George Miller, M.D.

Team play in surgical education: a simulation-based study
Marr, Mollie; Hemmert, Keith; Nguyen, Andrew H; Combs, Ronnie; Annamalai, Alagappan; Miller, George; Pachter, H Leon; Turner, James; Rifkind, Kenneth; Cohen, Steven M
2012 Jan;69(1):63-69, Journal of surgical education
BACKGROUND: Simulation-based training provides a low-stress learning environment where real-life emergencies can be practiced. Simulation can improve surgical education and patient care in crisis situations through a team approach emphasizing interpersonal and communication skills. OBJECTIVE: This study assessed the effects of simulation-based training in the context of trauma resuscitation in teams of trainees. METHODS: In a New York State-certified level I trauma center, trauma alerts were assessed by a standardized video review process. Simulation training was provided in various trauma situations followed by a debriefing period. The outcomes measured included the number of healthcare workers involved in the resuscitation, the percentage of healthcare workers in role position, time to intubation, time to intubation from paralysis, time to obtain first imaging study, time to leave trauma bay for computed tomography scan or the operating room, presence of team leader, and presence of spinal stabilization. Thirty cases were video analyzed presimulation and postsimulation training. The two data sets were compared via a 1-sided t test for significance (p < 0.05). Nominal data were analyzed using the Fischer exact test. RESULTS: The data were compared presimulation and postsimulation. The number of healthcare workers involved in the resuscitation decreased from 8.5 to 5.7 postsimulation (p < 0.001). The percentage of people in role positions increased from 57.8% to 83.6% (p = 0.46). The time to intubation from paralysis decreased from 3.9 to 2.8 minutes (p < 0.05). The presence of a definitive team leader increased from 64% to 90% (p < 0.05). The rate of spine stabilization increased from 82% to 100% (p < 0.08). After simulation, training adherence to the advanced trauma life support algorithm improved from 56% to 83%. CONCLUSIONS: High-stress situations simulated in a low-stress environment can improve team interaction and educational competencies. Providing simulation training as a tool for surgical education may enhance patient care
— id: 148733, year: 2012, vol: 69, page: 63, stat: Journal Article,

Effect of intra-operative fluid volume on peri-operative outcomes after pancreaticoduodenectomy for pancreatic adenocarcinoma
Melis M; Marcon F; Masi A; Sarpel U; Miller G; Moore H; Cohen S; Berman R; Pachter HL; Newman E
2012 Jan;105(1):81-4 L, Journal of surgical oncology
BACKGROUND: Excess use of intravenous fluid can increase post-operative complications. We examined the influence of intra-operative crystalloid (IOC) administration on complications following pancreaticodudenectomy (PD) for pancreatic adenocarcinoma. METHODS: We categorized 188 patients who underwent PD for adenocarcinoma (1990-2009) into two groups: Group I received <6,000 ml and Group II received >/=6,000 ml IOC. Differences between groups in length of stay, overall morbidity, and 30-day mortality were evaluated. RESULTS: There were 86 patients in Group I and 102 in Group II. Group I patients were older and with higher percentage of women, but similar in regards to performance status, ASA score, underlying comorbidities, and administration of neo-adjuvant treatment. Group II patients had longer operations, increased blood loss, and higher rates of intra-operative blood transfusions. There were two post-operative deaths, both in the Group II (P = 0.5). Post-operative overall morbidity was 45.7%, without differences between the two groups (44.2% vs. 47.1%, P = 0.7). Likewise, length of post-operative stay was similar in both groups (13.8 days vs. 14.5 days, P = 0.5). CONCLUSIONS: The volume of IOC increased with duration of surgery, intra-operative blood losses, and intra-operative blood transfusion, but did not correlate with post-operative morbidity. J. Surg. Oncol (c) 2011 Wiley-Liss, Inc
— id: 136611, year: 2012, vol: 105, page: 81, stat: Journal Article,

The role of dendritic cell and pancreatic stellate cell cross-talk in chronic pancreatitis
Nguyen A.H.; Bedrosian A.S.; Connolly M.; Henning J.; Medina-Zea V.; Cieza-Rubio N.E.; Dorvil-Castro M.; Graffeo C.; Hackman M.; Rehman A.; Ibrahim J.; Miller G.
2012 ;(172):2-2, Journal of surgical research
Introduction: Chronic pancreatitis (CP) is characterized by fibro-inflammatory transformation of the pancreatic parenchyma. the precise cellular mediators in CP are incompletely understood. Dendritic cells (DC) have recently emerged as initiators of organ-specific inflammation. Pancreatic stellate cells (PSC) become potently pro-inflammatory in CP and are primarily responsible for deposition of extracellular matrix proteins and fibrillar collagen. We postulated that an intimate relationship between DC and PSC mediate the dramatic fibro-inflammatory changes in CP. Methods: DC were isolated from bone marrow aspirates and cultured for 8 days in complete RPMI supplemented with murine GMCSF. PSC were isolated aftermechanical and chemical digestion of pancreas, followed by density centrifugation and plastic adherence. DC-PSC co-culture was accomplished by culturing equal number of DC and PSC for 24 to 48 hours before washing off the non-adherent DC. Cell culture supernatant was assayed using cytometric bead or ELISA. for in vivo experiments, a three week caerulein model of chronic pancreatitis was employed in C57BL/6micewith selectmice receiving i. p. adoptive transfer of DC (1x106 thrice weekly). in vivo PSC activation was measured using monoclonal antibodies directed against Desmin and a-SMA. Results: in vitroDC-PSCco-culture resulted in activation ofPSCsurface phenotype and the production ofhigher levels ofPDGF,as well as numerous chemokines and cytokines byPSC(Table). Effectswere contingent on direct cellular interaction betweenDCand PSC as well as DCexpression of ICAM-1 and MyD88. in vivo i. p. adoptive transfer of DC in murine caerulein-induced chronic pancreatitis resulted in markedly increased fibro- inflammatory changes in the pancreas as well as 4-fold increase in percent desmin-positive acini, and approximately 80% a-SMA-positive acini (Figure). However, whereasDCinduced PSC to become pro-inflammatory, DC inhibited PSC proliferation, failed to stimulate PSC migration, and did not induce PSC to express higher levels of extra-cellular matrix proteins or Collagen I in co-culture experiments. Furthermore, our experimental data suggest bi-directional cross-talk asPSCprevented DCmaturation but acted as a potentDCchemoattractant. Conclusions: DCand PSC induce robust bidirectional crosstalk that affects CP. DCinduce PSC to become pro-inflammatory, but do cannot cause PSC to adopt fully mature myofibroblast-like properties. (Figure presented)
— id: 150878, year: 2012, vol: , page: 2, stat: Journal Article,

