Stuart G. Marcus, M.D.

Quality measurement in cancer care delivery
Wasif, Nabil; Cormier, Janice N; Ko, Clifford Y; McCahill, Laurence E; Edge, Stephen B; Wong, Sandra L; Anthony, Thomas; Kollmorgen, Daniel; Marcus, Stuart G; Bleznak, Aaron; Leong, Stanley P L
2011 Mar;18(3):611-618, Annals of surgical oncology
During the past decade, increasing emphasis has been placed on defining and measuring the quality of health care delivery. The Outcomes Committee of the Society of Surgical Oncology (SSO) was established in 2008 to explore and promote emerging outcomes-related topics that are most relevant to society membership. In recognition of the importance of health care quality, a mini-symposium was held at the SSO's 63rd Annual Cancer Symposium in St. Louis, Missouri, in March 2010. The primary objective of the symposium was to define what constitutes quality measurement in cancer care. This article presents an overview of the symposium proceedings
— id: 141821, year: 2011, vol: 18, page: 611, stat: Journal Article,

Evaluation of surgical outcomes and gallbladder characteristics in patients with biliary dyskinesia
Sabbaghian, M Shirin; Rich, Barrie S; Rothberger, Gary D; Cohen, Jonathan; Batash, Steven; Kramer, Elissa; Pachter, H Leon; Marcus, Stuart G; Shamamian, Peter
2008 Aug;12(8):1324-1330, Journal of gastrointestinal surgery
INTRODUCTION: This study was designed to compare symptomatic outcomes following cholecystectomy in patients with biliary dyskinesia. MATERIALS AND METHODS: From 1999 to 2006 at New York University Medical Center, 197 adults underwent hepatobiliary scintigraphy with cholecystokinin administration to evaluate gallbladder ejection fraction (GBEF). Biliary dyskinesia was demonstrated in 120 patients based on decreased GBEF of </=35%. Forty-four patients underwent cholecystectomy, and data from chart review and telephone questionnaires were available for 42 patients. Patients reported symptomatic improvement whether gallstones were present (25/27, 92.6%) or absent (13/15, 86.7%) prior to cholecystectomy (p = 0.90). The most common pathologic findings were chronic cholecystitis and cholesterolosis, regardless of the presence of gallstones. Additional data from 101 of the 120 patients with decreased GBEF demonstrated 74/101 (73.2%) patients were diagnosed with gastroesophageal reflux disease (GERD), and 59/101 (58.4%) patients were diagnosed with gastritis. RESULTS: The results of this study suggest that biliary dyskinesia should be considered as part of the spectrum of symptomatic gallbladder disease that can be successfully treated with cholecystectomy and that biliary dyskinesia is associated with GERD and gastritis
— id: 93321, year: 2008, vol: 12, page: 1324, stat: Journal Article,

Early evidence on the effects of regulators' suicidality warnings on SSRI prescriptions and suicide in children and adolescents
Gibbons, Robert D; Brown, C Hendricks; Hur, Kwan; Marcus, Sue M; Bhaumik, Dulal K; Erkens, Joelle A; Herings, Ron M C; Mann, J John
2007 Sep;164(9):1356-1363, American journal of psychiatry
OBJECTIVE: In 2003 and 2004, U.S. and European regulators issued public health warnings about a possible association between antidepressants and suicidal thinking and behavior. The authors assessed whether these warnings discouraged use of antidepressants in children and adolescents and whether they led to increases in suicide rates as a result of untreated depression. METHOD: The authors examined U.S. and Dutch data on prescription rates for selective serotonin reuptake inhibitors (SSRIs) from 2003 to 2005 in children and adolescents (patients up to age 19), as well as suicide rates for children and adolescents, using available data (through 2004 in the United States and through 2005 in the Netherlands). They used Poisson regression analyses to determine the overall association between antidepressant prescription rates and suicide rates, adjusted for sex and age, during the periods preceding and immediately following the public health warnings. RESULTS: SSRI prescriptions for youths decreased by approximately 22% in both the United States and the Netherlands after the warnings were issued. In the Netherlands, the youth suicide rate increased by 49% between 2003 and 2005 and shows a significant inverse association with SSRI prescriptions. In the United States, youth suicide rates increased by 14% between 2003 and 2004, which is the largest year-to-year change in suicide rates in this population since the Centers for Disease Control and Prevention began systematically collecting suicide data in 1979. CONCLUSIONS: In both the United States and the Netherlands, SSRI prescriptions for children and adolescents decreased after U.S. and European regulatory agencies issued warnings about a possible suicide risk with antidepressant use in pediatric patients, and these decreases were associated with increases in suicide rates in children and adolescents
— id: 148430, year: 2007, vol: 164, page: 1356, stat: Journal Article,

Relationship between antidepressants and suicide attempts: an analysis of the Veterans Health Administration data sets
Gibbons, Robert D; Brown, C Hendricks; Hur, Kwan; Marcus, Sue M; Bhaumik, Dulal K; Mann, J John
2007 Jul;164(7):1044-1049, American journal of psychiatry
OBJECTIVE: In late 2006, a U.S. Food and Drug Administration advisory committee recommended that the 2004 black box warning regarding suicidality in pediatric patients receiving antidepressants be extended to include young adults. This study examined the relationship between antidepressant treatment and suicide attempts in adult patients in the Veterans Administration health care system. METHOD: The authors analyzed data on 226,866 veterans who received a diagnosis of depression in 2003 or 2004, had at least 6 months of follow-up, and had no history of depression from 2000 to 2002. Suicide attempt rates overall as well as before and after initiation of antidepressant therapy were compared for patients who received selective serotonin reuptake inhibitors (SSRIs), new-generation non-serotonergic-specific (non-SSRI) antidepressants (bupropion, mirtazapine, nefazodone, and venlafaxine), tricyclic antidepressants, or no antidepressant. Age group analyses were also performed. RESULTS: Suicide attempt rates were lower among patients who were treated with antidepressants than among those who were not, with a statistically significant odds ratio for SSRIs and tricyclics. For SSRIs versus no antidepressant, this effect was significant in all adult age groups. Suicide attempt rates were also higher prior to treatment than after the start of treatment, with a significant relative risk for SSRIs and for non-SSRIs. For SSRIs, this effect was seen in all adult age groups and was significant in all but the 18-25 group. CONCLUSIONS: These findings suggest that SSRI treatment has a protective effect in all adult age groups. They do not support the hypothesis that SSRI treatment places patients at greater risk of suicide
— id: 148429, year: 2007, vol: 164, page: 1044, stat: Journal Article,

Results following resection for stage IV gastric cancer; are better outcomes observed in selected patient subgroups?
Lim, Suhsien; Muhs, Bart E; Marcus, Stuart G; Newman, Elliot; Berman, Russel S; Hiotis, Spiros P
2007 Feb 1;95(2):118-122, Journal of surgical oncology
BACKGROUND: Patients who present with stage IV gastric cancer are not commonly managed with surgical resection as effective palliation can usually be accomplished with systemic chemotherapy, endoscopic stenting, or surgical bypass procedures. Given the inherent morbidity and mortality associated with gastrectomy, palliative resection for stage IV gastric cancer should be reserved for ideal surgical candidates who are most likely to benefit from the procedure. The purpose of this study is to review outcomes following resection for stage IV gastric cancer, and to identify criteria predictive of improved outcomes following gastrectomy in this setting. METHODS: A retrospective review of a prospective GI oncology database was conducted. Sixty-three patients with stage IV gastric cancer managed with surgical resection between 1989 and 2001 were identified. Variables including demographic data, patterns of distant spread (ex: peritoneal, lymphatic, hematogenous), location of tumor, and type of gastrectomy were utilized to conduct survival analyses. RESULTS: Actuarial survival for all patients at one and 3-year intervals was 52% and 12%, respectively. Improved survival was observed for patients of East Asian race (median survival 20 vs. 12 months, P < 0.05, students t-test) and age less than 60 years (median survival 15 vs. 12 months, P < 0.05). This trend was also illustrated by Kaplan-Meier survival analysis. Other variables including pattern of distant spread, location of tumor, and type of gastrectomy were not associated with a significant difference in survival. Both East Asian race and age less than 60 years were statistically significant predictors of improved survival when assessed by univariate regression analysis. When variables were analyzed in a multivariate regression analysis, Asian race and age <60 both lost their statistical significance as independent predictors of improved survival. CONCLUSIONS: Long-term survival for patients with stage IV gastric cancer who are managed with surgical resection is achievable. Patient specific variables including East Asian race and age less than 60 years appear to be associated with prolonged survival when assessed by comparison of means, Kaplan-Meier analysis, and univariate regression analysis. However, multivariate regression analysis failed to demonstrate these factors as independent predictors of improved outcome. In conclusion, highly selected acceptable risk surgical candidates with stage IV gastric cancer should be considered for management with surgical resection in clinically appropriate scenarios
— id: 70877, year: 2007, vol: 95, page: 118, stat: Journal Article,

