NEW YORK (AP) — American International Group Inc. said Monday that its president and chief executive officer, Robert Benmosche, has been diagnosed with cancer.
The insurer said Benmosche is undergoing aggressive chemotherapy. He said in a statement his long-term prognosis is good.
The company announced Benmosche's diagnosis after the market closed …
The two child stars of 'Slumdog Millionaire' are at risk of losing their monthly stipend and their trust fund if they don't start attending school, a trustee for the fund said Thursday.
Azharuddin Mohammed Ismail, 11, and Rubina Ali, 10, shot to fame after starring in the Oscar-winning movie.
But these days, Azhar is only showing up at school 37 percent of the time, and Rubina has only a 27 percent attendance rate at her school, the trustee said.
"It's pathetic," said Noshir Dadrawala, who helps administer the Jai Ho trust established by the filmmakers to provide an education, living allowance and housing for the young stars, who both grew …
ATLANTA Gilligan's Island has nothing on the Cubs. There is anentire team stranded in the South, drowning under an 0-4 start. BobDenver might as well be playing shortstop because this comedy oferrors is starting to have surreal plot twists.
You never really bought it, did you, that the Gilligan castawayswere far from civilization? But you still tuned in. Same with theCubs.It might be hard to believe a team can lose with such varietyand entertainment value as this group of April fools, and yet theydraw more fans by accident than the White Sox can with financialpurpose.It must be like passing a car wreck. It's hard not to take apeek now and then …
PHNOM PENH, Cambodia (AP) — Cambodia's U.N.-backed genocide tribunal on Thursday formally indicted the four top surviving leaders of the Khmer Rouge regime blamed for 1.7 million deaths in the 1970s, paving the way for the panel's long-awaited second trial next year.
The frail, elderly defendants, who have been in detention since 2007, deny any guilt for their roles in the radical communist rule during which about a quarter of Cambodia's population was either executed or died due to starvation or overwork.
The trial, due to start by mid-2011, will bring to the stand Nuon Chea, 84, the group's ideologist; former head of state Khieu Samphan, 79; former Foreign Minister Ieng …
Secretary of State Condoleezza Rice insisted Saturday that U.S. beef is safe to eat and urged South Koreans to accept their government's decision to lift a ban on the products.
Rice also said she hoped the beef controversy won't distract from important issues facing the U.S. and South Korea, most notably the six-nation talks over North Korea's nuclear program.
"In terms of differences that sometimes arise from trade disputes, they are normal in relations between states," Rice told a joint news conference with South Korean Foreign Minister Yu Myung-hwan.
Rice arrived in Seoul a day after neighboring North Korea destroyed the cooling tower at …
Ex-NATO base chief accused of 4 affairs
WASHINGTON - A retired two-star Army general "engaged in a patternof inappropriate behavior" with the wives of four subordinates whilehe was the top American military officer at a NATO base in Turkey, aninternal Pentagon investigation concludes.
Maj. Gen. David Hale also sanctioned the misuse of governmentfunds for travel and made "false and misleading statements" toinvestigators and Pentagon officials, said the report by DefenseDepartment Inspector General Eleanor Hill.
A copy of the 49-page report was obtained Monday by The AssociatedPress.
The allegations involve a period from 1996 to 1997 while Hale …
As thunderous cheers erupted throughout the JFK Coliseum in Manchester N.H., Aug.4, the 94th Military Police Company, one of the longest serving units in Iraqi, marched in formation onto center stage before 1,000 family members, friends, and politicians.
Their arrival was presaged by several activities which heightened the crowd's desires to see their loved ones. First, dignitaries including New Hampshire Governor Craig Benson; Senator Judd Gregg (R-N.H.); Congressman Jeb Bradley (R-N.H. District One); Congressman Charles Bass, II (R-N.H. District Two); Robert Baines, mayor of Manchester, N.H.; Bishop John McCormack; New Hampshire U.S. Army Reserve Ambassador James A. Normand; MG …
Facing alarming budget deficits, New York City has come up with some unusual ways to save money and cut costs including steeper fees for red-carpet events and cheaper traffic signs.
