Biomedical subjects

B L Eisenberg

Publications and source records attributed to B L Eisenberg.

At least 19 recordsLinked to original sources

PubMed2001

Lobular carcinoma in situ increases the risk of local recurrence in selected patients with stages I and II breast carcinoma treated with conservative surgery and radiation.

BACKGROUND: Lobular carcinoma in situ (LCIS) is a known risk factor for the development of invasive breast carcinoma. However, little is known regarding the impact of LCIS in association with an invasive carcinoma on the risk of an ipsilateral breast tumor recurrence (IBTR) in patients who are treated with conservative surgery (CS) and radiation therapy (RT). The purpose of this study was to examine the influence of LCIS on the local recurrence rate in patients with early stage breast carcinoma after breast-conserving therapy. METHODS: Between 1979 and 1995, 1274 patients with Stage I or Stage II invasive breast carcinoma were treated with CS and RT. The median follow-up time was 6.3 years. RESULTS: LCIS was present in 65 of 1274 patients (5%) in the study population. LCIS was more likely to be associated with an invasive lobular carcinoma (30 of 59 patients; 51%) than with invasive ductal carcinoma (26 of 1125 patients; 2%). Ipsilateral breast tumor recurrence (IBTR) occurred in 57 of 1209 patients (5%) without LCIS compared with 10 of 65 patients (15%) with LCIS (P = 0.001). The 10-year cumulative incidence rate of IBTR was 6% in women without LCIS compared with 29% in women with LCIS (P = 0.0003). In both groups, the majority of recurrences were invasive. The 10-year cumulative incidence rate of IBTR in patients who received tamoxifen was 8% when LCIS was present compared with 6% when LCIS was absent (P = 0.46). Subsets of patients in which the presence of LCIS was associated with an increased risk of breast recurrence included tumor size < 2 cm (T1), age < 50 years, invasive ductal carcinoma, negative lymph node status, and the absence of any adjuvant systemic treatment (chemotherapy or hormonal therapy) (P < 0.001). LCIS margin status, invasive lobular carcinoma histology, T2 tumor size, and positive axillary lymph nodes were not associated with an increased risk of breast recurrence in these women. CONCLUSIONS: The authors conclude that the presence of LCIS significantly increases the risk of an ipsilateral breast tumor recurrence in certain subsets of patients who are treated with breast-conserving therapy. The risk of local recurrence appears to be modified by the use of tamoxifen. Further studies are needed to address this issue.

Adult↗

PubMed2001

Gastrointestinal stromal tumors.

Gastrointestinal stromal tumors (GISTs) are mesenchymal gut tumors that differ dramatically from other histologically similar neoplasms, such as leimomyomas, leiomyosarcomas (LMS), and neural tumors. Complete surgical removal remains the best current therapy for GISTs, but even major resections are associated with recurrence in approximately 90% of cases. GISTs are remarkably resistant to irradiation and standard chemotherapy; there is no role for treatment with those modalities. Treatment of advanced GIST patients with STI571, a novel selective tyrosine kinase inhibitor, results in remission rates that approach 60% and overall tumor control rates of 85%. Selected groups of patients, as based on tumor mutational status, have response rates as high as 80%. To date, STI571 therapy remains the only systemic treatment for GISTs to have meaningful clinical activity. Though other molecularly targeted therapies exist in oncology (eg, trastuzumab), STI571 is one of the first that applies a drug specifically designed to inhibit the product of a constitutively-activating mutation that drives pathogenesis of a solid tumor. Its use can serve as a paradigm for designing molecularly targeted therapies for other malignancies.

Antineoplastic Agents↗

PubMed2001

Trimodality therapy for advanced gallbladder cancer.

We conducted a retrospective review of all patients who underwent surgical extirpation for stage III, stage IV, or recurrent carcinoma of the gallbladder. Between 1991 and 1999 ten patients underwent surgical resection for advanced gallbladder cancer. All patients received adjuvant therapy either pre- or postoperatively. Radiotherapy was used in all patients and chemotherapy in 90 per cent of patients. Two patients subsequently underwent resection for locally recurrent disease. An additional patient with stage II disease initially was also treated surgically for a local recurrence. Surgical management involved cholecystectomy and resection of various amounts of liver surrounding the gallbladder bed and regional lymphadenectomy. Contiguously involved structures were resected en bloc. Resection of recurrent disease included excision of all gross tumor. The median overall survival excluding the one 30-day mortality was 53.6 months (range 8-73 months). Four patients have survived 4 or more years, and currently four patients are alive and disease free at 73, 49, 33, and 8 months. Median disease-free interval after each resection of recurrent disease was 13.8 months (range 4-28 months). We conclude that trimodality therapy in selected patients with stage III, IV, or recurrent carcinoma of the gallbladder is possible and may result in prolonged survival.

