Biomedical subjects

S K Libutti

Publications and source records attributed to S K Libutti.

At least 55 records · Page 3Linked to original sources

PubMed2000

Clinical and genetic analysis of patients with pancreatic neuroendocrine tumors associated with von Hippel-Lindau disease.

BACKGROUND: Patients with von Hippel-Lindau disease (VHL) may develop pancreatic neuroendocrine tumors (PNETs), which can behave in a malignant fashion. We prospectively evaluated size criteria for resection of lesions and the role of genotype/phenotype analysis of germline VHL mutations in predicting clinical course. METHODS: From December 1988 through December 1999 we screened 389 patients with VHL. The diagnosis of PNET was made by pathologic analysis of tissues or by radiographic appearance. Germline mutations were determined by quantitative Southern blotting, fluorescence in situ hybridization and complete gene sequencing. RESULTS: Forty-four patients with PNETs have been identified; 25 have undergone surgical resection, 5 had metastatic disease, and 14 are being monitored. No patient who has undergone resection based on tumor size criteria has developed metastases. Patients with PNETs were more likely to have missense mutations (58%), and 4 of 5 patients (80%) with metastatic disease had mutations in exon 3 compared with 18 of 39 (46%) patients without metastatic disease. CONCLUSIONS: Imaging for detection and surgical resection based on size criteria have resulted in the successful management of VHL patients with PNETs. Analysis of germline mutations may help identify patients at risk for PNET and which patients may benefit from surgical intervention.

Adolescent↗

PubMed2000

Forty-eight-hour fast: the diagnostic test for insulinoma.

Insulinoma causes fasting hypoglycemia due to inappropriate insulin secretion. Its diagnosis is based on demonstrating Whipple's triad during a supervised 72-h fast. For 75 yr, the 72-h fast has been the cornerstone for the diagnosis; however, it has never been critically assessed using newer assays for insulin, C peptide, and proinsulin. Thus, the aim of the current study is to assess the need for a full 72-h fast for the diagnosis of insulinoma. Patients with suspected hypoglycemia with documented glucose concentrations below 45 mg/dL were admitted to the NIH. Data obtained during the supervised fast of patients with pathologically proven insulinoma over a 30-yr period (1970-2000) were reviewed. We identified 127 patients with insulinoma. The average age of patients was 42.7 +/- 15.9 yr, with a predominance of females (62%). 107 patients had a benign tumor, 20 had malignant insulinoma, and 15 patients had multiple endocrine neoplasia type 1. The fast was terminated due to hypoglycemia in 44 patients (42.5%) by 12 h, 85 patients (66.9%) by 24 h, and 120 (94.5%) by 48 h. Seven patients fasted beyond 48 h despite subtle neuroglycopenic symptoms and glucose and insulin concentrations diagnostic of insulinoma. Immunoreactive proinsulin was elevated at the beginning of the fast in 90% of 42 patients. Proinsulin in noninsulinoma, in contrast to insulinoma, patients is usually suppressible; therefore, samples taken in the suppressed state have the greatest diagnostic value. We conclude that with the current available insulin and proinsulin assays, the diagnosis of insulinoma can be made within 48 h. Thus, the 48-h fast should replace the 72-h fast in textbooks and hospital protocols as the new diagnostic standard.

Adolescent↗

PubMed2000

Current status of isolated hepatic perfusion with or without tumor necrosis factor for the treatment of unresectable cancers confined to liver.

Metastatic or primary unresectable cancers confined to the liver are the sole or life-limiting component of disease for many patients with colorectal cancer, ocular melanoma, neuroendocrine tumors or primary colangio- or hepatocellular carcinomas. A number of regional treatment strategies including infusional chemotherapy and local ablative therapy are under clinical development and attest to the difficulty in adequately treating this condition. Isolated hepatic perfusion (IHP) was first clinically applied over 40 years ago, but because of its technical complexity, the attendant potential morbidity, and the lack of documented efficacy, it has not gained widespread application. In light of the remarkable antitumor activity with isolated limb perfusion with tumor necrosis factor (TNF) and melphalan in patients with unresectable extremity sarcoma or in transit melanoma, this regimen has been administered via IHP at several centers worldwide for unresectable liver cancers. IHP with TNF and melphalan can result in significant regression of advanced refractory cancers confined to the liver and, with additional clinical development, will most likely be a more routinely considered option for patients with this condition.