Follow-up care after a diagnosis of Helicobacter pylori infection in an Asian immigrant cohort
Cho, Alex; Chaudhry, Amina; Minsky-Primus, Lisa; Tso, Alan; Perez-Perez, Guillermo; Diehl, David L; Marcus, Stuart G; Gany, Francesca M
2006 Jan;40(1):29-32, Journal of clinical gastroenterology
GOAL: To study the rate at which Helicobacter pylori infection is treated in an immigrant cohort after diagnosis by esophagogastroduodenoscopy (EGD). BACKGROUND: Gastric cancer is the second leading cause of cancer death worldwide, and is especially prevalent in East Asia; immigrants from this part of the world remain at higher risk. Infection with H. pylori is a known risk factor for gastric cancer. There have been no studies of completion of H. pylori treatment in immigrant populations. STUDY: Prospective cohort study of East Asian immigrants diagnosed with H. pylori infection who underwent EGD in a gastric cancer screening protocol. Our primary outcome was self-report or chart evidence of completion of treatment of H. pylori. RESULTS: Sixty-eight of the 126 participants (54%) tested positive for H. pylori infection on EGD. Forty-nine (72%) were seen for a follow-up visit at one of the clinics involved in the study. According to clinic records, 39 of these 49 participants (57% of all H. pylori-positive participants) were prescribed treatment. Only 31 participants (46%) completed treatment. Of possible explanatory factors, only having a 'regular doctor' was significantly associated with treatment completion (odds ratio=5.6; 95% confidence interval, 1.2-25.0). CONCLUSIONS: In a sample of Asian immigrants, the rate of treatment of H. pylori infection, a potentially modifiable risk factor, was lower than expected. Having a 'regular doctor' appeared to increase the likelihood of receiving appropriate follow-up care
— id: 61482, year: 2006, vol: 40, page: 29, stat: Journal Article,

Acceptance of repeat esophagogastroduodenoscopy to detect gastric cancer in a chinese immigrant cohort
Cho, Alex; Chaudhry, Amina; Minsky-Primus, Lisa; Tso, Alan; Perez-Perez, Guillermo; Diehl, David; Marcus, Stuart G; Gany, Francesca M
2006 Aug;40(7):606-611, Journal of clinical gastroenterology
GOAL: To study the feasibility of using repeat esophagogastroduodenoscopy (EGD) to screen for Helicobacter pylori infection and gastric cancer in an Asian immigrant cohort. BACKGROUND: Immigrants in the United States (US) from countries with high per capita rates of gastric cancer remain at higher risk for gastric cancer. The existence of the possibly modifiable risk factor of H. pylori infection and the poor outcomes associated with late-stage disease make screening higher-risk groups with EGD an appealing possibility. It is unknown whether Asian immigrants in the US would accept an EGD-based strategy for gastric cancer screening. STUDY: Cross-sectional study of adult Chinese immigrants in New York City with dyspepsia who underwent EGD in an earlier gastric cancer detection study, who were offered a second EGD four years later. Our main outcome measure was acceptance or refusal of repeat EGD. RESULTS: Seventy-three of the 115 Chinese participants in the earlier study were successfully contacted for this current study. Twenty-three of 73 (32%) underwent repeat EGD. Leading reasons given for declining were lack of symptoms and lack of time. Significantly associated with acceptance of repeat EGD was the belief that EGD will find stomach cancer 'nearly always' in someone who has it (P=0.0054; odds ratio=14.0, 2.1 to 94.2 95% confidence interval). CONCLUSIONS: Acceptance of repeat EGD for gastric cancer detection in a cohort of Chinese immigrants was relatively low despite the mitigation of cost and language factors, 2 major barriers to healthcare access. Relocation seemed to be a factor as well. In this population, perceptions of the benefits of EGD may influence acceptance of testing for cancer detection purposes
— id: 68529, year: 2006, vol: 40, page: 606, stat: Journal Article,

Diagnostic laparoscopy in the evaluation of the viral hepatitis patient with potentially resectable hepatocellular carcinoma
Klegar, Eunjie K; Marcus, Stuart G; Newman, Elliot; Hiotis, Spiros P
2005 ;7(3):204-207, HPB : the official journal of the International Hepato Pancreato Biliary Association
Background. Despite significant recent improvements in liver imaging, preoperative evaluation of the potentially resectable patient with viral Hepatitis and Hepatocellular Carcinoma (HCC) is often inaccurate. Diagnostic laparoscopy may change management for patients with under-appreciated nodular cirrhosis or intrahepatic metastases, preventing unnecessary open exploration. The purpose of this study is to determine the effectiveness of routine laparoscopy as a separate procedure prior to resection in the evaluation of patients with potentially resectable HCC. Methods. Patients with potentially resectable HCC were evaluated preoperatively with routine blood tests and axial imaging. All study patients also underwent diagnostic laparoscopy with laparoscopic ultrasonography. Laparoscopy was performed in an inpatient hospital setting, with 23 hour stays in most cases. Results. Among 65 patients evaluated with Hepatocellular Carcinoma between July 2001 and November 2003, 20 patients with potentially resectable disease were evaluated by diagnostic laparoscopy. All patients had viral Hepatitis: 16 with Hepatitis B and 4 with Hepatitis C. All study patients had cirrhosis; 18 classified as Child's-Pugh A and 2 as Child's-Pugh B. Diagnostic laparoscopy changed the management in 9/20 (45%) cases. Management was changed because of severe nodular cirrhosis in 4 cases, inaccurate assessment of intrahepatic metastases in 2 cases, inability to identify an HCC in 1 case, peritoneal carcinomatosis in 1 case, and inability to tolerate induction to general anesthesia in 1 case. Discussion. Diagnostic laparoscopy is useful in the evaluation of the potentially resectable patient with HCC. Information obtained from laparoscopy may change the clinical management in up to 45% of cases
— id: 105907, year: 2005, vol: 7, page: 204, stat: Journal Article,

Perforated duodenal diverticulitis: a report of three cases
Miller, George; Mueller, Claudia; Yim, Duke; Macari, Michael; Liang, Howard; Marcus, Stuart; Shamamian, Peter
2005 ;22(3):198-202, Digestive surgery
BACKGROUND: Duodenal diverticuli are present in up to 22% of the population. However, perforation of a duodenal diverticulum with spillage of enteric contents into the retroperitoneum is rare. METHODS: We report three cases of perforated duodenal diverticulitis. RESULTS: Clinical presentations varied widely from patients with acute abdominal findings and generalized sepsis to a patient with mild symptoms of abdominal discomfort. CT scanning was the imaging modality used to make an accurate diagnosis. Treatment approaches for the most stable patient included nonoperative management with antibiotics, bowel rest and parenteral alimentation, while the less stable patients underwent definitive surgery with complete diversion of gastric contents and biliary flow from the affected area of duodenum. CONCLUSIONS: This report highlights the salient issues in the presentation, diagnosis and modern management of patients with this potentially catastrophic disease
— id: 61257, year: 2005, vol: 22, page: 198, stat: Journal Article,

Postoperative intraperitoneal (IP) 5'-fluoro-2'-deoxyuridine (FUDR) added to chemoradiation in patients curatively resected (RO) for locally advanced gastric and gastroesophageal junction (GEJ) adenocarcinoma
Newman, E; Chang, RY; Potmesil, M; Donahue, B; Marcus, SG; Hiotis, SP; Iqbal, S; Ryan, T; Hochster, HS; Muggia, FM
2005 JUN 1 ;23(16):348S-348S, Journal of clinical oncology
— id: 57796, year: 2005, vol: 23, page: 348S, stat: Journal Article,

Neoadjuvant chemotherapy, surgery, and adjuvant intraperitoneal chemotherapy in patients with locally advanced gastric or gastroesophageal junction carcinoma: a phase II study
Newman, Elliot; Potmesil, Milan; Ryan, Theresa; Marcus, Stuart; Hiotis, Spiros; Yee, Herman; Norwood, Brendan; Wendell, Marc; Muggia, Franco; Hochster, Howard
2005 Dec;32(6 Suppl 9):S97-100, Seminars in oncology
A phase II trial, using neoadjuvant chemotherapy and intraperitoneal (IP) consolidation, was conducted in patients with locally advanced, potentially resectable gastric cancer or cancer of the gastroesophageal junction, both staged as T3N0, T4N0, or any TN1 or TN2 disease. Preoperative chemotherapy consisted of two cycles of irinotecan 75 mg/m(2) with cisplatin 25 mg/m(2)/week for 4 weeks followed by a 2-week break. Unless disease progression was encountered, surgery was performed and followed by two courses of adjuvant therapy with IP floxuridine 3 g x 3 days plus IP cisplatin 60 mg/m(2) on day 3. Of 32 evaluable patients, 29 (90.6%) underwent surgery, and 25 (86.2%) had R0 on resection. Evidence of primary-tumor downstaging was documented in at least one half of the patients. Toxicity of induction therapy was primarily grade 3/4 neutropenia (38.2%/8.8%), grade 3 diarrhea (20.6%), and grade 3 nausea/vomiting (14.7%). Except for three catheter complications, toxicities with IP therapy were infrequent. After a median follow-up of 28.0 months in 32 patients, 10 patients (31.3%) had no evidence of disease, 4 (12.5%) were alive with disease, 13 (40.6%) had died from disease, and 5 (15.6%) died from unrelated causes. Among 25 patients who underwent R0 resection, there were no local recurrences. Sites of first recurrences were outside the abdominal cavity in seven patients, in the liver in two, and in the abdominal cavity in four patients. Median overall survival for all 32 patients was 36.5 months from the start of treatment after median follow-up of 28 months, whereas median disease-specific survival had not been reached at the time of this analysis. For patients with R0 resection, median overall survival was 48 months after median follow-up of 35 months. The data suggest that an approach consisting of systemic induction therapy, curative surgery with high R0 resection rates, and IP adjuvant therapy has acceptable toxicity and encouraging survival outcomes
— id: 62748, year: 2005, vol: 32, page: S97, stat: Journal Article,

