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Biomedical subjects

A D Hill

Publications and source records attributed to A D Hill.

At least 19 recordsLinked to original sources
PubMed2000

Tumour micrometastases: the influence of angiogenesis.

INTRODUCTION: Many cancer patients have undetected micrometastatic disease at first presentation which ultimately progresses. Angiogenesis-the development of an independent blood supply-is a key event in the growth of metastases. Improved understanding of the influence of angiogenesis on micrometastatic growth may lead to new therapeutic intervention. METHODS: This study examines current concepts of the significance of micrometastases and the role of angiogenesis in their development and destruction. A comprehensive review of the literature on micrometastasis and angiogenesis was performed using the Medline database between 1966 and 1999. CONCLUSIONS: Advances in technology have improved our ability to diagnose metastatic disease, but micrometastases in loco-regional lymph nodes and at distant sites can only be detected by sophisticated histological techniques. While the significance of micrometastases remains controversial, there is increasing evidence that micrometastatic status provides useful prognostic information and should be part of standard staging techniques. Anti-angiogenic therapy has the potential to favourably influence management of certain cancers by manipulating a number of key events in the metastatic process.

Bone Marrow Neoplasms↗
PubMed1999

Sentinel lymph node biopsy in breast cancer: unfiltered radioisotope is superior to filtered.

BACKGROUND: The combination of gamma-probe radiolocalization and blue-dye mapping of sentinel lymph nodes (SLNs) has been advocated as the most accurate method for staging the clinically negative axilla in breast cancer patients, but the technical aspects of these procedures are not fully characterized in the literature. In this study, we compared the success of SLN localization in 134 consecutive breast cancer patients using blue dye plus two different preparations of radiocolloid. STUDY DESIGN: A retrospective analysis of a prospectively maintained data base was performed to assess SLN localization in two cohorts of patients. Unfiltered technetium-99m (Tc-99m) sulfur colloid (in 77 patients; group I) was compared with filtered Tc-99m sulfur colloid (in 57 patients; group II). All patients had a peritumoral injection of blue dye and isotope, followed immediately by lymphoscintigraphy to confirm radioactivity at the injection site and to image the SLN. Statistical analysis was performed using the Pearson chi-square test. RESULTS: Unfiltered Tc-99m sulfur colloid was superior to the filtered radiocolloid in localizing the SLN (88% versus 73%; p = 0.03). SLN imaging by lymphoscintigraphy was also more successful in the unfiltered group. Using the combination of blue dye and radiolocalization, SLNs were identified in 94% of patients. CONCLUSIONS: For optimal localization of the SLN in breast cancer patients, surgeons should use the combined technique of blue-dye mapping and gamma-probe localization using unfiltered Tc-99m sulfur colloid.

Biopsy↗
PubMed1999

Intraoperative lymphatic mapping and sentinel lymph node biopsy for Merkel cell carcinoma.

BACKGROUND: Merkel cell carcinoma is a rare cutaneous neoplasm which commonly spreads to the regional lymph nodes. The feasibility of identifying the sentinel node in patients with clinically node-negative Merkel cell carcinoma was evaluated. METHODS: Sentinel lymphatic mapping was performed in 18 patients with stage 1 Merkel cell carcinoma using the combination of isosulphan blue dye and 99mTc-radiolabelled sulphur colloid. Patients with tumour metastasis in the sentinel node underwent complete dissection of the remainder of the lymph node basin. RESULTS: Eighteen patients underwent removal of 35 sentinel nodes. Two patients demonstrated metastatic disease in the sentinel lymph nodes; complete dissection of the involved nodal basin revealed no additional positive nodes suggesting that the sentinel lymph node had been identified. The node-negative patients received no further surgical therapy, with no evidence of recurrent disease in the sentinel nodal basin at a median of 7 months' follow-up. CONCLUSION: Sentinel node biopsy is feasible in patients with Merkel cell carcinoma. It can be used to stage patients and provides important prognostic information. In those with subclinical nodal disease, it may direct early regional lymphadenectomy but the effect of such surgery on survival remains unclear.

Adult↗
PubMed1999

Lessons learned from 500 cases of lymphatic mapping for breast cancer.