Dendritic cells promote pancreatic viability in mice with acute pancreatitis
Bedrosian, Andrea S; Nguyen, Andrew H; Hackman, Michael; Connolly, Michael K; Malhotra, Ashim; Ibrahim, Junaid; Cieza-Rubio, Napoleon E; Henning, Justin R; Barilla, Rocky; Rehman, Adeel; Pachter, H Leon; Medina-Zea, Marco V; Cohen, Steven M; Frey, Alan B; Acehan, Devrim; Miller, George
2011 Nov;141(5):1915-1926.e14, Gastroenterology
BACKGROUND & AIMS: The cellular mediators of acute pancreatitis are incompletely understood. Dendritic cells (DCs) can promote or suppress inflammation, depending on their subtype and context. We investigated the roles of DC in development of acute pancreatitis. METHODS: Acute pancreatitis was induced in CD11c.DTR mice using caerulein or L-arginine; DCs were depleted by administration of diphtheria toxin. Survival was analyzed using Kaplan-Meier method. RESULTS: Numbers of major histocompatibility complex II(+)CD11c(+) DCs increased 100-fold in pancreata of mice with acute pancreatitis to account for nearly 15% of intrapancreatic leukocytes. Intrapancreatic DCs acquired a distinct immune phenotype in mice with acute pancreatitis; they expressed higher levels of major histocompatibility complex II and CD86 and increased production of interleukin-6, membrane cofactor protein-1, and tumor necrosis factor-alpha. However, rather than inducing an organ-destructive inflammatory process, DCs were required for pancreatic viability; the exocrine pancreas died in mice that were depleted of DCs and challenged with caerulein or L-arginine. All mice with pancreatitis that were depleted of DCs died from acinar cell death within 4 days. Depletion of DCs from mice with pancreatitis resulted in neutrophil infiltration and increased levels of systemic markers of inflammation. However, the organ necrosis associated with depletion of DCs did not require infiltrating neutrophils, activation of nuclear factor-kappaB, or signaling by mitogen-activated protein kinase or tumor necrosis factor-alpha. CONCLUSIONS: DCs are required for pancreatic viability in mice with acute pancreatitis and might protect organs against cell stress
— id: 139730, year: 2011, vol: 141, page: 1915, stat: Journal Article,

Dendritic cell depletion exacerbates acetaminophen hepatotoxicity
Connolly MK; Ayo D; Malhotra A; Hackman M; Bedrosian AS; Ibrahim J; Cieza-Rubio NE; Nguyen AH; Henning JR; Dorvil-Castro M; Pachter HL; Miller G
2011 Sep 2;54(3):959-68 L, Hepatology
Acetaminophen (APAP) overdose is one of the most frequent causes of acute liver failure in the United States and is primarily mediated by toxic metabolites that accumulate in the liver upon depletion of glutathione stores. However, cells of the innate immune system, including natural killer (NK) cells, neutrophils, and Kupffer cells, have also been implicated in the centrilobular liver necrosis associated with APAP. We have recently shown that dendritic cells (DCs) regulate intrahepatic inflammation in chronic liver disease and, therefore, postulated that DC may also modulate the hepatotoxic effects of APAP. We found that DC immune-phenotype was markedly altered after APAP challenge. In particular, liver DC expressed higher MHC II, costimulatory molecules, and Toll-like receptors, and produced higher interleukin (IL)-6, macrophage chemoattractant protein-1 (MCP-1), and tumor necrosis factor alpha (TNF-alpha). Conversely, spleen DC were unaltered. However, APAP-induced centrilobular necrosis, and its associated mortality, was markedly exacerbated upon DC depletion. Conversely, endogenous DC expansion using FMS-like tyrosine kinase 3 ligand (Flt3L) protected mice from APAP injury. Our mechanistic studies showed that APAP liver DC had the particular capacity to prevent NK cell activation and induced neutrophil apoptosis. Nevertheless, the exacerbated hepatic injury in DC-depleted mice challenged with APAP was independent of NK cells and neutrophils or numerous immune modulatory cytokines and chemokines. Conclusion: Taken together, these data indicate that liver DC protect against APAP toxicity, whereas their depletion is associated with exacerbated hepatotoxicity. (HEPATOLOGY 2011;)
— id: 137961, year: 2011, vol: 54, page: 959, stat: Journal Article,

Pan-negative bone marrow-derived cells dramatically worsen pancreatitis VIA an ICAM-1 dependent mechanism
Graffe C.S.; Hackman M.; Rehman A.; Rahim S.; Nguyen A.; Medina-Zea M.; Lebovics H.; Dorvil-Castro M.; Marr M.; Henning J.; Miller G.
2011 ;40(8):1323-1323, Pancreas
Background: Chronic pancreatitis (CP) is characterized by progressive fibro-inflammatory organ injury leading to exocrine and endocrine dysfunction. As bone marrow-derived cells (BMC) are known to be associated with inflammatory tissue injury, our goal was to investigate the role ofBMC in CP. We postulated that BMC exacerbate pancreatic inflammation and fibrosis. Methods: We FACS sorted BMC into three phenotypic subpopulations: hematopoetic progenitor cells (HPC: Lin^-CD34⁺), hematopoetic stem cells (HSC: Lin-CD34-c-Kit⁺Sca⁺), and pan-negative cells (PN: Lin^-CD34-c-Kit^- Each subpopulation was adoptively transferred (1x10⁶ cells i.p. injection, thrice weekly) to mice undergoing caerulein pancreatitis (seven consecutive hourly i.p. injections [50Kg/kg] thrice weekly for three weeks). Results: BMC migration to the pancreas was increased in CP. HSC and HPC were noted to mildly exacerbate CP, while PN were associated with severe disease exacerbation as indicated by marked edema, advanced fibrosis, and pronounced inflammation. Further characterization of PN cells revealed that they acquired granulocyte-like characteristics in vitro and in vivo. PN cells required expression ofICAM-1 to affect pancreatic injury. Furthermore, effects were CD4⁺ and CD8⁺ T cell dependent. Conclusions: PN cells dramatically worsen CP via an ICAM-1 dependant mechanism. As such, PN cells may make an attractive target for experimental therapeutics in CP
— id: 140547, year: 2011, vol: 40, page: 1323, stat: Journal Article,

Impact of socioeconomic status and sociodemographic factors on melanoma presentation among ethnic minorities
Wich, Lindsay G; Ma, Michelle W; Price, Leah S; Sidash, Stanislav; Berman, Russell S; Pavlick, Anna C; Miller, George; Sarpel, Umut; Goldberg, Judith D; Osman, Iman
2011 Jun;36(3):461-468, Journal of community health
Minority melanoma patients have worse survival. In this study, we evaluated the impact of socioeconomic and demographic factors on minority melanoma patients presenting to two different New York City hospitals (one public and one private) managed by the same multidisciplinary team. Sociodemographic and clinicopathologic characteristics were retrieved for melanoma patients presenting to Bellevue Hospital Center (BHC), a public hospital, and the New York University Cancer Institute (NYUCI), a private cancer center. Socioeconomic data was obtained from the United States Census Bureau database. The Kruskal-Wallis and chi-square tests were used to evaluate the associations between race/ethnicity and continuous and categorical variables (e.g. income, stage at presentation), respectively. Minorities comprised 2% (27/1296) of melanoma patients at the NYUCI compared to 42% (50/119) at BHC. Those presenting to the NYUCI were more likely to have a higher median household income (P = 0.05), a higher educational level (P = 0.04), and an earlier stage at presentation (P = 0.02) than those at BHC. NYUCI patients were predominantly covered by commercial insurance (70%), whereas Medicaid (62%) was common among BHC patients. Only 19% of Hispanic patients at BHC chose English as their preferred language. Our data demonstrate that language and health care system factors affect melanoma presentation in minorities
— id: 138281, year: 2011, vol: 36, page: 461, stat: Journal Article,

