic abnormality which has been described in these tumors is loss of heterozygosity (LOH) of the short arm of chromosome 1 (1p). This finding is particularly interesting because the predisposition gene for the hereditary form of these tumors has been mapped to chromosome 10, but LOH on chromosome 10 in MEN-2 tumors is found rarely. We have used a battery of 1p DNA probes to elucidate the region of loss of 1p in 18 pheochromocytomas and 27 MTCs. Using restriction fragment length polymorphism analysis, we identified loss of all or a portion of 1p in 12 of 18 pheochromocytomas. 1p LOH was identified in nine of nine pheochromocytomas in MEN-2A and -2B patients, compared with only two of seven sporadic pheochromocytomas. We also found 1p LOH in one of two von Hippel-Lindau patients. LOH on 1p was noted in only three of 24 informative MTCs, and these were from patients with MEN-2A. In most of the pheochromocytomas, the entire short arm of chromosome 1p appears to have been lost; however, in three of the non-MEN pheochromocytomas and in three MEN-2A MTCs, the region of loss is smaller, allowing estimation of the smallest region of overlap. The combined data for MTCs and pheochromocytomas suggest that the smallest region of overlap of LOH is bounded by D1S15 (1pter-p22) and D1Z2 (1P36.3), excluding a region around MYCL (1p32). Although other regions of 1p should not be completely ruled out, the data suggest that this region may harbor a tumor suppressor gene or genes whose inactivation is important in the development of these tumors. Furthermore, the strong association between 1p LOH and the MEN-2 syndromes, especially in pheochromocytomas, suggests a relationship between the predisposition gene on chromosome 10 and the loss of the suppressor gene on 1p. Alternatively, other loci may be more important in sporadic disease.

Allelic imbalance of the mutant and wild-type RET allele in MEN 2A-associated medullary thyroid carcinoma.

Germline mutations of the RET proto-oncogene are responsible for the familial tumor syndrome called multiple endocrine neoplasia type 2 (MEN 2) that includes medullary thyroid carcinoma (MTC). Although inherited mutations of RET lead to tumor formation in patients with MEN 2, it is not understood why only selected cells develop into tumors. We have recently shown that duplication of the mutated RET allele or loss of the wild-type allele might represent mechanisms of tumorigenesis in patients with MEN 2A-related pheochromocytoma. We now analysed 19 DNA samples of MTC (15 of which were non-microdissected, four of which were microdissected) from patients with MEN 2A. Using polymorphic marker and phosphorimage densitometry analyses, we found allelic imbalance of the mutated and wild-type RET allele in six of 19 DNA MTC samples. Of note, two of the four microdissected tumor DNA samples showed allelic imbalance of RET, whereas only four of the 15 non-microdissected MTC samples did. These results underscore the significance of microdissection in the analysis of tumor DNA. In our study, some of the non-microdissected tumor DNA samples may have failed to display allelic imbalance of RET, because of contamination of tumor DNA with nonneoplastic DNA or noninformative microsatellite marker analysis. Taken together, our results suggest allelic imbalance between mutated and wild-type RET as a possible mechanism for tumor formation in some patients with MEN 2A-related MTC.

Confirmation that chromosome 18q allelic loss in colon cancer is a prognostic indicator.

PURPOSE: Recent studies suggest that allelic loss of sequences from the long arm of chromosome 18 may be a useful prognostic indicator in colorectal cancer. The aim of the present study was to confirm whether 18q loss of heterozygosity (LOH) is of prognostic value in patients with colon cancer. METHODS: Genomic DNA was prepared from archival tumor and corresponding normal tissue specimens from 151 patients who had undergone potentially curative surgery for adenocarcinoma of the colon. Polymerase chain reaction (PCR) was used to assess allelic loss of five chromosome 18q microsatellite markers in the tumors. The relationship between allelic loss and disease-free and disease-specific survival was investigated. RESULTS: LOH was detected in 67 of 126 tumors. Chromosome 18q allelic loss was a negative prognostic indicator of both disease-free (relative risk [RR], 1.65; P = .01) and disease-specific survival (RR, 2.0; P = .003). 18q loss was also associated with significantly reduced disease-free and disease-specific survival in patients with stage II (P = .05 and P = .0156) and III (P = .038 and P = .032) disease. CONCLUSION: Chromosome 18q allelic loss is a prognostic marker in colorectal cancers. Chromosome 18 LOH studies may be useful in identifying patients with stage II disease who are at high risk for recurrence, and as such might benefit from adjuvant chemotherapy.

