Sentinel node biopsy is not an alternative to axillary dissection in breast cancer.
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Axilla↗
Biomedical subjects
F L Moffat
Publications and source records attributed to F L Moffat.
High-fat diets suppress CD3 and CD25 expression on the surface of murine lymphocytes.
To determine the effects of dietary fats on surface antigen expression, we tested the effects of amount and type of dietary fat on murine lymphocytes. Mice were fed diets with 12 en%, 23 en%, or 47 en% fat containing coconut, olive, safflower, or linseed oil. After 2 wk of ad libitum feeding, the mice were killed and splenic lymphocytes were harvested. Lymphocytes were incubated with fluorescent-tagged monoclonal antibodies and assayed for mean and total surface expression using flow cytometry. Our results show that high-fat (47 en%) diets suppress expression of CD3 and CD25 antigens. We also found that linseed-oil diets suppress expression of CD11a but enhance expression of CD25 antigens. Both CD3 and CD25 are critical for lymphocyte activation, and we conclude that immunosuppression associated with high-fat diets may be associated with suppression of these surface antigens.
Animals↗
Dietary olive oil enhances murine lymphocyte calcium uptake.
BACKGROUND: Dietary lipids enhance immune function and improve outcome from injury or infection in animal models. We tested the hypothesis that amount, type, or both, of dietary lipid increases intracellular calcium concentration, a surrogate for lymphocyte activation. METHODS: Mice were fed 2 weeks on semipurified diets with 5% (by weight [w/w]), 10% (w/w), or 20% (w/w) dietary fat consisting of coconut, olive, safflower, or linseed oil. Changes in intracellular calcium concentration after mitogen stimulation of splenic lymphocytes was estimated by using flow cytometry. RESULTS: Olive oil diets increase intracellular calcium concentration after concanavalin A, lipopolysaccharide, and CD3 stimulation. On the other hand, linseed oil (which is high in omega-3 fatty acids, which have been shown in other studies to enhance immune function) depresses intracellular calcium levels. The amount of dietary fat had no effect on intracellular calcium. CONCLUSION: Olive oil merits further study in the application of nutritional pharmacology to immunomodulation of the critically injured, because it may enhance lymphocyte function.
Analysis of Variance↗
Introduction: management of cancer in the Canadian Healthcare System.
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Canada↗
Cancer care in Ontario: accessible oncology on sale, or cheque's in the mail?
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Delivery of Health Care↗
Pregnancy after breast carcinoma: the ultimate medical challenge.
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Antineoplastic Agents↗
A new CD44V3-containing isoform is involved in tumor cell growth and migration during human breast carcinoma progression.
CD44 isoforms belong to a family of cell adhesion molecules expressed on the cell surface of many tumor cells during human breast cancer progression. In this study we have analyzed the expression of CD44v3-containing isoforms [containing heparan sulfate addition sites for growth factor binding] in primary breast tumors, axillary nodal metastases and normal breast tissue. Using reverse transcriptase-polymerase chain reaction (RT-PCR) followed by Southern blot, cloning, nucleotide sequencing and RT-in situ-PCR analyses, we have found that at least two CD44v3-containing isoforms, including one new species of CD44v2,deltav3-10 (deltav3 defined as a v3 exon lacking the first 24 base pairs) and another previously reported CD44v3,8-10 are preferentially expressed in human primary breast tumor and axillary nodal metastases but not in normal breast tissues. These finding suggest that these CD44v3-containing isoforms are closely associated with breast cancer metastasis.
Axilla↗
Unfiltered sulfur colloid and sentinel node biopsy for breast cancer: technical and kinetic considerations.
