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Biomedical subjects

C M Balch

Publications and source records attributed to C M Balch.

At least 109 records · Page 6Linked to original sources

Economic impact of reducing hospitalization for mastectomy patients.

In 1985, two policies designed to reduce hospitalization charges for mastectomy patients were instituted at the M.D. Anderson Cancer Center at Houston. The first was a policy of "same-day" admissions for elective surgery patients, and the second was early postoperative discharge for mastectomy patients with suction catheter drains in place. The economic savings resulting from these policies was analyzed by comparing demographics, operation, stage of disease, hospital stay, hospital charges, and complications for two groups of patients. Fifty-nine consecutive mastectomy patients treated between 1983 and 1984, before these policy changes, had "standard management" consisting of hospital admission 24 hours before surgery and discharge only after the surgical drains were removed. Sixty-one consecutive mastectomy patients treated between 1986 and 1987, after these policy changes went into effect, were admitted from the recovery room after surgery and were discharged with drainage catheters in place, usually within 72 hours. All operations were performed by the same faculty surgeon as a representative experience of the General Surgery faculty. The average hospital stay was reduced from 10.5 to 4.3 days. A mean 39% reduction in hospital charges (from $4867.00 to $2981.00) was achieved by instituting the policies of "same-day" admission and early postoperative discharge with drainage catheters in place. Complication rates were not changed. Implementation of this policy resulted in an estimated savings of $750,000.00 in the hospital care of approximately 400 patients treated at the M.D. Anderson Cancer Center at Houston each year. Adjustments in patient care delivery systems from a predominantly inpatient to an outpatient setting required changes in outpatient nursing responsibilities (although not in new personnel). Patient education and written instructions for home care of surgical wounds and drainage catheters were essential for implementing an early discharge policy. With these facts in mind, hospital admission on the day of operation and early postoperative discharge with drainage catheters in place should be the goal for most mastectomy patients.

Cancer Care Facilities↗

The role of elective lymph node dissection in melanoma: rationale, results, and controversies.

Elective lymph node dissection (ELND) for patients with clinically occult metastatic melanoma in regional lymph nodes has the goal of curing metastases with a surgical treatment. This is in contrast to the low probability for surgical cure in patients with clinically detectable lymph node metastases. The rationale for elective node dissection is based on a hypothesis that melanoma metastasizes sequentially via lymph nodes and then to distant sites. A subgroup of melanoma patients with high risk for regional node micrometastases but low risk for distant micrometastases has been identified from prognostic factors analysis of large patient series, as well as surgical results of nonrandomized clinical trials. However, two nonrandomized surgical trials have failed to show a survival benefit for ELND. These studies were largely performed in female patients with extremity melanomas and there were limitations that preclude a definitive conclusion. No randomized trials have been conducted involving melanomas of the trunk or head and neck. Two prospective randomized surgical trials are now being conducted in North America and in Europe. Until the results of these trials are available, physicians are encouraged to enter patients into these ongoing clinical trials or consider ELND in selected patients where the benefit-risk ratio justifies it. Factors to be considered in this decision include intermediate tumor thickness (ie, 1 to 4 mm thickness), anatomic site, histology (ulceration and growth pattern), and the risk of the operation in individual patient settings.

Clinical Trials as Topic↗

Recombinant interleukin 4 (RIL4) inhibits interleukin 2-induced activation of peripheral blood lymphocytes.