Strategy for identification of novel glucose transporter family members by using internet-based genomic databases.

BACKGROUND: We previously reported that medullary thyroid carcinomas and pheochromocytomas avidly take up the glucose analog fluoro-deoxyglucose on positron emission tomography but do not express any of the known human facilitative glucose transporters. We therefore hypothesized that a novel glucose transporter is responsible for glucose uptake in these tumors. METHODS: Internet-based Expressed Sequence Tags and high throughput genome sequence databases were screened for novel sequences homologous to the known glucose transporters. Derived clones were used to screen cDNA libraries. Sequence comparison and hydropathic analysis of the putative proteins were performed. RESULTS: We identified 2 novel genes (GLUT8 and GLUT9) that are members of the facilitative glucose transporter family. The putative GLUT8 and GLUT9 proteins have 44% and 31% sequence identity to GLUT5 and GLUT3, respectively. Hydropathic analysis showed both have exofacial and transmembrane domains consistent with a hexose transporter. CONCLUSIONS: By using the Expressed Sequence Tags database, we identified novel members of the glucose transporter family. Further work will establish function and expression patterns in medullary thyroid carcinomas and pheochromocytomas. Internet-based genomic databases allow rapid screening and identification of candidate sequences of novel members of human gene families.

Laparoscopic detection of hepatic metastases in patients with residual or recurrent medullary thyroid cancer.

BACKGROUND: After initial operations for medullary thyroid cancer (MTC), reoperation with removal of metastatic disease confined to the neck may benefit some patients. The identification of distant metastases precludes the possibility of curative reoperation. METHODS: Forty-one patients with hypercalcitoninemia after initial surgical treatment for MTC underwent laparoscopic (n = 36) or open (n = 5) examination and biopsy of the liver. Thirty-seven of these patients underwent imaging by computed tomography (CT), magnetic resonance imaging (MRI) of the liver, or both, and 17 underwent selective venous catheterization (SVC) with measurement of hepatic and peripheral vein stimulated calcitonin levels. RESULTS: Liver metastases were found in eight patients, seven by laparoscopy and one by open examination. Seven of these patients had normal CT or MRI scans of the liver. Laparoscopy or open liver examination revealed metastases in 2 of 11 patients with elevated hepatic vein-peripheral vein stimulated calcitonin ratios (greater than 1.3). Metastases appeared as small (less than 5 mm), bright white nodules on the surface of the liver. CONCLUSIONS: Direct examination and biopsy of the liver by laparoscopy may show small deposits of metastatic MTC in patients with normal CT and MRI scanning.

Evaluation of fluorodeoxyglucose-positron emission tomographic scanning and its association with glucose transporter expression in medullary thyroid carcinoma and pheochromocytoma: a clinical and molecular study.

BACKGROUND: Imaging of metastatic sites of medullary thyroid carcinoma (MTC) is successful in less than 60% of cases of residual or recurrent disease. Positron emission tomography (PET) with [18F]fluoro-2-deoxy-D-glucose (FDG) takes advantage of the fact that malignant tumors are capable of increased uptake and use of glucose, which is mediated by the members of the glucose transporter family of proteins (GLUT 1 through GLUT 5). METHODS: FDG-PET images of 10 patients with recurrent or persistent MTC after primary operation were compared with images by computed tomography or magnetic resonance imaging. Identified metastatic lesions were assessed by intraoperative findings and pathology reports. Expression of GLUT 1 through GLUT 5 was examined by Western blot analysis of tumor tissue from eight of the patients evaluated and an additional panel of 10 MTCs and seven pheochromocytomas. RESULTS: FDG-PET identified 31 foci of FDG accumulation in 10 patients, and 16 of these metastatic sites were resected and confirmed by histologic analysis. Only 11 foci were demonstrated by computed tomographic or magnetic resonance imaging. None of the glucose transporters examined displayed significant expression. Two pheochromocytomas were successfully imaged by FDG-PET. CONCLUSIONS: FDG-PET imaging can be useful in the localization of cervicomediastinal MTC metastases and pheochromocytoma. The increased glucose uptake in these tumors, as evidenced by FDG-PET, does not appear to be attributable to the expression of the glucose transporter proteins GLUT 1 through GLUT 5.

Reoperation for recurrent or persistent medullary thyroid cancer.