Antineoplastic Agents↗

PubMed2000

A phase 2 study of radio frequency interstitial tissue ablation of localized renal tumors.

PURPOSE: Small renal tumors are frequently detected during the screening of patients with a hereditary type of renal cancer. The development of nonsurgical treatment modalities would greatly improve quality of life in these patients. We present our experience with radio frequency interstitial tissue ablation, a heating device approved by the Food and Drug Administration for treating soft tissue tumors. MATERIALS AND METHODS: Patients underwent radio frequency interstitial tissue ablation of small renal tumors just before surgical excision. Pathological examination of the renal tumors was done to evaluate the treatment effect. Computerized tomography and renal function testing were performed before and after therapy to evaluate toxicity. RESULTS: Four patients underwent treatment of a total of 14 tumors with the radio frequency interstitial tissue ablation device just before surgical removal of the tumors. All lesions were brown after ablation, in contrast to the normal pink appearance of untreated lesions that were resected. On color Doppler ultrasound blood flow to each tumor evident before was not visualized after treatment. The Wilcoxon rank sum test demonstrated no difference preoperatively and postoperatively in blood urea nitrogen, serum creatinine, creatinine clearance or differential renal function. We identified no toxicity associated with radio frequency interstitial tissue ablation. Of the excised tumors 11 were renal cell carcinoma and 3 fibrotic hemorrhagic cysts. For renal cell carcinoma the treatment effect involved the loss of nuclear detail and nonvisualization of nucleoli. These changes were not observed in any tumors resected without radio frequency interstitial tissue ablation. The treatment effect was noted in 10 of the 11 lesions, and in 1 case the treatment effect involved 35% of the tumor. CONCLUSIONS: No toxicity was associated with radio frequency interstitial tissue ablation. Percutaneous treatment of renal tumors is planned to evaluate the treatment effect better and further evaluate toxicity.

Adult↗

PubMed2000

A phase I-II study of isolated hepatic perfusion using melphalan with or without tumor necrosis factor for patients with ocular melanoma metastatic to liver.

There are no satisfactory treatment options for patients with ocular melanoma metastatic to liver, and after liver metastases are identified, median survival is only between 2 and 7 months. Because liver metastases are the sole or life-limiting component of disease in the vast majority of patients who recur, we reasoned that complete vascular isolation and perfusion of the liver might result in clinically meaningful regression of disease. Between September 1994 and July 1999, 22 patients (13 women and 9 men; mean age, 49 years) with ocular melanoma metastatic to liver were treated with a 60-min hyperthermic isolated hepatic perfusion (IHP) using melphalan alone (1.5-2.5 mg/kg, n = 11) or with tumor necrosis factor (TNF, 1.0 mg, n = 11). Via a laparotomy, IHP inflow was via the hepatic artery alone (n = 17) or hepatic artery and portal vein (n = 5) and outflow from an isolated segment of inferior vena cava. Most patients had advanced tumor burden with a mean percentage of hepatic replacement of 25% (range, 10-75%) and a median number of metastatic nodules of 25 (range, 5 to >50). Complete vascular isolation was confirmed in all patients using a continuous intraoperative leak monitoring technique with 131I radiolabeled albumin. There was one treatment mortality (5%). The overall response rate in 21 patients was 62% including 2 radiographic complete responses (9.5%) and 11 partial responses (52%). The overall median duration of response was 9 months (range, 5-50) and was significantly longer in those treated with TNF than without (14 versus 6 months, respectively; P = 0.04). Overall median survival in 22 patients was 11 months. These data indicate that a single 60-min IHP can result in significant regression of advanced hepatic metastases from ocular melanoma. TNF appears to significantly prolong the duration of response.

Adult↗

PubMed2000

Parametric images of blood flow in oncology PET studies using [15O]water.