In hepatic fibrosis, liver sinusoidal endothelial cells acquire enhanced immunogenicity
Connolly, Michael K; Bedrosian, Andrea S; Malhotra, Ashim; Henning, Justin R; Ibrahim, Junaid; Vera, Valery; Cieza-Rubio, Napoleon E; Hassan, Burhan U; Pachter, H Leon; Cohen, Steven; Frey, Alan B; Miller, George
2010 Aug 15;185(4):2200-2208, Journal of immunology
The normal liver is characterized by immunologic tolerance. Primary mediators of hepatic immune tolerance are liver sinusoidal endothelial cells (LSECs). LSECs block adaptive immunogenic responses to Ag and induce the generation of T regulatory cells. Hepatic fibrosis is characterized by both intense intrahepatic inflammation and altered hepatic immunity. We postulated that, in liver fibrosis, a reversal of LSEC function from tolerogenic to proinflammatory and immunogenic may contribute to both the heightened inflammatory milieu and altered intrahepatic immunity. We found that, after fibrotic liver injury from hepatotoxins, LSECs become highly proinflammatory and secrete an array of cytokines and chemokines. In addition, LSECs gain enhanced capacity to capture Ag and induce T cell proliferation. Similarly, unlike LSECs in normal livers, in fibrosis, LSECs do not veto dendritic cell priming of T cells. Furthermore, whereas in normal livers, LSECs are active in the generation of T regulatory cells, in hepatic fibrosis LSECs induce an immunogenic T cell phenotype capable of enhancing endogenous CTLs and generating potent de novo CTL responses. Moreover, depletion of LSECs from fibrotic liver cultures mitigates the proinflammatory milieu characteristic of hepatic fibrosis. Our findings offer a critical understanding of the role of LSECs in modulating intrahepatic immunity and inflammation in fibro-inflammatory liver disease
— id: 111819, year: 2010, vol: 185, page: 2200, stat: Journal Article,

Distinct populations of metastases-enabling myeloid cells expand in the liver of mice harboring invasive and preinvasive intra-abdominal tumor
Connolly, Michael K; Mallen-St Clair, Jon; Bedrosian, Andrea S; Malhotra, Ashim; Vera, Valery; Ibrahim, Junaid; Henning, Justin; Pachter, H Leon; Bar-Sagi, Dafna; Frey, Alan B; Miller, George
2010 Apr;87(4):713-725, Journal of leukocyte biology
The liver is the most common site of adenocarcinoma metastases, even in patients who initially present with early disease. We postulated that immune-suppressive cells in the liver of tumor-bearing hosts inhibit anti-tumor T cells, thereby accelerating the growth of liver metastases. Using models of early preinvasive pancreatic neoplasia and advanced colorectal cancer, aims of this study were to determine immune phenotype, stimulus for recruitment, inhibitory effects, and tumor-enabling function of immune-suppressive cells in the liver of tumor-bearing hosts. We found that in mice with intra-abdominal malignancies, two distinct CD11b(+)Gr1(+) populations with divergent phenotypic and functional properties accumulate in the liver, becoming the dominant hepatic leukocytes. Their expansion is contingent on tumor expression of KC. These cells are distinct from CD11b(+)Gr1(+) populations in other tissues of tumor-bearing hosts in terms of cellular phenotype and cytokine and chemokine profile. Liver CD11b(+)Gr1(+) cells are highly suppressive of T cell activation, proliferation, and cytotoxicity and induce the development of Tregs. Moreover, liver myeloid-derived suppressor cells accelerate the development of hepatic metastases by inactivation of cytotoxic T cells. These findings may explain the propensity of patients with intra-abdominal cancers to develop liver metastases and suggest a promising target for experimental therapeutics
— id: 108918, year: 2010, vol: 87, page: 713, stat: Journal Article,

In liver fibrosis, dendritic cells govern hepatic inflammation in mice via TNF-alpha
Connolly, Michael K; Bedrosian, Andrea S; Mallen-St Clair, Jon; Mitchell, Aaron P; Ibrahim, Junaid; Stroud, Andrea; Pachter, H Leon; Bar-Sagi, Dafna; Frey, Alan B; Miller, George
2009 Nov;119(11):3213-25, Journal of clinical investigation
Hepatic fibrosis occurs during most chronic liver diseases and is driven by inflammatory responses to injured tissue. Because DCs are central to modulating liver immunity, we postulated that altered DC function contributes to immunologic changes in hepatic fibrosis and affects the pathologic inflammatory milieu within the fibrotic liver. Using mouse models, we determined the contribution of DCs to altered hepatic immunity in fibrosis and investigated the role of DCs in modulating the inflammatory environment within the fibrotic liver. We found that DC depletion completely abrogated the elevated levels of many inflammatory mediators that are produced in the fibrotic liver. DCs represented approximately 25% of the fibrotic hepatic leukocytes and showed an elevated CD11b+CD8- fraction, a lower B220+ plasmacytoid fraction, and increased expression of MHC II and CD40. Moreover, after liver injury, DCs gained a marked capacity to induce hepatic stellate cells, NK cells, and T cells to mediate inflammation, proliferation, and production of potent immune responses. The proinflammatory and immunogenic effects of fibrotic DCs were contingent on their production of TNF-alpha. Therefore, modulating DC function may be an attractive approach to experimental therapeutics in fibro-inflammatory liver disease
— id: 105172, year: 2009, vol: 119, page: 3213, stat: Journal Article,

Genome wide analysis and clinical correlation of chromosomal and transcriptional mutations in cancers of the biliary tract
Miller, George; Socci, Nicholas D; Dhall, Deepti; D'Angelica, Michael; DeMatteo, Ronald P; Allen, Peter J; Singh, Bhuvanesh; Fong, Yuman; Blumgart, Leslie H; Klimstra, David S; Jarnagin, William R
2009 ;28:62-62, Journal of experimental & clinical cancer research : CR
BACKGROUND: The pathogenesis of biliary cancers is ill-defined. This study investigates changes in gene expression and copy number in biliary cancers and correlates these changes with anatomical site of origin, histopathology and outcome. METHODS: We performed gene expression and CGH analysis on 34 biliary tract cancer specimens. Results were confirmed by RT-PCR. Clinical-pathologic correlation was made using functional over-representation analysis of the top 100 mutations associated with each variable. RESULTS: There were 545 genes with altered expression in extrahepatic cholangiocarcinoma, 2,354 in intrahepatic cholangiocarcinoma, and 1,281 in gallbladder cancer. Unsupervised hierarchical clustering analysis indicated there was no difference in the global gene expression patterns between each biliary cancer subgroup. CGH analysis revealed that short segments of chromosomes 1p, 3p, 6q, 8p, 9p, and 14q were commonly deleted across all cancer subtypes. Commonly amplified regions included segments of 1q, 3q, 5p, 7p, 7q, 8q, and 20q. Over-representation analysis revealed an association between altered expression of functional gene groupings and pathologic features. CONCLUSION: This study defined regions of the genome associated with changes in DNA copy number and gene expression in specific subtypes of biliary cancers. The findings have implications for identification of therapeutic targets, screening, and prognostication
— id: 111661, year: 2009, vol: 28, page: 62, stat: Journal Article,

Gastic MALT lymphoma
Miller G; Berman R
Advanced therapy in surgical oncology Hamilton ON : BC Decker, 2008,
— id: 5249, year: 2008, vol: , page: ?, stat: Chapter,

Gallbladder carcinoma
Miller, G; Jarnagin, W R
2008 Mar;34(3):306-312, European journal of surgical oncology
Although it is the most common cancer of the biliary tree, gallbladder carcinoma remains an uncommon disease. As a result, many clinicians rarely encounter it and there is uncertainty regarding proper management. Resection is the most effective and only potentially curative treatment. Early stage tumors are often curable with a proper resection; however, many patients present late in the course of the disease when surgical intervention is no longer effective. While other treatment modalities are used in patients with advanced disease, there is limited data on efficacy. In many cases, the diagnosis is made after a cholecystectomy has been performed and an incidental tumor is identified in the specimen. In such cases, reoperation and definitive resection is appropriate and effective for patients with invasive lesions
— id: 132227, year: 2008, vol: 34, page: 306, stat: Journal Article,