Acute Disease↗

PubMed2000

Pancreatic carcinoma deemed unresectable at exploration may be resected for cure: an institutional experience.

Only a minority of patients with a diagnosis of pancreatic adenocarcinoma (PA) have disease amenable to curative resection. Between April 1987 and March 1999, 40 patients with pancreatic adenocarcinoma deemed unresectable at exploration at other institutions were considered for neoadjuvant treatments and then re-evaluated for possible re-exploration. We retrospectively compared the clinical outcomes, including overall survival (OS), among three groups: Group A, 22 previously unresectable patients who were subsequently successfully resected, 20 after induction therapy; Group B, 31 patients who received preoperative chemoradiotherapy before their only operation; and Group C, 33 patients who were primarily resected, 27 of whom were then treated with adjuvant therapy. Of those resectable from Group A, 5 required portal venorrhaphy and 3 had hepatic artery reconstruction. Eighteen of the 40 patients were unresectable because of progression of disease with a mean OS of 8 months; 12 were assessed at second laparotomy; 6 were excluded from second operation on the basis of preoperative imaging studies. Kaplan-Meier curves showed no differences in OS among the three groups: OS in Group A was 34 months; Group B, 21; and Group C, 13 (P = 0.15). Margin status was comparable in all three groups (P = 0.52). As expected, nodal positivity was greatest in Group C (P = 0.001). There were no operative mortalities in Group A, and the morbidity rate was comparable with that of Groups B and C. Upon re-evaluation, many tumors (54%) previously deemed "unresectable" were surgically extirpated for cure with a median survival comparable with that of patients who did not undergo previous exploration.

Adenocarcinoma↗

PubMed1998

Phase I dose escalating trial of hyperfractionated pre-operative chemoradiation for locally advanced rectal cancer.

PURPOSE: To determine the acute toxicity, post-operative complications, pathologic response and extent of downstaging to high dose pre-operative radiation using a hyperfractionated radiation boost and concurrent chemotherapy in a prospective Phase I trial. MATERIALS & METHODS: To be eligible for this study, patients had to have adenocarcinoma of the rectum less than 12 cm from the anal verge with either Stage T4 or T3 but greater than 4 cm or greater than 40% of the bowel circumference. All patients received 45 Gy pelvic radiation (1.8 Gy per fraction). Subsequent radiation was given to the region of the gross tumor with a 2 cm margin. This "boost" treatment was given at 1.2 Gy twice daily to a total dose of 54.6 Gy for Level I, 57 Gy for Level II, and 61.8 Gy for Level III. 5-FU was given at 1g/m2 over 24 hours for a four day infusion during the first and sixth weeks of radiation, with the second course concurrent with the hyperfractionated radiation. Surgical resection was carried out 4-6 weeks following completion of chemoradiation (in curative cases) and additional adjuvant chemotherapy consisting of 5-FU and Leucovorin was given for an additional 4 monthly cycles Days 1 through 5 beginning four weeks post surgery. RESULTS: Twenty-seven patients, age 40-82 (median 61), completed the initial course of chemoradiation and are included in the analysis of toxicity. The median follow-up is 27 months (range 8-68). Eleven patients were treated to a dose of 54.6 Gy, nine patients to 57 Gy, and seven patients to 61.8 Gy. Twenty-one patients had T3 tumors, and six patients T4 tumors. Grade III acute toxicity from chemoradiation included proctitis (5 patients), dermatitis (9), diarrhea (five), leukopenia (1), cardiac (1). Grade IV toxicities included one patient with diarrhea (on dose Level I) and one patient (on dose Level III) with cardiac toxicity (unrelated to radiation). Surgical resection consisted of abdominal perineal resection in 16 and low anterior resection in 7. Four patients did not undergo a curative resection; three initially presented with metastases and one developed metastasis during the pre-operative regimen. Post-operative complications included pelvic or perineal abscess in two (on dose Levels I & II), and delayed wound healing in two (one of whom, on dose Level III, developed perineal wound dehiscence requiring surgical reconstruction). Of the 23 patients who had a curative resection, four manifested pathologic complete responses (17.4%). Thirteen of 23 patients (57%) had evidence of pathologic downstaging and only 1/23 patients (on dose Level I) had a positive resection margin. Of these 23 patients (with a minimum follow-up of 8 months), the patient with positive margins was the only one who developed a local failure (Fisher's Exact p=.04). The 3-year actuarial OS, DFS and LC rates are 82%, 72% and 96%, respectively. Twelve of 13 patients (92% at 3 years) > or = 61 years vs. 5/10 patients (45% at 3 years) < 61 years remained disease-free (log-rank p=0.017). CONCLUSION: This regimen of high dose pre-operative chemoradiation employing a hyperfractionated radiation boost is feasible and tolerable and results in significant downstaging in locally advanced rectal cancer. The vast majority of patients (96%) achieved negative margins, which appears to be a prerequisite for local control (p= 0.04). Older age (> or =61 years) was a significant predictor for improved DFS. This regimen (at dose Level III, 61.8 Gy) is currently being tested in a Phase II setting.