UNLABELLED: PET was used to measure tumor blood flow, which is potentially valuable for diagnosis and assessing the effects of therapy. To help visualize regional differences in blood flow and to improve the accuracy of region-of-interest placement, a parametric imaging approach was developed and compared with the standard region-of-interest method. METHODS: Five patients with renal cell metastases in the thorax were studied using [15O]water and dynamic PET. To assess the reproducibility of the blood flow measurements, multiple water studies were performed on each patient. Model fitting was done on a pixel-by-pixel basis using several different formulations of the standard single-compartment model. RESULTS: The tumors studied spanned a wide range of blood flows, varying from 0.4 to 4.2 mL/min/g. These values were generally high compared with those of most other tissues, which meant that the tumors could be readily identified in parametric images of flow. The different model formulations produced images with different characteristics, and no model was entirely valid throughout the field of view. Although tumor blood flow measured from the parametric images was largely unbiased with respect to a standard regional method, large errors were observed with certain models in regions of low flow. The most robust model throughout the field of view had only 1 free parameter and, compared with a regional method, gave rise to a flow bias of 0.3%+/-3.1% for tumor and 16%+/-11% for low-flow soft tissue (muscle plus fat). With this model, tumor blood flow was measured with an SD of 7.6%+/-4.0%. CONCLUSION: Parametric imaging provides a convenient way of visualizing regional changes in blood flow, which may be valuable in studies of tumor blood flow.

Blood Flow Velocity↗

PubMed2000

Serum endostatin levels are elevated and correlate with serum vascular endothelial growth factor levels in patients with stage IV clear cell renal cancer.

Clear cell renal carcinoma (CCRC) is a highly angiogenic tumor known to secrete vascular endothelial cell growth factor (VEGF). Endostatin is an endogenous antiangiogenic agent with antitumor activity in mice. The purpose of this study was to evaluate serum levels of endostatin in normal subjects and in patients with CCRC and to examine the relationship of these levels to circulating VEGF levels. Fifteen patients (mean age, 48 years) on a clinical protocol for stage IV CCRC at the National Cancer Institute were included in the study. Archived prenephrectomy serum samples were analyzed for endostatin and VEGF concentrations. Endostatin and VEGF levels were compared with those of an age-matched group of volunteer blood donors (n = 18) using a competitive enzyme immunoassay. Data were analyzed using the Mann-Whitney U test and the Spearman rank correlation. Median serum endostatin levels were 24.6 ng/ml (range, 15.1-54.0 ng/ml) in CCRC patients versus 14.1 ng/ml (range, 1.0-19.3 ng/ml) in healthy controls (P < 0.0001). Median VEGF levels were 3.4 ng/ml (range, 0.1-11.2 ng/ml) and 2.5 ng/ml (range, 0.1-4.2 ng/ml), respectively (P = 0.065). A highly significant correlation was observed between endostatin and VEGF levels among the CCRC patients (r = 0.81, P = 0.0003) but not among controls (r = -0.22, P = 0.37). Endostatin levels are detectable in serum from healthy subjects as well as from CCRC patients. Levels are significantly elevated and correlate with VEGF levels in CCRC patients. Elucidating the nature of this correlation may lend insight into the regulation of tumor angiogenesis in patients with renal cancer.

Adenocarcinoma, Clear Cell↗

PubMed1999

Sensitization of tumor necrosis factor alpha-resistant human melanoma by tumor-specific in vivo transfer of the gene encoding endothelial monocyte-activating polypeptide II using recombinant vaccinia virus.

Tumor necrosis factor alpha (TNF-alpha) is a proinflammatory cytokine with potent experimental antitumor activity. Its clinical use in cancer treatment is severely limited by its considerable toxicity after systemic administration, and it is currently confined to isolated limb and organ perfusion settings. In this report, we introduce a novel concept of TNF-alpha-based gene therapy using the TNF-sensitizing properties of endothelial cell monocyte-activating polypeptide II (EMAP-II). We hypothesized that transfer of the EMAP-II gene into established TNF-resistant human melanomas would render these tumors sensitive to subsequent systemic TNF-alpha treatment. To achieve tumor selective gene delivery, we constructed a recombinant vaccinia virus encoding the human EMAP-II gene (vvEMAP). In vitro transfection of human melanoma cells led to the production of EMAP-II by these cells. Supernatants of vvEMAP-transfected tumor cells mediated the induction of tissue factor in endothelial cells. We characterized the pattern of gene expression after systemic administration of a recombinant vaccinia virus encoding a reporter gene in a murine in vivo model of s.c. human melanoma. Gene expression in tumor tissue was increased 100-fold as compared with normal tissue, providing evidence for tumor-selective gene delivery. Finally, human melanomas in nude mice were sensitized in vivo by transferring the EMAP-II gene using vvEMAP. Subsequent systemic administration of TNF-alpha led to tumor regression and growth inhibition of these previously TNF-resistant tumors (P < 0.05). This approach using gene therapy to sensitize primarily unresponsive tumors toward TNF-alpha may enhance the usefulness of TNF-alpha in clinical treatment strategies by increasing the window for the therapeutic application of the cytokine, thus reducing the dose necessary for antitumor responses and subsequently reduce toxicity.

