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Biomedical subjects

David J Bentrem

Publications and source records attributed to David J Bentrem.

At least 19 recordsLinked to original sources
PubMed2007

Outcome of patients with known metastatic gastric cancer undergoing resection with therapeutic intent.

BACKGROUND: Metastatic gastric cancer has a dismal prognosis. We identified a subset of patients where surgical resection with therapeutic intent was undertaken in the setting of known metastatic disease. METHODS: Review of a prospectively maintained database of gastric cancer patients at a single institution over a 19-year period was performed. RESULTS: Thirty-seven patients with metastatic disease known prior to resection with therapeutic intent were identified out of 3384 patients with gastric cancer (1%). Twelve patients had positive peritoneal cytology as the only evidence of metastasis, 21 had gross metastasis limited to peritoneal surfaces, one had peritoneal and ovarian metastasis, one had liver metastasis, one had retropancreatic lymph node metastasis, and one had a malignant pleural effusion. Thirty-six patients (97%) received chemotherapy prior to resection, and 30 (81%) received postoperative chemotherapy. The median time from diagnosis to resection was 4.5 months (range 1-22) in patients receiving preoperative chemotherapy. Median survival was 12 months after resection with no three-year survivors. Predictors of worse prognosis were cytologic or pathologic evidence of persistent metastatic disease at the time of resection or at laparoscopy within six weeks of resection (P < .01), N3 disease (P = .03), and total gastrectomy or additional organ resection (P = .04). Metastatic disease as evidenced by cytology only was not associated with improved prognosis. CONCLUSIONS: Highly selected patients with metastatic gastric cancer undergoing surgical resection with therapeutic intent have a relatively poor prognosis. Persistent detectable metastatic disease after preoperative chemotherapy portends a particularly poor prognosis.

Adult↗
PubMed2006

Apigenin inhibits pancreatic cancer cell proliferation through G2/M cell cycle arrest.

BACKGROUND: Many chemotherapeutic agents have been used to treat pancreatic cancer without success. Apigenin, a naturally occurring flavonoid, has been shown to inhibit growth in some cancer cell lines but has not been studied in pancreatic cancer. We hypothesized that apigenin would inhibit pancreatic cancer cell growth in vitro. RESULTS: Apigenin caused both time- and concentration-dependent inhibition of DNA synthesis and cell proliferation in four pancreatic cancer cell lines. Apigenin induced G2/M phase cell cycle arrest. Apigenin reduced levels of cyclin A, cyclin B, phosphorylated forms of cdc2 and cdc25, which are all proteins required for G2/M transition. CONCLUSION: Apigenin inhibits growth of pancreatic cancer cells through suppression of cyclin B-associated cdc2 activity and G2/M arrest, and may be a valuable drug for the treatment or prevention of pancreatic cancer.

Apigenin↗
PubMed2005

Outcomes in oncologic surgery: does volume make a difference?

Commonly performed elective surgical procedures on the alimentary tract are carried out with low morbidity and low mortality in most hospitals in the United States. There are some procedures on the alimentary tract that are performed with a relatively low frequency and are associated with higher mortality. Volume is a surrogate marker associated with improved outcome, with relative differences being dependent on the complexity of the procedure and the frequency with which it is done. Both surgeon and institutional volume matters, but it seems that improved operative mortality can be reached with lower surgeon volume in high-volume institutions. It appears that volume can be substituted in part for by specialization and training, with improved outcomes based on specialist credentials and fellowship training.

Digestive System Surgical Procedures↗
PubMed2005

Predictors of intensive care unit admission and related outcome for patients after pancreaticoduodenectomy.