Surgical images: soft tissue. Necrotizing fasciitis of the abdominal wall
Miller, George; MacLean, Alexandra A; Hiotis, Karen
2008 Feb;51(1):56-56, Canadian journal of surgery = Journal canadien de chirurgie
— id: 76863, year: 2008, vol: 51, page: 56, stat: Journal Article,

Cancer of the biliary tract and gallbladder
Miller G; Janagin WR
Textbook of surgical oncology London : Informa Healthcare, 2007,
— id: 5250, year: 2007, vol: , page: ?, stat: Chapter,

Outcomes after resection of synchronous or metachronous hepatic and pulmonary colorectal metastases
Miller, George; Biernacki, Peter; Kemeny, Nancy E; Gonen, Mithat; Downey, Robert; Jarnagin, William R; D'Angelica, Michael; Fong, Yuman; Blumgart, Leslie H; DeMatteo, Ronald P
2007 Aug;205(2):231-238, Journal of the American College of Surgeons
BACKGROUND: Surgical resection of isolated hepatic or pulmonary colorectal metastases prolongs survival in selected patients. But the benefits of resection and appropriate selection criteria in patients who develop both hepatic and pulmonary metastases are ill defined. STUDY DESIGN: Data were prospectively collected from 131 patients with colorectal cancer who underwent resection of both hepatic and pulmonary metastases over a 20-year period. Median followup was 6.6 years from the time of resection of the primary tumor. Patient, treatment, and outcomes variables were analyzed using log-rank, Cox regression, and Kaplan-Meier methods. RESULTS: The site of first metastasis was the liver in 65% of patients, the lung in 11%, and both simultaneously in 24%. Multiple hepatic metastases were present in 51% of patients, and multiple pulmonary metastases were found in 48%. Hepatic lobectomy or trisegmentectomy was required in 61% of patients; most lung metastases (80%) were treated with wedge excisions. Median survival rates from resection of the primary disease, first site of metastasis, and second site of metastasis were 6.9, 5.0, and 3.3 years, respectively. After resection of disease at the second site of metastasis, the 1-, 3-, 5-, and 10-year disease-specific survival rates were 91%, 55%, 31%, and 19%, respectively. An analysis of prognostic factors revealed that survival was significantly longer when the disease-free interval between the development of the first and second sites of metastases exceeded 1 year, in patients with a single liver metastasis, and in patients younger than 55 years old. CONCLUSIONS: Surgical resection of both hepatic and pulmonary colorectal metastases is associated with prolonged survival in selected patients. Patients with a longer disease-free interval between metastases and those with single liver lesions had the best outcomes
— id: 74388, year: 2007, vol: 205, page: 231, stat: Journal Article,

The use of imaging in the diagnosis and staging of hepatobiliary malignancies
Miller, George; Schwartz, Lawrence H; D'Angelica, Michael
2007 Apr;16(2):343-368, Surgical oncology clinics of North America
This review addresses the optimal use of imaging in the diagnosis, staging, and treatment planning of patients with hepatobiliary neoplasms. We focus on primary liver cancers, including hepatocellular carcinoma and intrahepatic cholangiocarcinoma as well as extrahepatic biliary tract malignancies, including hilar cholangiocarcinoma and gallbladder cancer. In each section, we provide an overview of the staging requirements for each disease followed by a discussion of various imaging modalities that can be used to optimally stage the disease and plan therapy
— id: 74387, year: 2007, vol: 16, page: 343, stat: Journal Article,

Hypopharyngeal rupture associated with Hangman's fracture after blunt trauma
Wolf J; Miller G; Sultan R; Miglietta M; Frangos S
2007 Dec;:571-573, Surgical rounds
— id: 105480, year: 2007, vol: , page: 571, stat: Journal Article,

Pancreaticoureteral fistula following penetrating abdominal trauma
Wolf, Joshua H; Miller, George; Ashinoff, Russell; Dave, Jasmine; Lefleur, Richard S; Frangos, Spiros G; Miglietta, Maurizio A
2007 ;8(5):613-616, JOP: journal of the pancreas
CONTEXT: The main pancreatic duct can form a fistulous communication with another epithelium in the setting of prolonged inflammation, operative manipulation, or direct trauma. We present a rare complication of a pancreaticoureteral fistula following a trauma nephrectomy. CASE REPORT: A 17-year-old male who sustained a gunshot wound to the back arrived to our Emergency Room hyopotensive, tachycardic, and with free intraperitoneal fluid on focused assessment sonography for trauma (FAST) exam. He was taken to the operating room for an exploratory laporatomy where a left nephrectomy was performed to control active bleeding from the left renal hilum. Significant bleeding was also encountered at the portal venous confluence. After packing and damage control laparotomy, the periportal/pancreatic bleeding was controlled during a second procedure 6 hours later. After one month in the Intensive Care Unit with an open abdomen, a computed tomography (CT) scan revealed a fluid collection in the splenic fossa which was drained by catheter. Persistent drainage revealed a high amylase concentration (greater than 50,000 U/L). A fistulogram revealed interruption of the main pancreatic duct, and a fluid collection by the tail of the pancreas that was in communication with the left ureter. The patient's urine amylase was also elevated. The patient was treated non-operatively given the healing open abdomen and controlled fistula. He had an otherwise uncomplicated recovery. CONCLUSIONS: This is the second report of a pancreaticoureteral fistula in the literature. Treatment of this communication should be similar to that of other pancreatic fistulae
— id: 74304, year: 2007, vol: 8, page: 613, stat: Journal Article,

Casebook of small bowel obstruction
Miller G; Gordon PH
2006 ;14(12):1-2, Parkhurst exchange
— id: 74392, year: 2006, vol: 14, page: 1, 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,

Retroperitoneal perforation of the duodenum from biliary stent erosion
Miller, George; Yim, Duke; Macari, Michael; Harris, Marsha; Shamamian, Peter
2005 Sep-Oct;62(5):512-515, Current surgery
Endoscopically placed biliary stents have supplanted surgical decompression as the preferred treatment option for patients with obstructive jaundice from advanced pancreatic cancer. An unusual complication of indewelling biliary stents is duodenal perforation into the retroperitoneum. We describe the case of a patient with end-stage pancreatic cancer who presented with an acute abdomen from erosion of a previously placed bile duct stent through the wall of the second portion of the duodenum. Although our patient presented with advanced symptoms, clinical presentations can vary from mild abdominal discomfort and general malaise to overt septic shock. Definitive diagnosis is best made with computed tomography (CT) imaging, which can detect traces of retroperitoneal air and fluid. Treatment options vary from nonoperative management with antibiotics, bowel rest, and parenteral alimentation in the most stable patients to definitive surgery with complete diversion of gastric contents and biliary flow from the affected area in patients with clinical symptoms or radiologic evidence suggesting extensive contamination. Complications of management can include duodenal fistulization, residual retroperitoneal or intrabdominal abscess, and ongoing sepsis. This report highlights the salient issues in the presentation, diagnosis, and modern management of patients with this rare complication of indwelling biliary stents
— id: 61335, year: 2005, vol: 62, page: 512, stat: Journal Article,