Animals↗

PubMed1999

In vivo sensitivity of human melanoma to tumor necrosis factor (TNF)-alpha is determined by tumor production of the novel cytokine endothelial-monocyte activating polypeptide II (EMAPII).

Tumor necrosis factor (TNF)-alpha is a potent anticancer agent that seems to selectively target tumor-associated vasculature resulting in hemorrhagic necrosis of tumors without injury to surrounding tissues. The major limitation in the clinical use of TNF has been severe dose-limiting toxicity when administered systemically. However, when administered in isolated organ perfusion it results in regression of advanced bulky tumors. A better understanding of the mechanisms of TNF-induced antitumor effects may provide valuable information into how its clinical use in cancer treatment may be expanded. We describe here that the release of a novel tumor-derived cytokine endothelial-monocyte-activating polypeptide II (EMAPII) renders the tumor-associated vasculature sensitive to TNF. EMAPII has the unique ability to induce tissue factor production by tumor vascular endothelial cells that initiates thrombogenic cascades, which may play a role in determining tumor sensitivity to TNF. We demonstrate here that constitutive overexpression of EMAPII in a TNF-resistant human melanoma line by retroviral-mediated transfer of EMAPII cDNA renders the tumor sensitive to the effects of systemic TNF in vivo, but not in vitro. This interaction between tumors and their associated neovasculature provides an explanation for the focal effects of TNF on tumors and possibly for the variable sensitivity of tumors to bioactive agents.

Animals↗

PubMed1999

Management of symptomatic malignant melanoma of the gastrointestinal tract.

BACKGROUND: Melanoma metastatic to the gastrointestinal (GI) tract is asymptomatic or presents with pain, bleeding, or obstruction. To determine whether surgery influences outcomes, we reviewed our experience with this patient population. METHODS: Medical records of patients with metastatic melanoma to the GI tract were reviewed. Patients were divided into four groups, i.e., complete resection, partial debulking, unresectable, or unexplored. Analysis was performed using the Kaplan-Meier method. RESULTS: Fifty patients with melanoma metastatic to the GI tract were identified (40 men and 10 women; mean age, 44 years). Presenting symptoms included pain (62%), bleeding (28%), and obstruction (18%). Diagnosis was confirmed using contrast studies (38%), endoscopy (20%), or computed tomography (30%). Thirty-six patients (61%) underwent a total of 39 operations. Seventeen patients underwent complete resection, whereas 14 underwent partial debulking. Five patients had unresectable lesions, and 14 patients did not undergo exploration because of medical contraindications. The operative mortality rate was 2.5% (1 of 39). The mean survival times for the unexplored and unresected groups were similar (4.1 months). Patients who underwent partial resection exhibited a longer mean survival time (8.9 months) than did patients in the unresected group (P < .001). The complete-resection group demonstrated a mean survival time of 23.5 months, which was significantly longer than that for patients who underwent less than complete resection (P < .0001). CONCLUSIONS: Metastatic melanoma to the GI tract can result in significant morbidity and death. Surgical resection can be performed safely. Patients for whom all sites of disease are completely resected experience significant improvements in survival times, compared with patients who undergo less than complete resection. For selected patients, surgical treatment of metastatic melanoma involving the GI tract is appropriate therapy.

Adult↗

PubMed1999

Management of extremity recurrences after complete responses to isolated limb perfusion in patients with melanoma.

BACKGROUND: Despite high rates of complete responses (CRs) to isolated limb perfusion (ILP) for patients with in-transit melanoma (60% to 90%), extremity recurrences are common. We evaluated our experience with managing these recurrences to determine how best to treat these patients. METHODS: Between April 1992 and April 1998, 72 patients experienced CRs after hyperthermic ILP using Melphalan, with (n = 46) or without (n = 26) tumor necrosis factor. Of these, 25 patients (35%) experienced initial recurrences in the extremities, and they form the basis of this study. RESULTS: Three patients who underwent repeat ILP for treatment of their recurrences experienced a second CR and recurrence in the extremity (at 9, 15, and 16 months), allowing analysis of 28 cases. For 5 of 20 recurrences managed with excision, 2 of 6 managed with repeat ILP, and 0 of 2 managed with systemic treatment, the patient was free of disease at the last follow-up examination (median follow-up period, 11 months). CONCLUSIONS: Isolated extremity recurrences after CRs to ILP occurred in 35% of patients. Initially, these could be managed successfully by excision or repeat ILP for the majority of patients (92%). We recommend excision of small-volume recurrent disease, reserving repeat ILP for patients with increasing numbers of lesions or increasing rapidity of in-field recurrences.