BACKGROUND: Initial operations for medullary thyroid cancer (MTC) frequently do not eradicate all disease, as evidenced by persistently elevated levels of stimulated plasma calcitonin. METHODS: Thirty-two patients with MTC and elevated stimulated plasma calcitonin levels after thyroidectomy were studied between 1990 and 1993. Thirty-five repeat neck explorations and microdissections were performed. Four patients also underwent a median sternotomy and mediastinal dissection. RESULTS: In nine patients (group 1), stimulated plasma calcitonin levels were undetectable after reoperation, whereas in 13 cases (group 2) the calcitonin levels decreased by 40% or more. In 10 cases (group 3) the CT levels did not decrease. Primary tumors that exhibited invasive features (invasion of adjacent structures or extranodal or extracapsular spread) were found more often in patients from group 3 than in patients from groups 1 or 2 (p < 0.05, Fisher's exact test). CONCLUSIONS: Reoperation resulted in normalization of calcitonin levels in 28% of patients and a decrease in calcitonin levels by 40% or more in another 42% of patients. The data also suggest that patients whose primary MTC has invaded tissues beyond the thyroid gland or a lymph node capsule are less likely to benefit from repeat operation.

Preservation of the recurrent laryngeal nerves in thyroid and parathyroid reoperations.

BACKGROUND: The recurrent laryngeal nerve (RLN) is vulnerable to injury in thyroid and parathyroid reoperations because of the presence of scar tissue and displacement of the nerve from its normal position. METHODS: Since 1993, we have performed 132 reoperations for recurrence of thyroid or parathyroid carcinoma (102 cases), persistent hyperparathyroidism (21 cases), and recurrent goiter (9 cases). One or both RLNs were identified in all cases (208 nerves). Exposure of the nerve was accomplished by a lateral approach (159 nerves), a low anterior approach (41 nerves), or the identification of the nerve between the larynx and the upper pole of the thyroid, in parathyroid reoperations (8 nerves). Dissection was then done while the nerve was kept in view at all times. RESULTS: Preoperatively, unilateral vocal cord paralysis was noted in 6 patients. Resection of a functioning RLN encased with a tumor was intentionally carried out in 5 patients. The RLNs were identified and preserved in all other cases. Among these 121 patients, transient hoarseness lasting up to a month occurred in 12 patients. CONCLUSIONS: Careful identification and exposure of the RLN through a previously undissected area can be done safely in thyroid and parathyroid reoperations and resulted in no permanent recurrent nerve injuries in our experience.

Risk of malignancy in thyroid incidentalomas identified by fluorodeoxyglucose-positron emission tomography.

BACKGROUND: Thyroid tumors often exhibit increased metabolic activity, as evidenced by enhanced glucose uptake on positron emission tomography (PET) with use of (18)F-fluorodeoxyglucose (FDG). The incidence of new thyroid lesions found on routine FDG-PET has not been previously reported. METHODS: A retrospective review of all patients who underwent FDG-PET imaging at our institution from June 1, 1996, through March 15, 2001, identified patients with a newly diagnosed thyroid lesion. Thyroid incidentaloma was defined as a thyroid lesion seen initially on FDG-PET in a patient without a history of thyroid disease. Available follow-up data were documented. RESULTS: One hundred and two of 4525 FDG-PET examinations (2.3%) demonstrated thyroid incidentalomas. Eighty-seven of 102 patients had no thyroid histology because of other malignancies. Fifteen patients had thyroid biopsy: 7 (47%) with thyroid cancer, 6 (40%) with nodular hyperplasia, 1 with thyroiditis, and 1 with atypical cells of indeterminate origin. The average standardized uptake values were higher for malignant compared with benign lesions. CONCLUSIONS: Thyroid incidentaloma identified by FDG-PET occurred with a frequency of 2.3%. Of the thyroid incidentalomas that underwent biopsy, 47% were found to be malignant. Given the risk of malignancy, patients with new thyroid lesions on PET scan should have a tissue diagnosis if it will influence outcome and management. Standardized uptake values may be helpful in predicting benign versus malignant histology.

"Cold" single-strand conformational variants for mutation analysis of the RET protooncogene.