Recombinant interleukin 4 (rIL4) inhibited the proliferation and induction of lymphokine activated killer (LAK) cells in human peripheral blood mononuclear cells (PBMC) cultured in recombinant interleukin 2 (rIL2). Other recombinant cytokines, such as rIFN gamma, rTNF alpha, rIL1, and rIL3, did not inhibit LAK cell induction. rIL4-mediated suppression was dose dependent. As little as 1 U/ml of rIL4 significantly decreased both LAK activity and proliferation of cells induced by incubation of PBMC with 200 U/ml rIL2. Suppression was specific for the induction phase of LAK activity, because rIL4 did not suppress the cytotoxic capability of previously activated LAK cells. rIL4 directly suppressed rIL2-induced activation of precursors into LAK cells, since it inhibited both rIL2-induced proliferation and LAK cell activity in LGL-enriched cell fractions or in purified CD16+ NK cells. Suppressive effects of rIL4 were overcome by adding rIFN gamma to the culture. These results suggest that rIL4 is a potent inhibitor of rIL2-induced activation of PBL, and that the net LAK response in the host may be a function of the production of IL-2, IL-4 and rIFN gamma.

Cell Division↗

Three unresolved issues in the surgical treatment of melanoma.

The authors discuss the results of recent clinical trials on what constitutes an adequate resection margin in primary melanomas of varying thickness, concluding that it is still uncertain whether wider margins reduce the risk of regional cutaneous recurrences. Inherent in the issue of whether or not to perform elective node dissection is the difficulty of identifying patients who might benefit from the procedure. Proponents point to two recent studies, but actually the sample sizes were small. Isolated limb perfusion, while producing complete responses with long-term survival in some cases of regionally recurrent disease, is still questionable as a prophylactic treatment for high-risk primary disease.

Chemotherapy, Cancer, Regional Perfusion↗

Human lymphokine-activated killer (LAK) cells: identification of two types of effector cells.

We analyzed the antigenic phenotype of lymphokine-activated killer (LAK) effector cells. Human blood lymphocytes were cultured for 3 days with 100 U/ml recombinant interleukin 2 (rIL 2), subpopulations isolated with monoclonal antibodies and a fluorescence-activated cell sorter (FACS) and assayed for cytotoxic activity against 51chromium labeled noncultured melanoma tumor cells. Initial experiments compared the LAK effector function of CD5+ T lymphocytes vs CD5- cells (predominantly CD16+ NK cells). The mean percent specific release at a 10:1 effector:target (E:T) ratio was 25% +/- 16 for CD5- cells, 10% +/- 6 for CD5+ cells, and 22% +/- 9 for unsorted cells. In contrast, when lymphocyte subpopulations were isolated before rIL 2 culture (LAK precursors), CD5- cells but not CD5+ cells developed LAK activity (28% +/- 12 vs 1% +/- 1, mean percent specific release, 10:1 E:T ratio), confirming our previous results showing that only CD16+ cells were LAK precursors. The discrepancy between LAK effector and precursor phenotypes suggested that LAK precursors acquired CD5 determinants during rIL 2 culture; however, double label immunofluorescence of rIL 2 cultured CD16+ cells showed that this was not the case. The data suggested that in the presence of other cell types, some T lymphocytes may develop LAK activity, but purified blood T lymphocytes do not develop LAK function when cultured with rIL 2 alone. We also analyzed LAK effector function in lymphocyte subpopulations defined by CD4 and CD8 antigens. The data showed that lymphocytes with a low density expression of CD8 and no expression of CD4 were enriched for LAK effector cells, whereas CD4+ and CD8- had less activity than unsorted cells. Lymphocytes with a high density expression of CD8 had activity similar to unsorted cells. We also assessed the contribution of Leu-7 (HNK-1) granular lymphocytes to LAK effector function. After culture with IL 2, lymphocytes were depleted of Leu-7+ cells by antibody and complement treatment and then were sorted into CD5+ and CD5- fractions. The cytotoxic activity of Leu-7-CD5+ cells was a mean 5% +/- 5 vs a mean 14% +/- 8 for the total CD5+ population (20:1 E:T ratio). The activity of Leu-7- CD5- was slightly less than the total CD5- fraction (21% +/- 9 vs 28% +/- 14, 10:1 E:T ratio). In conclusion, LAK effector function was highest in non-T cell (CD5- CD16+) populations and some activity was also present in T cell populations (CD5+ and predominantly Leu-7+).

