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Biomedical subjects

E A Levine

Publications and source records attributed to E A Levine.

At least 19 recordsLinked to original sources

Adjuvant gemcitabine and concurrent radiation for patients with resected pancreatic cancer: a phase II study.

The safety and efficacy of gemcitabine and concurrent radiation to the upper abdomen followed by weekly gemcitabine in patients with resected pancreatic cancer was determined. Patients with resected adenocarcinoma of the pancreas were treated with intravenous gemcitabine administered twice-weekly (40 mg m(-2)) for 5 weeks concurrent with upper abdominal radiation (50.4 Gy in 5(1/2) weeks). At the completion of the chemoradiation, patients without disease progression were given gemcitabine (1000 mg m(-2)) weekly for two cycles. Each cycle consisted of 3 weeks of treatment followed by 1 week without treatment. Forty-seven patients were entered, 46 of whom are included in this analysis. Characteristics: median age 61 years (range 35-79); 24 females (58%); 73% stage T3/T4; and 70% lymph node positive. Grade III/IV gastrointestinal or haematologic toxicities were infrequent. The median survival was 18.3 months, while the median time to disease recurrence was 10.3 months. Twenty-four percent of patients were alive at 3 years. Only six of 34 patients with progression experienced local regional relapse as a component of the first site of failure. These results confirm the feasibility of delivering adjuvant concurrent gemcitabine and radiation to the upper abdomen. This strategy produced good local regional tumour control.

Adenocarcinoma↗

Cytoreductive surgery combined with perioperative intraperitoneal chemotherapy for the management of peritoneal carcinomatosis from colorectal cancer: a multi-institutional study.

PURPOSE: The three principal studies dedicated to the natural history of peritoneal carcinomatosis (PC) from colorectal cancer consistently showed median survival ranging between 6 and 8 months. New approaches combining cytoreductive surgery and perioperative intraperitoneal chemotherapy suggest improved survival. PATIENTS AND METHODS: A retrospective multicenter study was performed to evaluate the international experience with this combined treatment and to identify the principal prognostic indicators. All patients had cytoreductive surgery and perioperative intraperitoneal chemotherapy (intraperitoneal chemohyperthermia and/or immediate postoperative intraperitoneal chemotherapy). PC from appendiceal origin was excluded. RESULTS: The study included 506 patients from 28 institutions operated between May 1987 and December 2002. Their median age was 51 years. The median follow-up was 53 months. The morbidity and mortality rates were 22.9% and 4%, respectively. The overall median survival was 19.2 months. Patients in whom cytoreductive surgery was complete had a median survival of 32.4 months, compared with 8.4 months for patients in whom complete cytoreductive surgery was not possible (P <.001). Positive independent prognostic indicators by multivariate analysis were complete cytoreduction, treatment by a second procedure, limited extent of PC, age less than 65 years, and use of adjuvant chemotherapy. The use of neoadjuvant chemotherapy, lymph node involvement, presence of liver metastasis, and poor histologic differentiation were negative independent prognostic indicators. CONCLUSION: The therapeutic approach combining cytoreductive surgery with perioperative intraperitoneal chemotherapy achieved long-term survival in a selected group of patients with PC from colorectal origin with acceptable morbidity and mortality. The complete cytoreductive surgery was the most important prognostic indicator.

Adolescent↗

Surgical and ablative treatment for metastatic adenocarcinoma to the liver from unknown primary tumor.

