26 results on '"Bilimoria MM"'
Search Results
2. Irreversible loss of the oestrogen receptor in T47D breast cancer cells following prolonged oestrogen deprivation
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Pink, JJ, primary, Bilimoria, MM, additional, Assikis, J, additional, and Jordan, VC, additional
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- 1996
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3. Coil embolization of a lumbar artery to control vascular injury during intradiscal surgery.
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Karaikovic EE, Rattner Z, Bilimoria MM, Sener SF, McGee JP, Metrick LB, Szokol JW, Limthongkul W, Karaikovic, Eldin E, Rattner, Zachary, Bilimoria, Malcolm M, Sener, Stephen F, McGee, John P, Metrick, Lawrence B, Szokol, Joseph W, and Limthongkul, Worawat
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- 2010
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4. Effectiveness and Safety of Irreversible Electroporation When Used for the Ablation of Stage 3 Pancreatic Adenocarcinoma: Initial Results from the DIRECT Registry Study.
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Martin RCG 2nd, White RR, Bilimoria MM, Kluger MD, Iannitti DA, Polanco PM, Hammil CW, Cleary SP, Heithaus RE, Welling T, and Chan CHF
- Abstract
Background/objectives: Overall survival for patients with Stage 3 pancreatic ductal adenocarcinoma (PDAC) remains limited, with a median survival of 12 to 15 months. Irreversible electroporation (IRE) is a local tumor ablation method that induces cancerous cell death by disrupting cell membrane homeostasis. The DIRECT Registry study was designed to assess the effectiveness and safety of IRE when combined with standard of care (SOC) treatment for Stage 3 PDAC versus SOC alone in a real-world setting after at least 3 months of induction chemotherapy; Methods: Patients with Stage 3 PDAC treated with IRE plus SOC or SOC alone were prospectively enrolled in a multicenter registry study. Enrollment required 3 months of active multi-agent chemotherapy with no progression before enrollment. Endpoints were 30- and 90-day mortality and adverse events (AEs)., Results: Eighty-seven IRE and 27 SOC subjects were enrolled in the registry. Mean ages were 64.0 ± 8.4 and 66.4 ± 9.9 years, and mean anterior/posterior tumor diameters were 2.2 ± 0.7 cm and 3.2 ± 1.3 for the IRE and SOC groups respectively ( p = 0.0066). All IRE procedures were performed using an open approach. The 90-day all-cause mortality was 5/83 (6.0%) and 2/27 (7.4%) for the IRE and SOC groups, respectively. Two subjects in the IRE group died from treatment-related complications, and one patient in the SOC group died due to chemotherapy-related complications., Conclusions: Initial results from the DIRECT registry study indicate the use of IRE for curative intent tumor ablation in combination with induction chemotherapy has equivalent morbidity and mortality rates when compared to standard-of-care chemotherapy alone.
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- 2024
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5. Multicenter randomized controlled trial and registry study to assess the safety and efficacy of the NanoKnife® system for the ablation of stage 3 pancreatic adenocarcinoma: overview of study protocols.
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Narayanan G, Bilimoria MM, Hosein PJ, Su Z, Mortimer KM, and Martin RCG 2nd
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- Adenocarcinoma mortality, Adenocarcinoma pathology, Humans, Pancreatic Neoplasms mortality, Pancreatic Neoplasms pathology, Quality of Life, Randomized Controlled Trials as Topic, Registries, Survival Analysis, Treatment Outcome, Ablation Techniques methods, Adenocarcinoma surgery, Pancreatic Neoplasms surgery
- Abstract
Background: Irreversible electroporation (IRE) is a local ablation technique utilizing high voltage, low energy direct current to create nanopores in cell membrane which disrupt homeostasis and leads to cell death. Previous reports have suggested IRE may have a role in treating borderline resectable and unresectable Stage 3 pancreatic tumors., Methods: Patients with Stage 3 pancreatic ductal adenocarcinoma (PDAC) will be enrolled in either a randomized, controlled, multicenter trial (RCT) or a multicenter registry study. Subjects enrolled in the RCT must have no evidence of disease progression after 3 months of modified FOLFIRINOX (mFOLFIRINOX) treatment prior to being randomization to either a control or IRE arm. Post-induction and post-IRE treatment for the control and IRE arms, respectively, will be left to the discretion of the treating physician. The RCT will enroll 528 subjects with 264 per arm and include up to 15 sites. All subjects will be followed for at least 24 months or until death. The registry study will include two cohorts of patients with Stage 3 PDAC, patients who received institutional standard of care (SOC) alone and those treated with IRE in addition to SOC. Both cohorts will be required to have undergone at least 3 months of SOC without progression prior to enrollment. The registry study will enroll 532 patients with 266 patients in each arm. All patients will be followed for at least 24 months or until death. The primary efficacy endpoint for both studies will be overall survival (OS). Co-primary safety endpoints will be 1) time from randomization or enrollment in the registry to death or new onset of Grade 4 adverse event (AE), and (2 high-grade complications defined as any AE or serious AE (SAE) with a CTCAE v5.0 grade of 3 or higher. Secondary endpoints will include progression-free survival, cancer-related pain, quality of life, and procedure-related pain for the IRE arm only., Discussion: These studies are intended to provide Level 1 clinical evidence and real-world data demonstrating the clinical utility and safety of the use of IRE in combination with chemotherapy in patients with Stage 3 PDAC., Trial Registration: Clinicaltrials.gov NCT03899636 and NCT03899649. Registered April 2, 2019. Food and Drug Administration (FDA) Investigational Device Exemption (IDE) trial G180278 approved on May 3, 2019.