Multiorgan resection for gastric cancer: intraoperative and computed tomography assessment of locally advanced disease is inaccurate
Colen, Kari L; Marcus, Stuart G; Newman, Elliot; Berman, Russell S; Yee, Herman; Hiotis, Spiros P
2004 Nov;8(7):899-902, Journal of gastrointestinal surgery
Multiorgan resection of locally advanced gastric cancer has previously been associated with increased morbidity. This study was performed to determine the actual prevalence of pathologic T4 disease in multiorgan gastric resection specimens excised for presumed clinical T4 gastric cancer. A prospective oncology database was queried to identify gastric cancer patients who underwent en bloc multiorgan resection for clinical T4 lesions. Four hundred eighteen patients with gastric cancer underwent gastrectomy between 1990 and 2002. Multiorgan resection was performed in 21 of 418 (5%) patients. Multiorgan resection was not associated with a significant increase in morbidity or mortality. Pathologically confirmed T4 disease was present in only 8 of 21 (38%) patients; the pathologic T stage in all remaining patients was T3 (13 [62%]). Fifteen patients were evaluated by preoperative computed tomography scan. Preoperative computed tomography was inaccurate in assessing T4 lesions, with a positive predictive value of only 50%. Multiorgan resection was safely performed in patients with locally advanced gastric cancer. Pathologic T4 disease was present in only one third of multiorgan resections performed for en bloc excision of locally advanced gastric cancer. Improved methods for intraoperative assessment of disease extension to adjacent viscera should be investigated
— id: 50629, year: 2004, vol: 8, page: 899, stat: Journal Article,

Results following resection for stage IV gastric cancer: Are better outcomes observed in selected patient subgroups?
Lim, SH; Muhs, BE; Marcus, SG; Newman, E; Berman, RS; Hiotis, SP
2004 JUL 15 ;22(14):365S-365S, Journal of clinical oncology
— id: 48681, year: 2004, vol: 22, page: 365S, stat: Journal Article,

Complications of gastrectomy following CPT-11-based neoadjuvant chemotherapy for gastric cancer
Marcus, Stuart G; Cohen, Daniel; Lin, Ke; Wong, Kwok; Thompson, Scott; Rothberger, Adina; Potmesil, Milan; Hiotis, Spiros; Newman, Elliot
2003 Dec;7(8):1015-1022, Journal of gastrointestinal surgery
Potential benefits of neoadjuvant therapy for locally advanced gastric cancer include tumor downstaging and an increased R0 resection rate. Potential disadvantages include increased surgical complications. This study assesses postoperative morbidity and mortality by comparing patients undergoing gastrectomy with and without neoadjuvant chemotherapy. From October 1998 to July 2002, a total of 34 patients with locally advanced gastric cancer were placed on a phase II neoadjuvant chemotherapy protocol consisting of two cycles of CPT-11 (75 mg/m(2)) with cisplatin (25 mg/m(2)). Demographic, clinical, morbidity, and mortality data were compared for these patients (CHEMO) versus 85 patients undergoing gastrectomy without neoadjuvant chemotherapy (SURG). The CHEMO patients were more likely to be less than 70 years of age (P< or =0.01), have proximal tumors (P< or =0.01), and undergo proximal gastrectomy (P< or =0.025). Fifty-two percent of SURG patients had T3/T4 tumors compared to 19% of CHEMO patients, consistent with tumor downstaging. The R0 resection rate was similar (80%). Morbidity was 41% in CHEMO patients and 39% in SURG patients. There were five postoperative deaths (4.4%), two in the CHEMO group and three in the SURG group (P=NS). It was concluded that neoadjuvant chemotherapy with CPT-11 and cisplatin is not associated with increased postoperative morbidity compared to surgery alone. CPT-11-based neoadjuvant chemotherapy should be tested further in combined-modality treatment of gastric cancer
— id: 43617, year: 2003, vol: 7, page: 1015, stat: Journal Article,

Inhibition of matrix metalloproteinases reduces local and distant organ injury following experimental acute pancreatitis
Muhs, Bart E; Patel, Sundeep; Yee, Herman; Marcus, Stuart; Shamamian, Peter
2003 Feb;109(2):110-117, Journal of surgical research
BACKGROUND: Pulmonary complications from pancreatitis involve parenchymal destruction via proteolytic enzymes. Matrix metalloproteinases (MMPs) may play an important role in pulmonary injury following acute severe pancreatitis. We hypothesized that local and distant organ injury would be decreased by the presence of an MMP inhibitor (Batimistat; BB-94) following severe acute pancreatitis (AP). METHODS: Eighteen male rats were randomized into two groups: BB-94 (AP + 40 mg/kg/24 h BB-94 ip x three doses) or control (AP + 20 ml/kg/24 h normal saline ip x three doses). Necrotizing AP was induced by retrograde infusion of 5% sodium taurocholate (1.5 ml/kg) into the pancreatic duct. Twenty additional animals were randomized into BB-94 and control groups for the survival study. Serum was evaluated for amylase and MMP activity. Pancreatic sections were graded for edema, necrosis, neutrophil infiltrate, and hemorrhage. Myloperoxidase (MPO) activity was used to determine PMN infiltration in the lung. Evan's Blue dye extravasation was used to quantify vascular permeability. RESULTS: Animals in the BB-94 group had decreased amylase levels (1086.0 +/- 61.7 U/L vs 2232.7 +/- 309.9 U/L; P < 0.05), decreased cellular infiltrate (1.4 +/- 0.2 vs 2.3 +/- 0.2; P < 0.02), and decreased necrosis (4.1 +/- 0.3 vs 6.1 +/- 0.4; P < 0.005) compared to the control group. Lung tissue following pancreatitis in the BB-94 group demonstrated decreased MPO activity (41.5 +/- 2.4 units vs 57.3 +/- 2.9 units; P < 0.05) and decreased vascular permeability (18.3 +/- 2.8 mg/100 g vs 30.1 +/- 4.6 mg/100 g; P < 0.05). Animals treated with BB-94 had 100% survival compared to 50% survival in control at 72 h. CONCLUSIONS: Pancreatitis results in increased local and distant MMP activity. Pulmonary and pancreatic injury following AP can be abrogated by treatment with an MMP inhibitor (Batimistat; BB-94) which may result in decreased morbidity and mortality
— id: 34657, year: 2003, vol: 109, page: 110, stat: Journal Article,

Remembering September 11: reflections from Bellevue Hospital and New York University Medical Center
Marcus, Stuart G; Shamamian, Peter; Cushman, James
2002 Sep;132(3):502-505, Surgery
— id: 34660, year: 2002, vol: 132, page: 502, stat: Journal Article,

Neoadjuvant chemotherapy with CPT-11 and cisplatin downstages locally advanced gastric cancer
Newman, Elliot; Marcus, Stuart G; Potmesil, Milan; Sewak, Sanjeev; Yee, Herman; Sorich, Joan; Hayek, Mary; Muggia, Franco; Hochster, Howard
2002 Mar-Apr;6(2):212-223, Journal of gastrointestinal surgery
We examined the role of neoadjuvant therapy in downstaging locally advanced gastric cancer. Preoperative staging was performed with a combination of CT scans, endoscopic ultrasonography and/or laparoscopy, and laparoscopic ultrasonography. Patients with T > or =3 tumors and/or node-positive disease by preoperative clinical staging were eligible for entry. Neoadjuvant therapy consisted of two cycles of CPT-11 (75 mg/m(2)) with cisplatin (25 mg/m(2)) weekly four times every 6 weeks. This was followed by resection with D2 lymph node dissection and two cycles of intraperitoneal chemotherapy with floxuridine and cisplatin. Twenty-two patients were entered into the study (4 with T3N0 disease and 18 with T3N1 disease). Induction chemotherapy was well tolerated with major toxicities being neutropenia and diarrhea. A median of 78%/75% of the planned dosage of CPT-11/cisplatin was delivered. Two patients withdrew consent during the first cycle and were lost to follow-up. One patient progressed to stage IV disease during induction chemotherapy and did not undergo surgery. Nineteen patients underwent surgery. One patient had undetected stage IV disease (liver) and underwent a palliative R2 resection. Of the 18 remaining patients, 17 had curative R0 resections and one had a palliative R1 resection. A median of 21 lymph nodes (range 1 to 121) were examined histologically. There was one postoperative death. Surgical morbidity did not appear to increase after the neoadjuvant regimen. The median postoperative length of hospital stay was 9 days (range 3 to 75 days). Postoperative pathologic staging yielded 16% T3 lesions compared to 85% before treatment based on clinical staging; postoperative American Joint Committee on Cancer staging yielded 37% stage IIIA disease compared to 70% stage IIIA before treatment. With a median follow-up of 15 months, median survival has not yet been reached. We conclude that CPT-11-based neoadjuvant therapy downstages locally advanced gastric cancer. Further follow-up is necessary to determine the ultimate impact of this combination therapy on recurrence and survival
— id: 39653, year: 2002, vol: 6, page: 212, stat: Journal Article,

