Biomedical subjects

Richard Chang

Publications and source records attributed to Richard Chang.

28 records · Page 2Linked to original sources

PubMed2002

Blind distal pancreatectomy for occult insulinoma, an inadvisable procedure.

BACKGROUND: Fasting hypoglycemia with neuroglycopenic symptoms corrected by administration of glucose are the hallmarks for the diagnosis of insulinoma. Surgical resection is the treatment of choice for insulinomas, but localization of these lesions can be challenging. Blind distal pancreatectomy has been advocated for occult insulinomas not detected on imaging studies or during abdominal exploration. With the advent of newer localization techniques, we challenge the wisdom of this approach. STUDY DESIGN: The records of patients (multiple endocrine neoplasia excluded) with pathologically proved insulinoma who were screened at our institution or referred to us after a failed blind distal pancreatectomy were reviewed. All records included patient history and results of physical examination and routine blood and urine tests. The diagnosis of insulinoma was confirmed during a supervised fast. Patients with biochemically proved insulinoma underwent localization studies and operation. Studies included CT scans, MRI, transabdominal ultrasound, intraoperative ultrasonography, angiography (more recently, Ca++-stimulated arteriography), and venous sampling. RESULTS: From 1970 to 2000, 99 patients (34 men, 65 women; mean age 43 years) underwent operation. All patients with benign tumors (92) were cured after operation. Seventeen patients were referred to the NIH after a failed blind distal pancreatectomy. Of these, 5 were diagnosed as having factitious hypoglycemia. In the other 12 patients a tumor was localized in the pancreatic head. Two patients incorrectly diagnosed with nesidioblastosis after initial surgery were subsequently cured by resection of an insulinoma. CONCLUSIONS: The use of preoperative imaging studies, most notably Ca++-stimulated arteriography, and intraoperative ultrasonography permits detection of virtually all insulinomas, including reopcrated cases. When a tumor is not detected, the procedure should be terminated and the patient referred to a center capable of performing advanced preoperative and intraoperative localization techniques. With the preoperative and intraoperative imaging strategies currently available, the use of blind distal pancreatectomy for occult insulinoma should be abolished.

Adolescent↗

PubMed2002

Hepatic abscess in patients with chronic granulomatous disease.

OBJECTIVE: To evaluate the clinical presentation, diagnostic procedures, and surgical management of hepatic abscesses in patients with chronic granulomatous disease (CGD). SUMMARY BACKGROUND DATA: Chronic granulomatous disease is a rare inherited primary immunodeficiency in which phagocytes cannot destroy catalase-positive bacteria and fungi. Defects in the phagocytic cells' respiratory burst lead to life-threatening infections, including hepatic abscess. These abscesses are recurrent and often multiple and are treated differently from bacterial abscesses in patients without CGD. METHODS: Between 1980 and 2000, 61 cases of hepatic abscess in 22 patients with CGD were treated at the National Institutes of Health. Clinicopathologic features were investigated by retrospective review of the medical records, radiographs, and histopathology. RESULTS: Twelve of the 61 cases were primary hepatic abscesses. Twenty-nine of the cases were recurrent hepatic abscesses, and 20 cases were persistent hepatic abscesses. The median age at the time of initial hepatic abscess presentation was 14 years. Subjective fever was the most frequent presenting symptom, and the erythrocyte sedimentation rate was elevated in 98% of cases. Fifty-two cases were managed surgically and eight cases were managed with percutaneous drainage. One patient refused surgery. The surgical complication rate was 56%; however, there were no deaths directly related to the hepatic abscesses. Staphylococcus aureus was the most frequent organism identified in culture (88% of positive cultures). Aggressive surgery and antibiotics ultimately resulted in successful treatment of all patients. CONCLUSIONS: Hepatic abscesses occurring in patients with CGD represent a difficult diagnostic and treatment challenge. Early excision and treatment with antibiotics directed against S. aureus is necessary. General surgeons should be aware of this rare immunodeficiency and should aggressively manage hepatic abscesses in these patients.

Adolescent↗

PubMed2002

TGF-beta1-stimulated osteoblasts require intracellular calcium signaling for enhanced alpha5 integrin expression.