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- 2021
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6. Effect of hospital volume on margin status after pancreaticoduodenectomy for cancer.
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Bilimoria KY, Talamonti MS, Sener SF, Bilimoria MM, Stewart AK, Winchester DP, Ko CY, and Bentrem DJ
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- Adenocarcinoma pathology, Aged, Female, Humans, Male, Middle Aged, Pancreatic Neoplasms pathology, Adenocarcinoma surgery, Hospitals statistics & numerical data, Pancreatic Neoplasms surgery, Pancreaticoduodenectomy statistics & numerical data
- Abstract
Background: The volume-outcome relationship has been repeatedly demonstrated for pancreatectomy, but identifying underlying reasons for this association has been challenging. Some have suggested that differences in surgical technique may affect longterm survival, but it is unknown whether margin-positive resection rates vary by hospital volume. Our objective was to evaluate the effect of hospital pancreatectomy volume on margin status., Study Design: Patients who underwent pancreaticoduodenectomy for localized pancreatic adenocarcinoma were identified from the National Cancer Data Base (1998 to 2004). Regression modeling adjusting for patient, tumor, and hospital factors was used to assess predictors of margin involvement and to evaluate the effect of margin status on survival. Volume quintiles were based on average annual hospital pancreatectomy volume., Results: Of 12,101 patients, 24.4% had positive resection margins (14.6% microscopic/R1; 9.8% macroscopic/R2). From 1998 to 2004, there was not a significant change in margin-positive resection rates (p=0.43). On multivariable analysis, patients were more likely to have a margin-positive resection if they had a higher T classification or nodal involvement, were uninsured or living in lower-income areas, or underwent resection at lowest-volume hospitals compared with highest-volume hospitals (25.9% versus 22.6%, p < 0.0001; odds ratio, 1.21; 95% confidence interval, 1.01 to 1.43). On multivariable analysis, margin involvement was associated with a higher risk of longterm mortality compared with margin-negative resections (p < 0.0001)., Conclusions: Involved resection margins are a poor prognostic factor after a pancreaticoduodenectomy. Patients undergoing pancreaticoduodenectomy at low-volume centers are more likely to have margin-positive resections. Standardization of pathologic evaluation for pancreatectomy specimens is needed.
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- 2008
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7. Axillary recurrence after sentinel node biopsy.
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Jeruss JS, Winchester DJ, Sener SF, Brinkmann EM, Bilimoria MM, Barrera E Jr, Alwawi E, Nickolov A, Schermerhorn GM, and Winchester DJ
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- Axilla, Databases, Factual, Female, Humans, Lymphatic Metastasis diagnostic imaging, Middle Aged, Prognosis, Prospective Studies, Radionuclide Imaging, Sensitivity and Specificity, Breast Neoplasms pathology, Lymphatic Metastasis pathology, Neoplasm Staging methods, Sentinel Lymph Node Biopsy
- Abstract
Background: Sentinel node biopsy (SNB) has evolved as the standard of care in the surgical staging of breast cancer. This technique is accurate for surgical staging of axillary nodal disease. We hypothesized that axillary recurrence after SNB is rare and that SNB may provide regional control in patients with microscopic nodal involvement., Methods: With institutional review board approval, SNB was performed with peritumoral injection of 99mTc-labeled sulfur colloid. From 1996 to 2003, 1167 patients were entered into a prospective cancer database after surgical therapy; 916 patients consented to long-term follow-up. Fifty-two patients (5.7%) did not map successfully and were excluded, leading to a study population of 864 patients. The median follow-up was 27.4 months (range, 1-98 months)., Results: The median number of sentinel nodes harvested was 2, and 633 (73%) patients had negative sentinel nodes. Thirty (4.7%) of those sentinel node-negative patients underwent completion axillary dissection, whereas 592 (94%) patients were followed up with observation. A total of 231 (27%) had positive sentinel nodes: 158 (68%) of these patients underwent completion axillary dissection, and 73 (32%) were managed with observation alone. Two (.32%) patients who were sentinel node negative had an axillary recurrence; one of these patients had undergone completion axillary dissection. No patient in the observed sentinel node-positive group had an axillary recurrence (odds ratio, .37; P = .725)., Conclusions: On the basis of a median follow-up of 27.4 months, axillary recurrence after SNB is extraordinarily rare regardless of nodal involvement, thus indicating that this technique provides an accurate measure of axillary disease and may impart regional control for patients with node-positive disease.
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- 2005
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8. Pancreatic leak after left pancreatectomy is reduced following main pancreatic duct ligation.