A prospective evaluation of esophagogastroduodenoscopy (EGD) in a population at increased risk for gastric cancer
Marcus, SG; Tian, HG; Lam, Y; Wong, CT; Ortega, J; Newman, E; Shamamian, P; Garbers, S; Villanueva, G; Yee, H
2001 APR ;120(5):A488-A488, Gastroenterology
— id: 55036, year: 2001, vol: 120, page: A488, stat: Journal Article,

Increased matrix metalloproteinase expression and activation following experimental acute pancreatitis
Muhs BE; Patel S; Yee H; Marcus S; Shamamian P
2001 Nov;101(1):21-28, Journal of surgical research
BACKGROUND: The observation that matrix metalloproteinases (MMPs) are central to tissue remodeling and may contribute to organ failure prompted us to investigate the role of MMPs in acute pancreatitis. We hypothesize that increased expression and activation of MMP-2 and MMP-9 will correlate with organ injury following acute pancreatitis. METHODS: Acute pancreatitis was induced in five male rats by retrograde infusion of 5% sodium taurocholate into the pancreatic duct. Sham laparotomy was performed on five rats serving as a control. Pancreatitis was confirmed by histology and serum amylase levels. MMP-2 and MMP-9 activity and expression were assayed by gelatin zymography in the lungs and ascitic fluid of each animal. Lung permeability was assayed by Evans blue dye extravasation. Lung activity of MMP-2 and MMP-9 was confirmed by a specific fluorogenic MMP substrate assay. RESULTS: Lung permeability increased twofold in the animals with severe pancreatitis compared with sham. Analysis of the zymograms from lung homogenate revealed a threefold increase in active MMP-2 in severe pancreatitis compared with sham and no change in MMP-9 activity. Gelatin zymograms of peritoneal fluid from severe pancreatitis animals demonstrated increased levels of active MMP-2 and MMP-9 compared with the sham group. Increases in MMP activity were confirmed by MMP activity assay using a fluorogenic substrate. CONCLUSIONS: This study demonstrates a correlation between severity of acute pancreatitis and active MMP-2 and MMP-9 levels in the peritoneal fluid and MMP-2 activity in lung homogenate. The MMP-mediated degradation of the basement membrane offers a potential pharmacologic and therapeutic target for halting the final biologic outcome of severe pancreatitis
— id: 26592, year: 2001, vol: 101, page: 21, stat: Journal Article,

CPT-11/cisplatin neoadjuvant therapy downstages locally advanced gastric cancer
Newman, E; Marcus, SG; Potmesil, M; Hochster, H; Yee, H; Sewak, S; Hayek, M; Muggia, FM
2001 APR ;120(5):A129-A129, Gastroenterology
— id: 55029, year: 2001, vol: 120, page: A129, stat: Journal Article,

Molecular staging in colon cancer (CC) with the aid of sentinel lymph node (SLN) mapping
Newman, E; Marjanovic, N; Alexander, A; Mustalish, D; Shamamian, P; Marcus, S; Melamed, J; Scholes, J; Delgado, Y; Kaufman, A; Jacobson, D
2001 APR ;120(5):A472-A473, Gastroenterology
— id: 55035, year: 2001, vol: 120, page: A472, stat: Journal Article,

Activation of progelatinase A (MMP-2) by neutrophil elastase, cathepsin G, and proteinase-3: a role for inflammatory cells in tumor invasion and angiogenesis
Shamamian P; Schwartz JD; Pocock BJ; Monea S; Whiting D; Marcus SG; Mignatti P
2001 Nov;189(2):197-206, Journal of cellular physiology
Gelatinase A (MMP-2), a matrix metalloproteinase (MMP) involved in tumor invasion and angiogenesis, is secreted as an inactive zymogen (proMMP-2) and activated by proteolytic cleavage. Here we report that polymorphonuclear neutrophil (PMN)-derived elastase, cathepsin G, and proteinase-3 activate proMMP-2 through a mechanism that requires membrane-type 1 matrix metalloproteinase (MT1-MMP) expression. Immunoprecipitation of human PMN-conditioned medium with a mixture of antibodies to elastase, cathepsin G, and proteinase-3 abolished proMMP-2 activation, whereas individual antibodies were ineffective. Incubation of HT1080 cells with either purified PMN elastase or cathepsin G or proteinase-3 resulted in dose-and time-dependent proMMP-2 activation. Addition of PMN-conditioned medium to MT1-MMP expressing cells resulted in increased proMMP-2 activation and in vitro invasion of extracellular matrix (ECM), but had no effect with cells that express no MT1-MMP. MMP-2 activation by PMN-conditioned medium or purified elastase was blocked by the elastase inhibitor alpha(1)-antitrypsin but not by Batimastat, an MMP inhibitor, showing that elastase activation of MMP-2 is not mediated by MMP activities. The PMN-conditioned medium-induced increase in cell invasion was blocked by Batimastat as well as by alpha(1)-antitrypsin, showing that PMN serine proteinases trigger a proteinase cascade that entails proMMP-2 activation: this gelatinase is the downstream effector of the proinvasive activity of PMN proteinases. These findings indicate a novel role for PMN-mediated inflammation in a variety of tissue remodeling processes including tumor invasion and angiogenesis
— id: 26640, year: 2001, vol: 189, page: 197, stat: Journal Article,

Decreasing length of stay after pancreatoduodenectomy
Brooks AD; Marcus SG; Gradek C; Newman E; Shamamian P; Gouge TH; Pachter HL; Eng K
2000 Jul;135(7):823-830, Archives of Surgery (Chicago)
HYPOTHESIS: Decreased length of stay (LOS) after pancreatoduodenectomy is due to multiple factors, including a lower complication rate and more efficient perioperative care for all patients, with and without complications. DESIGN: A retrospective review, validation cohort. SETTING: A single university hospital referral center. PATIENTS: A consecutive sample of patients undergoing pancreatoduodenectomy from January 9, 1986, to December 21, 1992 (group 1 [n = 104]) and from February 16, 1993, to November 9, 1998 (group 2 [n = 111]). INTERVENTION: Mann-Whitney test and linear [correction of logistic] regression analysis applied to clinical variables and LOS. MAIN OUTCOME MEASURES: Difference in median LOS between early and late groups and identification of factors predictive of decreased LOS. RESULTS: Total LOS decreased between the 2 groups (26 days [range, 13-117 days] vs 15 days [range, 5-61 days]; P<.001), with a decrease in preoperative (4 days [range, 0-28 days] vs 2 days [range, 0-36 days]; P<.001) and postoperative (19 days [range, 11-95 days] vs 12 days [range, 4-58 days]; P<.001) LOS (data given for group 1 vs group 2). Major complications decreased from 49% in group 1 to 25% in group 2 (P<.001). Postoperative LOS decreased for patients with (25 days [range, 15-95 days] vs 20 days [range, 8-58 days]; P = .05) and without (15 days [range, 11-47 days] vs 11 days [range, 4-55 days]; P<.001) major complications (data given for group 1 vs group 2). Multivariate analysis identified age (P = .01), pancreatic fistula (P<.001), delayed gastric emptying (P<.001), biliary complications (P<.001), operative time (P<.005), extra-abdominal infection (P<.005), use of a percutaneous stent (P = .04), and year of operation (P<.001) as independent predictors of total LOS. CONCLUSION: A reduction in complications in combination with factors leading to a streamlining of perioperative care has contributed to the decreased LOS after pancreatoduodenectomy
— id: 9076, year: 2000, vol: 135, page: 823, stat: Journal Article,

A descriptive study of an epidemic of poisoning caused by heroin adulterated with scopolamine
Hamilton RJ; Perrone J; Hoffman R; Henretig FM; Karkevandian EH; Marcus S; Shih RD; Blok B; Nordenholz K
2000 ;38(6):597-608, Journal of toxicology. Clinical toxicology
OBJECTIVE: Adulterants, contaminants, and diluents are all examples of additives to street drugs. Some of these additives may be pharmacologically active; however, it is unusual for them to cause toxic side effects. In the spring of 1995, a new form of heroin appeared in New York City, spreading to other East Coast cities, that was adulterated with scopolamine. It caused severe anticholinergic toxicity in heroin users with patients often presenting to emergency departments in great numbers. This is a report of the demographics and clinical characteristics of the epidemic. METHODS: A combination of prospective and retrospective data collection from the New York City, New Jersey, Delaware Valley, and Maryland Poison Centers. The primary measurements were age, sex, route of drug use, vital signs, signs and symptoms, disposition, and treatment. RESULTS: Of the 370 cases reported to the participating poison centers, 129 were excluded from the final analysis because of insufficient data. Of the patients who used this product, 55% presented with signs and symptoms of heroin toxicity but then became severely agitated with anticholinergic symptoms when naloxone was used to reverse respiratory depression. Nasal insufflation was the route of administration in 34% of the cases. Seizures were rare (3%). Ninety percent required admission, and half were admitted to a critical care unit. CONCLUSIONS: Adulteration of street drugs can lead to toxic epidemics. Poison centers are essential for identification of these trends and are the primary source of information on diagnosis and treatment
— id: 39492, year: 2000, vol: 38, page: 597, stat: Journal Article,

Total carboxypeptidase A (T-CPA) activity in pancreatic cancer
Joseph, KAPR; Gilvarg, C; Marcus, S; Shamamian, P
2000 APR ;118(4):A1527-A1527, Gastroenterology
— id: 54576, year: 2000, vol: 118, page: A1527, stat: Journal Article,

