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B Niederle

Publications and source records attributed to B Niederle.

At least 19 recordsLinked to original sources

The relationship between specific RET proto-oncogene mutations and disease phenotype in multiple endocrine neoplasia type 2. International RET mutation consortium analysis.

OBJECTIVE: Multiple endocrine neoplasia type 2 (MEN 2) is an autosomal dominant disorder. The 3 recognized subtypes include MEN 2A, characterized by medullary thyroid carcinoma (MTC), pheochromocytoma (pheo), and hyperparathyroidism (HPT); MEN 2B, by MTC, pheo, and characteristic stigmata; and familial MTC (FMTC), by the presence of MTC only. The purpose of this study was to establish the relationship between specific mutations and the presence of certain disease features in MEN 2 which could help in clinical decision making. DESIGN: Correlative survey study of 477 MEN 2 families. SETTING: Eighteen tertiary referral centers worldwide. PATIENTS: A total of 477 independent MEN 2 families. MAIN OUTCOME MEASURES: Association between the position and type of germline mutation in the RET proto-oncogene and the presence or absence of MTC, pheo, HPT, and/or other features in a family. RESULTS: There is a statistically significant association between the presence of any mutation at a specific position (codon 634) and the presence of pheo and HPT. The presence of a specific mutation, CGC at codon 634, has yet to be associated with FMTC. Conversely, mutations at codons 768 and 804 are thus far seen only with FMTC, while codon 918 mutation is MEN 2B--specific. Rare families with both MEN 2 and Hirschsprung disease were found to have MEN 2-specific codon mutations. Patients with Hirschsprung disease presenting with such mutations should be monitored for the possible development of MEN 2 tumors. CONCLUSIONS: This consortium analysis suggests that genotype-phenotype correlations do exist and, if made reliably absolute, could prove useful in the future in clinical management with respect to screening, surveillance, and prophylaxis, as well as provide insight into the genetic effects of particular mutations.

Carcinoma, Medullary

Distinction between sporadic and hereditary medullary thyroid carcinoma (MTC) by mutation analysis of the RET proto-oncogene. "Study Group Multiple Endocrine Neoplasia Austria (SMENA)".

Germline and somatic mutations of the RET proto-oncogene are important pathogenetic factors in hereditary and sporadic forms of medullary thyroid carcinoma (MTC). We have therefore analysed exons 10, 11, 13, 14 and 16 of this gene in 85 individuals from 16 Austrian families who, according to clinical criteria, were at risk of suffering from hereditary forms of MTC. We found mutations (codons 620,634 and 804) in the germline of 3 families with familial medullary thyroid carcinoma (FMTC), of 5 with multiple endocrine neoplasia type 2A (MEN 2A; codon 634) and of 2 with multiple endocrine neoplasia type 2B (MEN 2B; codon 918). The codon 804 mutation in one FMTC family led to the substitution of Val (GTG) for Met (ATG) and has not been reported previously. Within these 10 families, 32 carriers and 32 non-carriers were identified. Somatic mutations in the tumors of 3 other families suggested a sporadic origin of the neoplasms. In the remaining 3 families, no mutations were identified. Fifty-nine individuals with an apparently sporadic MTC lacked germline mutations in the RET gene, whereas 7 of 24 available tumors (29%) contained a somatic mutation in codon 918. Our findings provide further evidence that molecular genetic evaluation of hereditary and sporadic forms of MTC is a necessary prerequisite for counselling and management of patients and their families.

Adult

In vitro and in vivo studies of three radiolabelled somatostatin analogues: 123I-octreotide (OCT), 123I-Tyr-3-OCT and 111In-DTPA-D-Phe-1-OCT.