Abdominal wall necrotizing fasciitis from dislodged percutaneous endoscopic gastrostomy tubes: a case series
MacLean, Alexandra A; Miller, George; Bamboat, Zubin M; Hiotis, Karen
2004 Sep;70(9):827-831, American surgeon
We report three cases of abdominal wall necrotizing fasciitis that occurred as a result of leakage from displaced percutaneous endoscopic gastrostomy tubes. This is the first report of such a series. Patients underwent extensive operative excisions of their abdominal walls down to their posterior fascia. All patients tolerated their initial surgery, however, two patients ultimately expired from respiratory complications. The surviving patient underwent multiple repeat debridements and reconstructive abdominal wall surgery. We review the epidemiology of patients at risk for this complication and discuss its presentation, as well as the appropriate workup and management. We also address the issues of closure of large abdominal wall defects and future alimentation in this patient group. Finally, abdominal wall necrotizing faciitis from gastrostomy tube leakage is a devastating complication, and the development of preventative strategies for patients at risk is of paramount importance
— id: 47840, year: 2004, vol: 70, page: 827, stat: Journal Article,

Potential impact of the 80-hour work week on interst in surgery as a career
Miller G
2004 ;21(3):16-17, Focus on surgical education
— id: 74390, year: 2004, vol: 21, page: 16, stat: Journal Article,

Adhesion-related bowel obstruction in men
Miller G; Gordon PH
2004 ;2:11-12, Adhesions news & views
— id: 74391, year: 2004, vol: 2, page: 11, stat: Journal Article,

Impact of mandatory resident work hour limitations on medical students' interest in surgery
Miller, George; Bamboat, Zubin M; Allen, Frederick; Biernacki, Peter; Hopkins, Mary Ann; Gouge, Thomas H; Riles, Thomas S
2004 Nov;199(4):615-619, Journal of the American College of Surgeons
BACKGROUND: The number of US medical students applying for general surgery residency has been declining. Recent studies have shown that the issue of 'controllable lifestyle' has become a critical factor in medical students' decision-making process. We postulate that widespread implementation of resident work hour limitations would bolster medical students' interest in pursuing surgical careers. STUDY DESIGN: Students from New York University School of Medicine were surveyed about their attitudes toward work hour limitations and its effect on their interest in pursuing a surgical residency. One hundred thirty-two students participated. RESULTS: Nearly 95% of respondents believed that work hour limitations were a positive change and, if all other factors were equal, they would choose a training program that used work hour limitations over one that did not. The most common reasons cited in favor of limits were improvements in resident lifestyle (42%) and patient safety (34%). Fifty-three percent of respondents indicated that presence of work hour limitations alone would increase their interest in considering a surgical residency and only 2% of medical students indicated that it would lessen their interest in surgery. Not surprisingly, intellectual interest in a specialty was the most important factor in choosing a residency for 86% of students. Nevertheless, work hour limitations were designated a higher priority than future salary by 55% of medical students. CONCLUSIONS: The presence of work hour limitations has a positive impact on medical students' interest in surgery. Widespread implementation of work hour limitations may bolster the number of applications for surgical residency
— id: 46084, year: 2004, vol: 199, page: 615, stat: Journal Article,

Attitudes of applicants for surgical residency toward work hour limitations
Miller, George; Bamboat, Zubin M; Allen, Frederick; Hopkins, Mary Ann; Gouge, Thomas H; Riles, Thomas S; Nalbandian, Matthew M
2004 Sep;188(2):131-135, American journal of surgery
BACKGROUND: There is an ongoing debate regarding the merits of resident work-hour limitations. We postulated that this issue would be a factor in the decision-making process of applicants to surgical residency. METHODS: Candidates for surgical residency at a university-based program completed an anonymous survey during their visit. Data was analyzed by analysis of variance and the chi-square test. RESULTS: Most candidates viewed work-hour limitations as being favorable to their future training. Nevertheless, work-hour limitations ultimately were not a critical factor in the decision-making process compared with issues such as quality of training and program reputation. Candidates ranked 'reading in surgery' the most likely way they would spend the leisure time afforded by work-hour limitations. CONCLUSIONS: Most applicants for surgical residency consider work hour-limitations as being favorable to their training and view the extra free time as an opportunity for furthering their education. However, other issues take precedence when choosing a residency
— id: 46008, year: 2004, vol: 188, page: 131, stat: Journal Article,

Natural killer cell depletion confounds the antitumor mechanism of endogenous IL-12 overexpression
Miller, George; Bleier, Joshua I; Antonescu, Cristina; Pillarisetty, Venu G; Shah, Alaap B; Lahrs, Svenja; DeMatteo, Ronald P
2004 Jun 20;110(3):395-402, International journal of cancer
IL-12 gene transfer to hepatocytes using a recombinant adenovirus vector (AdIL-12) has been shown to protect against primary and metastatic liver tumors in mice. However, the mechanism of protection has been elusive and studies using depleting monoclonal antibodies or transgenic mice have purported it to be independent of T and NK cells. We postulated that depletion of NK cells may distort the experimental model and misrepresent the antitumor mechanism by altering the magnitude and duration of transgene expression. We show in mice treated with AdIL-12 that NK depletion increased serum IL-12 levels by more than 250-fold and prolonged transgene expression by nearly 2 weeks compared to nondepleted mice. To determine the contribution of NK cells to tumor protection after AdIL-12 treatment, we analyzed NK cells from treated animals. Isolated NK cells were markedly activated in terms of their lytic activity and IFN-gamma secretion. Adoptive transfer of NK cells from mice that had been treated with AdIL-12 to naive mice was sufficient to confer protection against colorectal hepatic metastases. This protection was mediated in part by NK-cell production of IFN-gamma. Our findings indicate that NK-cell depletion distorts the model of systemic AdIL-12 administration by markedly altering transgene expression, which then may potentiate other antitumor mechanisms, and that endogenous IL-12 overexpression activates NK cells, rendering them sufficient to protect against liver metastases. These data have critical implications for investigating the immunologic mechanisms of experimental models that utilize gene transfer
— id: 74386, year: 2004, vol: 110, page: 395, stat: Journal Article,

Liver dendritic cells are less immunogenic than spleen dendritic cells because of differences in subtype composition
Pillarisetty, Venu G; Shah, Alaap B; Miller, George; Bleier, Joshua I; DeMatteo, Ronald P
2004 Jan 15;172(2):1009-1017, Journal of immunology
The unique immunological properties of the liver may be due to the function of hepatic dendritic cells (DC). However, liver DC have not been well characterized because of the difficulty in isolating adequate numbers of cells for analysis. Using immunomagnetic bead and flow cytometric cell sorting, we compared freshly isolated murine liver and spleen CD11c+ DC. We found that liver DC are less mature, capture less Ag, and induce less T cell stimulation than spleen DC. Nevertheless, liver DC were able to generate high levels of IL-12 in response to CpG stimulation. We identified four distinct subtypes of liver DC based on the widely used DC subset markers CD8alpha and CD11b. Lymphoid (CD8alpha+CD11b-) and myeloid (CD8alpha-CD11b+) liver DC activated T cells to a similar degree as did their splenic DC counterparts but comprised only 20% of all liver DC. In contrast, the two more prevalent liver DC subsets were only weakly immunostimulatory. Plasmacytoid DC (B220+) accounted for 19% of liver DC, but only 5% of spleen DC. Our findings support the widely held notion that liver DC are generally weak activators of immunity, although they are capable of producing inflammatory cytokines, and certain subtypes potently activate T cells
— id: 74385, year: 2004, vol: 172, page: 1009, stat: Journal Article,