Mayor Michael Bloomberg, who has staked his campaign for a third consecutive term next year on his promise to save the city from financial ruin, delivered a budget update this week that predicts gaps of $303 million this fiscal year and $3.7 billion next year.
He's already warning of tax hikes while slashing spending, eliminating jobs and tossing out two pieces of property tax relief for homeowners. The actions, Bloomberg said Thursday, are "not pretty, but if we take them …
Maldon Art Trail Various Venues, Maldon Until Saturday, October 8Now in its' fourth year, the trail goes from strength to strengthdue to the wealth of talent in the area. With an installation piecein Moot Hall on the theme of the Mad Hatter's Tea Party. JohnDoubleday and artist Vasant Chinchwadkar will give a talk on TribalArt of India at Goat Lodge Farm, Great Totham, on Friday, October 7at 6pm. The talk will last one hour with light refreshments servedafter. Free but pre-booking required. For more details call theTourist Information Centre on 01621 856503.
Drawn To Nature exhibition Hayletts Gallery, Maldon Until October8 Last chance to see the work of two …
NEW YORK - Wall Street extended its decline Friday as investors already anxious after the second-biggest market drop this year cast aside a stronger-than-expected read on the economy.
Investors clearly had a selling bias a day after the market shuddered amid worries over the U.S. mortgage and corporate lending markets, sending the Dow down by as much as 450 points before it closed with a deficit of 311. Investors globally took flight from equities, shifting cash into safer investments in Treasurys.
Although the market has often rebounded after a steep drop - and has done so in recent weeks - investors appeared unable Friday to set aside their concerns about a weakening …
The 16-nation euro rose slightly Tuesday against the U.S. dollar even after Germany, Europe's largest economy, reported a plunge in exports.
In morning European trading the euro purchased $1.3908, up from $1.3891 the night before in New York. The British pound rose to $1.6124 from $1.6045 in New York, while the dollar slipped to buy 98.19 …
NEW YORK (AP) — Jason Reitman was under the same impression many are of Charlize Theron. He knew she was a fiercely talented actress, prone to burying her stunning beauty behind gritty, intense performances like her Academy Award-winning one as a murderous prostitute in 2003's "Monster."
Then she told him a dirty joke.
Theron approached Reitman at last year's Oscars to tell him how much she liked his then recent film "Up in the Air" and that she'd love to work with him.
"I got a tap on the shoulder and I turn around and it's ... Charlize Theron," recalls Reitman. "I was really understandably intimated."
But when Theron, already a few drinks into the night, revealed a more depraved sense of humor than her image would suggest, Reitman realized they had more in common than he expected: "I was like, 'Oh! I like you.'" (Theron, for her part, doesn't recall the joke, but, with a glimmer in her eye, acknowledged, "That sounds about correct.")
The meeting was both fortuitous, in that it directly led to Theron staring in Reitman's new film "Young Adult," and an early hint to the tone of their collaboration. In "Young Adult" (which was written by Diablo Cody of "Juno"), Theron plays Mavis Gary, a teen fiction ghost writer who returns to her hometown in rural Minnesota to lure her now-married former boyfriend. As a woman whose nostalgia has swelled to demented proportions, Theron is bitingly caustic and hilariously candid.
The performance not only reveals Theron's comedic side, but shows more of her true nature than her previous work. Not that Theron is anything like Mavis' more deplorable aspects, but she shares Mavis' sharp elbows and sharper wit.
"Most people who know me who have seen the film are not that shocked," Theron said in a recent interview during which she was self-deprecating, unguardedly foul-mouthed and thoughtful. "The film is way more my personality and closer to anything that I've done."
It's also Theron's first film in nearly three years. In between, she prepared to star in an ambitious "Mad Max" sequel, "Fury Road," which was repeatedly delayed and still hasn't been shot. She worked on developing projects with her production company, including a drama series for HBO with David Fincher. She also split with the Irish actor Stuart Townsend after nearly a decade together.
"I'll be very honest: I wasn't missing it," Theron says of acting. "It's hard to miss something when nothing was kind of sparking that instrument to get excited about."