BACKGROUND: There are few clinical data on technical limitations and radiocolloid kinetics related to sentinel lymph node (SLN) biopsy for breast cancer. METHODS: In 70 clinical node-negative patients, unfiltered 99mTc sulfur-colloid was injected peritumorally and cutaneous hot spots were mapped with a gamma probe. SLN biopsy was performed followed by axillary lymph node dissection. Missed radioactive nodes (nodes not under hot spots) were removed from axillary lymph node dissection specimens and submitted separately. RESULTS: At least one hot spot was mapped in 69 patients (98%) and SLNs were retrieved in 62 (89%). No radiolabeled nodes were found in five (7%) and only nodes not under hot spots were retrieved in three patients (4%). Residual nodes not under hot spots were retrieved in 17 patients (24%) in whom at least one SLN specimen had been found. Diffuse radioactivity around the radiocolloid injection site impeded identification of all radiolabeled nodes during SLN biopsy, and was responsible for one of two false negatives (20 node-positive patients; false-negative rate 10%). Hot spot radioactivity, number of radiolabeled nodes, and nodal radioactivity did not change with time interval from radiocolloid injection to surgery (0.75-6.25 hours). CONCLUSIONS: Although SLN localization rate is high, intraparenchymal injection may predispose to failure of radiocolloid migration, failure to identify SLNs because of high radiation background, and false-negative outcomes. Alternative routes of radiocolloid administration should be explored.
Adult↗
Metastasectomy as a cytoreductive strategy for treatment of isolated pulmonary and hepatic metastases from breast cancer.
The authors sought to examine the utility of resection in conjunction with adjuvant chemotherapy for treatment of metastases from breast cancer isolated to the liver or lungs. Limitations of regional therapy were examined and potential agents for systemic therapy were reviewed. As resection of metastases is a controversial therapeutic approach, no clinical trials are available for review. Rather, evidence for a potential role for surgery rests on retrospective studies of small series of patients. Technical advances have rendered resection of liver and lung metastases safe. Long-term results as reported by other investigators support the role of metastasectomy in selected patients. The site of failure following ablation of liver metastases is usually in the liver. Following resection of lung metastases, nonpulmonary and disseminated recurrences are most common. Adjuvant therapy with docetaxel or any other agent or combination with significant activity against visceral metastases might potentiate long-term results.
Breast Neoplasms↗
A thousand points of light or just dim bulbs? Radiolabeled antibodies and colorectal cancer imaging.
Radioimmunoscintigraphy (RIS) is coming into its own as an imaging modality in clinical oncology. Early experience with indium-111-labeled intact murine monoclonal antibodies (MoAbs) in colorectal cancer suggested that RIS images hepatic metastases poorly. Moreover, an antimurine immune response was frequently provoked, precluding multiple follow-up RIS studies in individual patients due to reticuloendothelial sequestration of the radioimmunoconjugate before tumor targeting could occur. Recent trials of technetium-99m-labeled antibody fragments and human MoAbs have demonstrated significant improvement in imaging efficacy, and repeated or serial imaging is possible because of the absence of associated immunogenicity. RIS is demonstrably more sensitive than conventional diagnostic modalities (CDM) such as computed tomography (CT) for detection of extrahepatic abdominal and pelvic colorectal carcinoma and is complementary to CDM in imaging liver metastases. In a surgical decision-making analysis comparing CT, RIS (IMMU-4 99mTc-Fab'; CEA-Scan), and CT plus RIS in patients with recurrent or metastatic colorectal cancer, CT plus RIS improved correct prediction of resectability by 40% and correct prediction of unresectability by 100% compared with CT alone. At the present time, RIS used in combination with CDM contributes an incremental improvement in diagnostic accuracy in colorectal cancer patients with known or suspected recurrent disease. Basic and clinical research currently in progress promises to yield agents and methods that provide rapid high-resolution imaging, high tumor-to-background ratios in all organs at risk for tumor recurrence or metastasis, negligible immunogenicity and toxicity, and a significant further improvement in the accuracy of clinical decision making in oncology patients.
Antibodies, Monoclonal↗
Radical surgery for extensive rectal cancer: is it worthwhile?
