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C M Balch

Publications and source records attributed to C M Balch.

At least 145 records · Page 8Linked to original sources
PubMed1984

Head and neck melanoma in 534 clinical Stage I patients. A prognostic factors analysis and results of surgical treatment.

Single and multifactorial analyses were used to evaluate prognosis and results of surgical treatment in 534 clinical Stage I patients with head and neck cutaneous melanoma treated at the University of Alabama in Birmingham (U.S.A.) and the University of Sydney (Australia). This computerized data base was prospectively accumulated in over 90% of cases. Melanomas were about equally distributed between men and women. They were located on the skin of the face in 47%, neck in 27%, scalp in 13%, and the ear in 13% of patients. Both the results of the prognostic factors analyses and the surgical treatment demonstrated that lentigo maligna melanoma (LMM) was distinct from the other two growth patterns, superficial spreading melanoma and nodular melanoma (SSM and NM). In a multifactorial analysis of the 453 patients with SSM and NM, the dominant prognostic variables were tumor thickness (p less than 0.00001), anatomic subsite (p = 0.0213), and ulceration (p = 0.0289). Patients with melanomas on the scalp or neck subsites fared worse than those with tumors located on the face or ear. The results differed for LMM, where thickness was not a significant predictor of survival, and the most dominant prognostic variable was ulceration (p = 0.0042). Local recurrence rates were low, being 2.4% for tumors less than 2.5 mm in thickness, but were 12.3% for tumors greater than or equal to 4.0 mm in thickness. Patients with SSM and NM lesions located on the head and neck had a lower survival rate than those with extremity melanomas in every tumor thickness category, although only those in the 0.76 to 1.49 mm thickness subgroup were significantly different (p = 0.0007). After 5 years of follow-up, patients who underwent an elective lymph node dissection for SSM and NM with a thickness range of 1.5 to 3.99 mm had a better survival (72%) than patients with melanomas of equivalent thickness whose initial treatment was wide excision alone (45%). LMM had a less aggressive biologic behavior compared to SSM or NM and was treated more conservatively. Thus, LMM lesions had an 85% 10-year survival rate with wide excision only, and there was no significant improvement in survival with ELND. Growth patterns, tumor thickness, ulceration, and anatomic subsites should be considered when evaluating risk factors and when making treatment decisions in head and neck melanoma patients.

Head and Neck Neoplasms↗
PubMed1984

Characterization of a subset of human natural killer cells that express OKM1 but lack HNK-1 (Leu-7) antigens.

The HNK-1(Leu-7) monoclonal antibody selectively identifies a population of human granular lymphocytes with natural killer (NK) cell activity. We previously reported that the HNK-1+ cell fraction purified from blood mononuclear cells accounted for virtually all NK activity in six individuals. In this study we analysed additional normal individuals and found that in eight out of 14 donors HNK-1+ cells, purified with a fluorescence-activated cell sorter (FACS), exhibited greatly enriched NK cell activity, whereas HNK-1- cells did not have significant activity. In four donors the HNK-1+ cells were enriched in NK activity compared with HNK-1- cells; however, the HNK-1- cells also had moderate levels of activity. In the two remaining donors, NK activity was not enriched in the HNK-1+ fraction in comparison with the HNK-1- fraction. To determine the cell type responsible for NK activity in the HNK-1- subset, these cells were further sorted with the FACS onto OKM1+ and OMK1- fractions and analysed for morphology and function. HNK-1- OKM1- cells were found to be small- to medium-sized lymphocytes devoid of NK activity in all donors tested, whereas most HNK-1- OKM1+ cells were granular lymphocytes and in some donors demonstrated NK function at a level comparable to HNK-1+ cells. Thus some individuals have an important subset of granular lymphocytes with NK-cell activity and the HNK-1- OKM1+ phenotype. It is important to account for these cells in studies involving granular lymphocytes and NK cell function.

Antibodies, Monoclonal↗
PubMed1984

Current status and future prospects for adjuvant therapy of melanoma.