That period, though, appears to be over. Following "Young Adult" — which is earning Theron her best reviews since "Monster" — she'll be seen in Ridley Scott's "Prometheus" and the fantasy "Snow White & the Huntsman," which also stars Kristen Stewart.
Theron, 36, grew up on a farm outside Johannesburg, South Africa. While she was a teenager, her mother shot and killed Theron's alcoholic and abusive father. When she was 16, she became a model in Milan. She later moved to New York to train as a ballet dancer, but a knee injury pushed her out of dance and toward acting.
After a number of small roles as girlfriend types in films such as "The Devil's Advocate" and "The Cider House Rules," her performance in "Monster" changed her trajectory considerably. When she won best actress at the Oscars, Nelson Mandela hailed her for putting South Africa "on the map."
Since then, Theron, who lives in Los Angeles, received a second Oscar nomination for her performance as a miner in "North Country." Though the science fiction "Aeon Flux" bombed, Theron drew acclaim again for a supporting role in the somber anti-war film "In the Valley of Elah" and for the atypical superhero film "Hancock."
But all the while, there were hints in her filmography of comedic leanings. In 2005, she had a memorable arc on "Arrested Development" as the love interest of Jason Bateman's character. Her character was mentally disabled, but the joke was on those around her, who didn't notice because of her British accent.
The opportunity arose when "Monster" director Patty Jenkins directed an episode of the series, and Theron asked her to relay to creator Mitch Hurwitz her pleading to be on the show. She calls the experience a "great, great learning experience" in how comedy needn't be played for comedy, but rather portrayed realistically.
Theron also appeared on an early episode of Zach Galifianakis' faux-interview Web series "Between Two Ferns," as revered of a comedy calling-card as there is. On it, Theron flirted with Galifianakis before pulling the rug out from him, cackling at the idea of her being attracted to a "fat garden gnome."
"The bizarre thing is that I've always had kind of a sick, twisted sense of humor," says Theron. "But my work, for some reason, has always veered to the dramatic stuff. I think that's because I've never really been that driven by genre, but I find that I want to play people that feel real. I do think in comedy it's harder to find non-caricatures. I always said that I would love to do something like that kind of comedy that the Coen brothers do, that more character study stuff. And that stuff is hard to come by, and I feel like my career was setting itself up to be another thing."
The comedian-actor Patton Oswalt, who plays an old high school acquaintance of Mavis' who turns into a drinking buddy in "Young Adult," said at the Gotham Awards that Theron "has the kind of humor that someone who looks like me has."
The two found an unlikely chemistry in "Young Adult" right from the start. Before ever meeting, they did a table read in Reitman's dining room and immediately connected.
"I realized I was going to be working with a really great actor," says Oswalt. "It made me work even harder so that I could be on her playing field. She is so instinctual and already ready to go every shot."
Whether it's "Monster" or "Hancock" or "Young Adult," Theron typically commits fully to a character. Asked how she manages that, she doesn't miss a beat: "Alcohol."
But thinking a little more about it, she says that ballet instilled in her a relish for performance. Though she acknowledges she's not a trained actor, she says she learned from other actors as her career unfolded.
"It was amazing to watch Al Pacino at 3 in the morning and suck ... and then be brilliant," says Theron, recalling "The Devil's Advocate." ''It was one of the greatest teachings that I could have been given. He taught me that in order to be great, you have to be willing to fall on your face."
BARCELONA
MUSEU D'ART CONTEMPORANI DE BARCELONA
October 5, 2007-January 7, 2008
Curated by Serge Guilbaut and Manuel Borja-Villel
Navigating French historian Serge Guilbaut's theory that America swiped postwar modernism from war-ravaged Western Europe is like driving an old Citroen instead of a new Ford. The oddball design and hydraulics may take getting used to, but its concept is, well, interesting. For a test drive, Guilbaut's 1983 book How New York Stole the Idea of Modern Art may be a bit ambitious; better just to see the theory realized. "BF-BOMB: The Transatlantic War of Images and All That Ja//., 1946-1956," which gathers together some four hundred works by approximately 150 artists, represents the period when modern art's center moved from Paris to New York. But whether the work of artists like Alfred Manessier and Marcel Barbeau supports Guilbaut's claim that American critics unjustly considered postwar French art "pointless and meaningless" is an open question. - Peter Plagens
A 28-year-old man died yesterday and another man was injuredwhen they were overcome by fumes while working on a sewer on the WestSide.