High-volume centers have low morbidity and mortality after pancreaticoduodenectomy (PD). Less is known about treatment pathways and their influence on intensive care unit (ICU) utilization. Patients who underwent PD at a tertiary cancer center during the five-year period between January 1998 and December 2003 were identified from a prospective database. Preoperative and intraoperative factors relating to ICU admission and outcome were analyzed. Five hundred ninety-one pancreaticoduodenectomies were performed during the study period. Of these, 536 patients had complete records for analysis. Of the 536 patients, 51 (10%) were admitted to the ICU after surgery. Admission to the ICU was associated with decreased overall survival (P < .0001). Of the preoperative predictors of ICU admission, serum creatinine, albumin, and increased body mass index (BMI) were associated with ICU admission (P = .02, .05, and .002, respectively). Age, blood glucose, diagnosis of diabetes mellitus, and chronic obstructive pulmonary disease were not predictive of ICU admission on univariate analysis. Of the intraoperative factors, longer operative time and estimated blood loss (EBL) correlated with ICU admission (P = .003 and .0001, respectively). On multivariate analysis, only preoperative BMI and intraoperative EBL were independent predictors of ICU admission (P = .03 and .003, respectively). Patients with a preoperative BMI greater than 30 had a substantially higher risk of ICU admission (relative risk 2.4). The majority of patients who undergo PD do not require admission to the ICU. Factors most associated with ICU admission after PD are increased preoperative BMI and intraoperative blood loss.

Adult↗
PubMed2005

T1 adenocarcinoma of the rectum: transanal excision or radical surgery?

BACKGROUND: Recent studies suggest local excision may be acceptable treatment of T1 adenocarcinoma of the rectum, but there is little comparative data with radical surgery to assess outcomes and quantify risk. We performed a retrospective evaluation of patients with T1 rectal cancers treated by either transanal excision or radical resection at our institution to assess patient selection, cancer recurrence, and survival. METHODS: All patients who underwent surgery for T1 adenocarcinomas of the rectum (0-15 cm from anal verge) by either transanal excision (TAE) or radical resection (RAD) between January 1987 and January 2004 were identified from a prospective database. Data were analyzed using Fisher exact test, Kaplan-Meier method, and log-rank test. RESULTS: Three hundred nineteen consecutive patients with T1 lesions were treated by transanal excision (n = 151) or radical surgery (n = 168) over the 17-year period. RAD surgery was associated with higher tumor location in the rectum, slightly larger tumor size, a similar rate of adverse histology, and a lymph node metastasis rate of 18%. Despite these features, patients who underwent RAD surgery had fewer local recurrences, fewer distant recurrences, and significantly better recurrence-free survival (P = 0.0001). Overall and disease-specific survival was similar for RAD and TAE groups. CONCLUSION: Despite a similar risk profile in the 2 surgical groups, patients with T1 rectal cancer treated by local excision were observed to have a 3- to 5-fold higher risk of tumor recurrence compared with patients treated by radical surgery. Local excision should be reserved for low-risk cancers in patients who will accept an increased risk of tumor recurrence, prolonged surveillance, and possible need for aggressive salvage surgery. Radical resection is the more definitive surgical treatment of T1 rectal cancers.

Adenocarcinoma↗
PubMed2005

Surgical therapy for metastatic disease to the liver.

The liver is a common site of hematogenous metastasis. In the past, patients with liver metastases were often deemed inoperable, and medical therapy conferred only minor survival benefit. However, advances in surgical techniques and chemotherapeutic agents during the past two decades have led to effective treatments for selected patients with metastases to the liver. Up to approximately 80% of the liver can be resected, and partial hepatectomy is now routinely performed with a perioperative mortality rate of <5%. Surgical resection of colorectal cancer metastatic to the liver results in a 5-year survival rate of 40%. These results are expected to improve even further with multimodality approaches that include newer chemotherapy regimens. Liver metastases from other primary tumors, such as neuroendocrine carcinoma and genitourinary tumors, are also treated effectively with liver resection. The indications for surgical treatment of liver metastases are broadening as a variety of novel therapies are being developed, including hepatic artery embolization, hepatic artery infusion of chemotherapy, and radiofrequency ablation.

Carcinoma, Neuroendocrine↗
PubMed2004

Advance directive use among patients undergoing high-risk operations.