Metastatic adenocarcinoma to the liver from an unknown primary tumor (UPT) carries a poor prognosis, with a median survival of 5 months. Chemotherapy has not significantly improved outcome, and effective treatment is yet to be established in these patients. We examined our experience with surgical resection and ablation of this disease to determine clinico-pathologic characteristics and treatment outcomes. We undertook a retrospective chart review of 157 patients who were treated for metastatic disease to the liver with resection or radiofrequency ablation (RFA) between 1999 and 2003. Seven patients were identified with unknown primary malignancy. Evaluation of the seven patients included complete history and physical examination, complete blood count, routine chemistries, stool Hemoccult test, chest radiograph, and computed tomography (CT) of the abdomen and pelvis. In addition, the three female patients had breast examinations and mammography. Adenocarcinoma histology was determined via CT-guided liver biopsy in all patients. Other diagnostic tests, including whole-body positron emission tomography to the measurement of various serum tumor markers, were performed in the majority of the patients. There were nine total lesions treated; six with RFA and three with hepatic resection. Median diameter of the lesions was 5.4 cm (range, 1.3-15). Two patients were treated with adjuvant and three patients with neoadjuvant and adjuvant chemotherapy. Extrahepatic sites of metastases, adrenal and skeletal, were discovered in 1 patient prior to treatment. With a median follow-up of 9 months, 1 patient is currently alive with no evidence of disease, 4 patients are alive with disease, and 2 patients died of disease. Median disease-free-interval following treatment was 6.5 months. To date, optimal treatment for metastatic adenocarcinoma to the liver UPT remains unclear. Localized treatment involving RFA or hepatic resection may be a promising addition to chemotherapy in the management of this disease.

Adenocarcinoma↗

PROGINS Alu insertion and human genomic diversity.

A polymorphic Alu element belonging to the young Ya5 subfamily of Alu repeats located in the progesterone receptor gene has been characterized. Using a polymerase chain reaction (PCR)-based assay, the genetic diversity associated with the PROGINS Alu repeat was determined in a diverse array of human populations. The level of insertion polymorphism associated with PROGINS suggests that it will be a useful marker for the study of human evolution. In addition, we determined the distribution of the PROGINS Alu insertion in two groups of women from greater New Orleans, LA with breast cancer. The PROGINS Alu insertion was not associated with breast cancer in the populations tested.

Alu Elements↗

Incidental thyroid carcinoma identified by positron emission tomography scanning obtained for metastatic evaluation.

Positron emission tomography (PET) scanning is an emerging technology with substantial implications for patients with solid tumors. PET is useful in identifying sites of metastatic disease as well as primary malignancy and evaluating suspicious findings found via other imaging modalities. PET is becoming a standard modality for metastatic evaluation of a variety of malignancies. However, this imaging is not limited by histology and may reveal clinically occult second lesions. We present five cases of a clinically occult thyroid cancer found in patients who underwent PET scanning for metastatic evaluations. The principal diagnoses included two patients with malignant melanoma, one each with gastric, rectal, and colonic adenocarcinoma. None of the cases had findings on physical examination. Increased uptake in the region of the thyroid was evident on the PET scan, and fine-needle aspiration biopsy indicated papillary carcinoma of the thyroid in all five cases. Although evaluation of metastatic disease is the primary purpose for PET in this setting the discovery of occult thyroid malignancy is an additional benefit of such imaging. This emphasizes the importance of investigating suspicious areas found by PET and not simply assuming that these are all sites of metastatic disease. Furthermore incidental findings of uptake in the region of the thyroid make consideration of a primary carcinoma mandatory.

Aged↗

Paraneoplastic hypercalcemia in a patient with adenosquamous cancer of the colon.