Advances in the treatment of melanoma have resulted mainly from improved surgical management of the primary tumour assisted by a greater appreciation of major prognostic factors in the natural history of the disease. Further improvement in the treatment of melanoma will depend largely on introduction of methods to prevent recurrence of the disease. The present review discusses criteria for selection of patients with a high risk of recurrent disease and the adjuvant treatment that has been used in past studies to prevent recurrences. With few exceptions various regimens of chemotherapy, non-specific immunotherapy with bacterial products or combinations of these treatments have not increased disease free or survival periods. Immunotherapy with various sources of melanoma antigens or with viral lysates of melanoma cells have produced encouraging results in uncontrolled studies and require further evaluation. Several advances appear to provide scope for new initiatives in immunotherapy. These include an appreciation of the role of suppressor cells in regulation of immune responses against tumour cells and possible methods to inhibit their activity. A second is the definition of various lymphokines involved in generation of immune responses (particularly interleukin 2) and development of in vitro methods for large scale production of these factors. Thirdly, methods are becoming available to define the heterogeneity of tumour cells in terms of cell surface antigens or their release of soluble factors which may help select treatments appropriate to each patient.

Antigens, Neoplasm↗
PubMed1984

Immune response against vaccinia virus in rhesus monkeys: no evidence for primary MHC-restricted cytolytic T cells.

Rhesus monkeys were tested in vitro for their cellular immune response after infection with vaccinia virus, employing lymphocyte preparations from various lymphoid tissues. Although virus-infected target cells were lysed by lymphoid cells from immunized, but not from uninfected, rhesus monkeys, we could neither find evidence for MHC-restricted T cells nor for antibody-dependent cellular cytotoxicity. Kinetics of target cell lysis, the killing patterns of immune lymphocytes measured on syngeneic, allogeneic, and xenogeneic target cells, and the influence of protein A on cytotoxic activity in vitro suggest induction predominantly of natural killer cells in vivo which exhibit lytic activity on virus-infected target cells in vitro.

Animals↗
PubMed1984

Prostaglandin E2-mediated suppression of cellular immunity in colon cancer patients.

The immune regulation of phytohemagglutinin (PHA) and concanavalin A (Con A) mitogen responses by prostaglandin (PG)-producing suppressor monocytes was examined in 57 patients with colorectal cancer and 55 normal individuals. The blood lymphocyte responses to either PHA or Con A were significantly depressed in 74% of patients compared to normal controls. The mean PHA response for the patients was significantly lower than that for controls (17,649 versus 25,549 cpm, P = 0.02), while the mean Con A response for the patients was also depressed but not as significantly (13,551 versus 18,623 cpm, P = 0.09). The depression of immune competence was greatest in older patients and those with metastatic disease. The addition of indomethacin (1 microgram/ml) to cell cultures of both patients and normal individuals enhanced the mitogen response, suggesting that PGE-producing suppressor cells were operative in both groups. Among the patient group, however, a differential modulation of the immune response by indomethacin was observed. Thus, the addition of indomethacin restored the PHA response in patients almost to normal levels, while the Con A increase was less pronounced. Even after indomethacin treatment, the Con A proliferative response by lymphocytes was significantly depressed in patients as compared to controls (P = 0.002). To prove that indomethacin was blocking excessive PG production by suppressor monocytes in colon cancer patients, we directly measured PGE2 production by peripheral blood mononuclear cells (PBMCs) using a radioimmunoassay. PBMCs from the patients produced significantly greater amounts of PGE2 compared to controls (10.1 versus 5.1 ng/ml, P = 0.0001). This comparison was still significant after adjustment for age and sex. The increased PGE2 production appeared to be selective, since the levels of two other arachidonic acid metabolites, PGF1 alpha and thromboxane B2, were the same or less than control levels. PG-mediated immune suppression of mitogenesis thus appears to be abnormally increased in colon cancer patients, particularly for the PHA response. This abnormality was partially corrected in vitro by incubation of the PBMCs with indomethacin, a prostaglandin synthetase inhibitor.

Adult↗
PubMed1984

Suppression of immunoglobulin synthesis by lymphocyte subpopulations in patients with Crohn's disease.

