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Biomedical subjects

S R Schell

Publications and source records attributed to S R Schell.

15 recordsLinked to original sources
PubMed2001

Local excision and postoperative radiation therapy for rectal adenocarcinoma.

Sixty-seven patients with early-stage adenocarcinoma of the rectum who had lesions thought to be unsuitable for either local excision alone or endocavitary irradiation were treated with local excision followed by postoperative radiation therapy. The purpose of this study was to evaluate the effectiveness of local excision followed by radiation therapy for treatment of rectal adenocarcinoma. The patients were treated between 1974 and 1999; follow-up time was 6 to 273 months (median, 65 months). All living patients had follow-up for at least 2 years. The indications for postoperative irradiation included equivocal or positive margins, invasion of the muscularis propria, endothelial-lined space invasion, poorly differentiated histology, and perineural invasion. Cox proportional hazards regression analysis was performed using six explanatory variables including tumor size, configuration (exophytic vs. ulcerative), histologic differentiation, pathologic T stage, endothelial-lined space invasion, and margin status. The time interval between treatment and development of recurrent disease was in the range of 11 to 48 months. The 5-year results were as follows: local-regional control, 86%; ultimate local-regional control, 93%; distant metastasis-free survival, 93%; absolute survival, 80%; and cause-specific survival, 90%. When the Cox proportional hazards regression analysis was performed for these endpoints, margin status influenced absolute survival (P = 0.0074), cause-specific survival (P = 0.0405), and ultimate local-regional control (P = 0.0439). Tumor configuration marginally influenced cause-specific survival (P = 0.0577). None of the variables had an influence on the endpoints' local-regional control, ultimate local-regional control with sphincter preservation, or distant metastasis. Five patients (7%) had severe complications; no complication was fatal. Local excision and postoperative radiation therapy results in a high probability of local-regional control and survival for selected patients with relatively early-stage rectal adenocarcinoma. Patients with ulcerative tumors may have a lower likelihood of cause-specific survival.

Adenocarcinoma↗
PubMed2001

Radiofrequency ablation treatment of refractory carcinoid hepatic metastases.

BACKGROUND: Our institution has experienced excellent success using hepatic artery embolization for treating symptoms and slowing tumor progression for patients with unresectable hepatic metastases for carcinoid tumors. Our previous treatment strategies used hepatic artery embolization alone, examining control of symptoms and dependence on octreotide therapy. However, some patients exhibit hepatic metastases that are unresponsive to embolization. This report describes the use of radiofrequency ablation (RFA) as salvage treatment for these refractory metastases. METHODS: Thirteen patients with unresectable bilobar hepatic metastases from biochemically confirmed carcinoid tumors were treated with selective hepatic artery embolization using Lipiodol/Gelfoam between 1994 and 2000. Three patients developed symptoms resistant to embolization treatment resulting from progression of existing metastases or development of new metastases. These patients underwent surgical exploration and intraoperative ultrasound of their refractory lesions, followed by treatment with RFA. Tumor size, symptoms of carcinoid syndrome, and octreotide requirements were monitored postoperatively. RESULTS: Median follow-up for the three patients treated with RFA was 6 months. During the first 3-month interval following RFA, all three patients demonstrated decrease in the size of treated lesions. Using our previously developed symptom scoring system, all three patients demonstrated decreased symptoms following treatment. One patient was able to discontinue octreotide treatment, and the other two patients required decrease octreotide dosages. CONCLUSIONS: This study demonstrates that utilization of RFA treatment for carcinoid metastases refractory to hepatic artery embolization may represent a useful adjunct for symptomatic control, decreased octreotide dependence, and slowing of disease progression.

Adult↗
PubMed1999

Laparoscopic adrenalectomy for nonmalignant disease: improved safety, morbidity, and cost-effectiveness.