BACKGROUND: The Patient Self-Determination Act requires that patients entering hospitals be asked if they have an advance directive. This has led to increased awareness of advance directives, yet surgeons have paid little attention to their use among patients undergoing even major surgery. We sought to evaluate the use of advance directives in patients undergoing pancreaticoduodenectomy and esophagectomy. METHODS: Patients undergoing these operations between 1996 and 2001 at a university teaching hospital were identified and reviewed for statement of advance directive, its presence in the chart, and impact on patient care. RESULTS: A total of 252 patients met inclusion criteria. The number of patients with an advance directive increased, but had little impact on patient care. CONCLUSIONS: More patients having major surgery have advance directives, but the number present in the medical record remains low. Further attention to advance directives would foster increased communication between surgeons and patients and extend patient autonomy.

Advance Directives↗
PubMed2004

Failure of sentinel lymph node mapping in patients with breast cancer.

BACKGROUND: Lymphatic mapping with sentinel lymphadenectomy (SL) has become more widely used as an alternative to axillary dissection for the staging of breast cancer. This study was conducted to evaluate the potential associations of patient and tumor characteristics with the lymphatic mapping failure rate. STUDY DESIGN: Between September 1996 and April 2003, 1,094 breast cancer patients participated in a single-institution prospective SL protocol, which was conducted using technetium 99 m sulfur colloid alone to identify sentinel lymph nodes. During the validation phase, consisting of the first 80 patients, all patients had SL followed by axillary dissection. Beginning with the 81st patient, the standard technique consisted of radiolabeled colloid injection in a peritumoral distribution 16 to 24 hours before the operation, followed by SL alone for node-negative patients. RESULTS: Of 1,094 consecutive patients, 62 (5.7%) did not map. Patients having more than 10 involved lymph nodes had a significantly higher incidence of mapping failure (40.9%) than those who were node-negative (5.3%) (odds ratio = 9.19, p = 0.002). Age was a factor predictive of mapping failure for node-negative patients 70+ years of age (odds ratio = 3.14, p = 0.018). Biopsy technique, tumor size, tumor location, cell type, and surgeon experience were not predictors of mapping failure, regardless of node status. CONCLUSIONS: The lymphatic mapping failure rate was associated with both anatomic and pathologic factors. Patients with extensive nodal involvement had a significantly greater chance of mapping failure. Among node-negative patients, those who were older were more likely to have mapping failure than those who were younger, suggesting that decreased breast density in postmenopausal women might provide an anatomic explanation for nonmapping.

Aged↗
PubMed2003

Stable transfection of an estrogen receptor beta cDNA isoform into MDA-MB-231 breast cancer cells.

We previously reported stable transfection of estrogen receptor alpha (ERalpha) into the ER-negative MDA-MB-231 cells (S30) as a tool to examine the mechanism of action of estrogen and antiestrogens [J. Natl. Cancer Inst. 84 (1992) 580]. To examine the mechanism of ERbeta action directly, we have similarly created ERbeta stable transfectants in MDA-MB-231 cells. MDA-MB-231 cells were stably transfected with ERbeta cDNA and clones were screened by estrogen response element (ERE)-luciferase assay and ERbeta mRNA expression was quantified by real-time RT-PCR. Three stable MDA-MB-231/ERbeta clones were compared with S30 cells with respect to their growth properties, ability to activate ERE- and activating protein-1 (AP-1) luciferase reporter constructs, and the ability to activate the endogenous ER-regulated transforming growth factor alpha (TGFalpha) gene. ERbeta6 and ERbeta27 clones express 300-400-fold and the ERbeta41 clone express 1600-fold higher ERbeta mRNA levels compared with untransfected MDA-MB-231 cells. Unlike S30 cells, 17beta-estradiol (E2) does not inhibit ERbeta41 cell growth. ERE-luciferase activity is induced six-fold by E2 whereas neither 4-hydroxytamoxifen (4-OHT) nor ICI 182, 780 activated an AP-1-luciferase reporter. TGFalpha mRNA is induced in response to E2, but not in response to 4-OHT. MDA-MB-231/ERbeta clones exhibit distinct characteristics from S30 cells including growth properties and the ability to induce TGFalpha gene expression. Furthermore, ERbeta, at least in the context of the MDA-MB-231 cellular milieu, does not enhance AP-1 activity in the presence of antiestrogens. In summary, the availability of both ERalpha and ERbeta stable breast cancer cell lines now allows us to compare and contrast the long-term consequences of individual signal transduction pathways.