The osteoactive factor, transforming growth factor beta1 (TGF-beta1), influences osteoblast activity and bone function. We recently characterized a Smad-independent TGF-beta1-induced Ca(2+) signal in human osteoblasts (HOB) and demonstrated its importance in cell adhesion. Here, we further elucidate the role of the TGF-beta1 Ca(2+) signal in the mechanics of HOB adhesion. Osteoblast interaction with fibronectin (FN) through alpha5beta1 integrin is principally responsible for osteoblast-substrate adhesion. Our results show that the TGF-beta1 intracellular Ca(2+) signal is responsible, in part, for stimulation of alpha5 integrin expression, but not beta1 integrin or FN expression. Increased alpha5 integrin protein and mRNA expression was seen as early as 12 h after TGF-beta1 treatment, but was inhibited by cotreatment with nifedipine, a Ca(2+) channel blocker. TGF-beta1 increased both FN and beta1 integrin protein production within 48 h, independent of nifedipine cotreatment. Immunofluorescence observations revealed that TGF-beta1 increased alpha5 integrin staining, clustering, and colocalization with the actin cytoskeleton, effects that were blocked by nifedipine. The TGF-beta1 Ca(2+) signal, a pathway crucial for HOB adhesion, enhances alpha5 integrin expression, focal contact formation, and cytoskeleton reorganization. These early events are necessary for osteoblast adhesion; thus they determine the fate of the cell and ultimately affect bone function.

Actins↗

PubMed2002

Pancreatic islet transplantation using the nonhuman primate (rhesus) model predicts that the portal vein is superior to the celiac artery as the islet infusion site.

We've established a nonhuman primate islet allotransplant model to address questions such as whether transplanting islets into the gut's arterial system would more safely and as effectively support long-term islet allograft survival compared with the traditional portal vein approach. We reasoned that islets make up <2% of pancreatic cell mass but consume an estimated 20% of arterial blood flow, suggesting an advantage for the arterial site. Access to the arterial system is also easier and safer than the portal system. Pancreatectomized rhesus macaques were transplanted with allogeneic islets infused into either the portal vein (n = 6) or the celiac artery (n = 4). To prevent rejection, primates were given daclizumab, tacrolimus, and rapamycin. In five of six portal vein experiments, animals achieved normoglycemia without exogenous insulin. In contrast, none of the animals given intra-arterial islets showed even transient insulin independence (P = 0.048). Two of the latter animals received a second islet transplant, this time to the portal system, and both achieved insulin independence. Thus, intraportal islet transplantation under conventional immunosuppression is feasible in primates and can result in long-term insulin independence when adequate immunosuppression is maintained. Arterial islet injection, however, does not appear to be a viable islet transplantation technique.

Animals↗

PubMed2002

Percutaneous radio frequency ablation of small renal tumors: initial results.

PURPOSE: Thermal tissue ablation with radio frequency energy is an experimental treatment of renal tumor. We report early results of an ongoing trial of percutaneous radio frequency ablation for small renal tumors. MATERIALS AND METHODS: Patients with percutaneously accessible renal tumors were evaluated for radio frequency ablation. Tumors were solid on computerized tomography (CT), 3 cm. or less in diameter and enlarging during at least 1 year. Ablation was performed at the Interventional Radiology suite under ultrasound and/or CT guidance. A 50 W., 460 kHz. electrosurgical generator delivered radio frequency energy via a percutaneously placed 15 gauge coaxial probe. At least 2, 10 to 12-minute ablation cycles were applied to each lesion. Patients were observed overnight before discharge from hospital and reevaluated 2 months later. RESULTS: A total of 24 ablations were performed in 21 patients with renal tumor, including solid von Hippel-Lindau clear cell tumor in 19 and hereditary papillary renal cancer 2. Most (22 of 24) procedures were performed with patients under conscious sedation. At 2 months postoperatively mean tumor diameter plus or minus standard deviation decreased from 2.4 +/- 0.4 to 2.0 +/- 0.5 cm. (p = 0.001), and a majority of tumors (19 of 24, 79%) ceased to be enhanced on contrast CT. Mean serum creatinine plus or minus standard deviation was unchanged during this interval (1.0 +/- 0.2 mg./dl.). No major and 4 minor complications were encountered, including 2 episodes each of transient psoas pain and flank skin numbness. CONCLUSIONS: Percutaneous radio frequency ablation of small renal tumor is well tolerated and minimally invasive. It will remain experimental until procedural and imaging parameters that correlate with tumor destruction are validated.