Hypercalcemia is a well-known manifestation of paraneoplastic syndromes associated with a variety of malignancies. However, colon cancer has only rarely been associated with hypercalcemia of malignancy. We present the case of a patient with recurrent adenosquamous carcinoma of the ascending colon found to have hypercalcemia. The patient is a 76-year-old white woman who initially presented with colon cancer in the cecum and underwent a right hemicolectomy. All lymph nodes and surgical margins were free of tumor. Pathological examination at that time revealed adenosquamous carcinoma of the colon. Eight months later she complained of dizziness, anorexia, and constipation and was found to have a calcium level of 13.6 mg/dL. CT scan revealed a mass measuring 10.5 to 12.7 cm in the right hepatic lobe, and a bone scan was normal. Her intact parathyroid hormone (PTH) level was 6 pg/mL (normal 12-72) and her PTH-related protein (PTHrP) level was 25.7 pmol/L (normal <1.3). She then underwent a hepatic resection. The serum PTH, calcium, and PTHrP levels normalized after resection. Hypercalcemia of malignancy in colon cancer is rare and has an association with adenosquamous histology. The hypercalcemia is attributed to PTHrP, and here we demonstrate this in the serum and tumor specimens. The effects of PTHrP are shown to be short-lived postoperatively. We find only 14 other cases in the literature of hypercalcemia related to a colonic neoplasm, and this is the only patient reported to be surviving. The diagnosis of a paraneoplastic syndrome mediated via PTHrP should be considered when hypercalcemia is encountered in the setting of metastatic colon carcinoma.

Aged↗

Chest wall metastasis from recurrent meningioma.

Meningiomas are generally considered benign lesions. A minority, however, are capable of metastasis. The ones most likely to do so are commonly recurrent or frankly malignant in nature. The optimal management of such metastases is unclear. This is the first reported case of meningioma presenting as an isolated metastasis to the chest wall. This case involves a 64-year-old woman without significant medical or family history who underwent resection of a meningioma of the right cerebral hemisphere. She was treated 10 years later for recurrence by stereotactic radiosurgery. Three years after that, the patient's family noticed a mass on the left chest wall. A CT scan revealed destruction of the ninth rib laterally and subpleural extension. The patient subsequently underwent resection of full-thickness chest wall for a presumed soft-tissue sarcoma. Further pathologic evaluation including electron microscopy and immunohistochemistry revealed metastatic meningioma. The patient received adjuvant radiation to the chest wall and is currently free of disease at the chest wall one year after surgery. This case illustrates the difficulty in establishing an accurate diagnosis of metastatic meningioma. Consequently in selected patients with a history of the disease the diagnosis of metastatic meningioma must at least be considered. Resection of an isolated metastasis in this setting appears warranted.

Bone Neoplasms↗

Prospective trial for the treatment of malignant peritoneal mesothelioma.

Malignant peritoneal mesothelioma (MPM) is a rare and often rapidly fatal disease with median survival of 5 to 12 months for untreated cases and 16 months reported after multimodality treatment. We report a prospective clinical treatment study using cytoreductive surgery combined with intraoperative intraperitoneal heated chemotherapy (IPHC) perfusion using mitomycin C for MPM. Twelve patients (11 male with a mean age 51 years) were treated. Seven patients presented with bulky disease and seven with ascites. All underwent exploratory laparotomy with histologically confirmed diagnosis of MPM. Surgical debulking as feasible was performed. Complete gross tumor removal was possible in only one patient. Cytoreduction was followed by a 2-hour closed low-volume IPHC using mitomycin C. One patient died 50 days postoperatively from complications relating to small bowel perforation. Hematologic toxicity of the procedure was minimal. Ascites was controlled in all patients and permanently in 86 per cent of patients presenting with ascites. To date median survival is 34.2 months with median follow-up of 45.2 months. One patient was re-explored for ventral hernia 2 years post-IPHC, had negative peritoneal biopsies, and remains disease-free at 5 years. Given the dismal prognosis associated with MPM the results of treatment with cytoreductive surgery combined with IPHC perfusion are encouraging. The rarity of MPM makes appropriately powered prospective randomized trials unlikely. Therefore, we now offer this approach off protocol; however, further study of this combined modality therapy is warranted.

Adult↗

A prospective study of seeding of the skin after core biopsy of the breast.