BACKGROUND: RET protooncogene mutation analysis is a routinely performed predictive DNA test in kindreds affected by multiple endocrine neoplasia (MEN) types 2A and 2B and familial medullary thyroid carcinoma (FMTC), and is a valuable diagnostic tool in newly diagnosed cases of medullary thyroid carcinoma (MTC). METHODS: We tested the suitability of the recently introduced "cold" single-strand conformational variant (SSCV) technique, which promises rapid, simple, nonradioactive detection of sequence variants in the identification of germline and somatic RET mutations. A total of 11 different mutations in exon 10 (codons 609, 611, 618, and 620) and 6 mutations in exon 11 (codon 634) were studied. RESULTS: Conditions were optimized so that conformational variants were demonstrated for all mutations examined in a single setting for exons 10 and 11. A novel six base pair (bp) inframe deletion between cysteines 630 and 634 was detected in a sporadic MTC. This adds to the evidence that not only cysteine deletions and substitutions but also changes in the spacing between cysteine residues have a pathogenic effect. CONCLUSIONS: Our results indicate that the cold SSCV method offers the advantages of simplicity, time savings, and nonradioactive detection for screening for RET sequence variants in hereditary and sporadic MTCs.

Outcomes analysis in patients undergoing laparoscopic adrenalectomy for hormonally active adrenal tumors.

BACKGROUND: Laparoscopic adrenalectomy (LA) has become the preferred method of removal of most adrenal neoplasms, but few studies have evaluated the functional outcomes of this approach. The purpose of this study was to analyze our operative results and the clinical and biochemical responses to LA in patients with various hormonally active adrenal tumors. METHODS: From 1993 through November 2000, 72 patients with functional adrenal tumors underwent attempted LA. Data were obtained retrospectively by review of medical records, during routine follow-up, and by patient questionnaire. RESULTS: Indications for adrenalectomy were pheochromocytoma (n = 35), aldosteronoma (n = 29), cortisol-producing adenoma (n = 5), and adrenocorticotropic hormone-dependent Cushing's syndrome (n = 3). LA was completed in 70 of 72 patients, with 2 conversions (3%) to open adrenalectomy. Mean operative time for unilateral LA was 176 +/- 60 minutes, and postoperative length of hospital stay averaged 3.0 +/- 1.7 days. Complications, most of which were minor, occurred in 19% of patients; there were no serious complications or perioperative deaths. Two patients were unavailable for follow-up. At a mean follow-up interval of 37.6 months after LA (range, 2-90 months), resolution of clinical and biochemical signs of adrenal hyperfunction was accomplished in 34 of 34 patients with pheochromocytomas, 25 of 26 patients with aldosteronomas, 5 of 5 patients with cortisol-producing adenomas, and 3 of 3 patients with andrenocorticotropic hormone-dependent Cushing's syndrome. Two patients with multiple endocrine neoplasia (MEN) type 2 had contralateral pheochromocytomas removed 4 and 5 years after the initial surgery. Persistent hypertension necessitating medication was present in 72% of patients with aldosteronomas, although 92% of these patients had improved blood pressure control after LA. Recurrent hypokalemia developed in 1 patient (4%) with a cortical nodule in the contralateral adrenal. No local or distant tumor recurrences have occurred. CONCLUSIONS: LA results in an excellent clinical outcome in patients with various functional endocrine tumors. LA is associated with few major complications, and clinical and biochemical cure rates are comparable with those of open adrenalectomy during long-term follow-up.

Laparoscopic adrenalectomy compared to open adrenalectomy for benign adrenal neoplasms.