OBJECTIVE: To evaluate the factors affecting the identification and accuracy of the sentinel node in breast cancer in a single institutional experience. SUMMARY BACKGROUND DATA: Few of the many published feasibility studies of lymphatic mapping for breast cancer have adequate numbers to assess in detail the factors affecting failed and falsely negative mapping procedures. METHODS: Five hundred consecutive sentinel lymph node biopsies were performed using isosulfan blue dye and technetium-labeled sulfur colloid. A planned conventional axillary dissection was performed in 104 cases. RESULTS: Sentinel nodes were identified in 458 of 492 (92%) evaluable cases. The mean number of sentinel nodes removed was 2.1. The sentinel node was successfully identified by blue dye in 80% (393/492), by isotope in 85% (419/492), and by the combination of blue dye and isotope in 93% (458/492) of patients. Success in locating the sentinel node was unrelated to tumor size, type, location, or multicentricity; the presence of lymphovascular invasion; histologic or nuclear grade; or a previous surgical biopsy. The false-negative rate of 10.6% (5/47) was calculated using only those 104 cases where a conventional axillary dissection was planned before surgery. CONCLUSIONS: Sentinel node biopsy in patients with early breast cancer is a safe and effective alternative to routine axillary dissection for patients with negative nodes. Because of a small but definite rate of false-negative results, this procedure is most valuable in patients with a low risk of axillary nodal metastases. Both blue dye and radioisotope should be used to maximize the yield and accuracy of successful localizations.

Adult↗
PubMed1999

Credentialing for breast lymphatic mapping: how many cases are enough?

OBJECTIVE: To evaluate credentialing issues for sentinel lymphatic mapping for breast cancer. SUMMARY BACKGROUND DATA: The sentinel lymph node (SLN) is defined as the first lymph node receiving lymphatic drainage from a tumor. The SLN accurately reflects the status of the axillary nodes in patients with early-stage breast cancer, and SLN mapping is gaining widespread acceptance. Few of the many published feasibility studies of lymphatic mapping for breast cancer have adequate numbers to assess credentialing issues for this new procedure. METHODS: Five hundred consecutive SLN biopsies were performed at one institution, over a 20-month period, by eight surgeons, using isosulfan blue dye and technetium-labeled sulfur colloid. The authors reviewed each surgeon's success rate in finding the SLN, and false-negative rate, relative to level of experience with the technique. RESULTS: Lymphatic mapping performed by an experienced surgeon (surgeon A, B, or C) was associated with a higher success rate (94%) than when it was performed by one with less experience (86%). Ten failed mapping procedures occurred in the first 100 cases. For each of the ensuing 100 cases, there were eight, six, six, and four failed mapping procedures, suggesting that increasing experience does not eradicate failed mapping procedures completely. The false-negative rate among 104 patients in whom axillary dissection was planned in advance was 10.6% (5/47). Most false-negative results occurred early in the surgeon's experience: when the first six cases of every surgeon were excluded, the false-negative rate fell to 5.2% (2/38). CONCLUSIONS: With increasing experience, failed SLN localizations and false-negative SLN biopsies occur less often. Combined dye and isotope localization, enhanced histopathology, a backup axillary dissection, and judicious case selection are required to avoid the high false-negative rate of one's early experience.

Adult↗
PubMed1999

Sentinel lymph node biopsy after percutaneous diagnosis of nonpalpable breast cancer.

PURPOSE: To determine the technical success rate of sentinel lymph node biopsy in women with nonpalpable infiltrating breast cancer diagnosed by using percutaneous core biopsy and to determine the frequency with which sentinel lymph node biopsy obviated axillary dissection. MATERIALS AND METHODS: Retrospective review revealed 33 women who underwent sentinel node biopsy after percutaneous core biopsy diagnosis of nonpalpable infiltrating breast cancer. Sentinel nodes were identified with radioisotope and blue dye; the procedure was technically successful if sentinel nodes were found at surgery. All sentinel nodes were excised. Axillary dissection was performed if tumor was present in sentinel nodes. RESULTS: Sentinel nodes were found at surgery in 30 women (91%). Sentinel nodes were identified with both radioisotope and blue dye in 22 (73%) of these women, with only radioisotope in six (20%), and with only blue dye in two (7%). Sentinel nodes were found in 12 (80%) of 15 women in the first half of the study versus all 18 (100%) women in the second half (P = .08). Sentinel nodes were free of tumor in 23 (77%) of 30 women. In six (86%) of seven women with tumor in sentinel nodes, the sentinel nodes were the only nodes with tumor. CONCLUSION: Sentinel node biopsy was successful in 30 women (91%) with nonpalpable infiltrating carcinoma diagnosed with percutaneous core biopsy and obviated axillary dissection in 23 women (70%). Using both radioisotope and blue dye may increase the success rate. A learning curve exists, and success improves with experience.

Adult↗
PubMed1998

Sentinel lymph node biopsy in breast cancer: initial experience at Memorial Sloan-Kettering Cancer Center.

