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Biomedical subjects

A E Chang

Publications and source records attributed to A E Chang.

At least 163 records · Page 9Linked to original sources
PubMed1978

Ultrastructure of malignant paraganglioma of organ of Zuckerkandl.

Electron microscopic study of a malignant paraganglioma of the organ of Zuckerkandl revealed similarities between the tumor and the normal paraganglia. The well-differentiated portion of the tumor recapitulated the structure of the basic functional units of the paraganglion. In addition there signs of anaplasia both at the histologic and ultrastructural level. Large neurosecretory granules were noted in some of the tumor cells, but most of the cells were agranular. Crystaloids resembling those seen in alveolar soft part sarcoma were also noted. The study supports the theory on the common origin and histogenesis of paragangliomas and alveolar soft part sarcomas.

Chromaffin System↗
PubMed1978

Comparison of computed and conventional whole lung tomography in detecting pulmonary nodules: a prospective radiologic-pathologic study.

Whole lung computed tomography (CT) was performed on 25 patients with clinical diagnoses including osteogenic sarcoma. Ewing's sarcoma, rhabdomyosarcoma, fibrosarcoma, and melanoma in whom conventional tomography had revealed from one to four parenchymal nodules in one lung deemed resectable for either staging or treatment purposes. Thoracotomy was performed within 3 weeks after conventional and computed whole lung tomography. All palpable nodules were resected, measured at the time of surgery, mapped by anatomic segment, and submitted for individual histologic evaluation. CT defined more nodules than conventional tomography in 48% of cases. The additional nodules were usually pleural or subpleural and 3--6 mn in diameter. CT identified 78% of all resected nodules greater than 3 mm in diameter, compared to 59% using conventional tomography. CT was also of value in detecting bilateral nodules earlier than conventional tomography and in documenting small nodule growth on successive examination. However, 60% of the additional nodules defined by CT and resected proved to be benign granulomas and pleural-based nodes at thoracotomy.

Adolescent↗
PubMed1978

Small bowel obstruction as a complication of disseminated varicella-zoster infection.

A 40-year-old woman with Sjögren's syndrome and mixed cryoglobulinemia, treated with corticosteroids, presented with small bowel obstruction temporally associated with cutaneous varicella-zoster (V-Z) infection. At laparotomy a portion of inflamed, necrotic small bowel was resected. Cells in the margin of the lesion exhibited characteristic intranuclear inclusion bodies. This case report emphasizes the multiple organ involvement that can occur with disseminated V-Z infection. Despite the rarity of gastrointestinal involvement, this infection must be included in the differential diagnosis of the acute abdomen in patients with cutaneous vesicles.

Adult↗
PubMedDate not supplied

Surgical therapy of primary cutaneous melanoma.

This review focuses on the surgical treatment of primary cutaneous melanoma. Interpretation of biopsy results and a rational approach to preoperative screening methods for metastases are examined. The marked changes in operative approach to melanoma over the past century are reviewed, with emphasis on the impact of prospective, randomized trials upon the width of surgical margins for melanoma. General principles of current surgical technique are discussed, with attention given to modifications of technique dictated by unique anatomic tumor sites.

Biopsy↗
PubMedDate not supplied

Diagnostic procedures and pretreatment evaluation of soft tissue sarcomas.

The diagnosis and preoperative evaluation of patients with a suspected soft tissue sarcoma involve several important considerations to ensure optimal treatment outcomes. Biopsy techniques must involve the retrieval of adequate tissue to establish the histologic diagnosis and grade of the tumor without compromising the subsequent definitive surgical resection. CT or MRI techniques represent the gold standard to evaluate the local extent of disease which is necessary to ascertain surgical resectability and/or the need for radiation therapy. CT scanning of the lungs is mandated for all patients with sarcomas to evaluate for metastatic disease and, for patients with abdominal or retroperitoneal tumors, scanning of the liver should also be included. Accurate staging of these patients will help define overall survival.

Biopsy↗
PubMedDate not supplied

Is mammography useful in screening for local recurrences in patients with TRAM flap breast reconstruction after mastectomy for multifocal DCIS?

BACKGROUND: Skin-sparing mastectomy with immediate transverse rectus abdominis musculocutaneous (TRAM) flap reconstruction is being used more often for the treatment of breast cancer. Mammography is not used routinely to evaluate TRAM flaps in women who have undergone mastectomy. We have identified the potential value of its use in selected patients. METHODS AND RESULTS: We report on four women who manifested local recurrences in TRAM flaps after initial treatment for ductal carcinoma in situ (DCIS) or DCIS with microinvasion undergoing skin-sparing mastectomy and immediate reconstruction. All four patients presented with extensive, high-grade, multifocal DCIS that precluded breast conservation. Three of four mastectomy specimens demonstrated tumor close to the surgical margin. Three of the four recurrences were detected by physical examination; the remaining local recurrence was documented by screening mammography. The recurrences had features suggestive of malignancy on mammography. CONCLUSION: We conclude that all patients undergoing mastectomy and TRAM reconstruction for extensive, multifocal DCIS should undergo regular routine mammography of the reconstructed breast. Our experience with this subgroup of patients raises concern about the value of skin-sparing mastectomy with immediate reconstruction for therapy. Adjuvant radiation therapy should be recommended for those patients with negative but close surgical margins.