Antibodies, Monoclonal↗

Does radical mastectomy still have a place in the treatment of primary operable breast cancer?

This study (Alabama Breast Cancer Project) reports the ten-year surgical results of a prospective randomized trial comparing Halsted radical mastectomy (RM) with modified radical mastectomy (MRM) for breast cancer. We entered 311 patients in the study between 1975 and 1978. Patients with histologically positive axillary lymph nodes were randomized after operation to receive melphalan or intermittent intravenous cyclophosphamide, methotrexate, and fluorouracil for one year. After a median follow-up of ten years, there was no significant difference in the survival of the two groups (RM, 71%; MRM, 64%). Local recurrence after RM was significantly lower than after MRM. A subset of patients with more advanced cancers (T3 and T2 with clinically positive axillary nodes) experienced significantly better survival at ten years following RM compared with MRM (59% vs 38%, respectively). These results indicate that overall survival is similar for patients treated by either RM or MRM. However, there is subset of patients with more advanced cancers whose ultimate survival can be favorably influenced by RM.

Breast Neoplasms↗

Lysis of fresh solid tumor targets in the presence of Con A is mediated primarily by Leu 7+ peripheral blood T lymphocytes: blocking by the anti-CD3 monoclonal antibody and comparison with recombinant interleukin 2-induced lysis by natural killer cells.

We investigated the lysis of fresh human solid tumor cells by peripheral blood T lymphocytes in the presence of lectins and anti-CD3 monoclonal antibodies (mAb). Addition of certain lectins (Con A, PHA, or WGA) directly into the 4-hr 51Cr-release assay caused significant lysis of (P less than 0.001) noncultured solid tumor targets by enriched populations of granular lymphocytes (GL). Significant levels (P at least less than 0.001) of Con A- or PHA-dependent solid tumor lysis by GL-enriched lymphocytes were observed in 32 of 39 donors (82%) and 14 of 20 donors (70%), respectively. In contrast, the addition of other lectins (PNA, PWM, or LPS) or anti-CD3 mAb did not cause cytotoxicity. The levels of Con A-dependent lysis were comparable to those of interleukin 2 (IL-2)-induced lysis by Leu 11b+ natural killer (NK) cells. The presence of lectins at the effector phase, but not of recombinant IL-2 (rIL-2), was required for the lysis of solid tumor targets. Both Con A-dependent and rIL-2-induced lysis were totally inhibited by treatment of the effector cells with the lysosomotropic agent L-leucine methyl ester (LeuOMe). Effector cells responsible for Con A-dependent lysis of solid tumors expressed T3 (CD3), T8 (CD8), and Leu 7 antigens, but lacked T4 (CD4) and Leu 11 (CD16) antigens as determined by both negative and positive cell selection studies. Con A-dependent lysis was inhibited at the effector phase by anti-CD3 (OKT3 or anti-Leu 4) or anti-CD2 (OKT11) mAb. On the basis of their phenotype (Leu 7+ CD3+ CD8+ CD16-), we hypothesize that these effector cells may contain a population of cytotoxic T cells (CTL) generated in vivo against autologous modified cells that can lyse fresh solid tumor target cells under conditions where the recognition requirements for the CTL are bypassed by lectin approximation.

Antibodies, Monoclonal↗

Spontaneous human T-cell cytotoxicity against murine hybridomas expressing the OKT3 monoclonal antibody: comparison with natural killer cell activity.