Adenocarcinoma↗

PubMed1998

A close or positive margin after mastectomy is not an indication for chest wall irradiation except in women aged fifty or younger.

INTRODUCTION: Indications for postmastectomy radiation include primary tumor size > or = 5 cm and/or > or = 4 positive axillary nodes. In clinical practice, patients with a close or positive margin after mastectomy are also often treated with postmastectomy radiation. However, there is little data regarding the risk of a chest wall recurrence in patients with close or positive margins who otherwise would be considered low risk (tumor size <5 cm and/or 0-3 positive nodes). To address this issue, we assessed the risk of a chest wall recurrence in women with Stage I-II breast cancer who underwent mastectomy and were found to have primary tumor size <5 cm and 0-3 positive nodes with a close or positive deep margin. METHODS AND MATERIALS: The pathologic reports from 789 patients treated by mastectomy between 1985 and 1994 at our institution were retrospectively reviewed. Of these, 136 (17%) had tumor within 1 cm of the deep resection margin. The study population consists of 34 of these patients with close or positive margins whose primary tumor size was <5 cm with 0-3 positive axillary nodes and who received no postoperative radiation. The median age was 43 years (range 29-76). Of these, 44% had T1 tumors and 56% T2 tumors. Pathologic axillary nodal status was negative in 65% and positive in 35%. The median number of positive nodes was 1. The deep margin was positive in 2 patients, < or = 2 mm in 17 patients, 2.1-4 mm in 7 patients and 4.1-6 mm in 8 patients. Of the 34 patients, 67% received adjuvant chemotherapy +/- tamoxifen and 21% received tamoxifen alone. The median follow-up was 59 months (range 7-143). RESULTS: There were 5 chest wall recurrences at a median interval of 26 months (range 7-127). One was an isolated first failure, one occurred concurrent with an axillary recurrence, and three were associated with distant metastases. The 5- and 8-year cumulative incidences of a chest wall recurrence were 9% and 18%. Patient age correlated with the cumulative incidence of chest wall recurrence at 8 years; age < or = 50 years had a rate of 28% vs. 0% for age >50 (p = 0.04). There was no correlation with chest wall failure and number of positive nodes, ER status, lymphovascular invasion, location of primary, grade, family history, or type of tumor close to the margin. Of 5 chest wall failures, 4 were in patients who had received adjuvant systemic chemotherapy +/- tamoxifen. Chest wall failures occurred in 1 patient with a positive deep margin, 3 patients with margins within 2 mm, and 1 patient with a margin of 5 mm. The estimated cumulative incidence probability of chest wall recurrence at 8 years by margin proximity was 24% < or = 2 mm vs. 7% 2.1-6 mm (p = 0.36), and by clinical size 24% for T2 tumors vs. 7% for T1 (p = 0.98). CONCLUSIONS: A close or positive margin is uncommon (< or = 5%) after mastectomy in patients with tumor size <5 cm and 0-3 positive axillary nodes but, when present, it appears to be in a younger patient population. The subgroup of patients aged 50 or younger with clinical T1-T2 tumor size and 0-3 positive nodes who have a close (< or = 5 mm) or positive mastectomy margin are at high risk (28% at 8 years) for chest wall recurrence regardless of adjuvant systemic therapy and, therefore, should be considered for postmastectomy radiation.

Adult↗

PubMed1998

Use of saline-filled tissue expanders to protect the small bowel from radiation.

Over the past 7 years, 58 saline-filled tissues expanders (TEs) have been temporarily placed in 57 patients. The indications for TE placement were: small bowel exclusion from external-beam radiation therapy (N = 25), interstitial RT (N = 16), or both (N = 13) when there was insufficient omentum to provide adequate exclusion. Of the 57 patients, 24 had primary tumors (4 colon, 4 endometrial, and 11 rectal cancer; 3 sarcomas, 1 schwannoma; and 1 vaginal cancer). The remaining 33 patients (58%) had recurrent cancers (3 anal, 8 colon, and 16 rectal cancers; and 6 sarcomas), of whom 26 (79%) had received prior RT. Of the 58 TEs, 15 were placed superior to the iliac vessels and 43 were placed in the pelvis. Complications included post-withdrawal enterocutaneous fistulae in four patients, TE deflation in three patients, and TE extrusion in one patient. Improvements in TE design and removal techniques have reduced the incidence of these complications. When no native tissue is available for small bowel exclusion, the saline-filled TE is a safe, effective substitute.