Scintigraphy with long-acting somatostatin (SST) analogues may be useful for the localization of tumours expressing receptors (R) for SST. In this study we have analysed the in vitro and in vivo binding properties of three SST analogues, 123I-octreotide (OCT), 123I-Tyr-3-OCT and 111In-DTPA-d-Phe-1-OCT. In vitro binding studies performed with a variety of primary tumours (n=48) as well as with several tumour cell lines (A431, HT29, PANC1, COLO320, HMC1, KU812) indicated significant in vitro binding of these three radiolabelled SST analogues to two subpopulations of SSTR, high (Kd 0.2-2.0 nM) and low (Kd 5-15 nM) affinity ones. The number of SSTR on tumour cells was at least a 1000-fold higher as compared with normal peripheral blood cells. Comparative scintigraphic studies using 123I-OCT and/or 123I-Tyr-3-OCT and/or 111In-DTPA-d-Phe-1-OCT were performed in 21 patients with histologically verified intestinal carcinoid tumours. Corresponding scintigraphic results were obtained in 18 of 21 patients investigated with two different SSTR ligands, either 123I-OCT/123I-Tyr-3-OCT (four of five), 123I-OCT/111In-DTPA-d-Phe-1-OCT (eight of nine), or 123I-Tyr-3-OCT/111In-DTPA-d-Phe-1-OCT (six of seven). We conclude that various tumours express high amounts of SSTR which are recognized by three radiolabelled SST analogues: 123I-OCT, 123I-Tyr-3-OCT and 111In-DTPA-d-Phe-1-OCT. Differences between these SST analogues in their in vitro binding and/or in vivo scanning properties are observed in a minority of patients. Thus, the labelling of OCT with iodine may be an alternative approach for those nuclear medicine departments for which 111In-DTPA-d-Phe-1-OCT is not easily available, or is too expensive.

Adolescent

Combined use of 111In-DTPA-D-Phe-1-octreotide (OCT) and 123I-vasoactive intestinal peptide (VIP) in the localization diagnosis of medullary thyroid carcinoma (MTC).

Although serum calcitonin and CEA are sensitive indicators for the presence of medullary thyroid carcinoma (MTC), the localization of tumor sites may be very difficult. In an approach to localize MTC lesions we performed comparative in vivo studies in 12 patients with primary MTC and in 4 patients with suspected recurrent MTC using 123I-VIP (150 MBq/1 microgram) and 111In-DTPA-D-Phe-1-octreotide (111In-OCT; 150 MBq/1 microgram). Despite elevated calcitonin values in all patients with suspected recurrent or metastatic lesions, both ultrasound and computed tomography (CT) were unable to localize a tumor site. 111In-OCT localized the primary tumor in the thyroid gland in 7 of 11 patients (63.5%). In 2 of 4 patients (50%) with suspected recurrent MTC, pathological uptake of 111In-OCT in the mediastinum or liver was demonstrable. In none of the 11 patients did 123I-VIP-receptor scanning indicate primary, recurrent, or metastatic tumor lesions. In vitro binding studies showed an absence of high-affinity VIP receptors in MTC tissue, whereas high-affinity 111In-OCT receptors were present in 4 of 6, and low-affinity 123I-VIP as well as 111In-OCT receptors were present in 6 of 6 MTC tissue samples. We conclude that somatostatin receptor scanning using 111In-OCT may visualize primary MTC, but it has only a low sensitivity in the detection of recurrent disease. The 123I-VIP-receptor scan is not helpful in the localization diagnosis of primary or recurrent MTC.

Adult

123I-vasoactive intestinal peptide (VIP) receptor scanning: update of imaging results in patients with adenocarcinomas and endocrine tumors of the gastrointestinal tract.

Recent data suggest that functional receptors (R) for vasoactive intestinal peptide (VIP) are expressed on various tumor cells. The high-level expression of VIPR on tumor cells provided the basis for the successful use of 123I-labeled VIP for the in vivo localization of intestinal adenocarcinomas and endocrine tumors. We here report an update of our imaging results using 123I-VIP (150-200 MBg/1 microgram/patient) in 169 patients. In patients with pancreatic adenocarcinomas without liver metastases, the primary/recurrent tumor was visualized in 16 of 18 patients (89%) and liver metastases were imaged in 15 of 16 patients. In 11 of 12 patients with colorectal adenocarcinomas, the primary/recurrent tumor (92%) was imaged by 123I-VIP. Also, in 21 of 25 patients, liver metastases (84%); in 3 of 6 patients, lung metastases (50%); and in 4 of 5 patients, lymph-node metastases (80%) were imaged by 123I-VIP. In 10 of 10 patients with gastric adenocarcinomas, the primary/recurrent tumor; in 3 of 4 patients, liver metastases; and in 2 of 2 patients, lymph-node metastases were visualized by 123I-VIP. 123I-VIP localized primary intestinal carcinoid tumors in 15 of 17 patients (88%) and 8 of 10 primary insulinomas (80%). We conclude that the 123I-VIPR scintigraphy localizes intestinal adenocarcinomas and endocrine tumors as well as metastatic tumor sites.