BACKGROUND: Laparoscopic adrenalectomy has rapidly gained widespread acceptance for treatment of benign adrenal neoplasms. A number of authors have compared various anatomic approaches to laparoscopic adrenalectomy, comparing length of inpatient stay, transfusion requirements, and perioperative complications. Separate studies have found inpatient stay reduced 40-60% with the use of laparoscopic adrenalectomy vs. an open procedure. METHODS: There have been no studies designed specifically to examine and compare perioperative morbidity, length of stay, and patient charges in patients undergoing laparoscopic adrenalectomy. This report examines the Johns Hopkins Hospital experience with laparoscopic adrenalectomy in 22 patients, comparing length of stay, perioperative morbidity, and patient charges. These data are compared with those seen in 17 patients undergoing open adrenalectomy within our institution and 70 patients at all other nonfederal hospitals in the state of Maryland. RESULTS: Outcomes after laparoscopic versus open adrenalectomy were compared. Resumption of diet (1.6 vs. 6.1 days), independent activity (1.6 vs. 7.9 days), inpatient length of stay (1.7 vs. 7.8 days), and total hospital patient charges ($8,698 vs. $12,610) were all significantly reduced in patients undergoing laparoscopic adrenalectomy at our institution. Similar findings were obtained when our data were compared against adrenalectomy performed at other hospitals within the state of Maryland. Length of stay (1.7 vs. 8.9 days) and total hospital patient charges ($8,698 vs. $13,867) were both significantly reduced compared to state-wide data in patients treated with laparoscopic adrenalectomy. CONCLUSIONS: Although a technically challenging procedure, laparoscopic adrenalectomy provides clear advantages over open procedures for the vast majority of adrenal neoplasms. Our data support the conclusion that laparoscopic adrenalectomy should be considered for all patients with benign adrenal neoplasms.

Adolescent↗
PubMed1997

Control of fecal incontinence: continued success with the Malone procedure.

BACKGROUND: Our center has previously reported the use of the Malone antegrade continence enema procedure in children. The procedure involves bringing the appendix to the surface of the abdominal wall to provide a nonrefluxing catheterizable channel that enables antegrade colonic lavage for the control of fecal incontinence. METHODS: This report critically evaluates 23 patients treated for fecal incontinence with up to 6 years of follow-up. After operation, specific scoring criteria were used for assessment. Success in surgical technique, control of fecal soiling, and improvement in quality of life were evaluated. RESULTS: More than 85% of patients achieved maximal or near-maximal scores in all three categories. Postoperative complications remain a relevant concern when this procedure is undertaken, but we have found that significant postoperative complications are few and can be minimized by meticulous follow-up. CONCLUSIONS: Overall, the Malone antegrade continence enema procedure has been shown to be safe and highly effective. There is the potential for wider application in older age groups where sphincter and pelvic floor muscles have been compromised as a result of trauma or cancer surgery.

Adolescent↗
PubMed1990

Evidence implicating utilization of different T cell receptor-associated signaling pathways by TH1 and TH2 clones.

We have reported recently that high concentrations of anti-CD3 mAb inhibited IL-2-dependent proliferation of TH1 but not TH2 clones. The selective inhibitory effect on TH1 clones suggested that the two helper T lymphocyte subsets might utilize different TCR-associated signal transduction mechanisms. In the present study, we demonstrate that this distinction was not due to a gross difference in the level of TCR expression by TH1 and TH2 clones. Inhibition of TH1 proliferation by anti-CD3 mAb appeared to depend on calcium for maximal effect, suggesting that a substantial elevation of intracellular free calcium concentration ([Ca2+]i) might not occur after ligation of the TCR complex of TH2 clones. Calcium ionophore inhibited IL-2-dependent proliferation of both subsets, suggesting that receptor/ligand systems which stimulate elevated [Ca2+]i would be expected to inhibit proliferation. Although elevated [Ca2+]i and generation of inositol phosphates were readily detected in TH1 clones, these second messengers were not detected following stimulation of TH2 clones via the TCR complex. In addition, lymphokine production by TH1 clones was more sensitive to inhibition by cholera toxin, 8-bromoadenosine 3':5'-cyclic monophosphate, and cyclosporin A than was lymphokine production by TH2 clones. Collectively, these results suggest that TH1 and TH2 clones utilize distinct TCR-associated signal transduction mechanisms for lymphokine gene expression. The difference in signaling mechanisms suggests a potential pharmacologic target for intervention in situations where inappropriate activation of TH1 or TH2 cells occurs in vivo.

8-Bromo Cyclic Adenosine Monophosphate↗
PubMed1989

Pretreatment of cloned helper T lymphocytes with IL-2 induces unresponsiveness to antigen and concanavalin A, associated with decreased inositol phosphate and diacylglycerol production.