Colorectal Neoplasms↗

PubMed1998

Comparison of liver function tests after hepatic lobectomy and hepatic wedge resection.

Prior studies have suggested that changes in liver function tests may vary with the postoperative time interval and may be related to the extent of hepatic resection. This study describes characteristic profiles in parenchymal liver enzymes and other serum liver function tests over a 4-week course comparing anatomic to nonanatomic hepatic resections. The records of 48 patients undergoing successful major hepatic resection during a 3-year period were retrospectively reviewed. Of these 48 patients, 28 underwent formal anatomic resection (hepatic lobectomy), and 20 underwent nonanatomic resections (wedge resection). Routine postoperative management in lobectomy patients included drawing liver function tests and enzymes daily for the first week, then at approximately 2 and 4 weeks postoperatively. These tests included: prothrombin time (PT), partial thromboplastin time, total serum bilirubin, total protein (TP), aspartate transaminase, lactate dehydrogenase (LDH), alkaline phosphatase, albumin (A), and glucose. Patients undergoing wedge resections had these values checked less frequently, approximately 3 to 5 days, 2 weeks, and 4 weeks postoperatively. Profiles of these values were plotted over the 4-week postoperative time course for each group of patients. Patients undergoing hepatic lobectomy showed a characteristic laboratory value profile. PT elevated within 48 hours to a mean high of 16.0 seconds, then returned to normal by postoperative day 4. Partial thromboplastin time levels remained normal throughout the entire perioperative course. Total bilirubin rose slightly, to a mean high of 2.6 mg/100 cc, then returned to normal by postoperative day (POD) 14. Parenchymal liver enzymes aspartate transaminase and LDH rose abruptly to very high levels, then returned abruptly to normal (by POD 5). TP and A both fell to approximately 50 per cent of normal, gradually rising to normal by POD 14. Glucose rose to a mean high of 199 mg/100 cc within the first 5 days, then returned to normal by POD 7. Alkaline phosphatase remained normal initially, then showed a progressive rise to a high of 288 mg/100 cc on POD 14. Patients undergoing wedge resections did not show the same changes in total serum bilirubin, but showed similar trends in all other tests, although the magnitude of these changes was smaller. TP and A levels fell acutely after resection, then began a slow rise toward normal by POD 21. TP and A profiles were similar for both lobectomy patients and those undergoing wedge resection. The only tests that may have altered clinical management were the PT and total bilirubin. Patients undergoing major hepatic resection have characteristic postoperative profiles of liver enzymes and liver function tests. These laboratory profiles differ with the extent of hepatic resection. The profiles reflect changes in volume status, parenchymal liver destruction, transient hepatic insufficiency, and postoperative hepatic regeneration. However, except possibly for PT and bilirubin, the routine use of these tests is not recommended, given that the results do not alter clinical management.

Follow-Up Studies↗

PubMed1998

Preoperative versus postoperative chemoradiation for patients with resected pancreatic adenocarcinoma.

Two groups of patients with adenocarcinoma of the pancreas treated with either preoperative chemoradiation (preop CTRT) or postoperative chemoradiation (postop CTRT) were retrospectively analyzed for various treatment-related parameters. Between November 1986 and October 1996, a total of 70 patients with pancreatic adenocarcinoma were enrolled into preop CTRT protocols at our institution. Twenty-five patients with adenocarcinoma of the head of the pancreas underwent pancreaticoduodenectomy with curative intent. After the closure of the preop CTRT protocols, we had the opportunity to perform 23 pancreatic resections without preop CTRT. After surgery, these patients were advised to undergo CTRT. These two groups of patients were therefore selected consecutively, dependent only on the time of referral and no other bias. These two cohorts of patients are compared for various intraoperative parameters, length of hospital stay, pathologic findings, time to recurrence, and survival. Mean age was 65 and 66 years in the preop and postop CTRT groups, respectively. Sex distribution was almost equal. Treatment breaks resulting in greater than 1 week delay in the radiotherapy occurred in 2 (8%) of 25 patients in the preop CTRT group (myelotoxicity in 1 case and biliary sepsis in 1 case), whereas no treatment breaks >1 week occurred in those receiving postop CTRT. Eleven patients in preop CTRT had grade 3 or 4 toxicity, whereas none was noted in those with postop CTRT. There was one postoperative death in the preop CTRT group and none in the postop CTRT group. Mean time to the start of CTRT was 45 days (range, 20-66 days) after pancreaticoduodenectomy. Delay of >60 days to the onset of CTRT occurred in 2 (22%) patients and was attributable to patient delays in time to recover from surgery or patient noncompliance. Furthermore, 5 of 23 patients (22%) in the postop CTRT group did not receive treatment for various reasons. Average estimated operative blood loss was 1933 mL (median 1550) and 1060 mL (median 1000) for preop and postop CTRT groups, respectively. Mean length of operation was 488 minutes (median 480) and 486 minutes (median 480). Median length of postoperative stay was 22 and 20 days (ranges, 9-144 and 10-38). Pathological findings in the resected specimens showed significantly fewer involved nodes in the preop CTRT group (28 vs 87%; P = 0.0006), whereas similar numbers of nodes/patient were counted in each group (14 vs 22, P = 0.11). More negative resection margins were observed in the preop CTRT group (28 vs 56%; P = not significant). A significantly greater amount of fibrosis replacing the tumor was observed in the preop CTRT group (70 vs 40%; P = 0.0001). There were no significant survival differences observed (median 20 months vs 25 months; P = 0.48), in follow-up that ranged from 4 to 76 months (median 44 months for surviving patients) for the preop group and 4 to 40 months (median 16 months for surviving patients) for those with postop CTRT. Local failure either alone or as a component of distant failure occurred in 16 per cent (4 of 25 patients) with preop CTRT and 16.6 per cent (3 of 18) with postop CTRT. Analysis of differences between those treated with preoperative and postoperative CTRT demonstrates similarity in toxicity and effects. However, 22 per cent of patients intended for postoperative therapy did not receive treatment.