Adult↗
PubMedDate not supplied

Cytokines as an adjuvant to tumor vaccines: efficacy of local methods of delivery.

BACKGROUND: We examined alternative methods of delivering cytokines as an adjunct for priming lymph node (LN) cells draining sites of vaccine inoculation for the purpose of generating immune cells for adoptive immunotherapy. METHODS: Using syngeneic murine tumors we examined the ability of IL-2, IL-4, or GM-CSF delivered locally to a site of tumor inoculum to induce antitumor reactive draining LN cells. Mice were inoculated subcutaneously with tumor cells transduced to secrete cytokine; tumor cells admixed with fibroblasts transduced to secrete cytokine; or intralesional inoculation of cytokine in established tumor to induce sensitized LN cells capable of mediating tumor regression in adoptive transfer. RESULTS: Both IL-4 and GM-CSF cytokines were effective in enhancing the antitumor reactivity of vaccine-primed LN cells compared to IL-2, which was ineffective. The local delivery of GM-CSF by autocrine or paracrine secretion of genetically engineered cells, as well as direct intratumoral delivery was capable of upregulating LN sensitization compared to systemic administration, which did not. CONCLUSIONS: The local delivery of GM-CSF as an adjuvant for tumor vaccination can be accomplished by various methods, including direct injection, which avoids the need for gene transfer.

Adjuvants, Immunologic↗
PubMedDate not supplied

Computed tomography in staging of patients with melanoma metastatic to the regional nodes.

BACKGROUND: This study addresses the yield and clinical impact of computed tomography (CT) imaging in otherwise asymptomatic patients with stage III melanoma metastatic to the regional nodes. METHODS: The database from the University of Michigan Mutlidisciplinary Melanoma Clinic was reviewed and identified 127 asymptomatic patients with stage III melanoma (regional nodal disease) who received CT scans of the head, chest, abdomen, and/or pelvis. Scans were confirmed as true positive, false positive, and normal. RESULTS: Four hundred twenty-six head and body CT scans were performed at the time of presentation of stage III disease. Twenty patients had a true-positive CT scan revealing unsuspected metastases. Fifteen patients had abnormal CT scans subsequently shown to be a benign process or second malignancy. The incidence of true-positive CT scans was not different between the groups of patients who had clinically apparent versus occult nodal disease. There was a significantly higher incidence of abdominal and pelvic metastatic sites identified by CT scan in patients with inguinal nodal disease compared with axillary or head and neck node-positive patients. CONCLUSIONS: The yield of detection of unsuspected metastases by CT scans in asymptomatic patients with stage III melanoma was not insignificant. Because patients with resected stage III disease are recommended to have adjuvant interferon-alpha for 1 year, CT staging plays an important role in identifying appropriate candidates for treatment. The toxicity of interferon-alpha therapy is not insignificant. The value of routine CT in asymptomatic patients with nodal metastasis deserves further prospective study.

Adolescent↗
PubMedDate not supplied

Enhanced adjuvant effect of granulocyte-macrophage colony-stimulating factor plus interleukin-12 compared with either alone in vaccine-induced tumor immunity.

Using the poorly immunogenic D5 murine melanoma, we examined the adjuvant effect of granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin-12 (IL-12) secretion by gene-modified tumor cells inoculated as a vaccine to prime tumor-draining lymph nodes (TDLNs). D5 transfectants that secreted IL-12 or GM-CSF alone were compared with a double transfectant that secreted equivalent amounts of both cytokines. TDLN cells harvested 9-10 days after subcutaneous tumor inoculation were cultured sequentially in anti-CD3 and IL-2 and assessed for antitumor reactivity against wild-type D5 tumor. The double transfectant-induced TDLN effector cells had greater cytotoxicity in a long-term assay than TDLN cells primed by single transfectants. In adoptive immunotherapy, the TDLN cells primed by the double transfectant were significantly better at mediating the regression of established tumors compared with the TDLN cells elicited by the single transfectants. Both IL-12 and GM-CSF had adjuvant effects in promoting tumor-reactive TDLN cells, but the combination was better than either alone. These observations suggest that the immunomodulation roles of IL-12 and GM-CSF are different and complementary.

Animals↗
PubMedDate not supplied

Interleukin-12 cDNA skin transfection potentiates human papillomavirus E6 DNA vaccine-induced antitumor immune response.

