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Biomedical subjects

B W Feig

Publications and source records attributed to B W Feig.

At least 19 recordsLinked to original sources

Alveolar soft part sarcoma: clinical course and patterns of metastasis in 70 patients treated at a single institution.

BACKGROUND: Alveolar soft part sarcoma (ASPS) is a rare form of soft tissue sarcoma. Brain metastases have been reported to be a common feature of Stage IV ASPS, and recent practice guidelines recommend routine intracranial imaging as part of the staging evaluation in all patients who present with ASPS. METHODS: The authors performed a comprehensive retrospective review of the clinical presentation, treatment, outcome, and patterns of failure in a consecutive series of patients with localized (American Joint Committee on Cancer [AJCC] Stages II/III) or metastatic (AJCC Stage IV) ASPS who presented to a tertiary care cancer center between 1959 and 1998. RESULTS: Seventy-four patients were identified from the database searches. The anatomic distribution of their primary tumors included: extremities, 44 patients (60%); trunk, 15 patients (20%); head and neck, 9 patients (12%); and retroperitoneum, 6 patients (8%). The median tumor size was 6.5 cm (range, 1.2-24 cm). The AJCC stage at presentation was Stage II or III in 35% of the patients and Stage IV in 65% of the patients. The 5-year actuarial local recurrence free, distant recurrence free, disease free, and overall survival rates among the 22 patients with localized ASPS were 88%, 84%, 71%%, and 87%, respectively. At a median follow-up of 9 years, 2 of 22 patients with localized disease had developed local recurrences and 3 had developed metastatic disease (all to the lung only). Brain metastases were noted in 9 of 48 patients who presented with Stage IV (M1) disease (19%) and always were noted in association with metastasis to other sites. The median survival of patients with M1 disease was 40 months, with a 5-year survival rate of 20%. CONCLUSIONS: Long term follow-up of patients with localized ASPS reveals a relatively indolent clinical course with relatively low rates of local and distant recurrence. In patients with Stage IV ASPS, brain metastases were observed only as part of more disseminated disease. The observations of the current study do not support current practice guidelines for the staging of patients with ASPS and suggest that selective rather than routine intracranial imaging should be used in patients presenting with ASPS.

Adenocarcinoma, Bronchiolo-Alveolar↗

Sentinel lymph node biopsy is accurate after neoadjuvant chemotherapy for breast cancer.

PURPOSE: Sentinel lymph node (SLN) biopsy has proved to be an accurate method for detecting nodal micrometastases in previously untreated patients with early-stage breast cancer. We investigated the accuracy of this technique for patients with more advanced breast cancer after neoadjuvant chemotherapy. PATIENTS AND METHODS: Patients with stage II or III breast cancer who had undergone doxorubicin-based neoadjuvant chemotherapy before breast surgery were eligible. Intraoperative lymphatic mapping was performed with peritumoral injections of blue dye alone or in combination with technetium-labeled sulfur colloid. All patients were offered axillary lymph node dissection. Negative sentinel and axillary nodes were subjected to additional processing with serial step sectioning and immunohistochemical staining with an anticytokeratin antibody to detect micrometastases. RESULTS: Fifty-one patients underwent SLN biopsy after neoadjuvant chemotherapy from 1994 to 1999. The SLN identification rate improved from 64.7% to 94.1%. Twenty-two (51.2%) of the 43 successfully mapped patients had positive SLNs, and in 10 of those 22 patients (45.5%), the SLN was the only positive node. Three patients had false-negative SLN biopsy; that is, the sentinel node was negative, but at least one nonsentinel node contained metastases. Additional processing revealed occult micrometastases in four patients (three in sentinel nodes and one in a nonsentinel node). CONCLUSION: SLN biopsy is accurate after neoadjuvant chemotherapy. The SLN identification improved with experience. False-negative findings occurred at a low rate throughout the series. This technique is a potential way to guide the axillary treatment of patients who are clinically node negative after neoadjuvant chemotherapy.

Adult↗

Impact of neoadjuvant chemotherapy on postoperative morbidity in soft tissue sarcomas.