Adenocarcinoma

Parathyroid adenomas in the aortopulmonary window.

PURPOSE: To describe localization studies in nine patients with ectopic parathyroid adenomas in the aortopulmonary window. MATERIALS AND METHODS: Nine patients with ectopic parathyroid tissue (eight adenomas, one hyperplastic gland) in the aortopulmonary window were examined with ultrasound (US), computed tomography (CT), magnetic resonance (MR) imaging, and scintigraphy. Diagnostic arteriography (n = 4) and venous sampling (n = 3) were performed in the first four patients; arteriography for the purpose of staining was attempted in the last five patients. RESULTS: The results of CT and MR imaging studies were positive in eight of nine patients (89%) and five of eight patients (63%), respectively. The results of thallium/technetium scintigraphy were negative in three patients scanned (0%), but the results of a repeat study in one patient were positive (33%). Sestamibi scans were positive in six of six patients (100%). Single photon emission CT was performed in all six patients and enabled distinction between adenomas in the aortopulmonary window and those in the thymus. CONCLUSION: Ectopic parathyroid glands in the aortopulmonary window are usually detected at sestamibi scintigraphy, and SPECT is helpful in distinguishing these adenomas from more common adenomas in the anterior mediastinum. CT and MR imaging studies can also enable this distinction, but imaging must extend below the aortic arch.

Adenoma

Palliative treatment of obstructing esophageal cancer with nitinol stents: value, safety, and long-term results.

OBJECTIVE: The purpose of our study was to evaluate the effectiveness of nitinol stents for palliation of dysphagia due obstructing esophageal cancer, safety of stent placement, and long-term results. SUBJECTS AND METHODS: Self-expanding uncoated nitinol stents were inserted either radiologically (14 patients) or endoscopically (12 patients) on an outpatient basis in 26 consecutive patients with dysphagia grade 3 or 4 caused by incurable malignant obstructions in the middle or distal third of the esophagus (n = 22) or at esophagojejunal anastomoses (n = 4). No esophagotracheal fistulas were seen in any patient. In 22 patients prior treatments had failed. Following insertion, the stent lumen was dilated to the maximum diameter. Finally, esophagography or esophagoscopy was done to confirm the position of the stent and patency of the esophageal lumen. Twenty-four hours after the procedure, esophageal function was investigated by a barium swallow. Patients were encouraged to ingest solid food thereafter. Improvement in dysphagia was evaluated 1 week after stent placement and during monthly interviews. Complications were defined as major (aspiration, bleeding, stent misplacement or dislocation, perforation) or minor (reflux esophagitis, chest pain, pharyngeal discomfort). Tumor ingrowth or overgrowth was considered a treatment failure. Twenty-three patients (88%) were followed until death: three patients (12%) were followed for a mean of 14 months. RESULTS: Exact positioning of the stent and dilation to its maximum diameter were technically feasible in all patients. No stents were placed in the stomach. Patency of the esophageal lumen was successfully restored in 25 patients. In one patient a broken strut of the stent after dilation caused a partial obstruction, which was detected endoscopically. Two patients had recurrent dysphagia due to tumor ingrowth or overgrowth, one after 1 month and the other after 3 months. In these patients an additional overlapping stent was successfully placed. No procedure-related mortalities or major complications occurred. The mean dysphagia grade of 3.5 was improved to a mean grade of 0.6 after stent placement. All patients could take liquids within the first 24 hr. Fifteen patients improved to dysphagia grade 0, seven patients to grade 1, and four patients to grade 2 within 1 week after the procedure. Twenty-three patients (88%) died during the follow-up period (mean survival, 5 months) as a result of their disease. Latest evaluation of the mean dysphagia grade was 0.7. Three patients (12%) are still alive (mean survival, 14 months) with a dysphagia grade 1 in one patient and grade 0 in two. CONCLUSION: Implantation of nitinol stents proved to be an effective and safe method of palliating severe dysphagia in patients with obstructing esophageal cancer. The improvement in dysphagia was impressive and long lasting. Placement of the stents was feasible without major procedure-related complications.