Human peripheral blood lymphocytes (PBL) exhibited spontaneous cytotoxicity against OKT3 monoclonal antibody (mAb)-expressing murine hybridoma cells (OKT3 hybridomas). In contrast, other murine hybridomas expressing OKT4, OKT8, anti-HLA DR, and anti-HLA A, B, and C mAb were not lysed. PBL showed much lower levels of cytotoxicity (3 folds) against OKT3 hybridomas as compared with NK activity against the K562 targets. Lymph node (LN) cells exhibited the inverse relationship of cytotoxicity levels. The addition of OKT3 mAb to the effector cells totally blocked both the binding and the lysis of OKT3 hybridoma targets, indicating that the CD3 antigen on the effector cells may be involved in recognition of the targets. The addition of concanavalin (Con A) also inhibited the cytotoxicity of OKT3 hybridomas. OKT4 mAb-expressing hybridomas became susceptible to lysis after chemical attachment of OKT3 mAb with CrCl3. The kinetics of lysis of OKT3 hybridomas resembled that of NK activity. Both cytotoxicities were detectable after 1 to 2 hr and reached plateau levels by 4 to 6 hr. Effector cells responsible for lysis of OKT3 hybridomas expressed T3, T8, and Leu 7 antigens, but lacked T4 and Leu 11b antigens, and were sensitive to the treatment with L-leucine methyl ester. These results indicate that T3+, T8+, Leu 7+ and T4-, and Leu 11- granular lymphocytes have a spontaneous cytotoxic activity against OKT3 hybridomas which is different from classic NK activity. These findings may provide a method for the assessment of T-cell cytotoxicity mediated presumably by in vivo generated cytotoxic T lymphocytes in blood and the other immune organs.

Antibodies, Monoclonal↗

Monocyte- and natural killer cell-mediated spontaneous cytotoxicity against human noncultured solid tumor cells.

Unstimulated human peripheral blood mononuclear cells from healthy donors exhibited spontaneous cytotoxicity against noncultured solid tumor targets in a 12- to 24-hr 51Cr release or 111In release assay. Both purified monocytes (greater than 99% monocytes) and natural killer (NK)-enriched lymphocytes exhibited comparable levels of spontaneous cytotoxicity against fresh melanoma tumor targets. This cytotoxicity was observed under endotoxin-free conditions. NK-depleted lymphocytes did not lyse the melanoma targets. Culture supernatants of monocytes incubated with the melanoma tumor cells did not exhibit cytotoxic activity against these targets. Purified monocytes lacked NK activity against the K562 targets in a 4-hr 51Cr release assay. Treatment of the monocytes with anti-Leu 1 1b and anti-Leu7 monoclonal antibodies plus complement did not reduce monocyte-mediated lysis of the melanoma targets, demonstrating that contaminating NK cells, if any, were not responsible for the lysis of noncultured melanoma targets by monocytes. In contrast, Leu 1 1b+ NK cells were responsible for the lysis of the melanoma targets by NK-enriched lymphocytes. The addition of recombinant interferon-gamma (rIFN-gamma), but not lipopolysaccharide, into the 51Cr release assay or pretreatment of monocytes with rIFN-gamma significantly increased their cytotoxicity against noncultured solid tumor cells. Monocytes cultured for 3 days with medium alone lost their cytotoxic activity. The addition of rIFN-gamma from the beginning of these cultures prevented the loss of the cytotoxic activity of monocytes. In summary, both unstimulated monocytes and NK-enriched lymphocytes exhibit comparable levels of spontaneous cytotoxicity against fresh solid tumor targets.

Cells, Cultured↗

Demonstration of NK cell-mediated lysis of varicella-zoster virus (VZV)-infected cells: characterization of the effector cells.