In previous studies, patients with mild or inactive Crohn's disease were found to have increased suppressor T-cell activity. To further characterize suppressor T cells in Crohn's disease, studies were carried out with the use of monoclonal antibodies. Excessive suppressor activity was eliminated by removal of OKT 8+ lymphocytes by complement-mediated lysis. However, the percentage of OKT 8+ (or Leu 2a+) cells and the ratio of OKT 4+ to OKT 8+ (or Leu 3a+ to Leu 2a+) cells were not significantly different from normal. Although the subgroup of patients with increased suppression of immunoglobulin synthesis had a significantly lower mean Leu 3a to Leu 2a ratio than that of normal subjects, in the whole group of Crohn's patients studied, neither the percentage of Leu 2a+ cells nor the ratio of Leu 3a+ to Leu 2a+ cells correlated with excessive suppression of immunoglobulin synthesis. A subpopulation of Leu 2a+ lymphocytes reactive with the monoclonal antibody HNK-1 (Leu 2a+ HNK-1+) was increased in patients with Crohn's disease. Furthermore, elimination of HNK-1-reactive lymphocytes by complement-mediated lysis diminished the excessive suppressor cell function in patients with Crohn's disease. The percentage of Leu 2a+ HNK-1+ lymphocytes correlated significantly with the suppression of pokeweed mitogen-stimulated immunoglobulin synthesis in vitro. Thus, patients with mild Crohn's disease have an increased suppressor cell activity in vitro which correlates with the presence of a subset of lymphocytes that have an HNK-1+ Leu-2a+ phenotype.

Adolescent↗
PubMed1984

Ineffectiveness of adjuvant chemotherapy using DTIC and cyclophosphamide in patients with resectable metastatic melanoma.

A randomized, prospective trial of adjuvant chemoimmunotherapy was compared in a group of 136 patients with melanoma after complete surgical resection of advanced regional metastasis (stage III) or isolated distant metastasis (stage IV). All patients received a 2-year course of nonspecific adjuvant immunotherapy of subcutaneous injections of Corynebacterium parvum (4 mg/m2 divided among the four extremities in 1- to 2-week cycles). Half of the patients also received a 6-month course of dimethyl triazeno imidazole carboxamide (DTIC) plus cyclophosphamide chemotherapy (each at 600 mg/m2 administered intravenously every 3 weeks for nine cycles) while the other half received no chemotherapy. Analysis of the data showed that adjuvant chemotherapy did not provide any demonstrable therapeutic effect, either in terms of disease-free survival or overall survival. No benefit was observed in subgroups of patients categorized by disease stage, site of metastasis, or sex. The drugs did cause a substantial rate of morbidity, however, since 42% of the patients had severe nausea and vomiting, while 13% had hair loss. The C. parvum was well tolerated in almost all patients. This is a particularly high-risk group for subsequent metastases since only 24% of the patients were free of disease for 1 year and 12% after 2 years. Adjuvant DTIC and cyclophosphamide had no observable therapeutic effect on this population of high-risk patients with melanoma.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1984

Heterogeneity of natural killer lymphocyte abnormalities in colon cancer patients.

p6e monoclonal antibody HNK-1 reacts exclusively with human granular lymphocytes that comprise 16 +/- 1.4% of blood mononuclear cells. In normal individuals, almost all natural killer (NK) and killer (K) cell function resides in this lymphocyte subset. The level of HNK-1+ granular lymphocytes, their stage of differentiation, and NK cell function were examined in 70 colon cancer patients and the results compared with data for 114 age-matched normal individuals. Median levels of granular lymphocytes were significantly depressed in colon cancer patients compared to controls (9% versus 16.5%, P less than 0.0001). Despite the depressed numbers of circulating HNK-1+ cells, NK cell function in the colon cancer patients was essentially the same as in normals (P = 0.78). The HNK-1+ lymphocyte level correlated exactly with NK cell function in about two thirds of normal individuals but only one third of colon cancer patients (P = 0.025). Three possible mechanisms for this dichotomy were examined. First, lymphoid cell subpopulations purified with a fluorescence-activated cell sorter (FACS) were examined for altered NK cell functional activity. HNK-1+ cells from the colon cancer patients exhibited significantly less NK functional activity compared to normals (796 versus 1046 lytic units, P = 0.04). Interestingly, the HNK-1- fraction (predominantly T lymphocytes) had increased NK cell functional activity in the colon cancer patients compared to normals (373 versus 218 lytic units, P = 0.0001). Purified monocytes did not contribute to NK cell functional activity. Second, the functional maturity of the HNK-1+ lymphocytes was correlated with NK activity. Two subsets of HNK-1+ cells were identified by surface membrane markers and purified with the FACS. The more mature HNK-1+ subset (i.e., HNK+Leu-4-M1+) exhibited almost ten times more NK cell functional activity than did the less mature cell fraction (i.e., HNK+Leu-4+M1-) cells in normal individuals (2230 versus 286 lytic units/10(7) cells). Further analysis demonstrated that the ratio of mature to immature HNK+ cells in normal individuals was 3:1, while it was decreased to a 1:1 ratio in colon cancer patients P = 0.005). Third, the influence of prostaglandin-mediated suppression on NK cell activity was examined. PGE2 did not appear to influence NK cell function, since NK cell function was unchanged in vitro in the presence of a prostaglandin synthesis inhibitor.(ABSTRACT TRUNCATED AT 400 WORDS)