PURPOSE: The purpose of this study was to test the hypothesis that neoadjuvant chemotherapy (NeoCT) does not increase morbidity in patients undergoing radical surgery for soft tissue sarcomas. PATIENTS AND METHODS: The records of 309 patients who presented to The University of Texas M.D. Anderson Cancer Center for definitive surgical management of primary soft tissue sarcomas were retrospectively reviewed. One hundred five patients who received NeoCT were compared with 204 patients who had surgery first (Surg). Patients had extremity sarcomas (71 NeoCT patients and 130 Surg patients) or retroperitoneal/visceral sarcomas (34 NeoCT and 74 Surg). RESULTS: NeoCT patients had larger tumors (median, 12 v 8 cm), more frequently had high-grade tumors (90% v 64%), and were younger (median age 47 v 55 years). The incidence of surgical complications was not different for NeoCT patients than for Surg patients, both in those with extremity sarcomas (34% v 41%) and in those with retroperitoneal/visceral sarcomas (29% v 34%). The most common complications were wound infections and other wound complications. Preoperative radiation therapy, autologous flap coverage, and extremity tumors were associated with increased wound complications. No significant differences in length of hospital stay, rate of readmission, or rate of reoperation for complications were found between the NeoCT and Surg groups. One of the three postoperative deaths in our series occurred in the NeoCT group. CONCLUSION: In this retrospective review, there was no evidence that NeoCT increased postoperative morbidity in patients with soft tissue sarcomas. Prospective, randomized studies are needed to confirm these results.

Antibiotics, Antineoplastic↗

Prospective trial of preoperative concomitant boost radiotherapy with continuous infusion 5-fluorouracil for locally advanced rectal cancer.

RATIONALE: To evaluate the response to a concomitant boost given during standard chemoradiation for locally advanced rectal cancer. METHODS AND MATERIALS: Concomitant boost radiotherapy was administered preoperatively to 45 patients with locally advanced rectal cancer in a prospective trial. Treatment consisted of 45 Gy to the pelvis with 18 mV photons at 1.8 Gy/fraction using a 3-field belly board technique with continuous infusion 5FU chemotherapy (300mg/m(2)) 5 days per week. The boost was given during the last week of therapy with a 6-hour inter-fraction interval to the tumor plus a 2-3 cm margin. The boost dose equaled 7.5 Gy/5 fractions (1.5 Gy/fraction); a total dose of 52.5 Gy/5 weeks was given to the primary tumor. Pretreatment tumor stage, determined by endorectal ultrasound and CT scan, included 29 with T3N0 [64%], 11 T3N1, 1 T3Nx, 2 T4N0, 1 T4N3, and 1 with TxN1 disease. Mean distance from the anal verge was 5 cm (range 0-13 cm). Median age was 55 years (range 33-77 years). The population consisted of 34 males and 11 females. Median time of follow-up is 8 months (range 1-24 months). RESULTS: Sphincter preservation (SP) has been accomplished in 33 of 42 (79%) patients resected to date. Three patients did not undergo resection because of the development of metastatic disease in the interim between the completion of chemoradiation (CTX/XRT) and preoperative evaluation. The surgical procedures included proctectomy and coloanal anastomosis (n = 16), low anterior resection (n = 13), transanal resection (n = 4). Tumor down-staging was pathologically confirmed in 36 of the 42 (86%) resected patients, and 13 (31%) achieved a pathologic CR. Among the 28 tumors (67%) located <6 cm from the anal verge, SP was accomplished in 21 cases (75%). Although perioperative morbidity was higher, toxicity rates during CTX/XRT were comparable to that seen with conventional fractionation. Compared to our contemporary experience with conventional CTX/XRT (45Gy; 1.8 Gy per fraction), improvements were seen in SP (79% vs. 59%; p = 0.02), SP for tumors <6 cm from the anal verge (75% vs. 42%; p = 0.003), and down-staging (86% vs. 62%; p = 0.003). CONCLUSION: The SP rate with concomitant boost radiation has been highly favorable with rates of response which are higher than those previously reported for chemoradiation without administration of a boost. Further evaluation of this radiotherapeutic strategy appears warranted.