Adenocarcinoma↗

PubMed1997

Identification of women with T1-T2 breast cancer at low risk of positive axillary nodes.

BACKGROUND AND OBJECTIVES: The diagnostic and therapeutic significance of axillary dissection has been questioned. We sought to define a subgroup of patients with early-stage breast cancer who are at low risk for positive axillary nodes. METHODS: Between 1970 and 1995, 1,598 women with stage I and II breast cancer underwent level I-II axillary dissection with a minimum of 10 nodes removed. The following factors were examined in univariate analysis for predicting positive nodes: race, method of detection, location of the primary tumor, age, menopausal status, obesity, ER status, PR status, pathologic tumor size, lymphatic vascular invasion, tumor grade, and histology. RESULTS: Four hundred and forty-five of the 1,598 patients (27.8%) had histologically positive axillary nodes. Significant factors in univariate analysis for positive nodes included: tumor size, lymphatic vascular invasion, grade, method of detection, primary tumor location, and age. The only group of women with a 0% risk of axillary nodes were those in whom the pathologic tumor size was < or = 5 mm and mammographically detected. A 5-10% risk of positive axillary nodes was identified in women with (1) pathologic tumor size 6-10 mm, mammographically detected, and age < or = 40 years, and (2) tubular carcinoma < or = 10 mm. Tumors detected on physical examination with or without mammography and women < or = 40 years had a significantly increased risk of nodes. In multivariate analysis lymphatic vascular invasion (P < 0.001), method of detection (P = 0.026), location (P = 0.01), and pathologic tumor size (P = 0.002) were significant predictors of positive axillary lymphadenopathy. CONCLUSIONS: The decision to forego an axillary dissection should be considered in (1) tumors mammographically detected and < or = 5 mm (2) mammographically detected, pathologic size 6-10 mm, age > 40 and (3) tubular carcinoma < or = 10 mm. All other groups had a > 10% risk of nodes and may benefit from axillary dissection.

Adult↗

PubMed1997

Cryosurgical ablation of hepatic metastases from colorectal carcinomas.

Surgical resection remains the only curative therapy for hepatic metastases from colon and rectal carcinoma. Many patients will be unresectable or have close microscopic margins. Cryoablation may improve local control and survival in those cases. From February 1992 to May 1995, patients with metastatic colon and rectal carcinoma who underwent cryoablation of surgical margins following hepatic resection or cryoablation of hepatic metastases were reviewed with attention to patient and tumor characteristics, clinical course, local control, and survival. Twenty-four patients (10 female, 14 male) with a mean age of 63 years (range, 34-84 years) underwent cryosurgical ablation for hepatic metastases. Twelve were for central lesions and 12 for gross or microscopically positive resection margins. Surgery was performed with curative intent for 21 and for palliation in 3 patients. The mean hospital stay was 8.4 days (range, 5-15 days). Complications included three cases of parenchymal cracking and a single bile leak. Two of 14 patients who developed pleural effusions required treatment. Perioperative mortality was 8.3 per cent (2 of 24): one myocardial infarction and one cerebrovascular accident. Four of 21 treated for cure had hepatic recurrence, and six had only extrahepatic recurrence. Median time to recurrence was 9.5 months. With median follow-up of 19 months, mean actuarial disease-free (DFS) and overall survival (OS) rates are as follows. Those with central lesions (n = 12) had a mean OS rate of 31 months and a mean DFS rate of 23 months. Those with close resection margins (n = 12) had a mean OS rate of 31 months and a median DFS rate of 19.5 months. Total patients (n = 24) had a mean OS rate of 32.7 months and a mean DFS rate of 23.5 months. We conclude that cryoablation of unresectable hepatic metastases or close resection margins is safe and may allow for improved survival in selected patients with metastatic colon and rectal carcinoma.