BACKGROUND: Sentinel node biopsy (SNB) has emerged as a potential alternative to routine axillary dissection in clinically node-negative breast cancer. STUDY DESIGN: From September 1995 to June 1996 at Memorial Sloan-Kettering Cancer Center, 60 patients with clinically node-negative cancer underwent SNB, which was immediately followed by standard axillary dissection. Both blue dye and radioisotope were used to identify the sentinel node. SNB was compared with standard axillary dissection for its ability to accurately reflect the final pathologic status of the axillary nodes. RESULTS: The sentinel node was successfully identified by lymphoscintigraphy in 75% (42 of 56), by blue dye in 75% (44 of 59), by isotope in 88% (52 of 59), and by the combination of blue dye and isotope in 93% (55 of 59) of all 59 evaluable patients. Of the 55 patients in this study where sentinel nodes were identified, 20 (36%) were histologically positive. The sentinel node was falsely negative in three patients, yielding an accuracy of 95%. SNB was more accurate for T1 (98%) than for T2-T3 tumors (82%). CONCLUSIONS: Lymphatic mapping is technically feasible, reliably identifies a sentinel node in most cases, and appears more accurate for T1 tumors than for larger lesions. Blue dye and radioisotope are complementary techniques, and the overall success of the procedure is maximized when the two are used together.

Biopsy↗
PubMed1997

Ductal carcinoma in situ of the breast--current management.

The management options in the treatment of patients with ductal carcinoma in situ of the breast are reviewed. Results of treatment by mastectomy, wide local excision, and local surgery followed by radiotherapy are analysed. Factors which incline the surgeon towards recommending mastectomy and the conditions which should be fulfilled for breast conservation are discussed.

Breast Neoplasms↗
PubMed1997

Hereditary breast cancer.

BACKGROUND: Hereditary breast cancer is thought to account for less than 10 per cent of all breast cancers. Recently there have been significant advances in understanding of the genetics, with the sequencing of the genes BRCA1 and BRCA2 which are associated with hereditary breast cancer. METHODS AND RESULTS: Current understanding of hereditary breast cancer and its impact on the management of women with this disease is reviewed. CONCLUSION: Problems in accurate testing for breast cancer-associated genes remain. No reliable simple test exists because of the large number of mutations present in these genes. The implications of different mutations remain poorly understood. Guidelines for the management of carriers of the breast cancer-associated genes remain controversial.

Breast Neoplasms↗
PubMed1997

A 25 year review of parotid surgery.

At a single institution over 25 years, 110 patients were operated upon for a mixture of parotid disease. The mean duration of symptoms for benign disease was 40.8 months compared with 15.6 months for malignant disease. Pain was a significant feature of malignant parotid disorders (46.1% compared with 17.8% for benign conditions). The pathology of these masses was diverse, with pleomorphic adenoma being the commonest (44%). Superficial parotidectomy was the commonest procedure employed (69/110) with local excision being performed only prior to 1984 (15/110). There were five cases of permanent facial palsy, all following radical resection for malignancy. One patient developed Frey's syndrome. Recurrence rate for pleomorphic adenomas was 7/48 (15%), three following enucleations prior to 1984. In primary malignancy of the parotid, 3/21 (14%) developed recurrences. Parotid tumours have a low incidence. Surgery for these tumours can be safely performed by those with a special interest in parotid surgery.

Female↗
PubMed1996

Granulocyte-macrophage colony-stimulating factor inhibits tumor growth during the postoperative period.

BACKGROUND: Granulocyte-macrophage colony-stimulating factor (GM-CSF) may have important antineoplastic properties because it induces macrophage tumoricidal activity in vitro. We examined the inhibitory effect of GM-CSF on tumor growth in a murine carcinoma model and whether this inhibitory effect would persist during the postoperative period. Potential macrophage-mediated mechanisms were studied. METHODS: The effect of GM-CSF on macrophage function in vitro was assessed by measuring superoxide anion and interleukin-6 production, percentage phagocytosis of Candida albicans, and percentage Ia expression. GM-CSF's effect on tumor volume was assessed first in a murine tumor model and second to examine whether these effects also occurred during the postoperative period in the same model after laparotomy. Macrophage function in the latter study was assessed by measuring superoxide anion, cytotoxicity, and tumor necrosis factor production. RESULTS: GM-CSF treatment was associated with a decrease in tumor volume on day 4 after the initiation of GM-CSF treatment (0.93 +/- 0.08 cm3 for control versus 0.34 +/- 0.08 cm3 for GM-CSF; p < 0.05). This effect was also seen after laparotomy (1.07 +/- 0.2 cm3 for laparotomy+saline versus 0.16 +/- 0.04 cm3 for laparotomy+GM-CSF, p < 0.05). In vivo macrophage function showed increased superoxide anion, cytotoxicity, and tumor necrosis factor-alpha production from macrophages obtained from GM-CSF treated animals compared with saline treated controls. CONCLUSIONS: Tumor growth is inhibited by GM-CSF treatment, and this effect also occurs after laparotomy. Thus, GM-CSF may have a therapeutic role in the treatment of the tumor bearing host after operation.