Cornelius Roberts, of 2014 W. 71st St., was pronounced deadyesterday afternoon at Holy Cross Hospital, a spokeswoman there said.
Walter Carnahan, 55, of 2334 61st Ct., Cicero, was treated atthehospital and released.
Police said the men, employees of A&A Star Sewer Service inCicero, were working on a sewer at Lang Exterior Manufacturing Co.,2323 W. 59th St., at about noon yesterday.
Carnahan entered the sewer first and passed out after he wasovercome by fumes, police said. Roberts went in to save Carnahan,but he also passed out.
Other workers called the Fire Department. Paramedics rushedboth men to the hospital, but doctors were unable to revive Roberts.
An autopsy will be performed today.
LAKE ARIEL, Pennsylvania (AP) — A U.S. man is accused of fatally striking his newborn with a cinderblock twice because he and his girlfriend couldn't afford a second child.
The parents of the man, Christopher Fitzpatrick, told investigators their son had admitted killing the girl May 28 and burying her near the landscaping business where he worked.
Detectives visited the home of Fitzpatrick's parents last week seeking his girlfriend, Jennifer Barrise, 28, on a domestic relations warrant, according to arrest papers.
Fitzpatrick's parents told investigators their daughter was with their son and his girlfriend when Barrise gave birth in a car. Fitzpatrick dropped them off at the couple's home, then left with the apparently healthy baby, a police affidavit said.
Investigators said the girl told her parents about the baby and when they confronted their son, he claimed to have dropped off it off at a hospital. But he later admitted killing the baby, police said.
Fitzpatrick, 20, subsequently led police to the baby's body, telling them he decided to kill it because the couple already had a 1-year-old child and couldn't afford another baby, according to police.
Fitzpatrick and Barrise were arrested Friday. They are both charged with criminal homicide and concealing the death of a child. Fitzpatrick is also charged with abuse of a corpse. Online court records do not list an attorney for either of them.
Preliminary hearings were scheduled for Wednesday.
A Chicago jury has acquitted R&B superstar R. Kelly on all counts at his child pornography trial.
The verdict came six years after the singer was first charged with appearing on a graphic videotape with a girl prosecutors said was as young as 13 at the time.
Both Kelly and the now 23-year-old alleged victim had denied they were on the tape. Neither testified during the trial.
The prosecution's star witness was a woman who said she engaged in three-way sex with Kelly and the girl prosecutors said was on the tape. Defense attorneys argued the man on the tape didn't have a large mole on his back and Kelly does.
The singer had faced 15 years in prison. His hits include "I Believe I Can Fly," "Bump N' Grind" and "Ignition."
* Marriages The following people applied for marriage licenses inPutnam County between Feb. 24 and March 2. n David G. Wills, 40, ofHico, and Anne Morris Hudson, 50, of Scott Depot * Divorces Thefollowing people filed for divorce in Putnam County between Feb. 27and March 3. * Stephen Jeffrey Bailey from Greta Mae Bailey * GretaBailey from Stephen Jeffrey Bailey * Allen D. Bowling from ChristieM. Bowling * Natasha Renee Matthews from Billy Jo Matthews * CarmenL. Johnson from Parris D. Johnson * Samuel Douglas Roberts Sr. fromLoretta Maxine Roberts * Sherry Lynn Coulter from Josy Wade Coulter *Lisa Seals from Walter Seals * Property transfers The followingproperty transfers of more than $50,000 were recorded in PutnamCounty between Feb. 23 and March 1. * Marty P. and Noelle B. Phillipsto James E. and Tracy D. Jones. Parcel, Hurricane District, $149,900.