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Bilimoria MM, Cormier JN, Mun Y, Lee JE, Evans DB, and Pisters PW
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- Adenocarcinoma surgery, Adolescent, Adult, Aged, Aged, 80 and over, Carcinoma, Renal Cell surgery, Child, Child, Preschool, Female, Humans, Ligation, Lymph, Male, Middle Aged, Pancreatectomy adverse effects, Pancreatic Neoplasms surgery, Prospective Studies, Retroperitoneal Neoplasms surgery, Retrospective Studies, Sarcoma surgery, Stomach Neoplasms surgery, Pancreatectomy methods, Pancreatic Ducts surgery, Postoperative Complications prevention & control
- Abstract
Background: Although much is known about the long-term outcome of patients undergoing left (distal) pancreatectomy for malignancy, comparatively little is known about the optimal management strategy for the residual transected pancreatic parenchyma and the divided pancreatic duct. Clinicopathological and operative factors that may contribute to postoperative pancreatic leak were evaluated., Methods: A retrospective review of the medical records of 126 patients who underwent left pancreatectomy between June 1990 and December 1999 at the University of Texas M. D. Anderson Cancer Center was performed., Results: Indications for left pancreatectomy included pancreatic neoplasms (n = 42; 33.3 per cent), en bloc resection for management of retroperitoneal sarcoma (n = 21; 16.7 per cent), gastric adenocarcinoma (n = 14; 11.1 per cent), renal cell carcinoma (n = 11; 8.7 per cent) and other tumours or benign conditions (n = 38; 30.2 per cent). Pancreatic parenchymal closure was accomplished by a hand-sewn technique, mechanical stapling, or a combination of the two in 83, 20 and 15 patients respectively. No form of parenchymal closure was used in eight patients. Identification of the pancreatic duct and suture ligation was performed in 73 patients (57.9 per cent). Twenty-five patients (19.8 per cent) developed a pancreatic leak. For subgroups having duct ligation or no duct ligation, pancreatic leak rates were 9.6 per cent (seven of 73 patients) and 34.0 per cent (18 of 53 patients) respectively (P < 0.001). Multivariate analysis including clinicopathological and operative factors indicated that failure to ligate the pancreatic duct was the only feature associated with an increased risk for pancreatic leak (odds ratio 5.0 (95 per cent confidence interval 2.0 to 10.0); P = 0.001)., Conclusion: Pancreatic leak remains a common complication after left pancreatectomy. The incidence of leak is reduced significantly when the pancreatic duct is identified and directly ligated during left pancreatectomy.
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- 2003
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9. Tumor volume as a prognostic factor for sarcomatosis.
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Bilimoria MM, Holtz DJ, Mirza NQ, Feig BW, Pisters PW, Patel S, Pollock RE, Benjamin RS, Papadopoulos NE, Plager C, Murphy A, Griffin JR, Burgess MA, and Hunt KK
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- Adult, Aged, Female, Gastrointestinal Neoplasms pathology, Humans, Male, Middle Aged, Prognosis, Retrospective Studies, Sarcoma therapy, Soft Tissue Neoplasms therapy, Survival Rate, Tomography, X-Ray Computed, Sarcoma mortality, Sarcoma pathology, Soft Tissue Neoplasms mortality, Soft Tissue Neoplasms pathology
- Abstract
Background: The appropriate therapeutic interventions for sarcomatosis, or sarcoma characterized by intraabdominal dissemination, remain unclear. The authors performed a retrospective analysis of their recent experience with patients diagnosed with sarcomatosis to determine the overall survival and the effects of clinicopathologic features on survival rates at two and four years., Methods: A query of the authors' prospective soft tissue sarcoma database identified 51 patients with a diagnosis of sarcomatosis who were evaluated at the authors' institution between June 1996 and June 1999. Clinical and pathologic factors were evaluated, and survival was calculated using a Kaplan-Meier survival analysis. Disease was categorized as low or high volume based on findings at surgical exploration or computed tomography scan evaluation. Disease was classified as low/intermediate grade or high grade based upon histologic examination., Results: Twenty five patients were male and 26 were female. The median time from the initial diagnosis of sarcoma to the development of sarcomatosis was 0.9 years (range, 0-26 years). Thirty nine patients were treated with surgery, whereas 32 received primarily nonsurgical treatment. Histology revealed gastrointestinal stromal tumor (GIST) in 33 patients and other histologies in 18 patients. The two year overall survival rate of patients with GIST was similar to that of patients with other types of sarcoma (38% versus 42%, respectively, P = 0.77). Patients with low volume disease had an overall two year survival rate of 82%, compared with only 24% for patients with high volume disease (P = 0.008). There was no difference in the overall survival rates of patients with low grade (n = 18) versus high grade tumors (n = 33, P = 0.29). With a median followup of 2.7 years (range, 0.5-26.4 years), the median time from sarcomatosis to death was 13 months (range, 4-42 months)., Conclusions: Evaluating volume of disease at the time of diagnosis permits stratification of patients into prognosis based subsets. We found no significant difference in two or four year survival rates in patients with GIST and those with non-GIST sarcomatosis., (Copyright 2002 American Cancer Society.DOI 10.1002/cncr.10504)
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- 2002
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10. Prophylactic surgery in hereditary cancer syndromes: an ounce of prevention may be the only cure.
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Bilimoria MM
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- Breast Neoplasms genetics, Colorectal Neoplasms, Hereditary Nonpolyposis prevention & control, Colorectal Neoplasms, Hereditary Nonpolyposis surgery, Genes, BRCA1, Genes, BRCA2, Humans, Multiple Endocrine Neoplasia genetics, Neoplastic Syndromes, Hereditary genetics, Risk, Neoplastic Syndromes, Hereditary prevention & control, Neoplastic Syndromes, Hereditary surgery
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- 2002
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11. Hepatitis B or C virus serology as a prognostic factor in patients with hepatocellular carcinoma.
