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A J Cochran

Publications and source records attributed to A J Cochran.

178 records · Page 10Linked to original sources
PubMedDate not supplied

Management of the regional lymph nodes in patients with cutaneous malignant melanoma.

One of the most difficult decisions in the management of patients with melanoma remains whether or not to dissect electively the regional lymph nodes of patients with high risk primary tumors. There is abundant evidence that a proportion of such patients will eventually develop nodal metastases and that the probability of metastasis increases with increasing tumor thickness and depth of invasion. If elective node dissection is performed on all patients with high risk primaries, most patients (who have no tumor in the nodes) will be subjected to a potentially morbid operation from which they can achieve no benefit. On the other hand, a "wait and see" policy accepts that a minority of patients will go on to develop nodal metastases and that if definitive therapy is delayed until metastases are detected clinically their likelihood of survival is much reduced. We describe a new technique of dye-directed selective lymphadenectomy that allows accurate and objective identification of individual patients who have subclinical metastases, the individuals who a priori are most likely to benefit from lymphadenectomy. We also discuss new approaches to the assessment of prognosis after lymphadenectomy for node-spread melanoma, a group of patients in whom the prognosis is not uniformly bad. We end with a consideration of quality assurance aspects of the pathological evaluation of lymphadenectomy specimens.

Humans↗
PubMedDate not supplied

Metastasis of unknown origin.

Metastasis of unknown origin (MUO) constitutes between 5% and 10% of all noncutaneous cancers. An MUO is defined as a metastatic tumor for which the site of origin is not suggested by thorough history, physical examination, chest x-ray studies, routine blood and urine studies, and histologic evaluation. Two major groups of MUO can be defined: MUO to lymph nodes only (N1-3), and MUO to visceral sites. The prognosis may be quite good for patients with MUO limited to lymph nodes in the mid to high cervical, axillary, and groin areas. However, MUO in other lymph node areas is far more serious, with the possible exception of that in patients with a new syndrome, i.e., "advanced poorly differentiated carcinoma of unknown primary origin." There is some suggestion that these patients may respond to cisplatin-based combination chemotherapy. Patients with MUO to visceral sites have a poor prognosis. However, metastases from some primary tumors are sensitive to chemotherapy and a limited search for these tumors should be undertaken. These tumors include leukemia-lymphoma, germ cell tumors, small cell carcinoma of the lung, adenocarcinomas of the breast, ovary, endometrium, thyroid, or prostate, and possibly adrenal carcinoma. We start by reviewing the biochemical events of metastasis that may be targets for therapy. The importance of a correct tissue diagnosis is then considered, including the role of standard histochemistry, electron microscopy, enzyme histochemistry, and immunohistochemistry. The relatively limited value of radiologic tests in localizing the primary site of origin of the tumor is emphasized, as well as the limited role of currently available biomarkers. We conclude by discussing the treatment of each of the subtypes of MUO.

Adenocarcinoma↗
PubMedDate not supplied

Proposed reclassification of melanoma: a meeting held at the XVIth International Pigment Cell Congress, 3rd November 1996.

The current classification of cutaneous melanoma was developed in 1972 and revised in 1982. Since that time, new concepts and terminology have evolved that require consideration of a further revision. Regional meetings of interested parties have been held to review the Classification and there will be an open meeting on the topic at the 1997, 4th World Conference on Melanoma in Sydney, Australia. This paper reports on a meeting to discuss some of the concepts that will form part of that process, held on November 3, 1996 as part of the XVIth International Pigment Cell Conference. A questionnaire is included that will allow the interested reader to provide comments on the topic.

Humans↗
PubMedDate not supplied

Is the node of Cloquet the sentinel node for the iliac/obturator node group?

PURPOSE: Some surgeons question the survival advantage of ilioinguinal lymphadenectomy for metastatic melanoma because they believe that deep nodal involvement signifies a poor prognosis that is unchanged by surgery. However, several series, including our own, have reported 5-year survival rates reaching 30%. New adjuvant therapies may further improve survival after ilioinguinal lymphadenectomy, but this applies only to nodal basins with metastatic disease. We hypothesized that the node of Cloquet accurately reflects the pathologic status of the iliac/obturator nodes, allowing deep pelvic lymphadenectomy to be selectively performed. PATIENTS AND METHODS: Between 1972 and 1998, 691 patients with primary cutaneous melanoma underwent both elective and therapeutic complete (superficial and deep) ilioinguinal lymphadenectomy. Of the 204 (30%) patients with tumor-positive inguinal and/or iliac/obturator nodes, 68 had a node of Cloquet identified during pathologic review of the lymphadenectomy specimen. Chart and computer database review of these 68 patients was undertaken to determine the association between the tumor status of Cloquet's node and that of deep pelvic nodes. Immunohistochemical analysis was performed on eight of 11 negative Cloquet's nodes in patients with positive iliac/obturator nodes. Paraffin blocks of the other three negative nodes of Cloquet were unavailable for immunohistochemistry, and they were excluded from analysis. RESULTS: Tumor-positive deep nodes were identified in the lymphadenectomy specimen from 20 of 30 (67%) patients with a positive Cloquet's node and from eight of 35 (23%) patients with a negative Cloquet's node (P = 0.0019). Re-examination of these eight tumor-negative Cloquet's nodes using immunostaining with S-100 and HMB45 identified tumor in 3 nodes, increasing the sensitivity of Cloquet's node for predicting deep nodal metastases from 71% to 82%. The 6.8 odds ratio of positive iliac/obturator nodes given a positive node of Cloquet increased to 12.4 after immunohistochemical analysis. The positive and negative predictive values were also enhanced from 67% to 70% and 77% to 84%, respectively. DISCUSSION: The tumor status of the node of Cloquet significantly reflects the tumor status of the iliac/obturator nodes, particularly when Cloquet's node is examined by immunohistochemical analysis. The node of Cloquet assumes the role of the sentinel node in patients whose superficial inguinal lymph nodes drain through Cloquet's node to the iliac/obturator nodes.