Adult↗

The feasibility of minimally invasive surgery for stage IIA, IIB, and IIIA breast carcinoma patients after tumor downstaging with induction chemotherapy.

BACKGROUND: Induction chemotherapy (IC) has become the standard of care for locally advanced breast carcinoma, frequently downstaging both the primary tumor and the axilla, and making patients eligible for less invasive surgical procedures. The usefulness of IC in earlier stage operable breast carcinoma is now being considered. METHODS: This study involved a subset of 129 patients from a series of 174 with T2-3, N0-1, M0 or T1, N1, M0 breast carcinoma (Stage IIA, IIB, or IIIA ) who were registered in a prospective IC trial using paclitaxel or a combination of fluorouracil, doxorubicin, and cyclophosphamide (FAC). The subset included patients who had received no preoperative radiation therapy but had completed 3-5 cycles of induction chemotherapy and had undergone a Level I-II axillary lymph node dissection. The objective was to evaluate the effectiveness of induction chemotherapy with paclitaxel or FAC in downstaging the primary tumor and axillary metastases in these early stage breast carcinoma patients. RESULTS: The median initial tumor size was 4 cm (range, 0.6-10.0); after IC, tumor size was downstaged to 1.6 cm (range, 0.0-7.0) (P < 0.0001). Clinical response to IC was complete in 24% of patients and partial in 36%. Primary tumor shrinkage was similar with paclitaxel and FAC. Among patients clinically classified as N1, 34% became histologically negative and 38% had only 1-3 positive lymph nodes after induction chemotherapy. CONCLUSIONS: IC with paclitaxel or FAC resulted in effective downstaging of primary tumors and axillary metastases in patients with Stage IIA, IIB, and IIIA breast carcinoma. However, a significant proportion of patients still had residual but low volume microscopic disease; such disease status may allow minimally invasive surgical approaches to locoregional therapy.

Adult↗

Prognostic implications of pathological lymph node status after preoperative chemotherapy for operable T3N0M0 breast cancer.

BACKGROUND: Although preoperative chemotherapy has become the standard of care for inoperable locally advanced breast cancer, its role for downstaging resectable primary tumors is still evolving. The purpose of this study was to determine whether the prognostic information from an axillary node dissection in patients with clinical T3N0 breast cancer was altered by preoperative chemotherapy compared with surgery de novo. METHODS: Between 1976 and 1994, 91 patients with clinically node-negative operable T3 breast cancer received doxorubicin-based combination chemotherapy on protocol at one institution. Fifty-three patients received both preoperative and postoperative chemotherapy (PreopCT), and 38 received postoperative chemotherapy only (PostopCT). All patients underwent axillary lymph node dissection as part of their definitive surgical treatment. There were no differences between the PreopCT and PostopCT groups in median age (51 vs. 49 years), median tumor size at presentation (6 cm vs. 6 cm), tumor grade, or estrogen receptor status (estrogen receptor negative 38% vs. 32%). The median follow-up time was 7 years. RESULTS: Patients in the PreopCT group had fewer histologically positive lymph nodes (median, 0 vs. 3, P < .01), and a lower incidence of extranodal extension (19% vs. 42%, P = .02). By univariate analysis, the number of pathologically positive lymph nodes (P < .01) and extranodal extension (P < .01) were predictors of disease-specific survival in PreopCT patients. Multivariate analysis showed that extranodal extension was the only independent prognostic factor in PreopCT patients (P < .01). Overall, PreopCT and PostopCT patients had similar 5-year disease-free survival rates (66% vs. 57%); however, PreopCT patients had worse disease-free (P = .01) and disease-specific survival (P = .04) when survival was compared after adjustment for the number of positive lymph nodes. Furthermore, PreopCT patients with 4-9 positive lymph nodes had a lower 5-year disease-free survival rate than PostopCT patients with 4-9 positive nodes (17 vs. 48%, P = .04). CONCLUSIONS: Axillary lymph node status remains prognostic after chemotherapy. Pathologically positive lymph nodes after preoperative chemotherapy are associated with a worse prognosis than the same nodal status before chemotherapy.

Adult↗

Ductal carcinoma-in-situ: long-term results of breast-conserving therapy.