Improving survival in an underserved minority population with gastric cancer
Marcus, SG; Dave, J; Kim, S; Kim, M; Newman, E
2000 APR ;118(4):A1522-A1522, Gastroenterology
— id: 54575, year: 2000, vol: 118, page: A1522, stat: Journal Article,

Topical hepatic hypothermia attenuates pulmonary injury after hepatic ischemia and reperfusion
Patel S; Pachter HL; Yee H; Schwartz JD; Marcus SG; Shamamian P
2000 Dec;191(6):650-656, Journal of the American College of Surgeons
BACKGROUND: Prolonged periods of hepatic ischemia are associated with hepatocellular injury and distant organ dysfunction in experimental models. Neutrophils (PMN) and tumor necrosis factor (TNF)-alpha have been implicated, mostly because of their local deleterious effects on the hepatocyte after hepatic ischemia and reperfusion (I/R) injury. We hypothesize that topical hepatic hypothermia (THH) reduces ischemia and reperfusion-induced hepatic necrosis, PMN infiltration, TNF-alpha release, and consequent acute pulmonary injury. STUDY DESIGN: Sprague-Dawley rats (250 to 300g) were evenly divided into three groups: 90 minutes of normothermic (37 degrees C) partial hepatic ischemia (normothermic I/R), 90 minutes of hypothermic (25 degrees C) partial hepatic ischemia (hypothermic I/R), and sham laparotomy (without ischemia). There were six animals in each experimental group per time point unless otherwise specified. Hepatic necrosis and PMN infiltration were evaluated and scored on hematoxylin and eosin-stained liver specimens 12 hours after reperfusion. Serum TNF-alpha levels were determined by ELISA at 0 minutes, 15 minutes, 30 minutes, 1 hour, and 12 hours postreperfusion. Pulmonary PMN infiltration and vascular permeability were measured by myeloperoxidase activity and Evans blue dye extravasation, respectively, to quantitate pulmonary injury 12 hours after reperfusion. RESULTS: Normothermic I/R results in a significant increase in TNF-alpha at 15 and 30 minutes (p < 0.005), PMN infiltration (p < 0.001), and hepatic necrosis (p < 0.001), compared with sham. Institution of THH reduced peak serum TNF-alpha levels by 54% at 15 minutes (p < 0.005) and by 73% at 30 minutes (p < 0.001) postreperfusion compared with normothermic I/R. Similarly, hepatic PMN infiltration and necrosis at 12 hours were reduced by 60% (p < 0.05) and 47% (p < 0.05), respectively. Myeloperoxidase activity and Evans blue extravasation (measures of acute lung injury) were reduced by 42% and 39%, respectively, with institution of THH compared with animals undergoing normothermic I/R (p < 0.001). CONCLUSIONS: These results demonstrate that THH protects the liver from ischemia and reperfusion-induced necrosis and PMN infiltration. In addition, THH reduces the serum levels of TNF-alpha and associated pulmonary injury. These data suggest that the ischemic liver is a potential source of inflammatory mediators associated with hepatic ischemia and reperfusion-induced pulmonary injury
— id: 34662, year: 2000, vol: 191, page: 650, stat: Journal Article,

Neutrophil-derived serine proteinases enhance membrane type-1 matrix metalloproteinase-dependent tumor cell invasion
Shamamian P; Pocock BJ; Schwartz JD; Monea S; Chuang N; Whiting D; Marcus SG; Galloway AC; Mignatti P
2000 Feb;127(2):142-147, Surgery
BACKGROUND: Matrix metalloproteinase-2 degrades a variety of basement membrane components and is essential for tumor invasion. We have previously reported that membrane type-1 matrix metalloproteinase (MT1-MMP) cooperates with neutrophil-derived serine proteinases (NDPs; elastase, cathepsin G, protease-3) to activate matrix metalloproteinase-2. We therefore hypothesized that NDPs enhance tumor-cell invasion. METHODS: Clones of human HT1080 fibrosarcoma cells transfected with MT1-MMP sense (HT-SE) or antisense CDNA (HT-AS) were used. These cells express either high (HT-SE) or extremely low levels (HT-AS) of MT1-MMP relative to nontransfected HT1080 cells (HT-WT). The cells were incubated in the presence or absence of purified NDP, with or without alpha 1-antitrypsin or the MMP inhibitor batimastat. Cell invasion was measured with the use of Boyden chambers with polycarbonate membranes coated with a reconstituted extracellular matrix. RESULTS: Under control conditions HT-WT and HT-SE cells were 4-fold more invasive than HT-AS cells. The addition of NDP increased HT-WT and HT-SE cell invasion 60% to 100% but had no effect on HT-AS cells. alpha 1-antitrypsin or batimastat did not decrease the baseline invasiveness of HT-WT and HT-SE cells; however, they abrogated the stimulatory effect of NDP. CONCLUSIONS: HT1080 cell invasion depends on MT1-MMP expression. MT1-MMP overexpression does not increase invasiveness by itself. NDPs increase invasion by MT1-MMP expressing cells by activating matrix metalloproteinase-2
— id: 9013, year: 2000, vol: 127, page: 142, stat: Journal Article,

Expression of Von Willebrand factor, an endothelial cell marker, is up-regulated by angiogenesis factors: a potential method for objective assessment of tumor angiogenesis
Zanetta L; Marcus SG; Vasile J; Dobryansky M; Cohen H; Eng K; Shamamian P; Mignatti P
2000 Jan 15;85(2):281-288, International journal of cancer
von Willebrand factor (vWF), a glycoprotein produced uniquely by endothelial cells and megakaryocytes, is routinely used to identify vessels in tissue sections. Vessel density in tumor specimens, as determined by immuno-histochemical staining for vWF or other endothelial cell markers, is a negative prognostic factor for many solid tumors. vWF is heterogeneously distributed throughout the vasculature, transcriptional control in response to the tissue microenvironment being responsible for local variations in endothelial cell levels of vWF. Here, we report that fibroblast growth factor-2 and vascular endothelial growth factor, potent angiogenesis inducers expressed in a variety of tumors, up-regulate expression of vWF mRNA and protein in cultured endothelial cells with a synergistic effect. Our data support the measurement of vWF mRNA in tumors to detect activated endothelium or angiogenesis. For this purpose, we developed a semi-quantitative RT-PCR for vWF mRNA. Preliminary results obtained with specimens from colon carcinoma and the corresponding normal colonic mucosa showed higher vWF mRNA levels in most tumors than in their normal counterparts. The differences in vWF mRNA levels were much larger than the differences in vessel counts between a tumor and the corresponding normal mucosa, indicating that high vWF mRNA levels in tumors may indeed be an early sign of activation of the endothelium. The rapidity, objectivity, sensitivity and specificity of this technique make it suitable for routine clinical application to identify aggressive, highly angiogenic tumors.
— id: 9014, year: 2000, vol: 85, page: 281, stat: Journal Article,

Magnetic resonance imaging with magnetic resonance cholangiopancreatography accurately predicts resectability of pancreatic carcinoma
Hochwald SN; Rofsky NM; Dobryansky M; Shamamian P; Marcus SG
1999 Sep-Oct;3(5):506-511, Journal of gastrointestinal surgery
Accurate preoperative staging of pancreatic malignancy aids in directing appropriate therapy and avoids unnecessary invasive procedures. We evaluated the accuracy of magnetic resonance imaging (MRI) with magnetic resonance cholangiopancreatography (MRCP) in determining resectability of pancreatic malignancy. Twenty-one patients with suspected pancreatic malignancy underwent dynamic, contrast-enhanced breath-hold MRI with MRCP prior to surgical evaluation. Results of this study were correlated with operative results and pathologic findings. The sensitivity, specificity, and accuracy of MRI with MRCP in detecting a mass, determining the nature of the mass, and predicting lymph node involvement and resectability were determined. MRI with MRCP correctly identified the presence of a pancreatic mass in all 21 of these patients. Following pathologic correlation, it was determined that MRI with MRCP was 81% accurate in determining the benign or malignant nature of the pancreatic mass and 43% accurate in predicting lymph node involvement. In predicting resectability, MRI with MRCP had a sensitivity of 100%, specificity of 83%, positive predictive value of 94%, negative predictive value of 100%, and accuracy of 95%. MRI with MRCP is an accurate, noninvasive technique in the preoperative evaluation of pancreatic malignancy. Information obtained from MRI with MRCP including identification of a mass and predicting tumor resectability may be of value in staging and avoiding unnecessary invasive diagnostic procedures in patients with pancreatic cancer
— id: 9015, year: 1999, vol: 3, page: 506, stat: Journal Article,

Roles of MT1-MMP in the regulation of cell surface proteolysis
Monea S; Roberts B; Marcus SG; Shamamian P; Mignatti P
1999 Jun 30;878:703-706, Annals of the New York Academy of Sciences
— id: 9016, year: 1999, vol: 878, page: 703, stat: Journal Article,

Magnetic resonance imaging (MRI) with magnetic resonance cholangiopancreatography (MRCP) predicts resectability and ductal abnormalities in benign and malignant pancreatic disease
Hochwald, SN; Dobryansky, M; Rofsky, N; Shamamian, P; Marcus, SG
1998 APR 15 ;114(4):A1392-A1393, Gastroenterology
— id: 53476, year: 1998, vol: 114, page: A1392, stat: Journal Article,