Selective loss of c-Rel compromises dendritic cell activation of T lymphocytes
Boffa, Daniel J; Feng, Biao; Sharma, Vijay; Dematteo, Ronald; Miller, George; Suthanthiran, M; Nunez, Rafael; Liou, Hsiou-Chi
2003 Apr;222(2):105-115, Cellular immunology
Dendritic cells initiate the immune response by presenting antigen in the context of varying levels of costimulation. The maturation state of the dendritic cell determines the quantity and quality (Th1, Th2) of the subsequent T cell response. Members of the NF-kappaB family of transcription factors have previously been implicated in dendritic cell development. Here, we used a mouse with a homozygous c-Rel deletion to investigate the role of c-Rel in the function of bone marrow derived dendritic cells. When direct presentation was evaluated, we found c-Rel(-/-) dendritic cells induce less allogeneic T cell stimulation than c-Rel(+/+) dendritic cells. In addition, T cell encounters with c-Rel(-/-) dendritic cells generate less IFN-gamma and IL-4 when compared to those with c-Rel(+/+) DCs. A similar degree of functional compromise was observed in antigen-specific T cells that were stimulated by c-Rel(-/-) dendritic cells. Functional deficits were not linked to differences in the ability to undergo maturation per se, as LPS exposure induced similar morphologic and cell surface changes in both c-Rel(+/+) and cRel(-/-) DCs. Although LPS induced a compensatory increase in the nuclear activity of fellow NF-kappaB family members, RelB and p65, LPS exposure was unable to negate the deficiencies in autologous T cell proliferation and cytokine production associated with the loss of c-Rel in dendritic cells. Taken together, our study supports a unique and non-redundant role for c-Rel in dendritic cell costimulatory capacity
— id: 74384, year: 2003, vol: 222, page: 105, stat: Journal Article,

Overexpression of interleukin-12 enables dendritic cells to activate NK cells and confer systemic antitumor immunity
Miller, George; Lahrs, Svenja; Dematteo, Ronald P
2003 Apr;17(6):728-730, FASEB journal
Dendritic cells (DC) are initiators of T cell-mediated immunity. However, less is known about the relationship between DC and natural killer (NK) cells, and direct evidence of their interaction in vivo is scarce. Interleukin (IL)-12 is an activator of both DC and NK cells. We postulated that secretion of IL-12 by DC would enable them to activate NK cells. Bone marrow-derived DC propagated only in granulocyte macrophage colony-stimulating factor did not activate NK cells. In contrast, DC engineered to express IL-12 markedly stimulated NK cells as determined by coculture experiments in vitro, assays of NK cells isolated from treated animals, and survival experiments in a systemic tumor model. Activation depended on both DC-NK cellular interaction and secretion of IL-12. Adoptive transfer of DC expressing IL-12 to mice markedly increased NK cell interferon-gamma production and lytic activity in vivo. Treated mice were also protected against B16 melanoma hepatic metastases. The in vivo effects on NK cells were DC-specific. Administration of IL-12 protein alone or melanoma cells or fibroblasts engineered to secrete IL-12 were only weakly activating. Our findings demonstrate that IL-12 expression by DC enables them to activate NK cells and provide evidence for a substantial DC-NK relationship in vivo
— id: 74380, year: 2003, vol: 17, page: 728, stat: Journal Article,

Optimization of dendritic cell maturation and gene transfer by recombinant adenovirus
Miller, George; Lahrs, Svenja; Shah, Alaap B; DeMatteo, Ronald P
2003 Jun;52(6):347-358, Cancer immunology immunotherapy
Dendritic cells (DC) have vast potential for immunotherapy. Transferring therapeutic genes to DC may enhance their inherent T cell-stimulatory capacity. Recombinant adenovirus is the most efficient vehicle for DC gene transfer and can alone mature DC. We sought to define the parameters of adenovirus infection of murine bone marrow-derived DC (BMDC) and the concomitant impact on BMDC maturation. The efficiency of adenoviral gene transfer to DC depended on the mouse strain, the organ source of DC, and the level of DC maturation. C57BL/6 BMDC consistently had higher transgene expression than BALB/c DC. While BMDC had considerable GFP expression after AdGFP infection, adenovirus was relatively ineffective in accomplishing transgene expression in freshly isolated hepatic or splenic DC. BMDC that were relatively immature because of a shorter duration of culture had higher transgene expression after infection. Nevertheless, pretreatment of DC with exogenous stimulants such as LPS or TNF-alpha resulted in higher transgene expression. Maturation of BMDC depended only on virus entry but not viral gene or transgene expression. Therefore, DC maturation was disproportionately high compared to the percentage of DC that actually expressed the adenoviral transgene. Maturation by adenovirus was only seen in BMDC, but not in liver or splenic DC, and was more pronounced in DC from later in culture (day 12 versus day 6). There was a dose-response relationship, up to a threshold dose, between adenovirus infection and both DC maturation and enhancement of DC activation of antigen-specific T cells. Our findings underscore the importance of optimizing gene transfer to DC in designing strategies for immunotherapy
— id: 74383, year: 2003, vol: 52, page: 347, stat: Journal Article,

Murine Flt3 ligand expands distinct dendritic cells with both tolerogenic and immunogenic properties
Miller, George; Pillarisetty, Venu G; Shah, Alaap B; Lahrs, Svenja; DeMatteo, Ronald P
2003 Apr 1;170(7):3554-3564, Journal of immunology
Human Flt3 ligand can expand dendritic cells (DC) and enhance immunogenicity in mice. However, little is known about the effects of murine Flt3 ligand (mFlt3L) on mouse DC development and function. We constructed a vector to transiently overexpress mFlt3L in mice. After a single treatment, up to 44% of splenocytes became CD11c(+) and the total number of DC increased 100-fold. DC expansion effects lasted for >35 days. mFlt3L DC were both phenotypically and functionally distinct. They had increased expression of MHC and costimulatory molecules and expressed elevated levels of B220 and DEC205 but had minimal CD4 staining. mFlt3L DC also had a markedly altered cytokine profile, including lowered secretion of IL-6, IL-10, IFN-gamma, and TNF-alpha, but had a slightly increased capacity to stimulate T cells in vitro. However, in a variety of in vivo models, DC expanded by mFlt3L induced tolerogenic effects on T cells. Adoptive transfer of Ag-pulsed mFlt3L splenic DC to naive mice actually caused faster rates of tumor growth and induced minimal CTL compared with control DC. mFlt3L also failed to protect against tumors in which human Flt3 ligand was protective, but depletion of CD4(+) T cells restored tumor protection. Our findings 1) demonstrate that mFlt3L has distinct effects on DC development, 2) suggest an important role for mFlt3L in generating DC that have tolerogenic effects on T cells, and 3) may have application in immunotherapy in generating massive numbers of DC for an extended duration
— id: 74382, year: 2003, vol: 170, page: 3554, stat: Journal Article,