BACKGROUND: The role of breast-conserving therapy (BCT) in the management of ductal carcinoma-in-situ (DCIS) is controversial because of reported high recurrence rates. We reviewed our experience to determine whether the rate and pattern of locoregional recurrence after BCT were similar in patients with DCIS and patients with early-stage (T1) invasive breast tumors and whether local recurrence affected survival. METHODS: Between 1973 and 1994, 87 patients with DCIS alone, 22 patients with DCIS with microinvasion (DCIS-M), and 646 patients with invasive breast cancer 2 cm or smaller in diameter were treated with BCT (wide local excision with radiotherapy) at The University of Texas M. D. Anderson Cancer Center. Survival was calculated by the Kaplan-Meier method. The median follow-up times were 11 years for patients with DCIS alone, 12 years for patients with DCIS-M, and 8 years for patients with invasive breast cancer. RESULTS: Eleven (13%) of 87 patients with DCIS and 5 (23%) of 22 patients with DCIS-M had developed locoregional recurrences at follow-up. Two patients with DCIS with locoregional recurrence died of breast cancer. Of the 646 patients with invasive breast cancer, 56 (9%) had a locoregional recurrence, and 16 (2%) died of breast cancer. The median time to locoregional recurrence was significantly longer in patients with DCIS or DCIS-M (9-10 years) than patients with invasive tumors (5 years). CONCLUSIONS: DCIS is a favorable disease with an excellent long-term survival. The locoregional recurrence rate in patients with DCIS treated with BCT is similar to that in patients with early-stage invasive breast cancer treated with BCT, but time to locoregional recurrence is significantly longer in patients with DCIS. In patients with DCIS treated with BCT, intense surveillance for locoregional recurrence needs to be maintained for the patient's lifetime.

Adult↗

Isolated limb perfusion for extremity sarcoma.

Isolated limb perfusion has been used in patients with extremity sarcomas for over 40 years. In the majority of patients this approach has been employed as a limb-sparing alternative for patients with amputation as their only treatment option. Despite this long history of use in the treatment of patients with extremity sarcomas, many questions remain with respect to the appropriate drug or combination of drugs to be used in the perfusion circuit, the role of hyperthermia in isolated perfusion, and the use of hyperthermic perfusion in the neoadjuvant or adjuvant setting. Although many non-randomized studies have been performed, they suffer from a variety of problems, including small patient numbers, variety of chemotherapeutic agents employed, multiple levels of hyperthermia, and subjective evaluation of what constitutes amputation as a potential treatment option.

Antineoplastic Agents↗

The correlation of axillary ultrasonography with histologic breast cancer downstaging after induction chemotherapy.

BACKGROUND: The goal of this study was to examine the role of ultrasonography in detecting axillary lymph node metastases in stage II breast cancer patients after induction chemotherapy (IC). METHODS: Of 172 consecutive patients with T1-3, N0-1, M0 breast cancer registered in a prospective IC trial, a subset of 130 evaluable patients were chosen, with (1) both physical and ultrasonographic examinations of the axilla before and after IC; (2) exactly four cycles of IC; (3) no presurgical radiation therapy; and (4) an axillary lymph node dissection. RESULTS: Before IC, 32 patients (25%) were negative for axillary involvement by both physical and ultrasonographic examinations. After IC, this number increased to 64 (49%). Of these, 31 (48%) were positive by pathology examination. In most cases, however, the residual tumor was minimal. CONCLUSIONS: Stage II breast cancer patients who were or became node negative by both ultrasonographic and physical examinations after IC had a 48% incidence of nodal metastases. Because the residual tumor was minimal, irradiation may be sufficient for adequate local control of the axilla.

Adult↗

Phase I study of irinotecan and concurrent radiation therapy for upper GI tumors.