BACKGROUND: Laparoscopic adrenalectomy has recently been used for removing a variety of adrenal neoplasms. The purpose of the present study was to compare results and outcomes in patients who underwent either laparoscopic or open adrenalectomy at our institution from 1988 to the present. STUDY DESIGN: The records of 66 consecutive patients with benign adrenal neoplasms who underwent adrenalectomy from 1988 through 1995 were retrospectively reviewed. Patients were divided into three groups based on the operative approach: group I (n = 25), open anterior transabdominal approach; group II (n = 17), open posterior retroperitoneal approach; and group III (n = 24), laparoscopic transabdominal flank approach. Various parameters were compared and statistical analyses were performed. RESULTS: The three groups were similar in age, gender, American Society of Anesthesiologists class, and distribution of unilateral compared with bilateral adrenalectomy. Mean tumor size was slightly larger in group I (3.4 +/- 1.4 cm) than in group II (2.4 +/- 1.4 cm) or group III (2.7 +/- 1.4 cm) (p = NS). Mean operative times for unilateral adrenalectomy were 142 +/- 38 minutes in group I, 136 +/- 34 minutes in group II, and 183 +/- 35 minutes in group III (p < 0.001, groups I and II compared with group III). For bilateral adrenalectomy, mean operative times were 205 +/- 71 minutes (group I), 328 +/- 11 minutes (group II), and 422 +/- 77 minutes (group III). Patients who underwent laparoscopic adrenalectomy had significantly less operative blood loss (mean, 104 mL compared to 408 mL in group I and 366 mL in group II, p < 0.001) and a lower incidence of perioperative blood transfusion. Laparoscopic adrenalectomy was also associated with significantly reduced parenteral pain medication requirements (p < or = 0.001) and more rapid resumption of a regular diet (p < or = 0.01) compared to open adrenalectomy. Postoperative length of stay was significantly longer in group I (8.7 +/- 4.5 days) and in group II (6.2 +/- 3.9 days) after open adrenalectomy than after laparoscopic adrenalectomy (3.2 +/- 0.9 days) (p < 0.01). Total hospital charges were similar for groups II and III but somewhat higher for group I. Patients were able to resume 100 percent activity an average of 10.6 +/- 4.9 days after laparoscopic adrenalectomy and returned to work a mean of 16.0 +/- 6.1 days postoperatively. CONCLUSIONS: Laparoscopic adrenalectomy is a safe and effective procedure and has several advantages over open adrenalectomy. Laparoscopic adrenalectomy should become the preferred operative approach for the treatment of patients with small, benign adrenal neoplasms.

Brain metastases from medullary thyroid carcinoma in a patient with multiple endocrine neoplasia type 2A.

Medullary thyroid carcinoma (MTC) is an uncommon thyroid cancer occurring in less than 10% of patients with thyroid cancer. Brain metastasis from MTC is exceedingly rare. Only six cases of brain metastasis from MTC have been reported in the literature and none had MTC as a part of multiple endocrine neoplasia (MEN) syndrome. We report a 42-year-old Caucasian male with MEN 2A who presented with neurological symptoms 25 years after total thyroidectomy with lymphadenectomy for MTC metastatic to local lymph nodes. A brain magnetic resonance imaging (MRI) showed a 4-cm cystic mass and a 1-cm nodule in the left frontal-parietal lobe in addition to a 0.8-cm cystic mass in the left frontal lobe and multiple tiny cerebellar metastatic lesions. Partial resection of the cerebral metastasis followed by whole brain radiotherapy resulted in resolution of the neurological symptoms. However, the patient had multiple systemic metastasis from the MTC and he died of systemic complications due to metastatic MTC. To our knowledge this is the first report of brain metastases from MTC in a patient with MEN 2A.

Laparoscopic ultrasound imaging of adrenal tumors during laparoscopic adrenalectomy.

BACKGROUND: The purpose of this study was to determine the usefulness of laparoscopic ultrasound (LUS) during laparoscopic adrenalectomy (LA) and to define the ultrasound imaging characteristics of various adrenal tumors. METHODS: LUS was utilized in 27 patients who underwent LA (including one bilateral adrenalectomy) from May 1994 to October 1998. Tumor size ranged from 1.0 to 5.5 cm (mean 3.3 cm), and a transabdominal lateral approach to LA was used. RESULTS: LUS localized the adrenal gland and tumor in all 28 adrenalectomies and demonstrated the relationship of the tumor to the kidney and adjacent vascular structures (renal artery/vein and inferior vena cava). The adrenal vein was visualized sonographically in only six cases (21 %). Pheochromocytomas were mild to markedly heterogenous, whereas most aldosteronomas and cortical adenomas were homogenous. LUS provided useful information to the surgeon in 11 of 28 cases (39%) by: 1) localizing the adrenal gland and tumor and/or guiding the dissection; 2) demonstrating that tumors > or =4 cm were confined to the adrenal gland; and 3) investigating suspected pathology in other organs. Mean operating time for LUS was 10.9 min (range 5 to 24 min) and calculated hospital charges were $602. CONCLUSIONS: LUS accurately localizes adrenal tumors, helps define their relationship to adjacent structures, and provides confirmation that larger tumors are amenable to laparoscopic resection. LUS is a useful adjunct to laparoscopic adrenalectomy in selected patients.

Medullary thyroid cancer.

Medullary thyroid cancer is a tumor of the thyroid C cells that occurs in sporadic and hereditary clinical settings. Genetic testing of at-risk individuals is available and has been applied to patient management. Plasma calcitonin levels are a very sensitive marker for the presence of disease. Surgery offers the best hope for cure and also is an effective modality for managing metastatic and recurrent disease.