Breast Neoplasms↗
PubMed2003

Pancreas: healing response in critical illness.

OBJECTIVE: The pathophysiology of acute pancreatitis represents a diverse mix of congenital, hereditary, and acquired problems associated with or causing acute pancreatic inflammation. Acute pancreatitis is characterized by acinar cell injury that may involve regional and systemic inflammatory responses. The systemic manifestations of acute pancreatitis are responsible for the majority of pancreatitis-associated morbidity and are due to the actions of specific inflammatory cytokines. This report summarizes this pancreatic injury, the role of cytokines in the pathogenesis of acute pancreatitis, and the pancreatic healing response that follows. DESIGN: A comprehensive literature review of experimental pancreatitis as well as reports of cytokine involvement and healing response during clinical pancreatitis was performed. RESULTS: Histamine release, bradykinin generation, and cytokine release play a significant role during acute pancreatic inflammation. Following an experimental insult, there is rapid expression of tumor necrosis factor-alpha, interleukin-6, interleukin-1, and chemokines by pancreatic acinar cells and/or transmigrated leukocytes. Preventing the action of these mediators has a profound beneficial effect in experimental animals. Pancreatic fibrosis is a central histologic response after pancreatitis. Transient collagen deposition with acinar necrosis occurs in acute pancreatitis; in chronic pancreatitis, permanent and disorganized pancreatic fibrosis and parenchymal cell atrophy occur. CONCLUSIONS: Inflammatory mediators are responsible for the systemic manifestations of acute pancreatitis and the associated distant organ dysfunction. After the acute injury, regeneration or pancreatic repair is characterized by decreased release of proinflammatory mediators and decreased infiltrating inflammatory cells. Differentiation and proliferation of pancreatic myofibroblasts or "stellate" cells may be responsible for increased extracellular matrix production. The predictable nature in which the inflammation and fibrosis are produced may stimulate novel approaches to disease treatment.

Acute Disease↗
PubMed2002

Contemporary surgical management of pheochromocytoma.

BACKGROUND: The availability of laparoscopic adrenalectomy led us to review our experience and management of adrenal and extraadrenal pheochromocytoma. METHODS: Seventeen patients undergoing pheochromocytoma resection from January 1997 to August 2001 were categorized as open, laparoscopic, or laparoscopic assisted depending on the surgical approach. Hospital records were reviewed. RESULTS: There was no significant difference between the groups in patient age, weight or preoperative blockade. Operative times for open, laparoscopic, and laparoscopic assisted adrenalectomies were 202, 218, and 260 minutes, respectively. Estimated blood loss was 562 cc, 187 cc, and 925 cc. The average hospital length of stay was 6.2, 3.0, and 5.8 days. CONCLUSIONS: Laparoscopic removal resulted in longer operative times than open, but less operative blood loss and a shorter hospital stay. The laparoscopic assisted approach did not save time nor did it lead to earlier discharge. Laparoscopic adrenalectomy was comparable to the open approach, and is preferential in tumors less than 6 cm. An open approach remains our choice for larger or extraadrenal tumors.

Adrenal Gland Neoplasms↗
PubMed2002

A mechanism of drug resistance to tamoxifen in breast cancer.