Adult↗

PubMed2002

Administration of a phorbol ester to patients with hematological malignancies: preliminary results from a phase I clinical trial of 12-O-tetradecanoylphorbol-13-acetate.

PURPOSE: Phorbol esters are capable of inducing a broad range of cellular effects,including the maturation/differentiation of hematopoietic cell lines (E. Huberman and M. F. Callaham, Proc. Natl. Acad. Sci. USA, 76: 1293-1297, 1979; J. Lotem and L. Sachs, Proc. Natl. Acad. Sci. USA, 76: 5158-5162, 1979; G. Rovera et al., Proc. Natl. Acad. Sci. USA, 76: 2779-2783, 1979; H. P. Koeffler, J. Clin. Investig., 66: 1101-1108, 1980). The ability to induce this differentiation at very low concentrations stimulated investigators to administer a phorbol ester, 12-O-tetradecanoylphorbol-13-acetate (TPA), to patients with myeloid leukemias in the People's Republic of China (Z. T. Han et al., Proc. Natl. Acad. Sci. USA, 95: 5357-5361, 1998). The tolerability of this therapy in China prompted Phase I studies of TPA in the United States. The purpose of this report is to demonstrate the tolerance of TPA at doses that result in detectable biological activity in blood and malignant cells. EXPERIMENTAL DESIGN: TPA was administered to patients with relapsed/refractory hematological malignancies. RESULTS: Phenotypic effects were detected in malignant cells and TPA-associated biological activity was present in blood for up to several hours after the infusion. CONCLUSIONS: These studies confirm the feasibility of TPA administration to humans and establish the foundation for the development of phorbol esters as therapy for patients with a variety of malignant and nonmalignant disorders.

Adult↗

PubMed2002

Hyperparathyroidism in hereditary syndromes: special expressions and special managements.

Hyperparathyroidism (HPT) in its hereditary variants assumes special forms, has special associations, and requires special managements. Familial hypocalciuric hypercalcemia (FHH or FBHH) and neonatal severe primary hyperparathyroidism (NSHPT) reflect heterozygous or homozygous mutations, respectively, in the calcium-sensing receptor. FHH and NSHPT represent the mildest and severest variants of HPT. Both cause hypercalcemia from birth and atypical HPT that always and uniquely persists after subtotal parathyroidectomy. Their HPT is likely polyclonal and nonneoplastic. In contrast, mono- or oligo-clonal parathyroid neoplasia underlays most other HPT variants: multiple endocrine neoplasia type 1 (MEN1), multiple endocrine neoplasia type 2A (MEN2A), and hyperparathyroidism-jaw tumor syndrome (HPT-JT). Familial-isolated HPT combines several diagnoses, including occult forms of the above syndromes. Each neoplastic variant has tumors in multiple parathyroids and a delayed, but still early age of onset for HPT (average age, 25-35 years). Each justifies special and similar approaches to parathyroidectomy: typically, identification of four glands, subtotal parathyroidectomy, rapid intraoperative parathyroid hormone (PTH) assays, and parathyroid cryopreservation. Outcomes of parathyroidectomy remain suboptimal in each. Each syndrome of parathyroid neoplasia associates with characteristic cancer(s): enteropancreatic neuroendocrine or foregut carcinoid tissues (MEN1), thyroidal C cells (MEN2A), or parathyroid (HPT-JT). HPT has promoted gene discovery more through its rare hereditary variants than through common adenoma; the main genes causing four of six hereditary variants are known. The RET mutation test became essential in management of MEN2A. The MEN1 test is less urgent, because it rarely guides a major patient benefit. The CASR test, perhaps least urgent, has largely been unavailable. Further progress in molecular genetics will enhance understandings, diagnosis, and therapy of HPT.