Aged

The value of lymph node dissection in hereditary medullary thyroid carcinoma: a retrospective, European, multicentre study.

Clinical data of 139 patients with hereditary medullary thyroid carcinoma (HMTC) from nine european centres surgically treated from 1980 to 1991 were reviewed retrospectively to analyse the value of systematic versus selective lymphadenectomy (LA). Biochemical cure rate was significantly higher in patients who underwent LA compared to patients who did not. In nodal-positive HMTC, systematic LA compared to selective LA improved biochemical cure in small but not large tumours. In nodal-negative HMTC, systematic LA compared to selective LA could not improve biochemical cure in either small or large primary tumours. To prevent local recurrences with the risk of increased surgical and tumour-related morbidity, systematic LA should be performed in all HMTC patients regardless of the primary tumour stage. However, an improvement of biochemical cure by systematic LA seems to be possible only in nodal-positive small primary tumours without distant metastases.

Adult

Pheochromocytoma in multiple endocrine neoplasia type 2: European study. The Euromen Study Group.

OBJECTIVES: Pheochromocytoma (pheo) is the second component of the multiple endocrine neoplasia type 2 (MEN 2) syndrome. Clinical expression is sometimes poor, and chronology between medullary thyroid carcinoma (MTC) and pheo is not well evaluated. Therefore, a retrospective study was done in eight European countries in order to precise the main characteristics of pheo in MEN 2. SUBJECTS: Data from 300 MEN 2 patients with pheo (274 MEN 2 A and 26 MEN 2 B) were obtained from cases registered by the EuroMen study group, and collected by a medical standardized questionnaire. These cases occurred between 1969 and 1992. RESULTS: Mean age at diagnosis of pheo was 39.5 years (range 14-68 years) in MEN 2A and 32.4 years (range 15-41 years) in MEN 2B patients. Pheo occurred first in 25.1% of the cases (2-15 years before diagnosis of MTC) and after MTC in 40.2% (2-11 years). In other cases (34.7%), MTC and pheo were diagnosed at the same time. Involvement was bilateral in 67.8% of cases. Malignancy was only 4%. Thirty-nine deaths occurred in these 300 patients, 64.1% were linked in pheo, 23.1% to MTC and 12.8% to other causes. Surgery was unilateral in 39.7% of the cases and bilateral adrenalectomy was the first procedure in 48.4%. A bilateral adrenalectomy in two steps had to be done in 11.9% of cases. In conclusion, these results justify systematic and prolonged biochemical screening of pheo during follow-up of MTC and address some questions about the best mode of surgery.

Adolescent

Primary hyperparathyroidism in multiple endocrine neoplasia type 2A.

The rarity of primary hyperparathyroidism (PHPT) in multiple endocrine neoplasia type 2A (MEN 2A) led us to study clinical findings, surgical therapy and outcome in 67 patients in order to evaluate our therapeutic strategy. The retrospective study was based on cases registered by the EUROMEN study group (nine participating centres) from 1972 to 1993. Characteristics of PHPT in 67 patients (41 females, 26 males) with MEN 2A were reviewed. All patients underwent exploratory neck surgery; PHPT was confirmed histologically and/or biochemically. The median age at diagnosis of PHPT was 38 years. In 75% of the patients, PHPT and medullary thyroid carcinoma were diagnosed synchronously, while in 4%. PHT was diagnosed earlier. In 18% of the patients, PHPT was diagnosed after thyroidectomy, and in 3%, after discovery of pheochromocytoma. Primary hyperparathyroidism was asymptomatic in 84% of the patients; 15% suffered from renal stones. Serum calcium was slightly elevated in 69% (2.9 +/- 0.2 mmol-1) and normal in 16% of subjects. A single adenomectomy was performed in 42% of the patients, subtotal parathyroidectomy in 31% and total parathyroidectomy with autotransplantation in 16%. Independent from the extent of resection, cure was achieved in 94% of the patients, including 13% with hypoparathyroidism; hypercalcaemia persisted in 3% and no information was available in 3%. In an 8-year follow-up, hypercalcaemia recurred in 12% of the patients, although half had undergone parathyroidectomy totally or subtotally. CONCLUSION. MEN 2A-related PHPT is characterized by a mild hypercalcemia which is mostly asymptomatic and can be cured by simple resection of an enlarged parathyroid gland in most cases.