* Michael D. and Kimberly A. Stewart to Mary R. and Noelle B.Phillips. Lot, Teays Valley District, $230,000. * NationalResidential Nominee Services Inc. to Harry J. Cook. Parcel, ScottDistrict, $128,500. * Christopher and Andrea Deel to Bryan S. and AmyB. Grant. Lot, Hurricane District, $147,500. * Sidney E. and Penny R.Warner to Ronald B. and Gail N. Childress. Lot, Hurricane District,$252,000. * William Franklin Luikart to Mounir Ghareeb. Tract, TeaysValley District, $80,000. * AB Contracting Inc. to Mark and DianaFerman. Lot, Scott District, $586,670. * Michael C. and Susan V.McCallister to Teddy Joe and Lora D. Bailey. Lot, Hurricane District,$55,680. * Sammy G. and Carolyn S. Stover to Mark E. Hawkins. Parcel,Union District, $60,000. * Monte E. and Sandra K. Chittum to SidneyE. and Penny R. Warner. Lot, Curry District, $177,000. * James H. andReba J. Gilmore to Lisa Jo Smalley. Lot, Scott District, $210,000. *Marie A. and Peter E. Vonderau Sr. to Christina Painter. Lot, PocaDistrict, $128,500. * AB Contracting Inc. to Debra W. and William A.Steffick II. Lot, Hurricane District, $254,900. * Ronald and DonaldHayes Inc. to Tina S. and Robert D. Edgar Jr. Lot, Teays ValleyDistrict, $222,500. * Robert L. and Janet S. Kosa to Matthew K. andAnna R. Conn. Lot, Scott District, $77,900. * Donald A. and Nancy L.Frazier to Marcus B. Handley. Parcel, Scott District, $129,900. * D.Raymond and Gloria Jean Peak to Short Stop Market Inc. Lot, HurricaneDistrict, $68,000. * Keslings Quality Homebuilders Inc. to David A.and Beth M. Boggess. Lot, Scott District, $286,000. * David W.Hammond to Jerry B. and Cynthia B. Jenkins. Lot, Scott District,$145,000. * Roger A. Summerfield to Eric E. and Tonya R. Kyle. Lot,Scott District, $176,000. * Gail N. Childress to Victor L. andLaquita Harris. Lot, Scott District, $192,500. * Charles J. Pifer toAlex M. and Sonya L. Nunnery. Lot, Curry District, $104,995. *Douglas R. Cook to Nitro Parking LLC. Lot, Poca District, $180,000. *Walter E. and Lisa E. Nordstrom to Levi and Julie Crouse. Lot, ScottDistrict, $228,000. * Steven D. and Cathleen R. Bragg to Bruno RF andSabrina M. Reyntjens. Lot, Teays Valley District, $171,000. * Eric E.and Tonya R. Kyle to Joseph T. and Ashley R. Rhodes. Lot, EleanorDistrict, $130,000.
Background: This study investigates the feasibility of performing advanced minimally invasive surgery (MIS) in a nonspecialized practice environment. Methods: We conducted a cross-sectional survey of all community general surgeons currently practising in Ontario. Results: Few community surgeons perform a high volume (> 10 procedures per yr) of advanced MIS. Most (70%) believe it is important to acquire additional skills in advanced MIS. The most appropriate methods for learning advanced MIS are believed to be expert mentoring (79.7%), courses (77.2%) and a colleague mentor (63.9%). A total of 57.6% of respondents have attended a course in MIS while in practice, and most have access to a reasonable variety of instrumentation. Respondents believe that 57.6% of assistants, 54.8% of nurses and 43.4% of anaesthetists are relatively inexperienced with advanced MIS. Barriers to establishing advanced MIS include limited operating room access (50%), resources or equipment (45.2%) and limited expert mentoring (43.6%). Surgeons with less than 10 years of practice found lack of trained nursing staff (7.9% v. 4.2%, p = 0.01) and experienced assistants (12% v. 6.2%, p = 0.008) to be more important barriers than did those with over 10 years of practice, respectively. Conclusion: Most general surgeons working in Ontario are self-taught with respect to MIS skills, and few perform a high volume of advanced MIS. Only one-half of all respondents have access to skilled MIS operating room nurses, surgical assistants or anesthesiology. Despite this, general surgeons perceive the greatest barriers to introducing advanced MIS procedures to be limited access to operating rooms, resources or equipment and limited mentoring. This study has shown that the role of the surgical team in advanced MIS may be underestimated by many general surgeons. These data have important implications in training general surgeons and in incorporating additional advanced MIS procedures into the armamentarium of general surgeons.