Actuarial Analysis↗

PubMed1997

Implications of fine-needle aspiration in patients with resectable pancreatic cancer.

A 9-year experience with fine-needle aspiration (FNA) in patients with resectable pancreatic adenocarcinoma was reviewed to determine whether this procedure is associated with positive peritoneal cytology, peritoneal recurrences, or decreased survival in patients who had pancreatic resection with curative intent. Forty-one patients underwent pancreatic resection for primary pancreatic adenocarcinoma from July 1987 to February 1996. Nine patients had open biopsies prior to definitive resection and were excluded from this study. Of the remaining 32 patients, 21 (66%) had preoperative computed tomography-guided or fluoroscopically guided FNA biopsy of the pancreas for diagnosis. FNA confirmed the diagnosis of adenocarcinoma in 17 of 21 patients (80%). Fifteen of 21 FNA biopsies were performed in patients who went on to receive neoadjuvant chemoradiation. Twenty-eight of 32 patients (87%) had peritoneal washings at the time of laparotomy. Five patients had suspicious or positive washings (18%), and 23 patients had negative washings (82%). Three of 18 patients (16.7%) who had both FNA and peritoneal washings and 2 of 10 patients (20%) who had no FNA but had peritoneal washings had positive or suspicious peritoneal cytology. Eight of 32 patients ultimately failed in the peritoneum. Six of 21 patients (28%) who had prior FNA and 2 of 11 (18%) who had no prior FNA failed in the peritoneum. Although the number of patients is small, none of these differences proved to be statistically significant. No difference in median survival was observed between the FNA and no FNA groups. We conclude that FNA is a safe and useful tool to confirm the diagnosis of pancreatic cancer when patients are to be treated with neoadjuvant chemoradiation.

Adenocarcinoma↗

PubMed1996

The impact of tamoxifen on breast recurrence, cosmesis, complications, and survival in estrogen receptor-positive early-stage breast cancer.

PURPOSE: To evaluate the impact of tamoxifen on breast recurrence, cosmesis, complications, overall and cause-specific survival in women with Stage I-II breast cancer and estrogen receptor positive tumors undergoing conservative surgery and radiation. METHODS AND MATERIALS: From 1982 to 1991, 491 women with estrogen receptor positive Stage I-II breast cancer underwent excisional biopsy, axillary dissection, and radiation. The median age of patient population was 60 years with 21% < 50 years of age. The median follow-up was 5.3 years (range 0.1 to 12.8). Sixty-nine percent had T1 tumors and 83% had histologically negative axillary nodes. Re-excision was performed in 49% and the final margin of resection was negative in 64%. One hundred fifty-four patients received tamoxifen and 337 patients received no adjuvant therapy. None of the patients received adjuvant chemotherapy. RESULTS: There were no significant differences between the two groups for age, race, clinical tumor size, histology, the use of re-excision, or median total dose to the primary. Patients who received tamoxifen were more often axillary node positive (44% tamoxifen vs. 5% no tamoxifen), and, therefore, a greater percentage received treatment to the breast and regional nodes. The tamoxifen patients less often had unknown margins of resection (9% tamoxifen vs. 22% no tamoxifen). The 5-year actuarial breast recurrence rate was 4% for the tamoxifen patients compared to 7% for patients not receiving tamoxifen (p = 0.21). Tamoxifen resulted in a modest decrease in the 5-year actuarial risk of a breast recurrence in axillary node-negative patients, in those with unknown or close margins of resection, and in those who underwent a single excision. Axillary node-positive patients had a clinically significant decrease in the 5-year actuarial breast recurrence rate (21 vs. 4%; p = 0.08). The 5-year actuarial rate of distant metastasis was not significantly decreased by the addition of adjuvant tamoxifen in all patients or pathologic node-negative patients. Pathologically node-positive patients had a significant decrease in distant metastasis (35 vs. 11%; p = 0.02). There were no significant differences in cause-specific survival for patients receiving tamoxifen when compared to observation (95% no tamoxifen vs. 89% tamoxifen; p = 0.24). Similar findings were noted for pathologically node-negative patients. However, axillary node-positive patients receiving tamoxifen had an improvement in 5-year actuarial cause-specific survival (90% tamoxifen vs. 70% no tamoxifen; p = 0.10). Cosmesis (physician assessment) was good to excellent in 85% of the tamoxifen patients compared to 88% of the patients who did not receive tamoxifen. CONCLUSION: The addition of tamoxifen to conservative surgery and radiation in women with Stage I-II breast cancer and estrogen receptor positive tumors resulted in a modest but not statistically significant decrease in the 5-year actuarial risk of a breast recurrence. Tamoxifen significantly decreased the 5-year actuarial risk of distant metastasis in axillary node-positive patients and there was a trend towards improvement in cause-specific survival that was not statistically significant. Tamoxifen did not decrease the 5-year actuarial rate of distant metastasis in axillary node negative, patients and in this group, there was no improvement in cause-specific survival. Tamoxifen did not have an adverse effect on cosmesis or complications.