Antibodies, Monoclonal↗
PubMed1984

Preoperative regional chemotherapy and rapid-fraction irradiation for sarcomas of the soft tissue and bone.

Conventional treatment for high grade and large sarcomas uses a radical surgical approach, including amputation, in many patients. We evaluated a limb-sparing treatment approach using preoperative regional Adriamycin chemotherapy and rapid-fraction radiation therapy. Thirty patients with soft tissue or skeletal sarcoma were treated in a prospective, nonrandomized clinical trial to evaluate local disease control and limb salvage in these patients who would otherwise require amputation or face a high risk of local recurrence with surgical excision. Almost all patients had large tumors with grade III histologic findings. All patients had a three day intra-arterial regional chemotherapy infusion with Adriamycin (100 milligrams total dose), followed within ten days by rapid-fraction irradiation (3,000 rads over a two week period) prior to surgical excision of the tumor. The size and location of the sarcoma permitted only a marginal resection in one-half of the patients, while the remainder could be excised in a three dimensional en bloc manner. Almost all patients received post-operative systemic Adriamycin chemotherapy (450 milligrams per square meter given intravenously over a six month period). Two of six patients with significant wound complications later required amputation. Only one patient (3 per cent) has had a local recurrence of sarcoma develop after a mean follow-up of 22 months (range nine to 42 months), and 90 per cent of the patients have a useful extremity. The three year survival rate was 68 per cent for soft tissue sarcomas, compared with an expected survival rate of 38 per cent for published historical control studies. The patient with osteogenic sarcoma has a projected 83 per cent survival rate at 18 months after treatment. This multimodality approach is an effective treatment for local disease control in patients with high risk sarcoma. It permits limb salvage in most patients without compromising the survival rates.

Adolescent↗
PubMed1984

Metastases to the upper levels of the axillary nodes in carcinoma of the breast and its implications for nodal sampling procedures.

An axillary lymphadenectomy is important for the staging and treatment of metastatic disease in patients with carcinoma of the breast, especially since the nodal status is a primary criterion for using systemic adjuvant chemotherapy. As more conservative operations combined with radiation therapy have been increasingly used for selected patients with carcinoma of the breast, an axillary node sampling instead of a complete axillary dissection has been advocated by some oncologists. However, the possibility exists that node "sampling" understages patients who would otherwise have received adjuvant chemotherapy to improve their chances for cure. We retrospectively examined this hypothesis in a group of 72 patients with documented nodal metastases who had a radical mastectomy (modified or Halsted). Overall, 18 of 72 patients (25 per cent) had metastatic involvement confined to the upper axillary nodes (Levels II and III). Of the patients with no clinically palpable nodes, 32 per cent had metastatic nodal involvement confined to the upper nodes. Medial quadrant lesions exhibited this tendency more than lateral quadrant lesions (50 versus 20 per cent). Larger primary tumors were associated with an increasing likelihood of involved nodes; however, even 14 per cent of the smallest primary lesions of the breast (less than 2 centimeters) had metastases exclusively to the upper axillary region. Since approximately 40 per cent of the patients with carcinoma of the breast have nodal metastases and since 25 per cent of these metastases are confined to the upper portion of the axilla, it is estimated that at least 10 per cent of all women with carcinoma of the breast (25 X 40 per cent) would be understaged by an axillary node sampling procedure.