Infection with varicella-zoster virus (VZV) rendered RAJI cells more susceptible to lysis by non-adherent blood lymphocytes. At an effector to target ratio of 80:1 the mean percentage of 51Cr release of VZV-infected RAJI cells was 41 +/- 12%, whereas that of uninfected RAJI cells was 15 +/- 6%. The increased susceptibility to lysis was associated with increased effector to target conjugate formation in immunofluorescence binding assays. The effector cells cytotoxic for VZV-infected RAJI cells were predominantly Leu-11a+ Leu-4- granular lymphocytes as demonstrated by fluorescence-activated cell sorting. The effector cell active against VZV-infected RAJI cells appeared similar to those active against herpes simplex virus (HSV)-infected cells, because in cold target competition experiments the lysis of 51Cr-labeled VZV-infected RAJI cells was efficiently inhibited by either unlabeled VZV-infected RAJI cells (mean 71% inhibition, 2:1 ratio unlabeled to labeled target) or HSV-infected RAJI cells (mean 69% inhibition) but not by uninfected RAJI cells (mean 10% inhibition). In contrast, competition experiments revealed donor heterogeneity in the overlap between effector cells for VZV- or HSV-infected RAJI vs K-562 cells.

Adult↗

Lysis of human solid tumor cells by lymphokine-activated natural killer cells.

The ability of NK cells to lyse noncultured solid tumor cells was investigated, and the results were compared with lysis of K562. Purified NK cell fractions separated by either Percoll centrifugation or a cell sorter exhibited higher level of lysis against noncultured melanoma cells than did NK-depleted cell fractions. However, the level of lysis was low (less than 10% lysis). Adding recombinant interleukin 2 (rIL 2) to the 4-hr assay induced significant lysis (more than 10%) of noncultured melanoma cells in 18 of 23 (78%) Percoll-enriched NK cell fractions and seven of 11 (64%) sorted Leu-11a+ cells at an E:T ratio of 80 and 10, respectively. In contrast, only two of 13 (14%) PBMC, five of 17 (29%) Percoll-decreased NK cell fractions, and one of 12 (8%) sorted Leu-11a- cells lysed noncultured melanomas in the presence of rIL 2. rIL 2 induced NK cells to lyse noncultured lung and breast cancer cells, as well as melanoma tumors. Exposure of NK cells to 2000 rad radiation abrogated the rIL 2-induced cytotoxicity against noncultured melanomas. Preculture of PBMC for 18 hr with recombinant interferon-gamma (rIFN-gamma) resulted in a modest level of lysis of non-cultured melanomas by sorted Leu-11a+ cells. Adding rIL 2 to the assay increased the cytotoxic activity in both rIFN-gamma-activated Leu-11a+ and Leu-7+ NK subsets. The level of noncultured tumor lysis correlated well with that of K562 lysis in all of the experiments. Purified NK cell fractions in rIL 2 cultures increased cytotoxic activity against noncultured tumor cells with incubation time for up to 3 days, and the level of NK cell-mediated lysis was dependent on both doses of rIL 2 and length of incubation. In contrast, both NK-depleted and sorted Leu-11a- cells demonstrated very low levels of solid tumor lysis after 3-day cultures with a high dose of rIL 2. Killer cell precursors induced by 3-day cultures of sorted cell fractions with rIL 2 and rIFN-gamma were found in both Leu-11a+ and Leu-7+ NK subsets, but not Leu-4+ or Leu-3a+ T lymphocytes. These results indicate that NK cells become cytotoxic for noncultured solid tumor cells by a brief contact with rIL 2, and increase cytotoxic activity after culture with rIL 2.

Adult↗

Surgery as palliative treatment for distant metastases of melanoma.

Sixty-five patients with distant metastatic melanoma amenable to surgical treatment had excision of 94 metastatic lesions from the brain, lung, abdomen, distant subcutaneous sites, and distant lymph nodes. Relief of symptoms, if present, was obtained after excision of 77% of brain metastases, 100% of lung metastases, 88% of distant lymph node and subcutaneous metastases, and 100% of abdominal metastases. Median survival after excision of brain metastases was 8 months, lung metastases 9 months, abdominal metastases 8 months, and distant subcutaneous and lymph node metastases 15 months. Sixteen per cent of patients lived for 2 years of longer. These results demonstrated that surgery can achieve an effective local disease control in selected patients with distant melanoma metastases and that a few have a relatively long-term survival.

Abdominal Neoplasms↗