BACKGROUND: The number of core biopsies done for breast abnormalities is increasing. The risk of skin seeding resulting from core biopsy is unknown. METHODS: Consecutive patients diagnosed with breast cancer were studied. The skin and subcutaneous fat surrounding the site of core needle penetration were excised and studied by routine histologic staining. Findings were correlated with other clinical variables. RESULTS: Eighty-nine consecutive patients were studied. Thirty-one had stereotactic core biopsies, 23 had vacuum-assisted biopsy, 8 had multiple-puncture biopsy, and 58 had ultrasound-guided core biopsy. Two patients who were biopsied using multiple-puncture biopsy were found to have nests of cancer cells in the dermis. One of these patients had recurrence in the skin biopsy site at 34 months. CONCLUSION: Skin seeding may be important in light of increasing use of image-directed biopsy, and particularly for cases in which the biopsy puncture site is outside the index quadrant and in which no radiation is anticipated.

Adenocarcinoma↗

Radiation-induced gastrointestinal stromal sarcoma of the esophagus.

Esophageal sarcoma is an uncommon tumor, sporadically reported in the literature. Radiation therapy is frequently employed in the treatment of carcinoma of the esophagus, and the increased risk of development of sarcoma arising in irradiated fields is well known. However, to our knowledge, the occurrence of radiation-associated sarcoma of the esophagus after radiation therapy for carcinoma of the esophagus has not been reported. We therefore report the case of a 43-year-old female who developed a gastrointestinal stroma sarcoma 9 years following radiation therapy for esophageal squamous cell carcinoma. The patient underwent resection of her gastrointestinal stromal sarcoma by transhiatal esophagectomy with cervical anastomosis and is doing well 18 months later. The increasing use of radiation therapy for esophageal carcinoma suggests that radiation-associated sarcoma of the esophagus may be seen more frequently in the future.

Adult↗

Sentinel lymph node mapping for carcinoma of the colon: a pilot study.

Sentinel lymph node (SLN) mapping has evolved into the standard of care for melanoma and may replace routine node dissection in the treatment of breast cancer. There are few data evaluating sentinel node mapping in patients with cancer of the colon. This trial represents our initial experience with SLN mapping for carcinoma of the colon. SLN mapping was performed in 22 patients most of whom had biopsy-proven adenocarcinoma of the colon. One milliliter of isosulfan blue was injected with a 25-gauge needle into the subserosa at four sites around the edge of the palpable tumor. The SLN was identified visually and excised. A standard lymphadenectomy was then performed. The SLN was analyzed with standard hematoxylin and eosin evaluation. Immunohistochemical techniques for carcinoembryonic antigen and cytokeratin (Imm) were performed if the H&E was negative. The mapping added approximately 5 minutes to the total operative time and no adverse reactions to the dye occurred. A SLN was identified in 20 of 22 cases. In cases with negative lymph nodes the SLN was predictive of all the regional nodes by both H&E and Imm (14 of 14). In patients with positive lymph nodes the SLN was predictive in all cases (six of six). In one case the only node with disease was the SLN, and in this case the diease was identified by only Imm; thus this patient was upstaged. SLN mapping is feasible and safe and can readily be performed in patients with colonic cancer. In conjunction with SLN mapping, Imm techniques may upstage a subset of patients likely to be at increased risk for metastatic disease. Consequently SLN mapping of colon cancer should be evaluated in large prospective trials.

Adenocarcinoma↗

Influence of erythropoietin on transfusion requirements in patients receiving preoperative chemoradiotherapy for rectal cancer.