Axilla↗
PubMed1984

Management of cutaneous melanoma in the United States.

Melanoma is an especially important malignant disease for surgeons to know about, since it can be cured with surgical treatment if diagnosed at an early stage. In the American College of Surgeons Melanoma Survey of 4,545 melanoma patients diagnosed during 1980, the typical melanoma was relatively thin (less than 1.5 millimeters), not ulcerated (except in 9 per cent) and did not invade into the reticular dermis or beyond (level IV or V). The melanomas were most commonly located on the trunk in men and on the lower extremities in women. Eighty-eight per cent of the patients had no clinical evidence of metastases to regional nodes or to distant sites at the time of initial diagnosis. Only a small proportion (1 per cent) of patients in the survey were black and in most of these patients, their melanoma were located on the feet or hands. The treatment of melanoma was surgical in 92.5 per cent of the patients, with the majority of patients undergoing a wide excision of the melanoma as the initial form of treatment. Only one-fifth of the patients underwent elective regional node dissection for suspected micrometastases, and most of these patients had a tumor thickness exceeding 1.5 millimeters or a lesion invading to the reticular dermis (level III, IV or V). While the Breslow Microstaging Method is now recognized as the most important parameter that predicts the clinical course of the patient, this parameter was reported in only 45 per cent of the patients in the survey. The natural history of melanoma is changing, since the disease is increasing in frequency and becoming more curable. Surgical treatment should be tailored to the biologic aggressiveness of each individual patient's melanoma. This can be estimated by integrating such prognostic factors as the melanoma thickness, the presence or absence of ulceration, the level of invasion, the anatomic site and the gender of the patient.

Adult↗
PubMed1983

Changing trends in cutaneous melanoma over a quarter century in Alabama, USA, and New South Wales, Australia.

Clinical and pathologic characteristics of melanoma were compared among 1647 clinical Stage I patients treated at the University of Alabama in Birmingham (USA) and The University of Sydney (Australia) between 1955 and 1980 to determine what changes occurred over a quarter century. Over this period, the number of patients treated annually has increased substantially. There was a steady increase in the proportion of patients presenting with localized disease (clinical Stage I). Melanomas became thinner, less invasive, less ulcerative and thus more curable. They also exhibited more of a radial growth phase. The median thickness of melanomas decreased in Australia from 2.5 mm prior to 1960 to 1.1 mm during the period 1976 to 1980, while in Alabama it has decreased from 3.3 to 1.4 mm. There was a significant increase in melanomas located on the trunk in males and a corresponding decrease in male head and neck melanomas. No significant change in the site distribution was observed for any major anatomical area on female patients. There were minimal differences in the incidence of both clinical and pathologic parameters among melanoma patients in Alabama, USA and in New South Wales, Australia even when accounting for their year of diagnosis. Long-term survival rates in patients with localized disease were found to increase slightly during the 25 year time frame of this analysis. The changes that have occurred are likely due to earlier diagnosis and changes in the biological nature of the disease.

Adult↗
PubMed1983

[Completely implantable infusion pump. A new therapeutic possibility for selected patients with liver tumors].

The action of floxuridine depends greatly on its concentration for treatment of liver metastases of colorectal carcinomas and other tumors. In isolated liver metastases it is best infused regionally in order to achieve a high concentration and to reduce systemic toxicity, particularly as it is almost entirely extracted by the liver. A totally implantable infusion pump has established itself as an effective, safe and reliable device of regional chemotherapy with floxuridine for palliative treatment of selected patients with metastases of colorectal carcinomas and other tumors. Life expectancy of patients with metastases of colorectal carcinomas was prolonged by 12-18 months when compared to a precedent control group without regional chemotherapy. This results require confirmation in a randomised phase III study. Patients with hepatocellular carcinoma can be treated with intraarterial doxorubicine and floxuridine infusions. Preliminary results are encouraging. The implantable system represents a major advance in drug administration, not only for the treatment of malignant disease but also a large number of other diseases. Continuous infusion of drugs using an implantable pump system will probably achieve greater importance in the future in the treatment of cancer.