Human papillomaviruses are associated with >90% of all cases of uterine cervical tumors. The E6 and E7 oncoproteins of human papillomavirus are potentially ideal targets of immune therapy for cervical cancer, because their expression is necessary for cellular transformation. Although both E6 and E7 proteins contain numerous predicted cytotoxic T lymphocyte (CTL) epitopes that are capable of binding to human leukocyte antigens, the majority of earlier in vivo tumor rejection studies have focused on E7. We show here that gene gun-mediated skin transfection of plasmid vector encoding the nontransforming, amino-terminal half of E6 resulted in the induction of E6-specific CTL activity and tumor rejection in a murine model. The use of recombinant murine interleukin-12 (rmIL-12) as a vaccine adjuvant has been shown to result in both an enhancement and suppression of immune responses, depending upon the doses of rmIL-12 and the experimental systems used. We demonstrate here that local expression of transgenic mIL-12 at the E6 DNA vaccination site potentiated E6-specific CTL responses and increased vaccine-induced antitumor therapeutic efficacy. Our results indicate that transfection of the mIL-12 gene at the vaccination site may represent an attractive adjuvant for cancer gene immunotherapy.

Animals↗
PubMedDate not supplied

CD95-mediated tumor recognition by CD4+ effector cells in a murine mammary model.

The authors examined cellular mechanisms involved in anti-tumor reactivity induced by the murine MT-9G1 mammary tumor line, which was transduced to secrete granulocyte macrophage-colony-stimulating factor (GM-CSF). Compared with the parental MT-901 tumor, MT-9G1 subcutaneous tumors elicited an influx of CD4+ cells and dendritic cells. Secondary in vitro activation of tumor-draining lymph node cells with anti-CD3 and interleukin-2 resulted in effector cells that can mediate regression of established pulmonary metastases after adoptive transfer. In vivo depletion of T-cell subsets showed that tumor regression required CD4+ tumor-draining lymph node cells rather than CD8+ cells. The activated CD4+ cells expressed CD95L and mediated lysis of CD95+ MT-901 tumor cells, which were major histocompatibility complex class II negative. The CD4+ cells also released GM-CSF in response to tumor stimulation. A Fas fusion protein inhibited tumor lysis and GM-CSF release by the CD4+ cells. These studies document an alternate pathway by which CD4+ immune cells may recognize major histocompatibility complex class II-deficient tumors in which CD95L-bearing T cells induced an anti-tumor response mediated via CD95L:CD95.

Adoptive Transfer↗
PubMedDate not supplied

Effects of tumor necrosis factor-alpha on the in vitro maturation of tumor-reactive effector T cells.

Culture methods that enhance the anti-tumor reactivity of primed T cells would be important in adoptive immunotherapy of cancer. Using several different syngeneic murine tumor models, the authors evaluated the effects of tumor necrosis factor-alpha (TNF-alpha) exposure on tumor-draining lymph node (TDLN) cells during in vitro activation. Mice were inoculated with weakly immunogenic (i.e., MCA 205, MCA 207 sarcoma) or the poorly immunogenic (i.e., D5 melanoma) tumor cells, and TDLN cells were harvested 9 or 10 days later for activation by an anti-CD3/interleukin-2 culture procedure. Human recombinant TNF-alpha (25 ng/mL) added during the activation culture resulted in a two-fold increase in interferon-gamma release (type 1 response) and a significant reduction of interleukin-10 (type 2 response) after tumor antigen stimulation. In an adoptive transfer model, TNF-alpha-cultured TDLN cells mediated significantly greater regression of established tumor than did TDLN cells cultured in the absence of TNF-alpha in five of five experiments. Neutralization of interleukin-10 monoclonal antibody further augmented the therapeutic efficacy of TNF-alpha-cultured TDLN cells. These studies document the ability of TNF-alpha to selectively promote a type 1 over a type 2 response in a bulk population of tumor-primed T cells during in vitro activation.

Animals↗
PubMedDate not supplied

Antitumor reactivity of lymph node cells primed in vivo with dendritic cell-based vaccines.

Tumor lysate-pulsed dendritic cells were used to generate nodal effector T cells in the murine MCA 205 tumor model. Dendritic cells were derived from bone marrow and cultured in granulocyte-macrophage colony-stimulating factor/interleukin 4 before pulsation with tumor lysate. Multiple subcutaneous administrations of tumor lysate-pulsed dendritic cells (TP-DCs) resulted in an approximately eightfold hypertrophy of the vaccine draining nodes, with an increased influx of dendritic (CD11c+/CD80+) cells and B (B220+) cells. The vaccine-primed lymph node (VPLN) cells were secondarily activated with anti-CD3/interleukin 2 and exhibited specific interferon-gamma release to tumor antigen. The adoptive transfer of TP-DC VPLN cells resulted in regression of established 3-day pulmonary metastases. The antitumor reactivity of TP-DC VPLN cells was comparable to anti-CD3/interleukin 2 activated tumor-draining lymph node cells. However, the admixture of keyhole limpet hemocyanin (KLH) with tumor lysate during pulsation of dendritic cells significantly enhanced the induction of tumor-reactive VPLN cells. Tumor lysate-pulsed dendritic cells can be used as a strategy to generate effector T cells for adoptive immunotherapy.