Magnetic resonance cholangiopancreatography accurately predicts the presence or absence of choledocholithiasis
Hochwalk SN; Dobryansky M BA; Rofsky NM; Naik KS; Shamamian P; Coppa G; Marcus SG
1998 Nov-Dec;2(6):573-579, Journal of gastrointestinal surgery
Accurate common bile duct (CBD) imaging in patients with biliary calculi is an important determinant of specific therapy. Noninvasive methods to evaluate calculi in the CBD have limited accuracy and rely mainly on ultrasonography and computed tomography. Magnetic resonance cholangiopancreatography (MRCP) is a new noninvasive modality available to evaluate the biliary system. This study was undertaken to assess the accuracy of MRCP in predicting the presence or absence of CBD stones in patients at increased risk for choledocholithiasis. The medical records of 48 patients with a final diagnosis of biliary calculous disease undergoing MRCP between November 1995 and April 1997 were retrospectively reviewed. Three groups were identified: choledocholithiasis (n = 19), gallstone pancreatitis (n 5 11), and uncomplicated cholelithiasis (n = 18). In all patients the presence or absence of CBD calculi, as determined by MRCP, was correlated with the final diagnosis obtained from endoscopic retrograde cholangiopancreatography (ERCP) (n = 19), intraoperative cholangiography (n = 6), CBD exploration (n = 13), or clinical follow-up (n = 10). Sensitivity, specificity, and accuracy of MRCP were determined. The major clinical indications for MRCP in the 48 patients ware abnormal liver function tests followed by hyperamylasemia. Twenty patients were diagnosed with CBD stones and 28 were not. MRCP correctly predicted the presence of CBD stones in 19 of 20 patients and failed to detect CBD stones in one patient with gallstone pancreatitis. MRCP incorrectly predicted the presence of CBD stones in 3 of 28 patients ultimately found to have gallstones and no CBD stones. MRCP correctly predicted the absence of CBD stones in the other 25 patients including 10 patients with gallstone pancreatitis. Overall, MRCP had a sensitivity of 95%, a specificity of 89%, and an accuracy of 92%. MRCP is an accurate, noninvasive test for evaluating the CBD duct for the presence or absence of calculi in patients suspected of having CBD stones. Our data support the use of MRCP in the preoperative evaluation of these patients as findings may influence therapeutic decisions
— id: 6187, year: 1998, vol: 2, page: 573, stat: Journal Article,

Predicting comorbidity in patients with pancreatic fistulae following pancreaticoduodenectomy
Karpoff, HM; Sivamurthy, N; Oh, C; Gouge, TH; Pachter, HL; Eng, K; Shamamian, P; Marcus, SG
1998 APR 15 ;114(4):A1398-A1398, Gastroenterology
— id: 53477, year: 1998, vol: 114, page: A1398, stat: Journal Article,

Endoscopic biliary drainage before pancreaticoduodenectomy for periampullary malignancies
Marcus SG; Dobryansky M; Shamamian P; Cohen H; Gouge TH; Pachter HL; Eng K
1998 Mar;26(2):125-129, Journal of clinical gastroenterology
Despite decreased operative mortality, pancreaticoduodenectomy (PD) remains a formidable operation with substantial morbidity. We have evaluated the influence of preoperative endoscopic biliary drainage (EBD) on morbidity after PD for malignant biliary obstruction by retrospectively reviewing the medical records of 182 patients undergoing PD between April 1985 and August 1996. Of 52 study patients with malignant obstructive jaundice, 22 underwent preoperative EBD, and 30 were not drained. Eighty-three patients were excluded for bilirubin levels less than 5 mg/dl, 43 had other biliary drainage, and 4 had jaundice with benign pathology. Preoperative, intraoperative, and postoperative factors were compared. The two groups were well matched for clinical presentation and operative characteristics except for lower preoperative values of liver chemistries in patients undergoing EBD. Length of postoperative hospitalization for patients undergoing EBD was 13.5 days, compared with 19 days for patients who were not drained (p = 0.02). Patients who were not drained tended to have more overall complications (p = 0.054). Multivariate analysis revealed time to regular diet (p < 0.0001) and no preoperative drainage (p = 0.04) to be independent factors significantly increasing the length of hospitalization. Endoscopic biliary drainage before PD significantly reduced the length of postoperative hospitalization and was associated with less postoperative morbidity. Further studies, including cost analysis, are warranted
— id: 7673, year: 1998, vol: 26, page: 125, stat: Journal Article,

Roles of MT1-MMP in the regulation of cell surface proteolysis
Monea, S; Roberts, B; Marcus, S; Shamamian, P; Mignatti, P
1998 NOV ;9(11):175A-175A, Molecular biology of the cell
— id: 53644, year: 1998, vol: 9, page: 175A, stat: Journal Article,

Matrix metalloproteinase (MMP) 2 and 9 activity in experimental acute pancreatitis
Patel, S; Schwartz, J; Chaung, N; Marcus, SG; Pachter, HL; Deutsch, E; Galloway, AC; Eng, K; Mignatti, P; Shamamian, P
1998 APR 15 ;114(4):A1416-A1416, Gastroenterology
— id: 53478, year: 1998, vol: 114, page: A1416, stat: Journal Article,

Soluble factor(s) released from neutrophils activates endothelial cell matrix metalloproteinase-2
Schwartz JD; Monea S; Marcus SG; Patel S; Eng K; Galloway AC; Mignatti P; Shamamian P
1998 Apr;76(1):79-85, Journal of surgical research
OBJECTIVE: Polymorphonuclear leukocyte (PMN) infiltration and microvascular injury are hallmarks of the tissue remodeling associated with multiple organ failure. These processes require the concerted action of various proteolytic enzymes, including serine and matrix metalloproteinases (MMPs). Matrix metalloproteinase-2 (MMP-2) plays an important role in the turnover of various ECM components, including type IV collagen, fibronectin, and gelatins. Like all MMPs, MMP-2 is secreted as an inactive zymogen (proMMP-2) and activated extracellularly by limited proteolytic cleavage. The physiologic mechanism(s) of proMMP-2 activation remains unclear. This study was designed to characterize the effect of PMNs on the activation of proMMP-2 produced by endothelial cells. METHODS: PMNs and human umbilical vein endothelial cells (HUVECs) were grown either separately or together for 2-16 h. To evaluate the role of cell-cell contact, cocultures were also established in which the two cell types were separated by a semipermeable polycarbonate membrane. Alternatively, PMN-conditioned medium was added to HUVEC cultures with or without various proteinase inhibitors (aprotinin, 1,10-phenanthroline, Batimastat, E-64, eglin c peptide, or pepstatin A). After incubation, the culture supernatants were analyzed by gelatin zymography to characterize the gelatinases. RESULTS: HUVECs produce MMP-2 in its inactive (72 kDa) form. PMNs produce high levels of MMP-9 (gelatinase B, 92 kDa) but no MMP-2. Coculture of PMNs with or addition of PMN-conditioned medium to HUVECs results in the production of active (62 kDa) MMP-2. ProMMP-2 activation by PMN-conditioned medium is not blocked by inhibitors of plasmin, cysteine-, acid-, or metalloproteinases. CONCLUSION: PMNs release a soluble factor that activates endothelial cell MMP-2 through a novel mechanism independent of cell-cell contact and not attributable to the activities of plasmin, cysteine-, acid-, or metalloproteinases. These findings may provide insight into the tissue remodeling that accompanies PMN-mediated microvascular injury
— id: 9018, year: 1998, vol: 76, page: 79, stat: Journal Article,

Activation of tumor cell matrix metalloproteinase-2 by neutrophil proteinases requires expression of membrane-type 1 matrix metalloproteinase
Schwartz JD; Shamamian P; Monea S; Whiting D; Marcus SG; Galloway AC; Mignatti P
1998 Aug;124(2):232-238, Surgery
BACKGROUND: Matrix metalloproteinase-2 (MMP-2), an enzyme involved in tumor invasion, is secreted as an inactive proenzyme and requires interaction with membrane-type 1 MMP (MT1-MMP) for activation. We have previously demonstrated that polymorphonuclear neutrophils (PMNs) release a soluble factor(s) that activates pro-MMP-2. Therefore, we tested the hypothesis that PMN-derived proteinases act in concert with MT1-MMP to activate pro-MMP-2. METHODS: Human HT-1080 cells transfected with MT1-MMP cDNA (HT-SE) or the corresponding antisense cDNA (HT-AS) or an empty vector (HT-V), which expressed differing levels of MT1-MMP, were incubated with serum-free, human PMN-conditioned medium with or without proteinase inhibitors. The culture supernatants were analyzed by gelatin zymography. RESULTS: Ht-1080 cells expressing basal (HT-V) or low levels (HT-AS) of MT1-MMP secreted MMP-2 in proenzyme from (72 kd). Ht-1080 cells with high levels of MT1-MMP (HT-SE) secreted pro MMP-2 and a 68 kd intermediate activation product. Addition of PMN-conditioned medium to either HT-SE or HT-V clones resulted in dose-dependent generation of active, 62 kd MMP-2. In contrast, when PMN-conditioned medium was added to HT-AS clones, no MMP-2 activation occurred. CONCLUSIONS: PMN-derived serine proteinases act in concert with MT1-MMP to activate proMMP-2. This finding indicates a potential role for inflammatory cells in promoting extracellular matrix breakdown during tumor invasion
— id: 9017, year: 1998, vol: 124, page: 232, stat: Journal Article,