In a small proportion of patients with extensive primary or locally recurrent rectal cancer, disease remains confined to the pelvis for a prolonged period. Symptoms are highly prejudicial to quality of life and often refractory to treatment short of extirpative surgery. Cure requires en bloc excision of all involved pelvic viscera with tumor-free margins. The pelvic exenterations (PE) are the most radical operations for rectal cancer. PE carries a high risk of perioperative morbidity and mortality, and has profound functional, psychological, and psychosexual implications for patients. Careful preoperative counseling regarding surgical risks and the impact of PE on body function and image is indispensable; the patient's consent must be truly informed. Patients with major medical or psychiatric/emotional comorbidity and those who are mentally incompetent are not candidates. Tenesmus and central pelvic/perineal pain are amenable to PE whereas radicular pain is not; sciatica and lower extremity lymphedema portend unresectability. Extrapelvic disease should be excluded preoperatively. While invaded sacrum can be resected en bloc with involved viscera (sacropelvic exenteration), fixity of tumor to the pelvic sidewall(s) in nonirradiated patients almost invariably implies unresectability. Other contraindications to PE include invasion of the proximal (S1 or higher) lumbosacral spine or lumbosacral plexus/sciatic nerves, ureteric obstruction proximal to the ureterovesical junctions, and encasement of the external or common iliac vessels by tumor. PE for advanced primary rectal carcinoma yields 5-year survival of over 40%; when performed for recurrent disease, long-term salvage rates are not as high. While radical surgery is rarely indicated for palliation, PE in carefully selected (good performance status and life expectancy, complete excision of all gross disease) incurable patients results in abrogation of disabling symptoms and reasonable intervals of high-quality survival.
Humans↗
Does a radiation dose-response relation exist concerning survival of patients who have soft-tissue sarcomas of the extremities? Radiation dose-response relation for soft-tissue sarcomas.
This study analyzes a single-institution experience by evaluating the impact on survival of increasing total dose of adjunctive irradiation in patients who had extremity soft-tissue sarcoma (ESTS). A retrospective review of the tumor registry at a university medical center from January 1984 through December 1992 yielded a total of 59 surgical patients of ESTS. With follow-up ranging from 30 to 135 months (median, 65 months), the 2-, 5-, and 8-year overall and disease-free survival for all patients was 86%, 71%, 58% and 76%, 70%, 56%, respectively. Multivariate analyses using the Cox proportional hazards model revealed that total radiation dose (p = 0.02), American Joint Committee on Cancer stage (p = 0.04), and tumor size (p = 0.006) were all significant prognostic factors of overall survival; however, only tumor size was predictive of disease-free survival (p = 0.02). When the effect of tumor size and disease stage were controlled in the Cox model, a dose-response curve between increasing total radiation dose and improved overall patient survival was indicated. This study demonstrates the significance of tumor size on predicting both overall and disease-free survival in patients who have soft-tissue sarcomas of the extremity. It also suggests, however, that a radiation dose-response relation may exist for overall survival. Future investigations should consider evaluating the minimal total radiation dose needed to optimize patient survival after limb-sparing surgery.
Adolescent↗
Somatostatin receptor expression in Hürthle cell cancer of the thyroid.
Somatostatin receptor expression, which was not a previously described marker for Hürthle cell cancer of the thyroid, was demonstrated by in vivo imaging with (111)In-pentetreotide in three patients. This phenomenon not only adds another imaging technique to the nuclear medicine armamentarium for detecting recurrent and metastatic cancer in patients with Hürthle cell cancer but also opens up an alternative therapeutic avenue with somatostatin analogs or their radiolabeled compounds.
Adenoma, Oxyphilic↗
Sentinel lymph node localization in early breast cancer.