Irinotecan (Camptosar) is an active chemotherapeutic agent for lung, gastric, esophageal, and colorectal cancers and a potent radiosensitizer. This phase I study was designed to assess the maximum tolerated dose of weekly irinotecan combined with concurrent radiotherapy for patients with locally advanced, unresectable gastric, gastroesophageal junction, or esophageal cancer. Patients who received previous chemotherapy (excluding irinotecan) or who experienced recurrent cancer after surgery were eligible for this protocol. The total dose of radiation did not exceed 50.4 Gy (28 fractions of 1.8 Gy each). The starting dose level of irinotecan was 30 mg/m2 infused over 90 minutes given weekly for 5 weeks. Subsequent dose levels were increased in 10 mg/m2 increments to 40, 50, 60, and 70 mg/m2. Of 15 patients who have been enrolled to date, all are evaluable for toxicities and 12 for response. Major hematologic toxicities (grade 3/4) were neutropenia, chills, hemorrhage, and anemia. Grade 3/4 gastrointestinal toxicities included nausea, vomiting, dehydration, anorexia, and constipation. Other severe nonhematologic toxicities included fatigue, hypotension, and hypothermia, as well as cardiovascular toxicities. There was no severe diarrhea and no treatment-related deaths. Of the 12 evaluable patients, 7 (58%) responded, including 2 complete responses; 4 (30%) had no change and 1 had progressive disease. Survival ranged from 1 month to 15 months, with a median survival of 8 months. When the total dose of irinotecan given concurrently with radiotherapy was higher than 250 mg/m2, patients experienced significantly more severe grade 3/4 toxicities than with lower doses (P = .04), with no improvement in response rate. It was concluded that weekly doses of irinotecan of up to 60 mg/m2 with concurrent radiotherapy given over 5 weeks was feasible and demonstrated good response. This regimen did not cause severe diarrhea or pneumonitis, but neutropenia and fatigue were major toxicities. The study continues to accrue.

Adolescent↗

Patterns of recurrence in extremity liposarcoma: implications for staging and follow-up.

BACKGROUND: Liposarcoma is one of the most common histologic types of soft tissue sarcoma and presents a wide spectrum of clinical behavior. The authors examined the correlation among histologic subtypes, outcomes, and patterns of recurrence among patients with extremity liposarcomas. METHODS. A retrospective review of all patients with intermediate and high grade extremity liposarcoma referred to the University of Texas M. D. Anderson Cancer Center from January 1, 1980, to December 31, 1992, was performed. Data on clinical presentation, treatment, patterns of treatment failure, and outcome were evaluated. RESULTS: During the 13-year study period, 122 patients with intermediate or high grade extremity liposarcoma were identified: 102 patients (84%) with myxoid subtype, 18 patients (15%) with pleomorphic subtype, and 2 patients (2%) with mixed histology. There were no differences between the myxoid and pleomorphic subtype groups in tumor size (T1 vs. T2), depth in relation to the muscular fascia, or anatomic site. The median follow-up was 70 months. The 5-year overall survival rate for all intermediate and high grade extremity liposarcoma patients presenting with primary disease (n=85) was 74%; the 5-year local recurrence free survival, distant recurrence free survival, and disease free survival rates were 93%, 78%, and 73%, respectively. Among the 102 patients with myxoid tumors, 33 had distant recurrences; 31 of these were to extrapulmonary soft tissue sites (e.g., the retroperitoneum, chest wall, pleura, pericardium, pelvic sidewall, and soft tissue of the back), and 2 were to the lung only. Among the 18 patients with pleomorphic tumors, 10 had distant recurrences; 3 occurred at extrapulmonary sites, and 7 occurred in the lung only (P < 0.05 for myxoid vs. pleomorphic subtypes). CONCLUSIONS: Myxoid liposarcomas often metastasized to extrapulmonary sites and did so significantly more frequently than pleomorphic tumors. Imaging of the abdomen, retroperitoneum, and extrapleural chest should be performed for accurate staging and posttreatment follow-up of patients with myxoid liposarcoma. Patients presenting with "primary" myxoid liposarcoma of the trunk should be carefully evaluated for an occult primary tumor in an extremity.

Adolescent↗

Port site recurrences after laparoscopy for malignant disease.