Carboxypeptidase A activity in pancreatic cancer and acute pancreatitis
Shamamian, P; Marcus, S; Deutsch, E; Maldonado, T; Liu, A; Stewart, J; Eng, K; Gilvarg, C
1998 APR 15 ;114(4):A1425-A1425, Gastroenterology
— id: 53479, year: 1998, vol: 114, page: A1425, stat: Journal Article,

Serial MR in gene therapy for recurrent glioblastoma: initial experience and work in progress
Deliganis AV; Baxter AB; Berger MS; Marcus SG; Maravilla KR
1997 Sep;18(8):1401-1406, AJNR. American journal of neuroradiology
PURPOSE: To describe the MR imaging findings in a pilot study evaluating gene therapy for treatment of patients with recurrent glioblastoma. METHODS: Serial MR examinations were evaluated retrospectively in patients treated with gene therapy that included a retroviral vector containing the herpes simplex virus thymidine kinase gene and intravenous ganciclovir. Images were obtained after tumor resection and after each cycle of treatment, at approximately 40-day intervals. The volume of enhancing tissue was measured on serial MR images. RESULTS: Eleven patients with recurrent glioblastoma were entered into the clinical trial of gene therapy and seven patients completed at least two cycles of treatment. Of these seven, three patients had an early (between 40 and 80 days) increase in the volume of enhancing tissue followed by a decrease or plateau in enhancing tissue volume. A fourth patient had a stable volume of enhancing tissue for 132 days. The remaining three patients had continuous increases in volume of enhancement on all subsequent MR examinations. CONCLUSION: Although animal data show striking tumor regression in response to similar gene therapy, only limited regression was observed among the seven patients we studied. The transient increases in enhancement seen in three of seven patients might reflect an inflammatory response to local injection of the viral vector
— id: 9019, year: 1997, vol: 18, page: 1401, stat: Journal Article,

Lexipafant inhibits platelet activating factor enhanced neutrophil functions
Schwartz JD; Shamamian P; Grossi EA; Schwartz DS; Marcus SG; Steiner F; Jacobs CE; Tayyarah M; Eng K; Colvin SB; Galloway AC
1997 May;69(2):240-248, Journal of surgical research
Platelet activating factor (PAF) enhances polymorphonuclear leukocyte (PMN) superoxide (.O2-) production, CD11b expression, and elastase release, all essential components in the pathophysiology of multiple-organ failure. This study was designed to determine the effects of Lexipafant, a PAF receptor antagonist, on PAF-mediated PMN functions. PMNs from 10 healthy volunteers were isolated and pretreated with various concentrations of Lexipafant (0-100 microM). PMNs were then incubated for 5 min with 200 nM PAF for .O2- detection or 2000 nM PAF for elastase measurement and activated with 1 microM N-formylmethionylleucylphenylalanine. The mean rate of .O2- production was determined by a cytochrome c reduction assay (nmole .O2-/min/1.33 x 10(5) PMN +/- SEM). Elastase release was measured by the cleavage of the synthetic elastase substrate Meo-Suc-Ala-Ala-Pro-Val-pNA (mean elastolytic activity +/- SEM). In parallel experiments, PMNs were incubated with 200 nM PAF for 30 min following pre-treatment with Lexipafant and CD11b expression was determined by flow cytometry (mean fluorescence intensity +/- SEM). Statistical analysis was performed using repeated-measures ANOVA (P < 0.05). Lexipafant inhibited PAF-enhanced PMN .O2- generation, CD11b expression and elastase release in a dose dependent fashion. The IC50 of Lexipafant for .O2- production, CD11b expression, and elastase release was 0.046, 0.285, and 0.05 microM, respectively. Lexipafant attenuated the PAF-mediated upregulation of PMN .O2- production, CD11b expression, and elastase release in a dose dependent fashion. These data support the hypothesis that Lexipafant may reduce the severity of the inflammatory response to injury produced by PAF-enhanced activation of PMNs
— id: 9020, year: 1997, vol: 69, page: 240, stat: Journal Article,

Use of double marking with retroviral vectors to determine rate of reconstitution of untreated and cytokine expanded CD34+ selected marrow cells in patients undergoing autologous bone marrow transplantation
Heslop HE; Brenner MK; Krance RA; Bowman L; Cunningham JM; Richardson S; Alexander B; Heideman R; Boyett JM; Srivastava DK; Marcus SG; Berenson R; Heimfeld S; Brown S
1996 Mar 20;7(5):655-667, Human gene therapy
— id: 9021, year: 1996, vol: 7, page: 655, stat: Journal Article,

Optimal management of the pancreatic remnant after pancreaticoduodenectomy
Marcus SG; Cohen H; Ranson JH
1995 Jun;221(6):635-645, Annals of surgery
OBJECTIVE: The authors evaluated methods of operative management of the pancreatic remnant after pancreaticoduodenectomy. SUMMARY BACKGROUND DATA: Despite reductions in mortality after pancreaticoduodenectomy, leakage from the pancreatic remnant still may cause significant morbidity. Patients with small, unobstructed pancreatic ducts or soft, friable pancreata are at particularly high risk. Although numerous surgical techniques have been described to avoid such complications, no single method is suitable for all patients. METHODS: The authors retrospectively reviewed the medical records of 114 consecutive patients who underwent pancreaticoduodenectomy. Sixty-nine patients were men (61%) and 45 were women (39%), with median age 66 years. Underlying disease was malignant in 87 (76%) and benign in 27 (24%). Patients were divided into groups based on risk for postoperative pancreatic fistula and on the operative management of the pancreatic remnant. Sixty-eight patients underwent end-to-side pancreaticojejunostomy, 13 of whom were high risk (group 1A) and 55 of whom were low risk (group 1B). Thirty-seven patients, all high risk, had either pancreatic duct closure by oversewing (N = 19, group 2) or end-to-end pancreaticojejunal invagination (N = 18, group 3). Nine patients underwent total pancreatectomy (group 4). Morbidity related to prolonged pancreatic drainage (PPD) of greater than 20 days was determined. RESULTS: Overall incidence of PPD was 17% and caused the only death. Patients considered high risk for postoperative pancreatic fistula had a 36% incidence of PPD compared with 2% in patients considered low risk (p < 0.0001). Prolonged pancreatic drainage frequency related to the method of pancreatic remnant management was as follows: group 1A, 15%; group 1B, 2%; group 2, 79%; and group 3, 6% (p < 0.001 for group 2 vs. other groups). No serious sequelae followed PPD in 15 patients (79%); however, 4 patients required reoperation for pseudocyst or abscess drainage; one in group 1A (who died) and three in group 2. Multivariate analysis revealed that operative technique (oversewing of the pancreatic duct) and male sex were significant factors predisposing a patient to the development of PPD. CONCLUSION: After pancreaticoduodenectomy, pancreatic remnant management by end-to-side pancreaticojejunostomy appeared safe in low-risk patients. In high-risk patients, end-to-end pancreaticojejunal invagination was the safest option. Morbidity was greatest after pancreatic duct closure without anastomosis
— id: 9022, year: 1995, vol: 221, page: 635, stat: Journal Article,

Pulmonary embolectomy for intravenous uterine leiomyomatosis
Marcus SG; Krauss T; Freedberg RS; Culliford AT; Weinreich DJ; Kronzon I
1994 Jun;127(6):1642-1645, American heart journal
— id: 6445, year: 1994, vol: 127, page: 1642, stat: Journal Article,

The use of interleukin-6 to generate tumor-infiltrating lymphocytes with enhanced in vivo antitumor activity
Marcus SG; Perry-Lalley D; Mule JJ; Rosenberg SA; Yang JC
1994 Feb;15(2):105-112, Journal of immunotherapy with emphasis on tumor immunology
Tumor-infiltrating lymphocytes (TIL) are cytotoxic T cells isolated from solid tumors and expanded in vitro in recombinant interleukin-2 (rIL-2). TIL have antitumor effects in murine models and in some patients with melanoma. In an effort to generate murine TIL with enhanced in vivo therapeutic efficacy, viable tumor cells were coinjected with a collagen matrix plus recombinant human IL-6 (rIL-6) subcutaneously into syngeneic mice to achieve sustained local concentrations of rIL-6 at the tumor site from which TIL were derived. In five separate experiments, single cell suspensions of tumors were admixed with either (a) Hanks' balanced salt solution (HBSS), (b) 2% (20 mg/ml) collagen matrix only, (c) 250 micrograms rIL-6 only, or (d) 250 micrograms rIL-6 in a 2% collagen matrix (prolonged release) before subcutaneous inoculation. These tumors were subsequently resected and TIL were isolated and expanded in vitro. TIL generated from tumors admixed with matrix plus rIL-6 were significantly more effective than TIL expanded from tumors admixed with HBSS (four of five experiments), TIL from tumors admixed with matrix only (five of five experiments), and TIL from tumors admixed with rIL-6 only (three of four experiments) in an established tumor treatment model. In no experiment was any other TIL culture superior to TIL grown from tumors augmented with collagen matrix plus rIL-6. These results suggest that strategies designed to increase the local concentrations of cytokines at tumor sites may lead to the generation of more potent TIL for clinical administration
— id: 9023, year: 1994, vol: 15, page: 105, stat: Journal Article,