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Ahmad SA, Bilimoria MM, Wang X, Izzo F, Delrio P, Marra P, Baker TP, Porter GA, Ellis LM, Vauthey JN, Dhamotharan S, and Curley SA
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- Carcinoma, Hepatocellular complications, Carcinoma, Hepatocellular surgery, Case-Control Studies, Disease-Free Survival, Female, Follow-Up Studies, Humans, Liver Neoplasms complications, Liver Neoplasms surgery, Male, Middle Aged, Neoplasm Recurrence, Local epidemiology, Prognosis, Retrospective Studies, Survival Analysis, Time Factors, Carcinoma, Hepatocellular mortality, Hepatitis B, Chronic complications, Hepatitis C, Chronic complications, Liver Neoplasms mortality
- Abstract
It is not clear whether chronic hepatitis B or C virus (HBV or HCV) infection is a prognostic factor for hepatocellular carcinoma. We performed this study to determine if chronic HBV or HCV infection had any impact on postresection survival or affected patterns of failure. The records of 77 patients undergoing surgical resection for hepatocellular carcinoma between January 1990 and December 1998 were reviewed. Forty-four patients (57%) had HCV infection, 18 patients (23%) had HBV infection, and 15 patients (20%) had negative serology. There were no differences in age, sex, or tumor size among the groups, and all patients had margin-negative resections. There was a significantly higher incidence of satellitosis and vascular invasion in patients with HCV infection (32% and 41% respectively; P <0.05 vs. other groups). With a median follow-up of 30 months, a significantly decreased local disease-free survival (LDFS) was seen in HBV-positive (5-year LDFS 26%) or HCV-positive (5-year LDFS 38%) patients compared to those with negative serology (5-year LDFS 79%; P <0.05). There was also a trend toward a decreased overall survival in patients with positive hepatitis serology compared to patients with negative serology (37% vs. 79%; P = 0.12). Univariate analysis revealed that only satellitosis was related to local recurrence and overall survival. Patients with positive serology for hepatitis B or C undergoing resection for hepatocellular carcinoma have a trend toward worse overall prognosis and a significantly decreased LDFS when compared to patients with negative serology.
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- 2001
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12. Pancreaticoduodenectomy in a patient with ampullary carcinoma and situs inversus.
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Bilimoria MM, Parsons WG, Small W Jr, and Talamonti MS
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- Adult, Cholangiopancreatography, Endoscopic Retrograde, Female, Humans, Situs Inversus diagnostic imaging, Tomography, X-Ray Computed, Ampulla of Vater, Carcinoma complications, Carcinoma surgery, Common Bile Duct Neoplasms complications, Common Bile Duct Neoplasms surgery, Pancreaticoduodenectomy, Situs Inversus complications, Situs Inversus surgery
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- 2001
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13. Underlying liver disease, not tumor factors, predicts long-term survival after resection of hepatocellular carcinoma.
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Bilimoria MM, Lauwers GY, Doherty DA, Nagorney DM, Belghiti J, Do KA, Regimbeau JM, Ellis LM, Curley SA, Ikai I, Yamaoka Y, and Vauthey JN
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- Adult, Aged, Aged, 80 and over, Carcinoma, Hepatocellular surgery, Female, Hepatectomy, Humans, Liver Neoplasms surgery, Logistic Models, Male, Middle Aged, Proportional Hazards Models, Retrospective Studies, Carcinoma, Hepatocellular complications, Carcinoma, Hepatocellular mortality, Liver Cirrhosis complications, Liver Neoplasms complications, Liver Neoplasms mortality
- Abstract
Hypothesis: A subset of patients can be identified who will survive without recurrence beyond 5 years after hepatic resection for hepatocellular carcinoma (HCC)., Design: A retrospective review of a multi-institutional database of 591 patients who had undergone hepatic resection for HCC and on-site reviews of clinical records and pathology slides., Setting: All patients had been treated in academic referral centers within university-based hospitals., Patients: We identified 145 patients who had survived for 5 years or longer after hepatic resection for HCC., Main Outcome Measures: Clinical and pathologic factors, as well as scoring of hepatitis and fibrosis in the surrounding liver parenchyma, were assessed for possible association with survival beyond 5 years and cause of death among the 145 five-year survivors., Results: Median additional survival duration longer than 5 years was 4.1 years. Women had significantly longer median additional survival durations than did men (81 months vs 38 months, respectively, after the 5-year mark) (P =.008). Surgical margins, type of resection, an elevated preoperative alpha-fetoprotein level, and the presence of multiple tumors or microscopic vascular invasion had no bearing on survival longer than 5 years. However, patients who survived for 5 years who also had normal underlying liver or minimal fibrosis (score, 0-2) at surgery had significantly longer additional survival than did patients with moderate fibrosis (score, 3-4) or severe fibrosis/cirrhosis (score, 5-6) (P<.001)., Conclusions: Death caused by HCC is rare beyond 5 years after resection of HCC in the absence of fibrosis or cirrhosis. The data suggest that chronic liver disease acts as a field of cancerization contributing to new HCC. These patients may benefit from therapies directed at the underlying liver disease.
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- 2001
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14. Standardized measurement of the future liver remnant prior to extended liver resection: methodology and clinical associations.