PURPOSE: Perioperative homologous blood transfusion has been suggested to have an adverse effect on survival in patients undergoing resection of colorectal cancers. Preoperative therapy is being increasingly used for rectal cancer patients and has an adverse effect on erythropoietic capacity. The objectives of this study were to evaluate the feasibility and safety of administration of recombinant human erythropoietin to patients receiving preoperative therapy for rectal cancer and to assess the impact of such treatment on blood transfusion requirements. METHODS: The study was an open-label, Phase I and II, nonrandomized, two-center trial. All patients received 50.4 Gy of irradiation with 5-fluorouracil infusions. Ten patients diagnosed with rectal cancer received 250 U/kg of recombinant human erythropoietin subcutaneously three times per week during preoperative radiation and chemotherapy. Oral iron was given to patients receiving erythropoietin. Ten contemporaneously treated patients who received both radiation and chemotherapy were used as controls. RESULTS: Of the 20 patients 13 were males; mean age was 64 years. Surgical procedures that patients underwent were abdominoperineal resection (14 patients), low anterior resection (4 patients), coloanal anastomosis (1 patient), or none (1 patient). There were no significant differences between groups in age, gender, stage or hemoglobin levels before therapy. No adverse reactions to erythropoietin were encountered. Hemoglobin levels were significantly higher in the treatment group during Weeks 1, 3, and 5 (P < 0.02 for each). Transfusion requirements were significantly decreased in patients who received erythropoietin (0.4 vs. 3.7 units; P < 0.0003). CONCLUSIONS: The data showed that use of erythropoietin during preoperative therapy can prevent the decline in hemoglobin that commonly occurs during therapy. Further, this was not associated with adverse events and significantly decreased the need for perioperative blood transfusions. This suggests that the use of erythropoietin in support of a preoperative chemoradiotherapy regimen for patients with rectal cancer is safe and should be considered. Whether such transfusion avoidance will translate into a survival benefit in this setting will require a large, prospective, clinical trial.

Adult↗

Intraoperative gamma detection of 125I-lanreotide in women with primary breast cancer.

BACKGROUND: Somatostatin receptors are present in most human breast cancers. We performed a pilot trial of intraoperative tumor-gamma detection using the radiolabeled somatostatin analog 125I-lanreotide in 13 women with 14 primary breast carcinomas. METHODS: All patients were given 125I-lanreotide intravenously before surgery. Patients underwent lumpectomy, and postresection margins were evaluated with the gamma probe. Axillary dissection specimens were evaluated ex vivo. RESULTS: Seven of 13 women had gamma probe-positive or clinically suspicious margins re-excised at the time of lumpectomy. Four of six probe-positive margins were histologically positive, and two of six probe-positive margins were histologically negative; a single clinically suspicious margin was histologically positive. A total of 270 axillary lymph nodes were evaluated ex vivo by gamma probe and histology. McNemar's contingency tests demonstrated a highly statistical correlation between histology and gamma probe counts (P < .0001). CONCLUSIONS: The overall accuracy of nodal evaluation with 125I-lanreotide/intraoperative gamma detection was 77%; the negative predictive value of this technique was 97%, however. This technique predicted the presence of tumor in 20% of axillary lymph nodes that were negative by routine histology. This technique appears safe and is able to detect positive tumor resection margins and accurately predict axillary lymph node negativity. Further trials of this technique are required to validate its utility.

Aged↗

Current role of scapulectomy.

Tumors of the scapula are an unusual clinical challenge. Partial or complete resection of the scapula, with its attached musculoaponeurotic tissue, is a seldom used technique for the treatment of primary bone and soft tissue tumors, as well as selected metastatic involvement of the scapula. Scapulectomy may allow wide margins of resection without amputation. The purpose of this study is to review our recent experience with scapulectomy. This study describes the recent experience with scapulectomy by the Section of Surgical Oncology and the Department of Orthopedics at Louisiana State Medical Center (New Orleans, LA). Between 1994 and 1998, 12 patients (between 16 and 79 years of age) underwent a resection of the scapula. Eleven of these patients had soft tissue tumors; one had a metastasis from a thyroid carcinoma. Six of these patients underwent a scapulectomy as a primary treatment, five for recurrence. Six patients also received postoperative radiation and/or chemotherapy. The follow-up ranged from 6 months to 4 years. There was no mortality or wound infection associated with scapulectomy. All patients had normal hand and wrist function after surgery. Three distant recurrences occurred, with no local or regional failures encountered during the follow-up period. Scapulectomy can result in excellent local tumor control. Whereas some loss of active shoulder motion may occur, hand, wrist and elbow function is preserved. Although maintenance of shoulder function should not take precedence over adequacy of resection, scapulectomy remains an excellent procedure for malignant disease that preserves hand, wrist, and elbow function.