GM-CSF expands dendritic cells and their progenitors in mouse liver
Pillarisetty, Venu G; Miller, George; Shah, Alaap B; DeMatteo, Ronald P
2003 Mar;37(3):641-652, Hepatology
Dendritic cells (DCs) are rare but ubiquitous antigen-presenting cells situated in lymphoid and nonlymphoid organs throughout the body. The study of DCs located in the liver has been restricted by their relative scarcity and the difficulty of their isolation. Because granulocyte-macrophage colony-stimulating factor (GM-CSF) is a critical growth factor for DCs in vitro, we postulated that it would expand hepatic DCs in vivo. We found that adenoviral-mediated GM-CSF overexpression in normal mice increased the number of liver DCs 400-fold to more than 100 million cells. GM-CSF-recruited DCs were CD11c(+)DEC205(-) and had high expression of major histocompatibility complex (MHC) class II, CD54, and CD80 but low CD40 and CD86 staining. Further maturation occurred after overnight culture. In addition to CD11c(+)DEC205(-) DCs, a population of CD11c(-)DEC205(low/-) cells resembling DC progenitors described previously in normal mice was expanded as serum GM-CSF levels increased. GM-CSF-recruited CD11c(+)DEC205(-) DCs and CD11c(-)DEC205(low/-) cells had different functional capabilities. CD11c(+)DEC205(-) DCs captured far more protein antigen in vivo, produced higher amounts of interleukin (IL)-6 and tumor necrosis factor (TNF)-alpha, and induced greater allogeneic and antigen-specific T-cell stimulation. A proportion of CD11c(-)DEC205(low/-) cells differentiated into CD11c(+) cells and gained T-cell stimulatory ability when cultured in the presence of GM-CSF. In conclusion, our findings show that GM-CSF can profoundly influence recruitment and development of DCs in murine liver
— id: 74381, year: 2003, vol: 37, page: 641, stat: Journal Article,

Immediate postlaparotomy small bowel obstruction: a 16-year retrospective analysis
Fraser, Shannon A; Shrier, Ian; Miller, George; Gordon, Philip H
2002 Sep;68(9):780-782, American surgeon
Small bowel obstruction (SBO) is a particularly vexing problem in the postoperative period. The goal of this study was to compare the results of operative versus nonoperative treatment. A secondary goal was to explore risk factors for necessitating reoperation in the immediate postoperative period. We conducted a historical cohort retrospective chart review at a university-affiliated hospital. The medical records of patients treated between 1985 and 2000 at the Sir Mortimer B. Davis Jewish General Hospital (Montreal, Quebec, Canada) who developed SBO after undergoing a laparotomy during that admission were reviewed. Postoperative SBO was defined as cessation of flatus or bowel movements after their resumption following operation. To compare operative versus nonoperative management of early postoperative mechanical SBO we used the following outcome measures: Reoperation rate, time to return of function, length of stay, and mortality. Of 52 patients who developed SBO in the immediate postoperative period 37 were male, 25 had colorectal surgery, and nine had a gastrectomy as the initial operation on admission; five had inflammatory bowel disease, six had a previous SBO, 22 had virgin abdomens before the current operation, and 11 had adhesions noted at the initial operation. The median time to the development of obstructive symptoms was 8 days (range 1-33). The reoperation rate was 42 per cent overall (67% in women and 32% in men, P = 0.02). For operatively treated patients the median time between onset of symptoms and surgery was 5 days [range 1-23, interquartile range (IQR) = 5]. The median time to the return of bowel function was greater in the operatively treated patients compared with nonoperatively treated patients [11.5 days (range 4-37, IQR = 11) vs 6 days (range 1-28, IQR = 7), P < 0.0001] as was median length of stay from onset of obstruction [23 days (range 6-60, IQR = 14) vs 12 days (range 2-45, IQR = 16), P < 0.009]. Operatively treated patients also stayed longer after their obstruction was relieved although not significantly longer [8 days (range 1-35, IQR = 11) vs 4.5 days (range 0-40, IQR = 10), P = 0.15]. There were 11 complications in nine of 22 patients who underwent operative treatment of their SBO. Immediate postoperative SBO can be treated nonoperatively in stable patients resulting in significantly quicker return of bowel function and shorter lengths of hospital stay. Definitive risk factors for immediate SBO could not be identified
— id: 74379, year: 2002, vol: 68, page: 780, stat: Journal Article,

Readmission for small-bowel obstruction in the early postoperative period: etiology and outcome
Miller, George; Boman, Jason; Shrier, Ian; Gordon, Philip H
2002 Aug;45(4):255-258, Canadian journal of surgery = Journal canadien de chirurgie
OBJECTIVES: To determine the frequency of readmission for early postoperative small-bowel obstruction (SBO), to highlight factors that may predispose to this condition, to define the risks of strangulation and to compare the immediate and long-term risks and benefits of operative versus nonoperative treatment. DESIGN: A chart review. SETTING: The Sir Mortimer B. Davis-Jewish General Hospital, a university-affiliated teaching hospital in Montreal. PATIENTS: Out of a total of 1001 cases of SBO in 552 patients, 30 patients were readmitted within 50 days of a previous laparotomy with the diagnosis of SBO. INTERVENTION: Selective nonoperative management and exploratory laparotomy. MAIN OUTCOME MEASURES: The value of nonoperative management and need for operation. RESULTS: Adhesions were the cause of the obstruction in most cases (24); other causes were Crohn's disease (2), hernia (1), malignant neoplasm (1) and a combination of adhesions and malignant disease (2). Thirteen (43%) of the procedures preceding the obstruction were primary small-bowel operations. There was only 1 episode of strangulated bowel. Of the patients readmitted for SBO, 7 (23%) were treated operatively with a long-term recurrence rate of 57% compared with 63% for those treated nonoperatively for the SBO. The median time to recurrence was 0.1 years (range from 0.02-6 yr) for those whose SBO was managed operatively, compared with 0.7 years (range from 0.08-5 yr) for those managed nonoperatively for the SBO. The median length of stay for patients managed operatively for SBO was 12 days (range from 9-17 d) compared with 6 days (range from 2-33 d) for those managed nonoperatively. CONCLUSIONS: Readmission for SBO within 50 days of a previous laparotomy represents a small percentage of all cases of SBO. They frequently follow small-bowel operations. Cases of strangulation are no more common than in general cases of SBO. Patients treated nonoperatively for SBO did not experience less favourable outcomes with respect to resolution of symptoms, length of stay, risk of recurrence and reoperation. Thus, operative intervention is not necessary in an otherwise stable patient
— id: 74376, year: 2002, vol: 45, page: 255, stat: Journal Article,

Adenovirus infection enhances dendritic cell immunostimulatory properties and induces natural killer and T-cell-mediated tumor protection
Miller, George; Lahrs, Svenja; Pillarisetty, Venu G; Shah, Alaap B; DeMatteo, Ronald P
2002 Sep 15;62(18):5260-5266, Cancer research
Dendritic cells (DCs) are potent antigen-presenting cells with the potential for cancer immunotherapy. Adenoviral-mediated gene transfer is an attractive means to manipulate the immunostimulatory properties of DCs for therapeutic advantage. Because adenovirus induces DC maturation, we postulated that it would significantly alter their immune functions. Infected DCs markedly increased allogeneic and antigen-specific T-cell proliferation, and augmented natural killer cell lytic activity and IFN-gamma production. The enhanced effector cell stimulation by infected DCs was dependent on their secretion of interleukin 12. Immunization with infected DCs pulsed with tumor antigen protected against flank tumors in 78% of mice and induced a memory response. Antitumor immunity was dependent on both T cells and natural killer cells. Antigen-pulsed, mock-infected DCs were nonprotective. The findings that adenoviral vectors alone critically alter DC immune functions and antitumor properties have important implications for the design and interpretation of immunotherapy regimens using vector-based gene transfer to modulate immunity
— id: 74378, year: 2002, vol: 62, page: 5260, stat: Journal Article,