Carcinoma, Hepatocellular↗
PubMed1983

Patient risk factors and surgical morbidity after regional lymphadenectomy in 204 melanoma patients.

A series of 204 melanoma patients were studied six months or longer after regional lymph node dissection of the neck (N = 48), axilla (N = 98) and groin (N = 58) in order to determine the degree of morbidity and analyze for risk factors associated with these procedures. Only one-quarter of the patients experienced wound-related, short-term complications that were common at all sites; however, these rarely resulted in long-term functional deficits. Seromas (22%), temporary nerve dysfunction or pain (14%), and wound infections (6%) were the most frequent short-term complications. Wound complications extended the mean hospital stay by 0.6 to 4.8 days. Residual lymphedema of the leg was measurable in 26% of groin dissection patients after six months or longer; most of the edema was confined to the thigh. Only 8% of patients had significant functional deficit from lymphedema. The risk of developing at least one complication for all patients was increased for obese patients (P = 0.05) and increasing age (P = .01). These risk factors should be considered when evaluating melanoma patients for regional lymph node dissection.

Adolescent↗
PubMed1983

Differentiation stages of human natural killer cells in lymphoid tissues from fetal to adult life.

Virtually all human granular lymphocytes expressed the HNK-1 differentiation antigen when examined in lymphoid compartments from adults, neonates, and fetuses. The HNK-1+ cells were distinguishable into three subsets having distinct antigenic phenotypes: HNK+T3-M1-, HNK+T3+M1-, and HNK+T3-M1+. Thus, greater than 70% of the HNK-1+ cells from 13-17 wk fetuses (less than 0.2% of nucleated cells) lacked T cell antigens (e.g., T3, T8, T4, and T6) and the M1 myeloid antigen. Morphologically, the HNK+T3-M1- cells consisted of three different types: small granular lymphocytes (less than 10% of HNK-1+ cells), agranular small lymphocytes with a narrow rim of cytoplasm (70-80%), and agranular giant cells (greater than 15 micrometers) with considerable neutrophilic cytoplasm (15%). The purified fetal HNK-1+ cells exhibited a low level of cytotoxicity against K562 target cells. On the other hand, almost all of HNK-1+ cells in neonatal tissues as well as adult bone marrow, lymph node, and thymus, exhibited the HNK+T3+M1- phenotype, contained sparse cytoplasmic granules, and had an intermediate level of NK functional activity. Only adult blood and spleen contained a majority of mature HNK-1+ cells. These cells had an HNK+T3-M1- phenotype, abundant cytoplasmic granules, and maximum NK function. We propose that human NK cells may generate from a separate cell lineage and that they alter their phenotype, morphology, and functional capability during differentiation.

Antigens, Surface↗
PubMed1983

Natural killer cells in systemic lupus erythematosus. Abnormal numbers and functional immaturity of HNK-1+ cells.

A monoclonal antibody, HNK-1, that detects a differentiation antigen on human granular lymphocytes with natural killer (NK) activity was used to enumerate this subpopulation in the peripheral blood of 14 patients with systemic lupus erythematosus (SLE). Nine patients had severely decreased numbers of HNK-1+ cells, 3 patients had elevated levels of HNK-1+ cells, and 2 patients had appropriate numbers of HNK-1+ cells compared with the levels in 112 normal controls. All SLE patients exhibited low NK killing ability against K562 target cells compared with controls. An increased proportion of the HNK-1+ cells was categorized as immature granular lymphocytes in over 50% of the SLE patients because their HNK-1+ cells coexpressed the OKT3 antigen and contained a paucity of cytoplasmic granules. The numbers of HNK-1+ cells or the HNK-1+ OKT3+ subgroup did not correlate with steroid therapy. This evidence suggests that levels of HNK-1+ lymphocytes are abnormal and functionally immature in most SLE patients. Longitudinal studies conducted over several months on a number of SLE patients demonstrated fluctuations in the ratio of mature and immature HNK-1+ cells and total HNK-1+ cells. Additional patients tested over longer periods of time will have to be studied to determine whether the proportion of mature NK cells (HNK-1+ OKT-) and immature NK cells (HNK-1+ OKT3+) will be useful in predicting the clinical course of disease.

Adolescent↗