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Vauthey JN, Chaoui A, Do KA, Bilimoria MM, Fenstermacher MJ, Charnsangavej C, Hicks M, Alsfasser G, Lauwers G, Hawkins IF, and Caridi J
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- Adult, Aged, Child, Female, Humans, Liver diagnostic imaging, Male, Middle Aged, Prospective Studies, Tomography, X-Ray Computed, Hepatectomy methods, Liver anatomy & histology
- Abstract
Background: There is no agreement regarding the preoperative measurement of liver volumes and the minimal safe size of the liver remnant after extended hepatectomy., Methods: In 20 patients with hepatobiliary malignancy and no underlying chronic liver disease, volumetric measurements of the liver remnant (segments 2 and 3 +/- 1) were obtained before extended right lobectomy (right trisegmentectomy). The ratios of future liver remnant to total liver volume were calculated by using a formula based on body surface area. In 12 patients, response to preoperative right trisectoral portal vein embolization was evaluated. In 15 patients who underwent the planned resection, preoperative volumes were correlated with biochemical and clinical outcome parameters., Results: The future liver remnants increased after portal vein embolization (26% versus 36%, P < .01). Smaller size liver remnants were associated with an increase in postoperative liver function tests (P < .05) and longer lengths of hospital stay (P < .02). Preliminary data indicates an increase in major complications for liver volumes < or = 25% (P = .02)., Conclusions: A simple method of measurement provides an assessment of the liver remnant before resection. It is useful in evaluating response to portal vein embolization and in predicating the outcome before extended liver resections.
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- 2000
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15. Postoperative liver failure.
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Bilimoria MM, Chaoui AS, and Vauthey JN
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- Hepatectomy methods, Humans, Risk Factors, Treatment Outcome, Carcinoma, Hepatocellular surgery, Hepatectomy adverse effects, Liver Failure, Acute etiology, Liver Neoplasms surgery
- Published
- 1999
16. Estrogen replacement therapy and breast cancer: analysis of age of onset and tumor characteristics.
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Bilimoria MM, Winchester DJ, Sener SF, Motykie G, Sehgal UL, and Winchester DP
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- Age of Onset, Aged, Breast Neoplasms pathology, Female, Humans, Middle Aged, Prospective Studies, Risk Factors, Breast Neoplasms epidemiology, Estrogen Replacement Therapy adverse effects
- Abstract
Background: The use of exogenous estrogen has been scrutinized as a risk factor for breast cancer formation. This prospective study addresses the relationship between the use of estrogen replacement therapy and the age of onset of breast cancer. In addition, an analysis of differences in pathological features of breast cancer between estrogen users and non-estrogen-users was evaluated., Methods: A total of 425 women (age, > or = 50 years) were evaluated during a 4-year period (1994-1997). Data, including the age at diagnosis, method of detection, family history, use of estrogen therapy, and tumor ploidy, S-phase fraction, histological category, estrogen receptor positivity, and grade, were prospectively collected. Data from a control group of 657 women without a diagnosis of breast cancer were obtained from the Evanston Northwestern division of the Women's Health Initiative. Significant associations between the use of estrogen and pathological parameters were determined using the chi2 test and t-test (P < .05)., Results: At the time of breast cancer diagnosis, 140 patients were currently receiving estrogen and 202 patients had no history of estrogen use. Eighty-three patients were excluded from analysis (76 patients had a history of previous but not current use of estrogen therapy, four women used only progesterone, and three patients provided incomplete information). There was no difference between patients with breast cancer using estrogen at the time of diagnosis and those with no history of estrogen use with respect to tumor size, age of menopause, family history, mammographic sensitivity, axillary lymph node status, and histological features. Women using estrogen at the time of diagnosis were younger at the time of breast cancer diagnosis, by an average of 5.1 years (61.3 years vs. 66.4 years, P < .001). Women without a history of breast cancer who were receiving estrogen therapy were an average of 2.4 years younger (63.3 years vs. 65.7 years, P < .001) than women without a history of breast cancer who were not receiving estrogen therapy. Patients with breast cancer receiving estrogen also tended to have more grade II tumors (45.9% vs. 36.5%, P = .045) and fewer grade III tumors (25.6% vs. 37.0%, P = .015), compared with women not receiving estrogen therapy at the time of their diagnoses. Estrogen receptor positivity was noted to be more frequent for estrogen users presenting with lobular carcinoma (85% vs. 76%, P = .042) and less frequent for estrogen users presenting with ductal carcinoma (72% vs. 85%, P = .003)., Conclusions: A significantly earlier age of diagnosis for women receiving estrogen therapy suggests that exogenous estrogen may accelerate the pathogenesis of postmenopausal breast cancer. Estrogen therapy may also play a role in altering the grade and estrogen receptor positivity for certain histological types of breast cancer.
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- 1999
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17. Effects of the antiestrogens tamoxifen, toremifene, and ICI 182,780 on endometrial cancer growth.