Reports of recurrent malignant disease developing at laparoscopic port sites has created considerable controversy among surgeons. Many have implicated the technique of laparoscopy as a cause of metastases and this has led to condemnation of laparoscopy in malignant disease by many surgeons. A review of the case reports, as well as animal studies, reveals the problem to be considerably more complex. Based on experimental models, reported cases, and our experience at the University of Texas M. D. Anderson Cancer Center, we have arrived at some substantive conclusions regarding this phenomenon. Port site recurrences (PSRs) after laparoscopy for malignant disease can occur as the only site of recurrence, but this is an extremely rare event, and the incidence does not appear to be significantly different from the development of wound recurrences after open laparotomy for malignancy. It is likely that port site recurrences reflect the underlying biology of the malignant disease, rather than an effect of the technique of laparoscopy.

Animals↗

Primary tumor response to induction chemotherapy as a predictor of histological status of axillary nodes in operable breast cancer patients.

BACKGROUND: Routine use of axillary lymph node dissection is being questioned, especially in clinically NO patients. The goal of this study was to determine whether primary tumor response to induction chemotherapy (IC) can predict the histological volume of residual axillary disease in patients who were candidates for breast conservation surgery after IC. METHODS: Forty-seven patients with stage II or IIIA breast cancer who received breast conservation surgery were selected from a population of patients randomized to receive four cycles of IC. Largest clinical tumor size before and after IC was determined by physical examination, mammography, and breast ultrasound. Clinical nodal status was determined by physical examination and axillary ultrasound and compared with histological findings. RESULTS: In patients with at least 50% reduction in primary tumor size after IC, 12 of 14 (86%) NO patients and 11 of 17 (65%) N1 patients were histologically negative. In patients with a less than 50% reduction, 0 of 3 NO patients and 2 of 13 (15%) N1 patients were histologically negative. CONCLUSIONS: There is significantly less axillary disease in responders than in nonresponders after IC. For NO responders, axillary irradiation may be an acceptable alternative to axillary lymph node dissection, and could easily be incorporated into the postsurgical radiotherapy that is standard protocol for breast conservation therapy. The more aggressive disease in nonresponders is best treated by axillary lymph node dissection, pending further study.

Adult↗

Laparoscopic splenectomy in patients with hematologic malignancies.

BACKGROUND: Although laparoscopic splenectomy (LS) for benign hematologic disease is well accepted, its role in hematologic malignancies is not clearly defined. This study examined the efficacy and feasibility of LS for hematologic malignancies. METHODS: Records were reviewed from patients who underwent LS at two university hospitals. Charts from 77 open splenectomies for malignancy (OM) during the same period were also reviewed. RESULTS: Fifty-three patients underwent LS, 22 for hematologic malignancies (LM) and 31 for benign hematologic disorders (LB). Median splenic weight was greater in the LM group (930 g) than in the LB group (164 g, P = 0.001). LM was associated with longer operations and greater blood loss than was LB. LM had a 41% conversion rate. Morbidity, mortality, and transfusion rates were similar. Median hospital stay was shorter for LM (4 days) than for OM (6 days, P = 0.001). CONCLUSIONS: LS is feasible in hematologic malignancies but is associated with increased operative time and blood loss and a high conversion rate. Morbidity and mortality, however, was similar. Shorter hospital stays for LM compared with OM may translate into earlier recovery and initiation of antineoplastic therapy.

Adult↗

Long-term outcome of patients with American Joint Committee on Cancer stage IIB extremity soft tissue sarcomas.

PURPOSE: It has been suggested that patients with small (< 5 cm), high-grade extremity soft tissue sarcomas (STS) have an excellent overall prognosis and, consequently, may not require adjuvant therapies. PATIENTS AND METHODS: A comprehensive review of all patients with extremity STS treated at a tertiary care cancer hospital over a 9-year period (January 1984 to December 1992) was performed. Prognostic factors, treatment data, and long-term outcome were evaluated in the subset of 111 patients with American Joint Committee on Cancer stage IIB (G3/4, T1a/b) disease. RESULTS: The median tumor size was 3.0 cm (range, 0.6 to 4.9 cm), and 55 tumors (50%) were deep in location. All patients underwent surgical resection; 68 (61%) received pre- or postoperative radiotherapy, and 32 (29%) received doxorubicin-based chemotherapy. The median follow-up was 76 months. Forty patients (36%) experienced 59 recurrences. First recurrences occurred at local, regional, and distant sites in 21, five, and 14 patients, respectively. The 5-year actuarial local recurrence-free, distant recurrence-free, disease-free, and overall survival rates were 82%, 83%, 68%, and 83%, respectively. The presence of a microscopically positive surgical margin was an independent adverse prognostic factor for both local recurrence (relative risk [RR] = 3.75; 95% confidence interval [CI], 1.25 to 11.25; P =.02) and disease-free survival (RR = 2.57; 95% CI, 1.33 to 4.98; P =.005). CONCLUSION: Event-free outcome for this subset of patients with high-grade STS does not seem as favorable as previously reported by other investigators. Patients who undergo maximal surgical resection with microscopically positive margins represent a subset of T1 STS patients who warrant consideration for adjuvant therapies.