Regression of metastatic renal cell carcinoma after cytoreductive nephrectomy
Marcus SG; Choyke PL; Reiter R; Jaffe GS; Alexander RB; Linehan WM; Rosenberg SA; Walther MM
1993 Aug;150(2 Pt 1):463-466, Journal of urology
Fewer than 1% of patients with renal cell carcinoma are reported to experience spontaneous regression of metastatic lesions after nephrectomy. We report on 4 of 91 patients (4.4%) with metastatic renal cell carcinoma who had spontaneous regression of all metastatic lesions after cytoreductive nephrectomy. These patients were carefully selected before surgery for the ability to receive high dose interleukin-2. One patient had recurrence at 2 months, 1 had recurrence at 11 months, and 2 had no evidence of disease at 3 and 4.5 years
— id: 9026, year: 1993, vol: 150, page: 463, stat: Journal Article,

Long-term outcome in 87 patients with low-grade soft-tissue sarcoma
Marcus SG; Merino MJ; Glatstein E; DeLaney TF; Steinberg SM; Rosenberg SA; Yang JC
1993 Dec;128(12):1336-1343, Archives of Surgery (Chicago)
OBJECTIVE: To describe the long-term clinical outcome of patients with low-grade soft-tissue sarcoma and identify factors that may predict or determine their prognosis. DESIGN: Retrospective chart review with multivariate analysis. SETTING: Large research hospital and referral center. PATIENTS: All patients treated between 1975 and 1990 at the National Cancer Institute (Bethesda, Md) who had a confirmed diagnosis of low-grade soft-tissue sarcoma. INTERVENTIONS: Surgery and radiation therapy. MAIN OUTCOME MEASURES: Local recurrence and overall survival. RESULTS: For patients with nonretroperitoneal lesions, overall survival was excellent, with a history of recurrence, a positive surgical margin, and an absence of adjuvant radiation therapy significantly associated with increased risks of local recurrence. Patients with retroperitoneal lesions not only had an increased risk of local recurrence, but significantly poorer overall survival. CONCLUSIONS: Low-grade soft-tissue sarcomas are associated with excellent overall survival, especially those confined to nonretroperitoneal sites. The risk of local recurrence after resection with negative margins and/or adjuvant radiation therapy is very low and most recurrences can be controlled with further therapy
— id: 9025, year: 1993, vol: 128, page: 1336, stat: Journal Article,

Hepatic abscess in cancer patients. Characterization and management
Marcus SG; Walsh TJ; Pizzo PA; Danforth DN Jr
1993 Dec;128(12):1358-1364, Archives of Surgery (Chicago)
OBJECTIVE: To identify factors that may aid in the diagnosis and treatment of patients with malignant neoplasms in whom hepatic abscesses develop. DESIGN: Retrospective review of medical records. PATIENTS: Thirty-seven oncology patients in whom hepatic abscesses developed at the National Cancer Institute, Bethesda, Md, between June 1954 and October 1989. RESULTS: Among 37 cancer patients, bacterial abscesses developed in 17 and fungal abscesses developed in 20. Among the patients with bacterial abscesses, 12 (71%) had a solid-tissue malignant neoplasm, 10 (59%) had a prior invasive procedure, and six (35%) had prior chemotherapy. In comparison, among the patients with fungal abscesses, 15 (75%) had a hematologic malignant neoplasm and five (25%) had a solid-tissue malignant neoplasm (P2 = .014). Two patients with fungal abscesses (10%) had a prior invasive procedure (P2 = .004) and 19 (95%) had prior chemotherapy (P2 < .0001). As compared with fungal abscesses, bacterial abscesses were larger (P2 < .00001) and fewer (P2 = .004). Antibiotics and percutaneous or surgical drainage effectively treated bacterial abscesses. Amphotericin B usually eradicated hepatic fungal infections. CONCLUSIONS: The results of this study reveal the importance of the clinical setting in the diagnosis of hepatic abscesses in cancer patients. Aggressive treatment of these abscesses is indicated and is frequently effective
— id: 9024, year: 1993, vol: 128, page: 1358, stat: Journal Article,

A phase I trial of fluorouracil, leucovorin, and recombinant interferon alpha-2b in patients with advanced malignancy
Taylor CW; Modiano MR; Woodson ME; Marcus SG; Alberts DS; Hersh EM
1992 Apr;19(2 Suppl 3):185-190, Seminars in oncology
We conducted a phase I trial of fluorouracil (5-FU), leucovorin, (LCV), and recombinant interferon-alpha-2b (rIFN-alpha-2b). The doses of each of the three agents were escalated sequentially. 5-FU and LCV were administered by IV bolus, weekly for 6 weeks and rIFN-alpha-2b was administered by subcutaneous injection, three times weekly for 6 weeks. Twenty-nine patients with advanced cancer (75% colon or pancreatic cancer) were treated. Partial remissions were observed in three patients (10%) with previously untreated colon cancer, colon cancer refractory to 5-FU plus LCV and previously untreated pancreatic cancer, respectively. An additional three patients with pancreatic, prostate, and rectal cancer had a 50% reduction in tumor markers but no change in objective tumor measurements. The toxicity of this regimen was tolerable. The most common toxicities were diarrhea, fatigue, flu-like symptoms, nausea/vomiting, and mucositis. However, no fatal or life-threatening toxicities were observed. We conclude that the combination of 5-FU, LCV, and rIFN-alpha-2b can be safely administered and recommend further evaluation of this regimen in patients with tumors of gastrointestinal origin using doses of 5-FU 600 mg/m2, LCV 500 mg/m2, and rIFN-alpha-2b 10 x 10(6) U
— id: 9027, year: 1992, vol: 19, page: 185, stat: Journal Article,

Intratumor administration of beta-interferon in recurrent malignant gliomas. A phase I clinical and laboratory study
Fetell MR; Housepian EM; Oster MW; Cote DN; Sisti MB; Marcus SG; Fisher PB
1990 Jan 1;65(1):78-83, Cancer
We administered doses of 5 to 180 x 10(6) IU of beta-serine-interferon (IFN-beta ser17) twice weekly to 20 patients with recurrent malignant gliomas in a Phase I study. Interferon was given through an Ommaya reservoir connected by a catheter to the tumor cavity. Side effects of interferon therapy occurred in only one patient and consisted of nausea, vomiting, fever, and chills after each treatment, presumably due to rapid diffusion of interferon into ventricular cerebrospinal fluid (CSF). Problems with the Ommaya reservoir (obstruction in two patients and infection in four patients) led to six patients being terminated from the study, and represent the major difficulty with this form of therapy. Although this was primarily a study of interferon toxicity, of 12 evaluable patients, 3 had stable disease for 148, 192, and 539 days; 9 had progressive disease. In addition, we tested the effect of IFN-beta ser17 on the growth of early passage in vitro cultures of malignant gliomas established from patients. Growth inhibition varied from 0% to more than 50%. In all cultures evaluated, the combination of recombinant gamma-interferon plus IFN-beta ser17 enhanced growth inhibition. Further clinical and laboratory study is necessary to better define the therapeutic efficacy of IFN-beta ser17 and the role of combinations of interferons in the treatment of malignant gliomas
— id: 9029, year: 1990, vol: 65, page: 78, stat: Journal Article,

A pilot study of recombinant interferon beta (IFN-beta ser) in patients with recurrent glioma
Yung WK; Castellanos AM; Van Tassel P; Moser RP; Marcus SG
1990 Aug;9(1):29-34, Journal of neuro-oncology
Recombinant interferon beta (IFN-beta ser) has been administered by intravenous bolus injection three times weekly at a dose of 90 x 10(6) IU to 14 patients with recurrent malignant glioma in an ongoing study. The treatment period has ranged from 1 to 40 weeks. The most common adverse experiences were fever, chills, malaise, and headache. Fever, chills and headache were worse with the first two doses and were usually relieved with acetaminophen. All patients tolerated subsequent treatments without any difficulties. No neurologic or hematologic toxicities were observed. Of ten evaluable patients, five had progressive disease in 4 to 8 weeks; three had stable disease for 12 to 21 weeks; one has had a minor response for 13 weeks; and one has had a complete resolution of tumor for 150 + weeks. IFN-beta ser appears to have activity in human glioma and is well tolerated at this dosage and schedule
— id: 9028, year: 1990, vol: 9, page: 29, stat: Journal Article,

Phase II trial of recombinant beta interferon in advanced colorectal cancer
Lillis PK; Brown TD; Beougher K; Koeller J; Marcus SG; Von Hoff DD
1987 Oct;71(10):965-967, Cancer treatment reports
Betaseron is a genetically altered recombinant beta interferon with in vitro properties equivalent to those of native beta interferon. Nineteen patients with measurable advanced colorectal carcinoma who had no previous chemotherapy were given 30 X 10(6) IU Betaseron by iv push on Days 1-5 and 8-12 of each 28-day cycle. One of 17 evaluable patients had a complete response after nine courses of treatment which has been sustained greater than 9 months. The overall response rate was 6% (95% confidence limits, 0%-18%). Treatment was well tolerated with toxic effects consisting of fever, flu-like symptoms, nausea and vomiting, and transient mild granulocytopenia and liver function abnormalities. All toxic effects were World Health Organization (WHO) grade less than or equal to 2. No interferon neutralizing antibody activity was detected. Phase I and preclinical data support further investigation of Betaseron with dose escalation to tolerance for individual patients, as well as investigation of concomitant therapy with 5-fluorouracil, in an attempt to improve the observed response rate in colorectal cancer
— id: 9030, year: 1987, vol: 71, page: 965, stat: Journal Article,