Adult↗

PubMed1996

Metabolic characterization of human soft tissue sarcomas in vivo and in vitro using proton-decoupled phosphorus magnetic resonance spectroscopy.

We applied 1H-decoupling and nuclear Overhauser enhancement to obtain well-resolved 31P magnetic resonance spectra accurately localized to 20 soft tissue sarcomas in vivo, using three-dimensional chemical shift imaging. Fifteen spectra had large phosphomonoester signals (21% of total phosphorus) that contained high amounts of phosphoethanolamine (compared to those of phosphocholine) but no signals from glycerophosphoethanolamine, and glycerophosphocholine was detected in only four cases. Prominent nucleoside triphosphates (52% of phosphorus) and low inorganic phosphate (10% of phosphorus) indicated that a large fraction of these 15 sarcomas contained viable cells, and this impression was confirmed histologically in 13 of the sarcomas. High-resolution in vitro 31P spectra of extracts of surgical specimens of four of the sarcomas studied in vivo and six additional sarcomas confirmed the in vivo assignments of metabolites and revealed considerable inter- and intratumoral variations of metabolite concentrations associated with histological variations in the relative amounts of cells and of matrix materials or spontaneous necrosis. Seven sarcomas, all high grade with pleomorphic or round cells rather than spindle cells, contained an unidentified phosphodiester signal in vivo; its absence in the extract spectra indicates that it may be from an abnormally mobile membrane component. We have documented a means to obtain new information about in vivo metabolism in human sarcomas and to provide a basis on which to examine the uses of 31P magnetic resonance spectroscopy in the clinical management of sarcomas.

Adult↗

PubMed1996

Does the placement of surgical clips within the excision cavity influence local control for patients treated with breast-conserving surgery and irradiation.

PURPOSE: A number of authors have demonstrated the importance of using surgical clips to define the tumor bed in the treatment planning of early-stage breast cancer. The clips have been useful in delineating the borders of the tangential fields, especially for very medial and very lateral lesions as the boost volume. If surgical clips better define the tumor bed, then a reduction in true or marginal recurrences should be appreciated. We sought to compare the incidence of breast recurrence in women with and without surgical clips, controlling for other recognized prognostic factors. METHODS AND MATERIALS: Between 1980 and 1992, 1364 women with clinical Stage I or II invasive breast cancer underwent excisional biopsy, axillary dissection, and definitive irradiation. Median follow-up was 60 months. Median age was 55 years. Seventy-one percent of patients were path NO, 22% had one to three nodes, and 7% had > than four nodes. Sixty-one percent were ER positive and 44% PR positive. Margin status was negative in 62%, positive in 10%, close in 9%, and unknown in 19%. Fifty-seven percent of women underwent a reexcision. Adjuvant chemotherapy + tamoxifen was administered in 29%, and tamoxifen alone in 17%. Surgical clips were placed in the excision cavity in 556 patients, while the other 808 did not have clips placed. All patients had a boost of the tumor bed. Patients had their boost planned with CT scanning or stereo shift radiographs. No significant differences between the two groups were noted for median age, T stage, nodal status, race, ER/PR receptor status, region irradiated, or tumor location. Patients without clips had negative margins less often, a higher rate of unknown or positive margins and more often received no adjuvant therapy compared to patients with surgical clips. RESULTS: Twenty-five and 27 patients with and without surgical clips, respectively, developed a true or marginal recurrence in the treated breast. The actuarial probability of a breast recurrence was 2% at 5 years and 5% at 10 years for patients without clips compared to 5 and 11%, respectively, for patients with clips (p=0.01). Comparing the breast recurrence rates for patients with and without clips there was no significant difference for the following factors: chemotherapy, tamoxifen, negative, positive or close margins, reexcision, N1, and central or inner primary. Increased rates of breast recurrence were noted for patients with clips for the following variables: no adjuvant treatment (p < 0.001), unknown margins (p < 0.001), a single excision (p = 0.003), path NO (p = 0.001), and outer location (p= 0.02). A forward stepwise multivariate analysis for all 1364 patients was performed using the aforementioned variables as well as the presence or absence of surgical clips and the primary surgeon. The surgeon (p = 0.03) and no adjuvant treatment (p = 0.01) significantly influenced breast recurrence. For patients with surgical clips the 10 year isolated breast recurrence rate was 21% for a single surgeon vs. 6% in the remainder of the group (p = 0.01). For patients with clips, this surgeon had unknown margins in 48% of cases compared to 10% overall (p = 0.001). Excluding this surgeon from analysis the isolated breast recurrence for patients with clips was 6 vs. 5% for patients without clips (p = 0.18). CONCLUSIONS: Overall, there was a significant difference in the 10-year breast recurrence rate favoring women without clips despite more adverse prognostic factors. There was no difference in the breast recurrence rate for patients with or without surgical clips if careful attention to margin status was addressed. Failure to ink the surgical specimen resulting in unknown margins cannot be compensated for with the placement of .