METHODS: Thirty-two patients with clinical node-negative breast cancer underwent sentinel node localization study as part of a National Cancer Institute-sponsored multicenter trial. Anatomical and histopathologic characteristics of sentinel lymph node (SLN) and a kinetic analysis of nodal uptake were studied. Patients were injected with 1 mCi/4 ml unfiltered 99mTc-sulfur colloid in four divided doses around the palpable lesion or immediately adjacent to the excision cavity if prior biopsy was performed. SLN biopsy was performed 1.5-6 hr (mean = 3 hr) postinjection. Intraoperative localization was performed using a gamma probe. All patients underwent complete axillary dissection. RESULTS: SLN was identified in 30 of 32 (94%) patients. There were no false-negative SLN biopsies. CONCLUSION: This study supports the clinical validity of SLN biopsy in breast cancer and confirms that, unlike the blue dye technique, the learning curve with unfiltered 99mTc-sulfur colloid and the gamma detection probe is short, and SLN localization is achievable in over 90% of cases by surgeons with modest experience. The use of unfiltered 99mTc-sulfur colloid (larger particle size) with larger injected volume permits effective localization of SLNs.
Adult↗
Use of carcinoembryonic antigen radioimmunodetection and computed tomography for predicting the resectability of recurrent colorectal cancer.
OBJECTIVE: The objective was to determine the role of arcitumomab (CEA-Scan; Immunomedics, Morris Plains, NJ), an anticarcinoembryonic antigen (CEA) Fab' labeled with technetium-99m, in the presurgical evaluation of patients with recurrent or metastatic colorectal carcinoma. SUMMARY BACKGROUND DATA: Surgical resection is the only method known to cure recurrent or metastatic colorectal carcinoma. The location and extent of disease must be determined before surgery. The role of antibody imaging, a new cancer detection modality, in preoperative evaluation for resection of locally recurrent or metastatic colorectal cancer has not been established, either alone or in combination with standard diagnostic modalities. METHODS: In a blinded analysis of 209 patients with known or suspected colorectal cancer, the accuracy of arcitumomab, alone and combined with computed tomography (CT), was compared to that of CT for predicting abdominopelvic tumor resectability by correlating the results with surgical and histopathologic findings. RESULTS: Arcitumomab alone or combined with CT was found to be significantly more accurate for predicting surgical outcome than CT alone. When the results of CT and arcitumomab were concordant for abdominopelvic resectability, nonresectability, or absence of disease, the prediction was accurate in 67%, 100%, and 64%, respectively. Thus, the concordance for nonresectability (100% correct) may obviate the need for other diagnostic modalities or exploratory surgery. When the two tests were discordant, arcitumomab was correct substantially more often than CT. Because the liver is the most common site of distant metastasis in colorectal cancer, a subset of patients with hepatic disease was also analyzed; findings were similar to the overall resectability results. The product's safety profile was excellent: the incidence of induction of an immune response against arcitumomab was <1% and that of potentially adverse events was 1.2%. CONCLUSIONS: The accuracy of arcitumomab for assessing resectability status is greater than that of CT, both in all patients undergoing evaluation for curative abdominopelvic resection of colorectal cancer and in the subset of patients with suspected or proven liver metastases. The additional use of arcitumomab with CT potentially doubles the number of patients who could be saved the cost, morbidity, and mortality of unnecessary abdominopelvic surgery and increases those who are potentially resectable for cure by 40%.
Adult↗
Gamma probe guided sentinel node biopsy in breast cancer.
Axillary lymph node status is the most important pathological determinant of prognosis in early breast cancer. Determination of axillary status is crucial in clinical decision-making. It is currently accepted that the total axillary lymphadenectomy is the most reliable staging procedure. However, routine axillary dissection does not benefit a majority of early breast cancer patients who are node-negative, and the patients sustain the potential morbidity and the economic cost of this procedure. There is substantial evidence that there is an orderly progression of breast cancer metastases in a lymphatic basin, sentinel node being the first node to receive lymphatic drainage from the tumor site. Sentinel lymph node biopsy may prove to be the optimal sampling technique for staging of breast cancer patients. A large multicenter trial to study the clinical validity of sentinel lymph node biopsy in breast cancer is underway. This paper addresses the rationale for sentinel lymph node biopsy and discusses the technical issues with regard to anatomy and physiology of breast lymphatics.