Endogenous granulocyte-macrophage colony-stimulating factor overexpression in vivo results in the long-term recruitment of a distinct dendritic cell population with enhanced immunostimulatory function
Miller, George; Pillarisetty, Venu G; Shah, Alaap B; Lahrs, Svenja; Xing, Zhou; DeMatteo, Ronald P
2002 Sep 15;169(6):2875-2885, Journal of immunology
GM-CSF is critical for dendritic cell (DC) survival and differentiation in vitro. To study its effect on DC development and function in vivo, we used a gene transfer vector to transiently overexpress GM-CSF in mice. We found that up to 24% of splenocytes became CD11c+ and the number of DC increased up to 260-fold to 3 x 10(8) cells. DC numbers remained substantially elevated even 75 days after treatment. The DC population was either CD8alpha+CD4- or CD8alpha-CD4- but not CD8alpha+CD4+ or CD8alpha-CD4+. This differs substantially from subsets recruited in normal or Flt3 ligand-treated mice or using GM-CSF protein injections. GM-CSF-recruited DC secreted extremely high levels of TNF-alpha compared with minimal amounts in DC from normal or Flt3 ligand-treated mice. Recruited DC also produced elevated levels of IL-6 but almost no IFN-gamma. GM-CSF DC had robust immune function compared with controls. They had an increased rate of Ag capture and caused greater allogeneic and Ag-specific T cell stimulation. Furthermore, GM-CSF-recruited DC increased NK cell lytic activity after coculture. The enhanced T cell and NK cell immunostimulation by GM-CSF DC was in part dependent on their secretion of TNF-alpha. Our findings show that GM-CSF can have an important role in DC development and recruitment in vivo and has potential application to immunotherapy in recruiting massive numbers of DC with enhanced ability to activate effector cells
— id: 74377, year: 2002, vol: 169, page: 2875, stat: Journal Article,

Adenoviral-mediated interleukin-12 gene transfer activates dendritic cells and enhances their anti-tumor immunity
Miller G; Lahrs S; DeMatteo RP
2001 ;52:241-242, Surgical forum
— id: 74389, year: 2001, vol: 52, page: 241, stat: Journal Article,

Etiology of small bowel obstruction
Miller, G; Boman, J; Shrier, I; Gordon, P H
2000 Jul;180(1):33-36, American journal of surgery
BACKGROUND: Small bowel obstruction (SBO) is a major cause of morbidity and financial expenditure in hospitals around the world. The leading cause of SBO in the western world has become adhesions. The goal of this study was to determine the causes of SBO. METHODS: The medical records of all patients admitted to one hospital between 1986 and 1996 with the diagnosis of SBO were reviewed retrospectively. This included 552 patients accounting for 1,001 admissions. RESULTS: The etiology of SBO was adhesions (74%), Crohn's disease (7%), neoplasia (5%), hernia (2%), radiation (1%), and miscellaneous (11%). Patients with Crohn's disease were younger than patients with other etiologies. Surprisingly, recurrence rates were similar for patients treated operatively as for those treated nonoperatively with the exception in the hernia group where higher recurrence rates were noted for patients initially treated in a nonoperative manner. CONCLUSION: The most common cause of SBO is adhesions followed by Crohn's disease and neoplasia
— id: 74374, year: 2000, vol: 180, page: 33, stat: Journal Article,

Natural history of patients with adhesive small bowel obstruction
Miller, G; Boman, J; Shrier, I; Gordon, P H
2000 Sep;87(9):1240-1247, British journal of surgery
BACKGROUND: Small bowel obstruction (SBO) is a major cause of morbidity and financial expenditure. The goals of this study were to determine factors predisposing to adhesive SBO, to note the long-term prognosis and recurrence rates for operative and non-operative treatment, to elicit the complication rate of operations and to highlight factors predictive of recurrence. METHODS: The medical records of all patients admitted to one hospital between 1986 and 1996 with the diagnosis of SBO were reviewed retrospectively. This included 410 patients accounting for 675 admissions. RESULTS: The frequency of previous operation by procedure type was colorectal surgery (24 per cent), followed by gynaecological surgery (22 per cent), herniorrhaphy (15 per cent) and appendicectomy (14 per cent). A history of colorectal surgery (odds 2.7) and vertical incisions (odds 2.5) tended to predispose to multiple matted adhesions rather than an obstructive band. At initial admission 36 per cent of patients were treated by means of operation. As the number of admissions increased, the recurrence rate increased while the time interval between admissions decreased. Patients with an adhesive band had a 25 per cent readmission rate, compared with a 49 per cent rate for patients with matted adhesions (P<0.004). At the initial admission 36 per cent of patients were treated surgically. Patients treated without operation had a 34 per cent readmission rate, compared with 32 per cent for those treated surgically (P not significant), a shorter time to readmission (median 0.7 versus 2.0 years; P<0.05), no difference in reoperation rate (14 versus 11 per cent; P not significant) and fewer inpatient days over all admissions (4 versus 12 days; P<0.0001). CONCLUSION: The likelihood of reobstruction increases and the time to reobstruction decreases with increasing number of previous episodes of obstruction. Patients with matted adhesions have a greater recurrence rate than those with band adhesions. Non-operative treatment for adhesions in stable patients results in a shorter hospital stay and similar recurrence and reoperation rates, but a reduced interval to reobstruction when compared with operative treatment
— id: 74373, year: 2000, vol: 87, page: 1240, stat: Journal Article,

Small-bowel obstruction secondary to malignant disease: an 11-year audit
Miller, G; Boman, J; Shrier, I; Gordon, P H
2000 Oct;43(5):353-358, Canadian journal of surgery = Journal canadien de chirurgie
OBJECTIVE: To determine the efficacy and long-term prognosis for operative versus nonoperative treatment of small-bowel obstruction (SBO) secondary to malignant disease. DESIGN: A chart review. SETTING: A university-affiliated teaching hospital. PATIENTS: The medical records of all patients with malignant disease as the established etiology of their obstruction who presented to the Sir Mortimer B. Davis-Jewish General Hospital, Montreal, between 1986 and 1996 were reviewed. There were 32 patients accounting for 74 admissions. INTERVENTIONS: Selective nonoperative management and exploratory laparotomy, immediate or delayed. MAIN OUTCOME MEASURES: The value of nonoperative management and need for operation. RESULTS: Colorectal and ovarian neoplasms were the principal primary malignant diseases that led to SBO. The median time between diagnosis of the malignant disease and SBO was 1.1 years. At their initial presentation, 80% of patients were treated by operation, but 47% of these patients had an initial trial of nonoperative treatment. Reobstruction occurred in 57% of patients who were operated on compared with 72% of patients who were not. The median time to reobstruction was 17 months for patients who underwent operation compared with 2.5 months for patients who did not. Also, 71% of patients were alive and symptom free 30 days after discharge from operative treatment compared with 52% after nonoperative treatment. Postoperative morbidity was 67%. Mortality was 13%, and 94% of patients eventually died from complications of their primary disease. CONCLUSIONS: SBO secondary to malignant disease usually indicates a grim prognosis. Operative treatment has better outcome than nonoperative management in terms of symptom free interval and reobstruction rates. However, it is marked by high postoperative morbidity. We recommend that, after short trial of nasogastric decompression, patients with obstruction secondary to malignant disease be operated on if clinical factors indicate they they will survive the operation
— id: 74375, year: 2000, vol: 43, page: 353, stat: Journal Article,