Adolescent↗

Inhibition of the transcription factor nuclear factor-kappa B by adenoviral-mediated expression of I kappa B alpha M results in tumor cell death.

BACKGROUND: The activation of transcription factor nuclear factor-kappa B (NF-kappa B) by extracellular stimuli has been shown to protect cells from apoptotic cell death. Inhibition of NF-kappa B activity should result in increased tumor cell killing in response to apoptotic stimuli. This study evaluated the effect of inhibition of NF-kappa B on a series of sarcoma and normal cell lines. METHODS: Human sarcoma cell lines (HT1080, SKLMS-1, and MFH) and normal cell lines (NLF and BSMC) were infected with an adenoviral dominant-negative mutant Ad5I kappa B alpha M in vitro. Control cells were infected with the empty adenoviral vector and mock-infected with media alone. Viable cell counts were determined by microscopic evaluation on days 1 to 6 after infection. Cell proliferation was determined at 48 hours by MTT (1-[4,5-dimethylthiazol-2-yl]-3,5-dephenylformazan) assay. RESULTS: All cell lines showed evidence of successful adenoviral infection as evidenced by the infection of all cell lines with the adenoviral marker gene Ad5 LacZ. All the tumor cells were found to have a significant decrease in cell viability and proliferation after treatment with the Ad5I kappa B alpha M gene compared with both mock-infected cells and cells infected with empty vector (P < .0001). The normal cell lines, although able to be successfully infected, did not show a significant decrease in cell viability or proliferation with adenoviral-mediated I kappa B alpha M infection. CONCLUSIONS: Inhibition of NF-kappa B through adenoviral-mediated infection of the dominant-negative inhibitor I kappa B alpha M resulted in a significant decrease in tumor cell viability and proliferation while having no deleterious effect on normal cell lines. The Ad5I kappa B alpha M gene therefore could be potentially used as a clinical treatment for patients with soft-tissue sarcoma.

Adenoviridae↗

Laparoscopy in 533 patients with abdominal malignancy.

BACKGROUND: Laparoscopy in patients with intra-abdominal malignancy remains controversial. This study evaluates the incidence of tumor recurrence at the port site after laparoscopy in patients with intra-abdominal malignancy. METHODS: The medical records of all patients with nongynecologic malignancies who underwent laparoscopic procedures between May 1, 1990, and June 30, 1996, at the University of Texas M.D. Anderson Cancer Center were reviewed. Data on extent of tumor, histologic findings, primary location, procedures performed, and complications were recorded. RESULTS: During this time, 533 patients with known intra-abdominal malignancies underwent laparoscopy. Mean follow-up time was 13.2 +/- 0.5 months (range 1 to 71 months; median 10.6 months). Four recurrences at the port site were identified (0.8%). Three of these patients had advanced intra-abdominal disease at the time of laparoscopy; 1 patient without advanced disease at the time of laparoscopy had a recurrence at the port site as the only site of recurrent disease (0.19%). The incidence of port site recurrences among patients with advanced intra-abdominal disease at the time of laparoscopy (3/71) was significantly greater than the risk of development of a recurrence at the port site among patients without advanced intra-abdominal disease at the time of laparoscopy (1/462; P < .0003, by chi-square analysis). CONCLUSION: Recurrence at the port site is very rare. When implantation at the port site does occur, it is most commonly associated with advanced intra-abdominal disease.

Abdominal Neoplasms↗