Adult↗

PubMed1999

Treatment of primary peritoneal mesothelioma by continuous hyperthermic peritoneal perfusion (CHPP).

BACKGROUND: Primary peritoneal mesothelioma is a locally aggressive disease that is difficult to treat or even palliate. Continuous hyperthermic peritoneal perfusion (CHPP) with cisplatin (CDDP) allows uniform, high regional delivery of chemotherapeutics and hyperthermia to the peritoneal surface for the treatment of peritoneal tumors. This article summarizes the results of 18 patients with peritoneal mesothelioma treated with CHPP. METHODS: From June 1993 through April 1998, 18 patients with primary peritoneal mesothelioma (13 male, 5 female; median age, 51 years) underwent surgical exploration and tumor debulking followed by a 90-minute CHPP with CDDP and hyperthermia as part of three consecutive phase I trials conducted at the National Cancer Institute. Seventeen of 18 patients had malignant peritoneal mesothelioma, 13 with associated ascites. One patient had a symptomatic, multiply recurrent, benign, cystic peritoneal mesothelioma. Three patients who had a recurrence after a prolonged progression-free interval (>6 months) after CHPP underwent re-treatment. CHPP parameters included median cisplatin dose of 530 mg (range, 187-816), perfusate volume 6.0 liter (range, 4-9), flow 1.5 liter/min (range, 1-2), intraperitoneal temperature 41 degrees C (range, 38.7-43.2), and central temperature 38.6 degrees C (range, 36.8-39.7). RESULTS: Median follow-up after CHPP is 19 months (range, 2-56) with no operative or treatment-related mortality. Overall operative morbidity was 24% and included two patients with superficial wound infection and one patient each with atrial fibrillation, pancreatitis, fascial dehiscence, ileus, line sepsis, and clostridium difficile colitis. The major treatment-related toxicity was systemic renal toxicity at doses above what was defined as the maximum tolerated dose of cisplatin. Nine of 10 patients had resolution of their ascites postoperatively. Three patients who developed recurrent ascites (27, 22, and 10 months after initial treatment) were re-treated and had resolution of their ascites with ongoing responses at 24, 6, and 4 months after the second perfusion. The median progression-free survival was 26 months, and the overall 2-year survival was 80%. The median overall survival has not been reached. CONCLUSIONS: CHPP with cisplatin can be performed safely with no mortality and minimal morbidity. In selected patients, successful palliation in the abdomen and long-term survival, compared with historical controls, can be achieved with aggressive surgical debulking and CHPP. Re-treatment after initial response can result in a second long-term response.

Adolescent↗

PubMed1999

Laparoscopic cytoreductive nephrectomy as preparation for administration of systemic interleukin-2 in the treatment of metastatic renal cell carcinoma: a pilot study.

OBJECTIVES: Cytoreductive nephrectomy is commonly performed in patients with metastatic renal cell carcinoma before systemic interleukin-2 (IL-2) therapy. Open nephrectomy is associated with prolonged recovery during which metastatic disease can progress. The feasibility of laparoscopic cytoreductive surgery in these patients with large renal tumors was examined. The role of tumor morcellation in reducing the recovery period and allowing earlier treatment with IL-2 was investigated. METHODS: Patients with metastatic renal cancer underwent either open nephrectomy (group 1, n = 19) or laparoscopic cytoreductive nephrectomy (n = 11; 6 with tumor morcellation [group 2], 5 with removal of the tumor through a small incision [group 3]). The three groups were compared to evaluate relative recovery, suitability for treatment with IL-2, and laparoscopic port site seeding. RESULTS: A group of 19 patients underwent open nephrectomy (group 1). Eleven patients with a median tumor volume of 377 cm3 (median tumor diameter 9 cm) underwent laparoscopic cytoreductive nephrectomy. Six of these patients underwent tumor morcellation (group 2) and 5 underwent laparoscopic assisted nephrectomy (group 3). There was no difference in patient age, sex, sites of metastatic disease, ECOG status, size of renal tumor, or surgical complication rates among groups. Patients whose tumor was morcellated had reduced postoperative parenteral narcotic requirements and were discharged sooner than patients undergoing open cytoreductive nephrectomy. Time to treatment with IL-2 was shortest in the morcellation group (median time to treatment 37 days). No port site seeding was observed. CONCLUSIONS: Laparoscopic cytoreductive nephrectomy in patients with bulky renal disease is a safe procedure in selected patients. This pilot study demonstrated a significant association of laparoscopic tumor morcellation with less postoperative pain, faster time to discharge, and shorter time to treatment with IL-2. A randomized study is warranted to determine the role of laparoscopic cytoreductive nephrectomy with tumor morcellation.