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O'Regan RM, Cisneros A, England GM, MacGregor JI, Muenzner HD, Assikis VJ, Bilimoria MM, Piette M, Dragan YP, Pitot HC, Chatterton R, and Jordan VC
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- Animals, Antineoplastic Agents, Hormonal adverse effects, Breast Neoplasms drug therapy, Disease Models, Animal, Estradiol adverse effects, Female, Fulvestrant, Mice, Mice, Nude, Ovariectomy, Endometrial Neoplasms chemically induced, Estradiol analogs & derivatives, Estrogen Antagonists adverse effects, Tamoxifen adverse effects, Toremifene adverse effects
- Abstract
Background: Tamoxifen has been shown to promote the growth of human endometrial tumors implanted in athymic mice, and it has been associated with a twofold to threefold increase in endometrial cancer. Toremifene, a chlorinated derivative of tamoxifen, and ICI 182,780, a pure antiestrogen, are two new antiestrogens being developed for the treatment of breast cancer. The effects of these drugs on endometrial cancer are currently unknown. Our objective was to evaluate the effects of toremifene and ICI 182,780 on the growth of human endometrial cancer in athymic mice., Methods: Athymic, ovariectomized mice were implanted with human endometrial tumors and treated with estrogen, tamoxifen, or the new antiestrogens., Results: The effects of tamoxifen and toremifene on the growth of either tamoxifen-stimulated or tamoxifen-naive endometrial tumors in athymic mice were not substantially different. ICI 182,780 inhibited the growth of tamoxifen-stimulated endometrial cancer, in both the presence and the absence of estrogen., Conclusions: Toremifene and tamoxifen produce identical effects in our endometrial cancer models. Therefore, it is possible that toremifene, like tamoxifen, may be associated with an increased incidence of endometrial cancer. In contrast, ICI 182,780 inhibited tamoxifen-stimulated endometrial cancer, both in the presence and in the absence of estrogen, suggesting that this drug may be safe with regard to the endometrium, even if it is used following tamoxifen, and that it may not result in an increased incidence of endometrial cancer. Indeed, it is even possible that ICI 182,780 may prove useful as an adjuvant agent in early stage endometrial cancer.
- Published
- 1998
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18. Characterization of a point mutation in the hormone binding domain of the estrogen receptor from an breast tumor.
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England GM, Bilimoria MM, Chen Z, Assikis VJ, Muenzner HD, and Jordan VC
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- Animals, Binding Sites, Cell Division drug effects, DNA Primers, Estradiol analogs & derivatives, Female, Fulvestrant, Glycine, Humans, Luciferases biosynthesis, Mice, Mice, Nude, Ovariectomy, Polymerase Chain Reaction, Polymorphism, Single-Stranded Conformational, Receptors, Estrogen biosynthesis, Receptors, Estrogen chemistry, Tamoxifen analogs & derivatives, Tamoxifen pharmacology, Transfection, Transplantation, Heterologous, Tumor Cells, Cultured, Valine, Breast Neoplasms genetics, Breast Neoplasms pathology, Estradiol pharmacology, Estrogen Antagonists pharmacology, Point Mutation, Receptors, Estrogen genetics, Transcription, Genetic drug effects
- Abstract
It is clear that growth of the MCF-7 breast cancer cell line is stimulated by estrogen and when estrogen is removed, growth slows. We have observed a tumor derived from MCF-7 cells that grows in athymic mice in the absence of estrogen stimulation. We hypothesized that a mutation in the estrogen receptor (ER) could be responsible for this constitutive growth. Using single stranded conformational polymorphism (SSCP) and DNA sequencing analysis, we have identified an ER containing a point mutation at position 415 (gly to val) within the hormone binding domain. The functional activity of this mutant was assessed in vitro and in vivo. Using transient transfection into an ER negative breast cancer cell with an ERE luciferase reporter gene, we found that both the wild-type and mutant receptors have similar efficacy. Additionally, the estrogenic responses were blocked by antiestrogens in a concentration related manner. We also found that tumors with the mutant receptor show similar growth response in athymic mice as wild-type: stimulation with estradiol and inhibition with antiestrogens. We conclude that the point mutation at position 415 (gly to val) is not responsible for constitutive growth.
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- 1998
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19. The duration of adjuvant tamoxifen therapy.
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Bilimoria MM and Jordan VC
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- Actuarial Analysis, Adult, Aged, Animals, Antineoplastic Agents, Hormonal adverse effects, Antineoplastic Agents, Hormonal therapeutic use, Breast Neoplasms chemically induced, Breast Neoplasms mortality, Breast Neoplasms therapy, Cardiovascular Diseases prevention & control, Chemotherapy, Adjuvant, Clinical Trials as Topic, Combined Modality Therapy, Disease-Free Survival, Drug Administration Schedule, Endometrial Neoplasms chemically induced, Estrogen Antagonists adverse effects, Estrogen Antagonists therapeutic use, Female, Humans, Menopause, Mice, Mice, Nude, Middle Aged, Neoplasm Recurrence, Local prevention & control, Neoplasms, Hormone-Dependent chemically induced, Neoplasms, Hormone-Dependent mortality, Neoplasms, Hormone-Dependent therapy, Neoplasms, Second Primary chemically induced, Randomized Controlled Trials as Topic, Research Design, Survival Analysis, Survival Rate, Tamoxifen adverse effects, Tamoxifen therapeutic use, Time Factors, Antineoplastic Agents, Hormonal administration & dosage, Breast Neoplasms drug therapy, Estrogen Antagonists administration & dosage, Estrogens, Neoplasms, Hormone-Dependent drug therapy, Tamoxifen administration & dosage
- Published
- 1998
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20. Mutations of the estrogen receptor in endometrial carcinoma: evidence of an association with high tumor grade.