Axilla↗
Supplemental L-arginine HCl augments bacterial phagocytosis in human polymorphonuclear leukocytes.
That L-arginine (L-Arg) augments the host response to acute bacterial sepsis suggests that this amino acid intervenes early in the immune response, perhaps via the nitric oxide synthetase (NOS) pathway. The effect of L-Arg supplementation on in vitro phagocytosis of fluorescein-labeled, heat-killed Staphylococcus aureus by peripheral blood neutrophils (PMNs) from 12 normal human volunteers was studied. Separated PMNs were incubated for 2 h with labeled bacteria, with and without supplemental L-Arg, D-arginine, glycine, and/or the NOS inhibitors L-canavanine, aminoguanidine, or L-NG-nitroarginine methyl ester. PMNs were fixed and extracellular fluorescence quenched with crystal violet. By flow cytometry and confocal microscopy, L-Arg supplementation was shown to result in a highly significant increase in PMN bacterial phagocytosis, the maximal effect being seen with L-Arg 380 microM and falling off with higher concentrations. This augmentation was completely abrogated by NOS inhibitors in molar excess, but inhibitors alone did not suppress phagocytosis below that of unsupplemented controls. Neither D-arginine nor glycine affected phagocytosis; the L-Arg effect was stereospecific and not related to utilization of L-Arg as an energy source. L-Arg supplementation significantly enhances bacterial phagocytosis in human neutrophils, perhaps by effects on cytoskeletal phenomena, and this appears to be mediated through NOS activity. Phagocytosis by nonspecific immune cells which intervene early in the response to sepsis is critically important, and beneficial effects of L-Arg on the clinical course of sepsis may be due at least in part to augmentation of phagocyte function.
Arginine↗
Involvement of CD44 and the cytoskeletal linker protein ankyrin in human neutrophil bacterial phagocytosis.
The leukocyte CD44 and CD45 cell surface receptors are associated via the linker proteins ankyrin and fodrin with the cytoskeleton, which itself is important in immune cell functions such as adherence, chemotaxis, and phagocytosis. The effects of rat antihuman CD44 and CD45 monoclonal antibodies on phagocytosis of fluoresceinated heat-killed Staphylococcus aureus 502A by normal human neutrophils (PMNs) during 2 hr incubation in RPMI-1640 was studied via flow cytometry and confocal microscopy. Flow cytometry was performed using an excitation wavelength of 488 nm, fluorescence being measured at 515-560 nm on 50,000 PMNs per sample. Confocal microscopy was performed on samples after further incubation with rhodamine-conjugated antiankyrin. Anti-CD44 resulted in an increase of 27-31% compared to control (P = 0.004) in the proportion of PMNs fluorescing, an increase of 17-24% (P = 0.001) in mean intracellular fluorescence per PMN, and an increase in total PMN fluorescence of 50-58% compared to control (P < 0.001). In contrast, anti-CD45 had little effect on phagocytosis. Colchicine (a microtubule-disrupting agent) enhanced, whereas cytochalasin-D (a microfilament inhibitor) inhibited bacterial phagocytosis; cytochalasin-D completely abrogated the effect of anti-CD44 on this PMN function. Hyaluronic acid augmented phagocytosis by an increment similar to that observed with anti-CD44. Two-color flow cytometry and confocal microscopy demonstrated that ankyrin always colocalized with ingested fluorescein isothiocyanate (FITC)-labeled bacteria. These data strongly suggest that CD44 is involved in bacterial phagocytosis, provide further evidence of CD44 receptor linkage to cytoskeletal elements in human leukocytes, and suggest that ankyrin has a significant role in the transport of phagosomes.
Ankyrins↗