Carcinoma, Renal Cell↗

PubMed1999

Heterogeneous gland size in sporadic multiple gland parathyroid hyperplasia.

BACKGROUND: The success rate for bilateral exploration in patients with primary hyperparathyroidism approaches 95%. Multiglandular parathyroid hyperplasia accounts for approximately 10% to 30% of primary hyperparathyroidism. The incidence of recurrent or persistent hyperparathyroidism is highest in familial forms of the disease, in which multiglandular disease is more common; this may be due to asymmetric enlargement of parathyroid glands. Because of improvements in tumor-imaging capability, some surgeons are now advocating unilateral exploration for primary hyperparathyroidism, but there is limited experience concerning how often these imaging methods fail. STUDY DESIGN: The outcomes of 7 patients who had sporadic primary hyperparathyroidism with multigland hyperplasia were reviewed. We gathered demographic data and laboratory values and reviewed radiologic tests, surgical findings, pathologic findings, and postoperative followup. RESULTS: All patients underwent preoperative localization with ultrasonography and technetium/sestamibi scans. The sensitivity of these two tests for the dominantly enlarged gland was 100% for both, but dropped to 0% and 5%, respectively, for all other enlarged glands. The sensitivity of CT and MRI for the dominant tumor was 67% (2 of 3) and 50% (1 of 2), respectively. Six of 7 patients underwent subtotal (3(1/2) gland) parathyroidectomy. The mean volume of all glands was 1.51+/-5.89 cm3 compared with a mean of 5.66+/-11.4 cm3 for all dominant glands and 0.123+/-0.1 cm3 for all nondominant hyperplastic glands. There was a large amount of variability between the volumes of dominant and other glands as demonstrated by large SDs from the mean. CONCLUSIONS: There is a marked heterogeneity in gland size in patients with sporadic multigland hyperplasia, which is similar to that found in multiple endocrine neoplasia type I. This heterogeneity may result in failure to recognize multigland disease if a unilateral neck exploration is performed. Intraoperative parathyroid hormone assay may prove to be an important adjunct in this population of patients who have unsuspected multigland disease.

Adult↗

PubMed1999

Results of heterotopic parathyroid autotransplantation: a 13-year experience.

BACKGROUND: The reported success of heterotopic parathyroid autotransplantation (HPA) in patients with primary hyperparathyroidism varies from 20% to 60%. The purpose of this study was to evaluate our results with HPA to help define its role in this patient group. METHODS: Between July 1985 and June 1998, 44 patients underwent 51 HPA procedures at our institution. Twenty to 25 fragments of parathyroid tissue measuring 1 to 3 mm3 each were placed into the forearm musculature. HPA results were scored as nonfunctional (requiring calcium and vitamin D), partially functional (normocalcemia on calcium alone), fully functional (normocalcemia without supplementation), or hyperfunctional (hypercalcemia without supplementation). RESULTS: Follow-up data were available for 39 patients who underwent 46 autografts (20 immediate and 26 cryopreserved). With a median follow-up of 35 months, 19 autografts (41%) were nonfunctional; 9 autografts (20%) were partially functional; 15 autografts (33%) were fully functional, and 3 autografts (7%) were hyperfunctional. Full function was observed in 35% of immediate and 31% of delayed autografts. CONCLUSIONS: One third of parathyroid autografts develop full function, and an additional one fifth develop partial function. Recurrent hyperparathyroidism is uncommon. No benefit was observed from immediate versus delayed HPA, and the modest success rate of HPA suggests that improvements in technique are warranted.