Calcium↗

PubMed2002

Role of preoperative localization and intraoperative localization maneuvers including intraoperative PTH assay determination for patients with persistent or recurrent hyperparathyroidism.

Patients with recurrent or persistent primary hyperparathyroidism have increased operative risk because of scarring in the operative field and the frequent presence of an ectopic gland. Preoperative imaging studies will identify the hyperfunctioning parathyroid gland in the majority of circumstances. The best types or combination of imaging tests has not been definitely established. However, because of their wide availability and demonstrated sensitivity, US and sestamibi scans are most commonly obtained. Based on the clinical setting, additional tests including CT or MRI may be useful. In circumstances when the noninvasive imaging modalities are inconclusive, invasive imaging tests including selective angiography venous sampling and/or direct fine needle aspiration should be used. IOUS, MIRP, and intraoperative PTH determination are useful adjuncts to the safe and successful conduct of reoperative parathyroid surgery: however, the benefit of the routine use of these modalities in reoperative parathyroid surgery has yet to be critically determined.

Adenoma↗

PubMedDate not supplied

Cell transfer therapy for cancer: lessons from sequential treatments of a patient with metastatic melanoma.

The development of effective autologous cell transfer therapies for the treatment of patients with cancer has been difficult, in part because the cells used to treat each patient are different, as are the patient's tumor and immune status. Much can thus be learned by sequential treatments of the same patient with the same cells, making single modifications in the treatments to determine which factors are critical. The authors have treated a single patient with five sequential administrations of the same cells with minor modifications in the mode of administration and the immune status of the patient. The treatment of this patient strongly suggested that 1) the highly avid recognition of tumor antigens in vitro by a transferred lymphocyte population does not necessarily predict in vivo antitumor activity; 2) the administration of highly avid antitumor autologous lymphocyte populations can be far more active in mediating tumor regression in vivo when administered after nonmyeloablative chemotherapy than when administered without this prior chemotherapy; 3) intra-arterial administration of highly avid antitumor autologous lymphocytes into the blood supply of the tumor can be more effective in mediating tumor regression than the intravenous administration of these same tumor infiltrating lymphocytes; 4) one mechanism of tumor escape from immunotherapy is loss of class I MHC antigen expression by the tumor due to mutation of the beta-2 microglobulin gene.

Adult↗

PubMedDate not supplied

Ectopic Cushing's syndrome caused by an esthesioneuroblastoma.

OBJECTIVE: To report a case of florid Cushing's hormone (ACTH) secretion related to the presence of an esthesioneuroblastoma (ENB). METHODS: We present clinical, laboratory, and pathologic findings in a 36-year-old Caucasian man presenting with Cushing's syndrome. Results of computed tomography (CT), magnetic resonance imaging (MRI), positron emission tomography (PET) scanning, and somatostatin receptor scintigraphy are presented, along with tumor pathology findings. RESULTS: After initial biochemical studies suggestive of ectopic Cushing's syndrome, CT of the chest and abdomen revealed multiple cavitated pulmonary lesions, an ischiorectal mass, and bilateral adrenal hyperplasia. MRI of the pituitary gland revealed normal findings. Both PET scanning with [18 F]-flurodeoxyglucose (FDG) and somatostatin receptor scintigraphy with 111 indium-penetetreotide (Octreoscan) revealed strong tracer uptake in the ethmoid region. CT and MRI of the sinuses and brain subsequently localized a 5-cm mass in the ethmoid sinuses with intracranial extension. On biopsy, pathology results were consistent with a diagnosis of ENB, and immunohistochemical analysis revealed that tumor cells were strongly positive for ACTH, synaptophysin, and S-100, providing definitive diagnosis of ACTH-producing ENB. Hypercortisolemia was initially controlled by metyrapone, then by external beam radiation therapy (RT). CONCLUSION: This case illustrates the usefulness of nuclear imaging in the diagnosis of ENB, and the importance of prompt control of hypercortisolemia in Cushing's syndrome.

ACTH Syndrome, Ectopic↗