Antineoplastic Agents, Hormonal↗

PubMed1996

Interleukin-2 activation of cytotoxic cells in postmastectomy seroma.

Lymphocytes were isolated from breast seroma fluids and used to study the mechanism of activation of cytotoxic lymphocytes and possible role of immunological potentiation following surgery in breast cancer patients. Single or serial samples were obtained from patients who had undergone mastectomy or lumpectomy with axillary node dissection. Lymphocytes were activated with rIL-2 (interleukin-2) and their cytotoxic activity was studied against Daudi and K562 cells and against a breast tumor line (SKBr-3). All of the patients (21/21) responded to IL-2 stimulation by significant activation of cytotoxic activity. The unstimulated cytotoxic activity of these cells against NK targets was low with less than 10% specific release in cytotoxicity assays. In simultaneous experiments, autologous seroma fluid was included during activation of lymphocytes to study possible regulatory molecules that may be present. In 17/21 patients, the presence of their seroma fluid, during the activation period, enhanced or did not effect the cytotoxic potential of their lymphocytes; inhibition was observed when seroma fluids from 4/21 patients were included. Analysis of the cytotoxic population derived from combined IL-2 and seroma treatments indicates the presence of cells with increased expression of CD56, and CD2, as well as in some cases CD16 expression. Cytotoxic lymphocytes derived from IL-2 and seroma treatments appeared to be more effective killers. Modulation of CD2 expression with seroma alone appeared to result in the generation of this highly cytotoxic population. This study demonstrates the role of CD2 expression in the effectiveness of LAK cell killing and also potential benefit of an immunotherapeutic approach to the postoperative treatment of carcinoma of the breast.

Adult↗

PubMed1996

Atraumatic method of intraoperative retrograde transhepatic biliary stent insertion.

A significant risk of hepatic injury remains using reported methods of intraoperative retrograde transhepatic stenting (IRTS). Our hypothesis was that we could minimize this risk by: (1) using a pliable sheath to create a stent tract that follows the curve of the biliary tree, (2) decreasing the stent diameter, and (3) avoiding the hepatic hilum. We evaluated the safety of a novel technique of intraoperative stenting employing these three concepts. Twenty-four patients underwent IRTS between 1992 and 1995 at our institution after potentially curative resection (one bypass). Malignant disease was present in 22 of 24 patients. Bile ducts were normal caliber in all patients. There was no operative mortality and 38% operative morbidity, all readily treated. All complications were due to stent dislodgment. There were no deaths. This novel atraumatic method of IRTS has acceptable morbidity and mortality. Complications due to stent insertion are minimal. The technique compares favorably with previous methods of IRTS and offers a viable alternative to the surgeon when a transhepatic stent is required. Anchoring the stent securely to the skin is essential to prevent catheter dislodgement.

Bile Duct Neoplasms↗

PubMed1996

Wound complications after resection and immediate postoperative brachytherapy in the management of soft-tissue sarcomas.

BACKGROUND: When used as the sole source of postoperative radiotherapy, brachyradiation therapy (BRT) (4,500-6,000 cGy) should be delayed beyond the fourth postoperative day to minimize wound complications. However, when 1,000-2,000 cGy BRT are given as a "boost" to the tumor bed, it is unclear if a similar treatment delay is necessary. The purpose of this review was to determine the incidence of wound complications when BRT (1,000-2,000 cGy) is administered < or = 48 h after soft-tissue resection. METHODS: The results of treatment in 21 patients with soft-tissue sarcomas of the extremity and superficial trunk treated with resection, immediate postoperative brachytherapy, and external beam radiation were reviewed. All patients were followed through the completion of radiation (median follow-up 30 months). A median of seven (range 3-24) after-loading catheters were placed at the time of resection and were loaded with iridium-192 a median of 2 days postoperative to deliver 1,000-2,000 cGy radiation. RESULTS: Eight patients (38%) experienced minor wound complications (seromas, wound separation, and flap edge necrosis) within 30 days of operation. There were no early complications that required reoperation or delayed further therapy. CONCLUSIONS: Brachytherapy (1,000-2,000 cGy) can be administered < or = 48 h postoperatively with a low risk of major wound complications. Minor wound complications are common but do not delay further treatment.

Adult↗