Adenoma↗

PubMed1999

Kinetic analysis of the rapid intraoperative parathyroid hormone assay in patients during operation for hyperparathyroidism.

BACKGROUND: Rapid intraoperative parathyroid hormone (RI-PTH) assay is used to guide adequacy of resection during operation for hyperparathyroidism. We compared the RI-PTH assay (15 minutes) with a standard PTH assay, determined whether the PTH half-life varied between patients, and constructed a kinetic analysis of the RI-PTH data. METHODS: Forty-five patients with hyperparathyroidism had blood sampled at baseline and at times after parathyroid resection. Intact PTH was determined using RI-PTH and a standard assay. Values were fitted to an exponential decay curve using the baseline and the follow-up time points. PTH half-life and the new postexcision baseline value were calculated from the decay curve. RESULTS: The RI-PTH assay and the standard PTH assay correlated well. Average PTH half-life was 1.68 +/- 0.94 minutes (0.42 to 3.81 minutes). A kinetic analysis yielded a formula for the generation of a PTH decay curve. Using a 50% reduction in RI-PTH at 5 minutes as the criterion for adequate resection, 2 patients were incorrectly classified as not being cured. These patients were correctly classified using the kinetic analysis. CONCLUSIONS: PTH half-life can vary substantially. A kinetic analysis may be more accurate in assessing adequacy of resection. This method allows the surgeon to interpret RI-PTH data independent of the timing of samples.

Adult↗

PubMed1999

Tumor angiogenesis and endothelial cell modulatory factors.

Angiogenesis is the ability of preexisting vasculature to send out capillary sprouts leading to the formation of new vasculature. It is now a well-accepted idea that progression of solid tumors is intrinsically dependent on angiogenesis for growth of the primary tumor and metastatic lesions. Investigations into tumor angiogenesis have focused on inhibition of tumor neovasculature as yet another possible mechanism for impairing tumor progression. Numerous studies have characterized cellular and molecular factors important to vascular formation and development and have led to the identification and understanding of requisite interactions between endothelium, angiogenic cytokines, and the supporting matrix. These studies have also led to the identification of cytokines involved in the proteolytic disruption of the basement membrane, the migration of endothelial cells, and the proliferation and formation of neoendothelium into functional vasculature. As therapies based on antiangiogenic strategies continue to evolve and clinical trials are conducted, these agents may become an important part of the arsenal against tumor proliferation, especially given their favorable toxicity profile. This review discusses the angiogenic cytokines which have been most intensely studied and the receptors they act upon. Additionally, we discuss select proteases and their importance in the development of neovasculature. A better understanding of these components will help in the development of novel therapeutic strategies.

Antineoplastic Agents↗

PubMed1999

Pharmacokinetics of cisplatin administered by continuous hyperthermic peritoneal perfusion (CHPP) to patients with peritoneal carcinomatosis.

The pharmacokinetics of cisplatin administered by continuous hyperthermic peritoneal perfusion (CHPP) was characterized in patients with peritoneal carcinomatosis. Cisplatin was added into the perfusate with escalating doses from 100 mg/m2 to 400 mg/m2. The hyperthermic perfusion was maintained for 90 minutes with a flow rate of 1.5 L/min and a target peritoneal temperature of 42.5 degrees C after a tumor debulking procedure. Samples of both the perfusate and blood were obtained during the perfusion and 30 minutes after the perfusion. Cisplatin plasma and perfusate concentrations were determined by flameless atomic absorption spectrometry with a lower limit of detection of 2 ng/ml and a coefficient of variation (CV) < 10%. Fifty-six patients were enrolled in the study. The mean (+/- SD) percentage of cisplatin present in the perfusate at the completion of perfusion was 27.8% +/- 20% of the total dose. The maximum cisplatin concentrations in the perfusate were 10 times higher than those in plasma. The area under the concentration-time curve (AUC) of the perfusate was 13 times higher than the AUC of plasma. A two-compartment model with an additional peritoneal cavity compartment fits to the data best based on the Akaike information criterion. However, the interpatient variability was considerably high (CV < 100%). In conclusion, cisplatin administered by hyperthermic peritoneal perfusion resulted in a pharmacological advantage by obtaining higher and direct drug exposure to the tumor in the peritoneal cavity while limiting systemic absorption and toxicity. Using a complex two-compartment model, the authors were able to characterize the pharmacokinetics of cisplatin given intraperitoneally via this technique.

Adult↗