Adolescent↗

A 60 kd MDM2 isoform is produced by caspase cleavage in non-apoptotic tumor cells.

The MDM2 oncogene product is a regulator of the p53 tumor suppressor. MDM2 is cleaved by Caspase 3 (CPP32) during apoptosis after aspartic acid-361, generating a 60 kd fragment. Here we report that human tumor cell lines often express high levels of a 60 kd MDM2 isoform (p60) in the absence of apoptosis. We demonstrate that p60 is a product of caspase cleavage of full length MDM2 after residue 361. The protease that cleaves MDM2 in non-apoptotic cells appears to be distinct from the apoptosis-specific Caspase 3, since Caspase 3 substrate poly(ADP-ribose) polymerase (PARP) is not cleaved in cells producing p60. The p60 form of MDM2 is a significant fraction of the p53-bound MDM2 protein in certain tumor cells, suggesting that it functions in the regulation of p53. p60 is also detected in breast tumors overexpressing MDM2. These observations suggest that MDM2 is regulated by caspase processing in non-apoptotic cells, and may account for the MDM2 proteins of similar mobility seen in tumors and other cell lines.

Amino Acid Sequence↗

Altered composition and increased endothelial cell proliferative activity of proteoglycans isolated from breast carcinoma.

BACKGROUND AND OBJECTIVES: Proteoglycans of the extracellular matrix are vital to the growth and evolution of malignant neoplasms. The present study determined the composition of proteoglycans isolated from paired specimens of normal breast and adenocarcinoma of the breast harvested from each patient (n = 8). The proteoglycans were then tested for their ability to stimulate endothelial cell proliferation. METHODS: Proteoglycans were isolated by extraction with 4 M guanidine hydrochloride and purified by CsCl density-gradient centrifugation. The proteoglycans were characterized and tested for their ability to simulate endothelial cell proliferation. RESULTS: In each case, the total proteoglycan content of the tumor was significantly greater than that of the corresponding normal tissue. The proteoglycans isolated from the carcinoma contained 32.2% (13.7/42.5) more chondroitin sulfate, 18.5% (5.6/30.2) less dermatan sulfate, and 29.6% (8.1/27.3) less heparan sulfate than did the proteoglycans of normal breast tissue. Proteoglycans from normal tissue did not stimulate endothelial cell proliferation, whereas those from malignant tissue stimulated proliferation by 1.3- to 1.5-fold. CONCLUSIONS: These results indicate that malignant breast tissue exhibits both qualitative and quantitative changes in proteoglycan composition, which, in turn, may stimulate endothelial cell proliferation.

Adenocarcinoma↗

Initial clinical experience with colonic stent placement.

BACKGROUND: The purpose of this study is to review initial experience with a colonic stent as an alternative to colostomy in patients with colonic obstruction. METHODS: Ten patients diagnosed with acute colonic obstructions from both benign and malignant causes underwent stent placement. Self-expandable metallic stents were deployed using fluoroscopic guidance. Patients were followed up clinically until removal of the stent or death. RESULTS: Nine of the 10 patients who underwent colonic stent placement achieved clinical decompression within 6 hours. Six patients underwent standard mechanical bowel preparation and elective resection of obstructing lesions. The other 4 patients received stent placement for palliative purposes. Complications included 4 cases of migration and 1 death. Migrated stents in the rectum were easily retrieved and replaced using fluoroscopic techniques. There were no perforations. CONCLUSION: Placement of self-expandable metallic stents for acute colonic obstructions may allow patients to undergo elective surgical resection avoiding possible colostomy.

Acute Disease↗