IL-2 pretreatment of cloned Th lymphocytes has been demonstrated to render these cells unresponsive to subsequent stimulation through the TCR. These cells remain unresponsive for up to 7 days after removal from IL-2. Cells rendered unresponsive to Ag by pretreatment with IL-2 also demonstrated reduced increases in intracellular calcium ([Ca2+]i) after stimulation, hence this unresponsiveness is believed to result from absence of sufficient [Ca2+]i for activation of lymphokine genes. We have confirmed these observations, and demonstrate that only that portion of the [Ca2+]i increase derived from extracellular sources is inhibited in IL-2 pretreated cells. Further, inositol degradation and diacylglycerol production after stimulation are observed to be markedly reduced in cells rendered unresponsive by IL-2 pretreatment, suggesting that signal transduction leading to cleavage of phosphatidylinositol 4,5-bisphosphate after Ag receptor engagement is incomplete in these cells. However, treatment of IL-2 pretreated cells with AlF4- results in both production of inositol phosphates as well as increased intracellular calcium, suggesting that phospholipase C remains active in these cells. It appears that chronic IL-2 exposure regulates Th activation by inhibiting the signal transduction which follows engagement of the TCR.

Aluminum↗
PubMed1989

Regulation of T-cell activation: differences among T-cell subsets.

Four regulatory phenomena appear to regulate differentially the activation of TH1, TH2, and CTL clones. First, IFN-gamma selectively inhibits proliferation of TH2 but not TH1 cells; lymphokine production by TH2 cells is not affected by IFN-gamma. In addition, when fresh OVA-specific HTL clones are derived in the presence of rIL-2 TH2 cells are preferentially obtained, whereas TH1 cells predominate if cloning is performed in rIL-2 plus rIFN-gamma. These results suggest that the presence of IFN-gamma during the course of an immune response would result in the preferential expansion of HTL of the TH1 phenotype. Proliferation of CTL clones is not influenced by IFN-gamma. Second, different APC populations appear to differentially activate TH1 and TH2 clones. Purified splenic B cells stimulate optimal proliferation of TH2 but not TH1 cells, whereas macrophage/dendritic cells appear to stimulate optimal proliferation of TH1 but not TH2 cells. Since both APC types stimulate lymphokine production by each of the HTL subsets, these results suggest the existence of TH1- and TH2-specific cofactors for growth. Third, high doses of immobilized anti-CD3 mAb inhibit IL-2-dependent proliferation of TH1 but not TH2 clones. Since this effect appears to require calcium, this observation suggests that TCR-mediated signalling events might differ between the two HTL subsets. Indeed, little or no increase in [Ca++]i can be detected in TH2 clones stimulated with Con-A, while such an increase is easily discernible in TH1 cells. Although high concentrations of immobilized anti-CD3 mAb inhibit IL-2-dependent proliferation of CTL clones, proliferation of these cells in response to immobilized anti-CD3 alone reaches a plateau. Since activation with anti-CD3 is thought to mimic antigenic stimulation, these results suggest that antigen concentration may play a role in determining which predominant T-cell types proliferate in a particular immunological situation. Fourth, pretreatment of TH1 cells, but not TH2 cells or CTL, with IL-2 results in decreased lymphokine production and proliferation in response to subsequent stimulation via the TCR. This antigen-responsive state appears to involve a defect in calcium-dependent signalling, providing additional evidence for different signalling mechanisms in TH1 and TH2 clones.(ABSTRACT TRUNCATED AT 400 WORDS)

Antigen-Presenting Cells↗
PubMed1987

The inhibitory effects of K+ channel-blocking agents on T lymphocyte proliferation and lymphokine production are "nonspecific".

The effect of K+ channel-blocking agents, tetraethylammonium (TEA) and 4-aminopyridine (4AP), on the responses of cloned murine helper and cytolytic T lymphocytes stimulated with mitogen, anti-T cell receptor monoclonal antibody, or interleukin 2 was examined. The addition of TEA and 4AP reduced [3H]thymidine incorporation and lymphokine production to levels observed in unstimulated cells. However, thymidine incorporation by the tumor cell lines P-815 and SP2/0, which replicate autonomously, also was inhibited by these drugs. Treatment of cloned murine helper T lymphocyte, L2, with TEA appeared to inhibit uptake of [3H]thymidine and [3H]phenylalanine after stimulation with interleukin 2. These results suggest that the inhibitory effects of the K+ channel-blocking agents TEA and 4AP may not be specific for the sequence of events that are initiated by activation of T lymphocytes through the antigen receptor. Instead, the observed inhibitory effects by these agents may result from inhibition of transport of thymidine, amino acids, and other essential metabolites across the cell membrane.