Analysis of Variance↗
PubMed1995

Antimicrobial effects of granulocyte-macrophage colony-stimulating factor in protein-energy malnutrition.

OBJECTIVES: To evaluate, in a murine model of protein-energy malnutrition, whether granulocyte-macrophage colony-stimulating factor (GM-CSF) improves the host response to a septic challenge and to determine the potential mechanisms involved. DESIGN: Nonblinded study of GM-CSF in mice with protein-energy malnutrition. SETTING: A university-based surgical laboratory and animal facility. INTERVENTION: In study 1, malnourished mice were randomized to receive either GM-CSF (120 micrograms/kg subcutaneously to receive either GM-CSF (120 micrograms/kg subcutaneously from day 4 to 7 of the protein-free diet) or saline vehicle as a control. On day 7, all mice were given Candida albicans (5 x 10(5) organisms intravenously). In study 2, malnourished mice received the same dose of GM-CSF or saline vehicle for 7 days of the protein-free diet. MAIN OUTCOME MEASURES: In study 1 mice were followed up for survival. In study 2, after 7 days of diets, splenic macrophages were harvested and were assayed for interleukin-6, superoxide anion, and nitric oxide production. Splenocytes were stimulated with concanavalin A (5 micrograms/mL) for interleukin-4, interleukin-10, and interferon-gamma production. RESULTS: Treatment with GM-CSF significantly enhanced survival in malnourished mice infected with C albicans. Treatment with GM-CSF was associated with increased production from splenic macrophages of interleukin-6, superoxide anion, and nitric oxide as well as decreased interleukin-4 production from splenocytes. CONCLUSIONS: This study suggests a beneficial role for GM-CSF in the malnourished host predisposed to infection. The antimicrobial properties of GM-CSF may function through enhanced production of nitric oxide and superoxide anion.

Animals↗
PubMed1995

Laparoscopic colonic surgery.

Laparoscopic surgical techniques have recently entered the field of colorectal surgery. Because the laparoscopic approach has revolutionized biliary surgery, it is hoped that similar advances will be possible in the more elderly population with colorectal disease. Early experience suggests that such advances have not been achieved and there is concern about developing minimal access surgical techniques in the face of potentially curable cancer. This article reviews the current state of knowledge based on published series; however, the current lack of controlled data in patients with extended follow-up makes this area highly controversial. Suggestions regarding the future of laparoscopic surgery are made and include the establishment of a national register and the development of controlled randomized trials.

Colon↗
PubMed1995

The effect of granulocyte-macrophage colony-stimulating factor on myeloid cells and its clinical applications.

Granulocyte-macrophage colony-stimulating factor (GM-CSF) is a naturally occurring growth factor produced by several cell types in response to a variety of stimuli. GM-CSF has potent stimulatory effects on the growth and maturation of hematopoietic cells and has profound effects on mature circulating effector cells. Clinical applications of GM-CSF include ameliorating chemotherapy-induced neutropenia and enhancing hematopoietic recovery after bone marrow transplantation. This review evaluates the effect of GM-CSF on myeloid cells and its clinical applications.

Acquired Immunodeficiency Syndrome↗
PubMed1995

Inflammatory markers following laparoscopic and open hernia repair.

Laparoscopic surgery may reduce the inflammatory response to surgery by the avoidance of a skin incision which is frequently the site of maximum tissue trauma. We hypothesized that the inflammatory response is less with minimally invasive procedures. The aim of this study was to evaluate the response of inflammatory mediators following laparoscopic and open hernia repair. Thirty-four patients undergoing unilateral primary inguinal hernia repair were prospectively assigned to either laparoscopic mesh hernia repair (n = 14), open mesh hernia repair (n = 11), or a Bassini repair (n = 9). Serum samples withdrawn prior to surgery, 6 h after surgery, and then again at 24 h after surgery were assayed for interleukin-6 and C-reactive protein content. Interleukin-6 levels at 24 h in the laparoscopic (13.1 +/- 3.1 pg/ml), open mesh (15.5 +/- 2.5 pg/ml), or Bassini group) (15.4 +/- 2.0 pg/ml) did not differ significantly. Neither did C-reactive protein levels at 24 h in the laparoscopic (12.4 +/- 2.7 pg/ml), open mesh (23.0 +/- 7.8 pg/ml), or Bassini group 18.6 +/- 6.6 pg/ml) differ significantly. The response of inflammatory mediators to hernia repair is not modified by undertaking the procedure laparoscopically.

C-Reactive Protein↗