Drug resistance to tamoxifen (Tam) is a significant clinical problem but the mechanism through which this occurs remains elusive. We have developed a number of xenograft models of Tam-stimulated growth that model breast cancer progression using estrogen receptor positive MCF-7 or T47D breast cancer cells. When estrogen-stimulated T47D:E2 tumors are treated long term with Tam, Tam-stimulated tumors develop (T47D:Tam) that are stimulated by both estrogen and Tam. When HER-2/neu status is determined, it is clear that the T47D:Tam tumors express significantly higher levels of HER-2/neu protein by immunohistochemistry and mRNA as measured by real-time RT-PCR. The T47D:Tam tumors also express higher levels of estrogen receptor and progesterone receptor protein than their estrogen-stimulated T47D:E2 counterparts. We compared out results to the MCF-7 model of Tam-stimulated growth. The MCF-7:Tam ST (estrogen- and Tam-stimulated) and MCF-7:Tam LT (estrogen-inhibited, Tam-stimulated) were bilaterally transplanted to account for any mouse to mouse variation and characteristic growth patterns were observed. TUNEL staining was performed on MCF-7:Tam LT treated with either estrogen or Tam and it was concluded that estrogen-inhibited tumor growth was a result of increased apoptosis. Three phases of tumor progression are described that involve increases in HER-2/neu expression, de-regulation of estrogen receptor expression and increases in apoptosis which in concert determine the phenotype of drug resistance to Tam.

Animals↗
PubMed2002

Is preoperative investigation of the thyroid justified in patients undergoing parathyroidectomy for hyperparathyroidism?

BACKGROUND: The finding of coexisting nodular thyroid disease during neck exploration for hyperparathyroidism (HPT) is reported to range from 20%-60%. Thus, the surgeon may encounter a second, unrelated lesion during open parathyroidectomy. Furthermore, with the recent introduction of minimally invasive surgery for HPT, the entire neck may not be explored, and it is important to know the potential risk of missing significant, concurrent thyroid disease. The diagnosis and timely treatment of associated thyroid abnormalities is desirable because a delay in operating would result in increased morbidity associated with a second neck exploration. DESIGN: We examined our 25-year experience at a large tertiary academic medical center, to determine the incidence and type of concurrent thyroid disease seen in patients with HPT. The computerized records of the Department of Pathology, from 1974-1999, were reviewed for patients with primary HPT who underwent surgery. RESULTS: A review of records from 580 patients who underwent surgery for primary HPT showed 103 (18%) patients with concomitant thyroid disease at surgery. All 103 underwent thyroid resection at the time of parathyroidectomy. Thyroid histology showed: 12 (12%): well-differentiated papillary carcinomas, 31 (30%): follicular adenomas, 49 (48%): nodular hyperplasias, 8 (8%): chronic lymphocytic thyroiditis, 1 benign cyst, 1 metastasis, and 1 normal. CONCLUSIONS: Synchronous thyroid disease was found in 18% of primary HPT patients undergoing surgery, and 12% of thyroid lesions were malignant. The overall malignancy rate was 2%. All primary malignancies found were papillary carcinomas, of which 7 of 12 (58%) were microcarcinomas. The significant association of simultaneous pathology in the two glands justifies preoperative thyroid imaging and fine-needle aspiration (FNA) biopsy to determine the best surgical approach for patients with HPT.

Adenoma↗
PubMed2002

Role of antiestrogens and aromatase inhibitors in breast cancer treatment.

This review explores the recent experience with, and the basis for, the use of selective estrogen receptor modulators to treat and prevent breast cancer. As new agents are unveiled, they will continue to be tested against tamoxifen. A number of new selective estrogen receptor modulators are in clinical development in an attempt to decrease the unwanted effects of tamoxifen. Raloxifene holds the promise of treating osteoporosis with the beneficial side effect of breast cancer prevention. Additionally, two different classes of hormonal agents, the aromatase inhibitors and estrogen receptor down-regulators, which have no estrogen-like properties at any site, appear to be promising new treatments for advanced breast cancer.

Aromatase Inhibitors↗