4-Aminopyridine↗
PubMed1984

Conservation surgery and irradiation as an alternative to mastectomy in the treatment of clinically favorable breast cancer.

The combination of conservation surgery and radiation therapy for early breast cancer is gaining acceptance as an alternative to radical mastectomy. This article reviews the results of randomized trials showing that there is no advantage to a radical mastectomy in patients with early breast cancer. In addition, the article will review multiple reports concerning the local and regional tumor control and survival of patients treated with conservation surgery and irradiation as well as a comparison of 1073 patients with TIS T1 T2 N0 N1 breast cancer treated at University of Texas (UT) M. D. Anderson Hospital between 1955 and 1980, of whom 345 were treated with conservation surgery and irradiation and 728 were treated with radical or modified radical mastectomy alone. The locoregional recurrence in the patients treated with an intact breast is 4.9%, and 5.6% in patients treated with radical or modified radical mastectomy. There is no significant difference in the 10-year disease-free survival rates between the two groups of patients. In addition, a comparison of 2467 patients with Stage I and Stage II breast cancer treated at the UT M. D. Anderson Hospital shows no significant difference in the incidence of consecutive second breast carcinoma as a result of the use of radiation therapy in the treatment of the first breast cancer.

Breast Neoplasms↗
PubMed1983

Conservation surgery and irradiation as treatment for early breast cancer.

Conservation surgery and irradiation were compared with radical or modified radical mastectomy, without irradiation, in the treatment of clinically favorable breast cancer. Patients with minimal breast cancer, stage I (T1 N0), and stage II (T1 N1, T2 N0, or T2 N1) were found to have similar five- and ten-year survival rates for the two types of primary treatment. Local recurrence rates were also similar: 0.8%, 4.4% and 8.4% for radical mastectomy, and 2.5%, 6.8%, and 4.9% for conservation surgery and irradiation, respectively, in each successive stage of disease. Cosmetic and functional results were deemed satisfactory and supported consideration and examination of this alternative to radical mastectomy for selected patients with early breast cancer.

Axilla↗
PubMed1982

Bilateral breast cancer in patients with initial stage I and II disease.

Between January 1947 and the end of 1975, of 2076 patients with Stages I and II breast cancer treated at M. D. Anderson Hospital, 126 received treatment for cancer in both breasts. Records of 94 patients who had only one cancer treated at U. T. M. D. Anderson Hospital and in whom staging and treatment details were not available and records of the patients who developed local, regional, or systemic failure prior to diagnosis of the second breast were excluded. Of 126 patients with bilateral breast cancer, 39 had simultaneous tumor (both cancers diagnosed within six months) and 87 had consecutive tumors. The disease-free 20-year survival rate shows no significant difference between patients with unilateral tumors and those with bilateral simultaneous or consecutive tumors. Analysis by radiotherapy modality or surgery alone shows, if anything, a lower incidence of cancer in the second breast in the irradiated patients, indicating that in patients with Stage I or Stage II lesions, the doses of radiation given in the management of the first breast cancer were not conducive to the development of a cancer in the remaining breast.

Breast Neoplasms↗
PubMedDate not supplied

Paraplegia following intraoperative celiac plexus injection.

The technique for percutaneous and open neurolytic celiac plexus injection, using ethanol or phenol, for relief of intractable pancreatic cancer pain has been well described. Prospective randomized studies, demonstrating safety and efficacy with few complications, have led to widespread acceptance and use of this palliative procedure. The complications of neurolytic celiac plexus injection are rare, and are usually minor. However, transient or permanent paraplegia has been reported previously in 10 cases. The case described herein represents the third reported case of permanent paraplegia following open intraoperative neurolytic celiac plexus injection using 50% ethanol. The literature surveying the indications for this procedure, routes of administration, known complications, and their pathophysiology are reviewed.

Adult↗