Adolescent

Hepatic artery embolotherapy of hepatic metastases from carcinoid tumors: value of using a mixture of cyanoacrylate and ethiodized oil.

OBJECTIVE: Transcatheter embolization of the hepatic arterial supply is a well-known palliative treatment of tumor deposits in the liver. We performed a prospective study to evaluate the use of a mixture of N-butyl-2-cyanoacrylate and ethiodized oil with which a permanent vascular occlusion can be obtained, as an embolizing agent for transcatheter hepatic artery embolization for treatment of carcinoid hepatic metastases. SUBJECTS AND METHODS: Six patients had clinical symptoms from hormonal release by carcinoid hepatic metastases as well as elevated levels of 5-hydroxyindole acetic acid (5-HIAA) in the urine. Unilobar sequential transcatheter embolization of both the hepatic artery and the segmental hepatic arteries of both lobes of the liver was performed with a mixture of N-butyl-2-cyanoacrylate and ethiodized oil. CT and CT arterial portography (CTAP) were done to assess hepatic metastases and were used to monitor follow-up. Each patient had three CTAP studies; the third CTAP, performed 3 months after complete arterial devascularization, was compared with the first CTAP to evaluate tumor size. CT studies were performed routinely every 3 months thereafter and were compared with the initial CT scan to evaluate further tumor regression or progression. Tumor decrease and biochemical and symptomatic response rates were defined according to World Health Organization criteria. All complications and side effects of the treatment were documented. RESULTS: All patients showed complete symptomatic relief after embolization. The previously elevated levels of 5-HIAA in the urine returned to normal in three patients and in the other three patients were reduced by a mean of 89% of preembolization values. A decrease in tumor size by more than 50% was demonstrable in one patient; in five patients, hepatic lesions decreased in size by 25-50%. No new sites of metastatic liver disease were demonstrable in any patient during follow-up. No deaths or serious complications were directly attributable to the embolization procedure. All patients are alive after 12, 17, 18, 19, 19, and 19 months (mean, 17.3 months), respectively, with permanent relief of symptoms so far. CONCLUSION: Transcatheter embolization of both the hepatic artery and the segmental hepatic arteries with a mixture of N-butyl-2-cyanoacrylate and ethiodized oil provided excellent palliation in patients with carcinoid hepatic metastases. Complete and long-lasting relief of symptoms, a significant decrease or normalization of levels of 5-HIAA in the urine, and a reduction of metastatic tumor in the liver seem most likely to be the effect of sustained ischemia obtained with this permanent embolizing agent.

Carcinoid Tumor

Vasoactive intestinal peptide receptor scintigraphy.

UNLABELLED: This study presents the biodistribution, safety and absorbed dose of 123I-VIP administered to 18 patients with intestinal adenocarcinomas or endocrine tumors. METHODS: To achieve high-specific activity, 123I-VIP was purified by HPLC. Following intravenous administration of 123I-VIP (172 +/- 17 MBq (4.65 +/- 0.5 mCi); < 300 pmole ( < 1 microgram)/patient), sequential images were recorded during the initial 30 min. Thereafter, whole-body images were acquired in anterior and posterior views at various time points. Dosimetry calculations were performed on the basis of gamma camera data, urine, feces and blood activities. RESULTS: After injection of labeled peptide, the lung was the primary site of 123I-VIP uptake. Peak lung activity represented 40% +/- 7% of the injected dose at 0.7 hr and declined to 21% +/- 7% at 3.5, to 14% +/- 3% at 7 and to 8% +/- 4% 22 hr postinjection. Radioactivity was excreted into the urine and amounted to 37% +/- 16% of the injected dose within 4, 68% +/- 12% within 8, 82% +/- 16% within 16 and 93% +/- 8% within 24 hr postinjection. The mean effective half-life of 123I-VIP in the lungs was 2.2 and 6 hr in the urinary bladder. The highest radiation absorbed doses were calculated for the lungs [67 muGy/MBq (248 mrad/mCi)], urinary bladder [77 muGy/MBq (284 mrad/mCi)] and thyroid gland [104 muGy/MBq (386 mrad/mCi)]. The effective dose was 28 muSv/MBq (104 mrem/mCi). CONCLUSION: HPLC-purified 123I-VIP shows favorable dosimetry and is a safe and promising peptide tracer for localization of tumors expressing receptors for VIP.