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Assikis VJ, Bilimoria MM, Muenzner HD, Lurain JR, and Jordan VC
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- DNA Mutational Analysis, DNA, Complementary genetics, DNA, Neoplasm genetics, Endometrial Neoplasms chemistry, Female, Humans, Middle Aged, Polymorphism, Single-Stranded Conformational, Endometrial Neoplasms genetics, Endometrial Neoplasms pathology, Point Mutation, Receptors, Estrogen genetics
- Abstract
The majority (60-70%) of endometrial cancers express estrogen receptor. Typically, estrogen-receptor-positive endometrial tumors are associated with a more favorable outcome. Despite this, there is often a discrepancy between estrogen receptor expression and clinical outcome of the disease. Although little is known about the exact role of the estrogen receptor in endometrial malignancies, in breast cancer, where such information is abundant, a number of mutations of the estrogen receptor have been identified. To investigate whether mutations of the estrogen receptor gene occur in endometrial cancers we performed single-stranded conformational polymorphism analysis (SSCP) on 35 human endometrial tumors. We detected four point mutations in three different patients. Interestingly, all the mutations were detected in patients who had aggressive endometrial tumors (grade 3). Although we found the incidence of mutations of the estrogen receptor to be low (8.5%) and thus unlikely to be associated with the majority of endometrial cancers, further investigation is needed to elucidate the role of aberrant estrogen receptor expression in the progression of endometrial malignancies.
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- 1996
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21. Is it time to develop an optimal endocrine therapy for premenopausal patients with axillary node positive and negative breast cancer?
- Author
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Bilimoria MM and Jordan VC
- Subjects
- Bone Density drug effects, Breast Neoplasms mortality, Breast Neoplasms pathology, Chemotherapy, Adjuvant, Female, Humans, Lipids blood, Lymphatic Metastasis, Neoplasm Staging, Randomized Controlled Trials as Topic methods, Survival Analysis, Antineoplastic Agents, Hormonal therapeutic use, Breast Neoplasms surgery, Ovariectomy, Premenopause, Tamoxifen therapeutic use
- Abstract
One hundred years ago ovarian ablation was shown to be an effective treatment for advanced breast cancer in premenopausal women. Since that time many different treatment modalities have been advocated to improve patient survival. The value of adjuvant ovarian ablation, however, has recently been established in the overview of breast cancer clinical trials. In fact, comparison of the efficacy of combination chemotherapy with earlier trials of oophorectomy demonstrate the superiority of oophorectomy. The effectiveness of chemotherapy may largely be the result of partial ovarian ablation produced in premenopausal patients. Based on this position, we propose a clinical trial that would establish the optimal therapy for premenopausal breast cancer. In addition, the beneficial effects of long-term tamoxifen as it pertains to serum lipids and bone density are highlighted. The use of tamoxifen maintenance in oophorectomized women might provide an optimal therapy for the control of breast cancer recurrence.
- Published
- 1996
- Full Text
- View/download PDF
22. An analysis of tamoxifen-stimulated human carcinomas for mutations in the AF-2 region of the estrogen receptor.
- Author
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Bilimoria MM, Assikis VJ, Muenzner HD, Wolf DM, Satyaswaroop PG, and Jordan VC
- Subjects
- Carcinoma metabolism, Endometrial Neoplasms metabolism, Female, Humans, Mutation drug effects, Neoplasms, Experimental genetics, Neoplasms, Experimental metabolism, Ovarian Neoplasms metabolism, Receptors, Estrogen antagonists & inhibitors, Sequence Analysis, DNA, Carcinoma genetics, Endometrial Neoplasms genetics, Estrogen Antagonists administration & dosage, Ovarian Neoplasms genetics, Receptors, Estrogen genetics, Tamoxifen administration & dosage
- Abstract
The estrogen receptor (ER) contains two transcriptional activation domains: AF-1 and AF-2. AF-2 is dependent on a highly species-conserved region of the ER. It has been shown that site-directed point mutations of conserved hydrophobic amino acids within this region reduce estrogen-dependent transcriptional activation. In addition, when these mutated ERs are transfected into HeLa cells, both tamoxifen and ICI 164,384 become strong agonists. The implication is that mutations in this region could account for the tamoxifen-stimulated tumors seen clinically. We performed single stranded conformational polymorphism (SSCP) analysis spanning the entire ER along with DNA sequencing of the AF-2 region of the ER isolated from two different tamoxifen-stimulated breast cancers, MCF-7/TAM and MCF-7/MT2, and a tamoxifen-stimulated endometrial cancer, EnCa 101. In addition, a tamoxifen-stimulated endometrial carcinoma cell line, the Ishikawa cell line, was also studied. There were no mutations found by SSCP analysis and sequencing of all four AF-2 regions also revealed no mutations. Mutations within the AF-2 region of the human ER do not appear to account for the growth of human breast and endometrial carcinomas that are used as reproducible laboratory models of tamoxifen-stimulated growth observed clinically.
- Published
- 1996
- Full Text
- View/download PDF
23. Motor-scooter handlebar syndrome: blunt traumatic injury of the femoral artery.
- Author
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Baker WE, Bilimoria MM, and Victor MG
- Subjects
- Adult, Femoral Artery diagnostic imaging, Femoral Artery surgery, Heparin therapeutic use, Humans, Male, Radiography, Rupture, Syndrome, Wounds, Nonpenetrating diagnosis, Wounds, Nonpenetrating surgery, Femoral Artery injuries, Motorcycles, Wounds, Nonpenetrating etiology
- Abstract
We present a case of "motor-scooter handlebar syndrome," i.e., intimal injury to the common femoral artery caused by a direct blow from a motorcycle handlebar, and review other potential mechanisms for similar arterial injuries. Our case is unique in that a clinical diagnosis was made before vascular studies or arterial occlusion. The mechanism of injury combined with physical examination findings of localized swelling, tenderness, and an overlying bruit prompted early heparinization with subsequent radiographic studies and surgical repair.