Adjuvants, Immunologic↗
PubMedDate not supplied

Hepatic perfusion during hepatic artery infusion chemotherapy: evaluation with perfusion CT and perfusion scintigraphy.

The standard method for the evaluation of hepatic perfusion during hepatic artery infusion (HAI) chemotherapy is planar hepatic artery perfusion scintigraphy (HAPS). Planar HAPS was performed with 2 mCi of [99mTc] macroaggregated albumin infused at 1 ml/min and compared with single photon emission CT (SPECT) HAPS and with a new study, CT performed during the slow injection of contrast material through the HAI catheter (HAI-CT). Thirteen patients underwent 16 HAI-CT studies, 14 planar HAPS studies, and 9 SPECT HAPS studies. In 13 of 14 studies (93%) HAI-CT and planar HAPS were in complete agreement as to the perfusion pattern of intrahepatic metastases and normal liver. In nine studies where all modalities were performed, the findings identified by HAI-CT and planar HAPS agreed in all cases, whereas the results of two SPECT scans disagreed with the other studies. With respect to perfusion of individual metastases, 14 of 14 HAI-CT studies, 12 of 13 planar HAPS studies, and 9 of 9 SPECT HAPS studies correctly demonstrated the perfusion status of individual lesions as indicated by the pattern of changes in tumor size determined on CT obtained before and after the perfusion studies. Hepatic artery infusion CT was superior for delineation of individual metastases, particularly small lesions, and for the evaluation of nonperfused portions of the liver. Planar HAPS detected extrahepatic perfusion in four patients, and this was not detected by HAI-CT. We conclude that HAI-CT and scintigraphy are complementary techniques. Hepatic artery infusion CT has advantages for the evaluation of intrahepatic perfusion, and planar HAPS is superior to HAI-CT for the detection of extrahepatic perfusion.

Adult↗
PubMedDate not supplied

Dual-phase helical CT of nonfunctioning islet cell tumors.

PURPOSE: The aim of this study was to evaluate the utility of dual-phase imaging in the assessment of nonfunctioning islet cell tumors (NFITs). METHOD: Six patients with histologically and biochemically proven NFIT were evaluated by arterial and portal venous dual-phase helical CT. Scan delay was 20 s for the arterial phase and 70 s for the portal phase. Each phase was assessed by consensus reading and specifically evaluated for tumor conspicuity, hepatic metastases, vascular encasement by tumor, and presence of lymphadenopathy. RESULTS: Overall, tumor conspicuity was greater in the arterial phase (5/6) than in the portal venous phase (1/6) with a mean tumor/normal pancreas attenuation difference of 31.8 HU in the arterial phase compared with 19.2 HU in the portal venous phase. The arterial phase detected a total of 17 liver metastases compared with 9 seen in the portal phase. Lymph node enlargement was noted in three patients, which, although visible in both phases, was more easily discernible in the arterial phase. Venous encasement by tumor was better evaluated on the delayed portal venous phase than the arterial phase. CONCLUSION: Dual-phase helical CT scanning leads to improvement in the detection and staging of NFITs.

Adult↗
PubMedDate not supplied

Dual-phase helical CT of nonfunctioning islet cell tumors.

PURPOSE: The aim of this study was to evaluate the utility of dual-phase imaging in the assessment of nonfunctioning islet cell tumors (NFITs). METHOD: Six patients with histologically and biochemically proven NFIT were evaluated by arterial and portal venous dual-phase helical CT. Scan delay was 20 s for the arterial phase and 70 s for the portal phase. Each phase was assessed by consensus reading and specifically evaluated for tumor conspicuity, hepatic metastases, vascular encasement by tumor, and presence of lymphadenopathy. RESULTS: Overall, tumor conspicuity was greater in the arterial phase (5/6) than in the portal venous phase (1/6) with a mean tumor/normal pancreas attenuation difference of 31.8 HU in the arterial phase compared with 19.2 HU in the portal venous phase. The arterial phase detected a total of 17 liver metastases compared with 9 seen in the portal phase. Lymph node enlargement was noted in three patients, which, although visible in both phases, was more easily discernible in the arterial phase. Venous encasement by tumor was better evaluated on the delayed portal venous phase than the arterial phase. CONCLUSION: Dual-phase helical CT scanning leads to improvement in the detection and staging of NFITs.

Adult↗