Adenocarcinoma

Videoradiography of free jejunal grafts for rehabilitation of speech in laryngectomized patients.

In laryngectomized patients a tracheo-esophageal artificial fistula can be used to achieve air flow from the trachea to the esophagus during speech. A one-way plastic valve is often used for the fistula. A free jejunal graft between the trachea and the esophagus can also be used. To avoid aspiration the transplant is attached to the submental area giving the graft a siphon-like shape. We performed 23 videoradiographic examinations using high-density barium in 14 such patients. The aim was to evaluate the protective function of these grafts against aspiration. Penetration of the bolus and a small amount of residual contrast material in the ascending limb of the graft was a normal finding. If the standard barium bolus reached the descending limb at any time during the examination, this was a sign of aspiration hazard. To avoid aspiration, the vertex of the speech siphon should be higher than the level of the hypopharyngeal anastomosis.

Anastomosis, Surgical

Scintigraphic pitfalls in giant parathyroid glands.

We report a case of hyperparathyroidism with surgically confirmed bilaterally enlarged parathyroid glands mimicking a normal thyroid gland. Technetium-99m-pertechnetate-201Tl chloride subtraction scintigraphy was inconclusive because of suppressed thyroidal [99mTc]pertechnetate uptake after coronary angiography. Technetium-99m-sestamibi double-phase scintigraphy showed homogeneous 99mTc-sestamibi uptake that mimicked a normal thyroid gland and no differential washout, thus leading to an erroneous visual interpretation of a normal scan. Semiquantitative assessment of tracer washout, however, can differentiate between normal thyroid tissue and symmetrical parathyroid uptake mimicking normal thyroid tissue. We conclude that semiquantitative assessment of tracer washout increases the diagnostic sensitivity of 99mTc-sestamibi double-phase scintigraphy if: (a) the interpreter is unaware of the anatomical situation, (b) the scintigraphic delineation of the thyroid is hampered by a blocked tracer uptake or (c) the visual interpretation reveals no differential washout in the neck region.

Aged

Vasoactive intestinal peptide-receptor imaging for the localization of intestinal adenocarcinomas and endocrine tumors.

BACKGROUND: Intestinal adenocarcinomas and various endocrine tumors express large numbers of high-affinity receptors for vasoactive intestinal peptide (VIP). We have evaluated the usefulness of scanning with VIP labeled with iodine-123 for tumor localization in patients with gastrointestinal tumors. METHODS: Radioiodinated VIP was purified by high-pressure liquid chromatography and administered as a single intravenous bolus injection (300 pmol [1 microgram]). Scanning with radiolabeled VIP was compared with computed tomography and scanning with somatostatin analogues in 79 patients with colorectal cancer, pancreatic carcinoma, gastric cancer, carcinoid tumor, or insulinoma. RESULTS: Visualization of gastrointestinal tumors and metastases was obtained with radiolabeled VIP. Binding of the labeled peptide by primary tumors and metastases was visible shortly after the injection and was still demonstrable at 24 hours. In patients with colorectal adenocarcinomas, primary or recurrent tumors were visualized in 10 of 10, liver metastases in 15 of 18, lung metastases in 2 of 3, and lymph-node metastases in 4 of 4. Primary pancreatic adenocarcinomas were visualized by imaging in 10 of 12 patients, and liver metastases were seen in 7 of 7. Primary or recurrent gastric adenocarcinomas were visualized in 5 of 5 patients, and liver metastases were seen in 2 of 2 patients. VIP scans were positive in 9 of 10 patients with carcinoid tumors and in 4 of 4 patients with insulinomas. Some tumors with positive VIP scans were also visualized with somatostatin analogues (4 of 17 colorectal adenocarcinomas, 8 of 9 carcinoids, and 2 of 2 insulinomas). In vitro binding studies confirmed the presence of VIP receptors on gastrointestinal tumors. CONCLUSIONS: Scanning with radiolabeled VIP can visualize intestinal tumors and metastases that express receptors for VIP.

Adenocarcinoma

Cross-competition between vasoactive intestinal peptide and somatostatin for binding to tumor cell membrane receptors.