Adult↗
PubMedDate not supplied

Occult metastases in the axillary lymph nodes of patients with breast cancer node negative by clinical and histologic examination and conventional histology.

We examined axillary lymph nodes from 80 women with node-negative breast cancer, by immunohistochemistry, utilizing polyclonal antibodies to cytokeratins and carcino-embryonic antigen and monoclonal antibodies to cytokeratins and milk fat globulin. Occult metastatic tumor, undetectable in hematoxylin and eosin stained slides, but visible by immunohistochemistry, was detected in 23 of 80 patients (29 per cent). Occult tumor was observed in patients with invasive ductal carcinoma (21/76-28 per cent) and in individuals with invasive lobular carcinoma (2/4-50 per cent). In patients with occult metastases the primary tumors were slightly larger (mean 2.39 cm, range 1.00-5.00 cm) than those of patients whose nodes were negative for tumor cells (mean, 2.03 cm, range, 0.60-4.50 cm). Information concerning clinical outcome is available for 61 patients followed for between 1 and 7 years (mean 3.2 years). Three of 17 patients (18 per cent) who had occult tumor in the nodes developed distant metastases, all less than 3 years after initial surgery. One of the 44 patients (2 per cent) whose nodes were free of occult tumor developed distant metastases 5 years following surgery. Local recurrences in the area of the mastectomy occurred in one of 17 patients with occult nodal tumor (6 per cent), less than 1 year after surgery. Local recurrences were seen in three of 44 patients without occult metastases (7 per cent), in two patients 5 years after mastectomy and in one patient 7 years after mastectomy.

Adult↗
PubMedDate not supplied

Immunostaining of tissue sections previously stained with hematoxylin and eosin.

S-100 protein was demonstrated in 28/31 melanoma tissue sections that had been previously stained by hematoxylin and eosin, including 17 from 19 primary melanomas and 11 from 12 metastases. Additional H & E stained sections from 11 metastatic and 13 primary melanomas were reacted with the monoclonal antibody NKI/C-3 and all stained positively. This approach is of value when additional sections are not available or when deeper cuts through a block do not contain tumor. The superimposition of the immunostaining does not reduce the record and diagnostic value of the double-stained sections.

Antibodies, Monoclonal↗
PubMedDate not supplied

Immunosuppression by melanoma cells as a factor in the generation of metastatic disease.

Studies of the regional nodes (RLN) of melanoma patients, using immunohistology with anti-S-100 protein and monoclonal antibodies have shown occult tumor cells (OTC) in nodes ostensibly tumor-free by H&E staining. OTC were demonstrated in 14% of Stage I patients, mainly those with deep, thick primaries and 30% of Stage II patients, mainly those with at least 3 tumor-positive nodes on H&E. The nodes containing OTC are those nearest to tumor on the direct lymphatic pathway (dye studies). Parallel studies show nodes in the same position to be immune suppressed (histology, immunohistology, response to mitogens, alloantigens and lymphokines) and to contain many suppressor T cells (Con-A). Melanoma-derived materials (gangliosides, prostaglandins, lipoprotein antigens) downregulate lymphocyte and macrophage functions, providing a possible mechanism for the suppressed function of nodes near tumor, a suppression that may facilitate tumor cells as evidenced by the survival of OTC.

Humans↗
PubMedDate not supplied

Immunological changes in cancer patients receiving BCG.

We employed immunological tests to assess patients with cancer, mainly melanoma, receiving BCG alone or combined with chemotherapy. A comparison of BCG recipients with similar cancer patients not receiving BCG showed differences in the frequency of Mantoux reactivity positivity in the leucocyte migration assay against tumour antigens and positivity in membrane immunofluorescence. Short term sequential studies showed conversion from negativity to positivity or strengthening of reaction to occur during initiation of BCG therapy. Extended sequential studies employing the leucocyte migration assay against tumour antigens and modifications to assess serum effects indicate that the changes are more related to the changing clinical status than to BCG. It may be possible to devise quantitative in vitro techniques to assay sensitivity to tuberculoproteins which may allow assessment of BCG effects in vitro. Current technology permits monitoring for varying clinical stage rather than the effects of immunotherapy.

Antigens, Neoplasm↗
PubMedDate not supplied

Clinical application of the clonogenic assay.

Simple methods were developed for cloning human solid tumors; 68 percent of the tumors processed formed at least 30 colonies within two to four weeks. The accuracy of the clonogenic assay for predicting clinical response was determined in a prospective, correlative study. Eight-four patients had objectively measurable disease and had at least one course of chemotherapy. Tumor types included melanoma (33), lung (12), colon (7), breast (7), stomach (4), ovarian (12), sarcoma (7), and hepatoma (2). For patients whose tumors were sensitive in vitro to a particular drug, clinical response was seen in 21/25 cases (84 percent). Tumor resistance was found in 59 instances, and 54 patients (92 percent) had no clinical response to the same drugs. Associations between in vitro chemosensitivities and clinical course were highly significant.

Antineoplastic Agents↗