- Published
- 1996
- Full Text
- View/download PDF
24. Should adjuvant tamoxifen therapy be stopped at 5 years?
- Author
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Bilimoria MM, Assikis VJ, and Jordan VC
- Subjects
- Animals, Bone and Bones drug effects, Cardiovascular Diseases prevention & control, Chemotherapy, Adjuvant, Clinical Trials as Topic, Drug Resistance, Neoplasm, Female, Humans, Lipids blood, Neoplasms chemically induced, Osteoporosis prevention & control, Risk Assessment, Time Factors, Breast Neoplasms drug therapy, Selective Estrogen Receptor Modulators therapeutic use, Tamoxifen therapeutic use
- Abstract
Toxifen, a nonsteroidal antiestrogen, is currently the most widely used adjuvant therapy for the treatment of breast cancer. Though the efficacy of tamoxifen has been well documented in clinical trials, the certainty over the duration of therapy is less clear. Clinical and laboratory evidence suggests that longer therapy is better; however, whether this means 5 years, 10 years, or indefinite therapy has not been established in clinical trials. Essential to any study of long-term tamoxifen therapy is consideration of its effects not only on breast cancer but also on other estrogen target tissues. The estrogenic effect of tamoxifen that lowers serum lipids results in fewer hospital admissions for heart disease and a reduction in fatal myocardial infarction. Similarly, tamoxifen maintains bone mass that may ultimately result in fewer fractures. The effects of tamoxifen appear to parallel the effects of estrogen, so results from clinical trials of estrogen replacement therapy will provide a useful guide of what to expect with tamoxifen. The negative aspect of the therapy is a modest increase in the incidence of endometrial cancer. However, the incidence of endometrial cancer after stopping either estrogen or tamoxifen remains elevated for at least 5 years after the drug is stopped. Nevertheless, it is important to stress that the overall prognosis remains unaffected. We conclude that it will be difficult to demonstrate survival differences between 5 and 10 years of tamoxifen in clinical trials unless significant tamoxifen-stimulated recurrences occur with continued therapy. The benefits of tamoxifen must be calculated using estimates of the decreased rates of heart disease, contralateral cancers, decreased hospitalizations for fractures, and reduced cancer relapses.
- Published
- 1996
25. A novel 80 kDa human estrogen receptor containing a duplication of exons 6 and 7.
- Author
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Pink JJ, Wu SQ, Wolf DM, Bilimoria MM, and Jordan VC
- Subjects
- Base Sequence, Chromosome Banding, Chromosome Mapping, Cloning, Molecular, Female, Humans, Molecular Sequence Data, Molecular Weight, Receptors, Estrogen genetics, Tumor Cells, Cultured, Breast Neoplasms metabolism, Exons genetics, Receptors, Estrogen isolation & purification
- Abstract
Alterations in the amino acid sequence of the estrogen receptor (ER) have been shown to have dramatic effects on its function. Recently, mutant ERs have been isolated from both clinical samples and established breast cancer cell lines, primarily through the use of the polymerase chain reaction (PCR). All previously reported mutations have given rise to either alterations or truncations of the ER protein. We determined the structure of a novel 80 kDa ER which is expressed in an estrogen independent subclone of the MCF-7 human breast cancer cell line (MCF-7:2A). This 80 kDa ER was initially detected by Western blot analysis using a variety of ER specific antibodies. PCR mapping and partial PCR mediated subcloning of the ER cDNA were used to demonstrate that this protein was an ER containing an in-frame duplication of exons 6 and 7. This type of duplication has not been previously described for any members of the steroid receptor superfamily. Karyotype analysis coupled with fluorescence in situ hybridization (FISH) demonstrated that MCF-7:2A cells contained 4-5 copies of the ER gene in contrast to 2 copies in MCF-7:WS8 cells. The ER gene was localized by FISH analyses in both the MCF-7:WS8 and MCF-7:2A cells on chromosome 6, which is the source of the ER in normal human cells. The relative expression level of 2:1 is consistent with DNA gene dosage analysis. Genomic PCR was then used to demonstrate that the 80 kDa ER mRNA was not derived from the trans-splicing of two ER mRNAs but was the result of a genomic rearrangement in which exons 6 and 7 were duplicated in an in-frame fashion. This variant ER may prove to be useful in elucidating the mechanism of estrogen action in breast cancer cells.
- Published
- 1996
- Full Text
- View/download PDF
26. The woman at increased risk for breast cancer: evaluation and management strategies.
- Author
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Bilimoria MM and Morrow M
- Subjects
- Adult, Aged, Aged, 80 and over, Animals, Breast Diseases complications, Breast Neoplasms diagnosis, Breast Neoplasms epidemiology, Breast Neoplasms genetics, Female, Humans, Mastectomy, Middle Aged, Risk, Risk Factors, Breast Neoplasms prevention & control
- Abstract
Increased understanding of risk factors for breast cancer, especially the identification of genes associated with a predisposition to breast cancer, has focused attention on the issue of breast cancer prevention. At present, the only clinically available method of breast cancer prevention is prophylactic mastectomy. However, there are no absolute indications for its use, and it is not often appropriate in relation to actual risk for disease. This article reviews what is known about major breast cancer risk factors, reviews the available data on prophylactic mastectomy, and discusses current strategies for the management of the woman at increased risk for breast cancer.
- Published
- 1995
- Full Text
- View/download PDF
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