Vasoactive intestinal peptide (VIP) is a 28-amino acid peptide with a wide range of biological activities. Recent data suggest that functional VIP receptors are expressed on various tumor cells. Somatostatin (SST) and its long-acting analogue octreotide (OCT) are potent inhibitors of tumor cell growth and secretion. In the present study, the interactions between VIP and SST/OCT on primary tumors (insulinomas, n = 3; VIPomas, n = 2; intestinal adenocarcinomas, n = 5; neuroblastomas, n = 5; papillary thyroid cancers, n = 7; carcinoids, n = 5; ductal breast cancers, n = 8; small cell lung cancers, n = 3; ACTH-producing hypophyseal adenomas, n = 5; pheochromocytomas, n = 5) as well as on tumor cell lines (A431, HT29, PANC1, COLO320, HMC1, and KU812 cells) were analyzed by use of 123I-labeled VIP and 123I-labeled Tyr-3-OCT. Cross-competition between VIP and SST/OCT for binding to tumor cells was observed. The rank-order of potency for displacement of 123I-labeled VIP binding to intact A431 cells was VIP [concentration causing half-maximal inhibition (IC50) = 2.9 +/- 1.9 (SD) nM] > OCT (IC50 = 9.3 +/- 1.7 nM) = SST > substance P = secretin (IC50 = 1 microM). Binding of 123I-labeled Tyr-3-OCT to A431 cells, in turn, was inhibited by OCT = Tyr-3-OCT (IC50 = 1.5 +/- 0.3 nM) = SST > VIP (IC50 = 4.9 +/- 1.1 nM). This rank-order of potency was also obtained for primary tumors and tumor cell lines. Furthermore, SST and OCT inhibited VIP-induced [3H]thymidine incorporation, cyclic AMP formation, and tyrosine kinase activity with IC50 values < 10 nM. Together, these data provide evidence for functional interactions between SST and VIP on various tumor cells. These interactions may involve peptide cross-competition at cellular binding sites and may have implications for the biology and pathophysiology of respective cells and disease states.

Adenosine Triphosphate

The value of obturator canal bypass. A review.

OBJECTIVE: To review the value of obturator canal bypass with respect to long-term results. DESIGN: Case series and literature review. SETTING: University of Vienna Medical School in Austria. PATIENTS/METHODS: Personal experience with 34 consecutive patients and 125 cases published since 1982 with respect to patient data, patency, and survival are compared and jointly analyzed retrospectively. INTERVENTIONS: Patients received obturator canal bypass for lesions of the pelvic or common femoral vessels precluding orthotopic reconstruction. MAIN OUTCOME MEASURES: The rates of patient survival, limb salvage, and graft patency were analyzed. RESULTS: The postoperative mortality rate in the present series was 14.7%. The limb salvage rate after 5 years was 76.5%. One- and 5-year secondary patency rates were 75.3% and 54.9%, respectively. All grafts in patients without atherosclerosis were patent at a median of 34 months. For 57 cases documented in the literature, 1- and 5-year patency rates were 70.8% and 59.7%, respectively. Combined analysis of 90 obturator canal bypasses revealed rates of 72.7% and 56.9% of patent grafts at 1- and 5-years, respectively. CONCLUSIONS: The use of obturator canal bypass is recommended in deep groin infections and especially in patients with lesions of the pelvic vessels due to other occlusive vascular disease.

Aged

Determination of optimal time window for liver scanning with CT during arterial portography.

PURPOSE: To determine the optimal time window for scanning the liver with computed tomography (CT) during arterial portography (CTAP). MATERIALS AND METHODS: After vasodilation and contrast medium injection into the superior mesenteric artery (80 mL at 5 mL/sec), 25 repeated scans were obtained at a single level within 83 seconds in 13 patients. Attenuation was measured on every scan, and time-attenuation curves were created. Enhancement characteristics of the portal vein, liver parenchyma, aorta, and tumors were evaluated. RESULTS: Parenchymal enhancement of more than 60 HU was achieved between 18 seconds +/- 4 (standard deviation) and 67 seconds +/- 15, and high parenchyma-to-tumor contrast of more than 50 HU occurred between 18 seconds +/- 3 and 62 seconds +/- 14. CONCLUSION: To scan the liver within such a narrow time window, a spiral CT technique is necessary. When the above injection parameters are used in CTAP, the spiral CT sequence should be started 20 seconds after the beginning of the injection.

Adult