Contexte : Cette �tude porte sur la faisabilit� d'une chirurgie � effraction minimale (CEM) avanc�e dans un milieu de pratique non sp�cialis�. M�thodes : Nous avons effectu� un sondage transversal aupr�s de tous les chirurgiens g�n�raux communautaires actifs en Ontario. R�sultats : Peu de chirurgiens communautaires pratiquent un volume �lev� de CEM avanc�es (> 10 interventions par ann�e). La plupart (70 %) croient qu'il est important d'acqu�rir des comp�tences suppl�mentaires en CEM avanc�e. On croit que les m�thodes qui conviennent le mieux pour apprendre la CEM avanc�e sont le mentorat par des experts (79,7 %), les cours (77,2 %) et le mentorat par un coll�gue (63,9 %). Au total, 57,6 % des r�pondants ont suivi un cours en CEM au cours de leur pratique et la plupart ont acc�s � un �ventail raisonnable d'instruments. Les r�pondants croient que 57,6 % des adjoints, 54,8 % des infirmi�res et 43,4 % des anaesthetists ont relativement peu d'exp�rience en CEM avanc�e. Les obstacles � l'implantation de la CEM avanc�e comprennent l'acc�s limit� aux salles d'op�ration (50 %) et le manque de ressources ou de mat�riel (45,2 %) et de mentorat par des experts (43,6 %). Par rapport aux chirurgiens qui comptent plus de 10 ans de pratique, ceux qui pratiquent depuis moins de 10 ans signalent davantage parmi les obstacles importants le manque de personnel infirmier d�ment form� (4,2 % c. 7,9 %, respectivement; p = 0,01) et d'adjoints chevronn�s (6,2 % c. 12 %, respectivement; p = 0,008). Conclusion : La plupart des chirurgiens g�n�raux qui travaillent en Ontario sont autodidactes quant aux comp�tences de CEM et peu d'entre eux pratiquent un volume �lev� de CEM avanc�es. La moiti� seulement des r�pondants ont acc�s � des infirmi�res de salle d'op�ration, des adjoints en chirurgie ou des anesth�siologistes qualifi�s en CEM. Les chirurgiens g�n�raux consid�rent n�anmoins que les obstacles les plus importants � l'implantation d'interventions de CEM avanc�e sont l'acc�s limit� aux salles d'op�ration et le manque de ressources ou de mat�riel et de mentorat. Cette �tude a d�montr� que beaucoup de chirurgiens g�n�raux sous-estiment peut-�tre le r�le de l'�quipe de chirurgie en CEM avanc�e. Ces donn�es ont des r�percussions importantes sur la formation de chirurgiens g�n�raux et l'ajout d'interventions suppl�mentaires de CEM avanc�e � la panoplie des chirurgiens g�n�raux.
There is good evidence for the safety and efficacy of advanced minimally invasive surgery (MIS) for gastrointestinal disease. However, few studies have addressed the effectiveness of these procedures (i.e., reproducibility by most surgeons). Many general surgeons entering community practice have been exposed to a variety of MIS procedures during training and may wish to integrate advanced MIS techniques into their surgical practice. Others currently in practice may wish to obtain further training to offer advanced MIS procedures to their patients. It is unclear whether advanced MIS procedures developed by experts are reproducible in all hospital or practice settings where resources and facilities may differ from the institutions in which these techniques were developed. Early studies have shown the positive impact that a focused environment and trained laparoscopic team can have on the outcomes after laparoscopic cholecystectomy (LC).1
The effectiveness of advanced MIS will be determined by the feasibility of performing these technically complex procedures in a broad range of operating environments. Few studies have clearly addressed this issue in appropriate detail.2 Moreover, the potential barriers to incorporating advanced MIS into surgical practice must be clearly characterized.
This study investigates the feasibility of performing advanced MIS in a nonspecialized practice environment. The information from this study characterizes the potential barriers to introducing advanced MIS techniques into practice. Ultimately, we hope this survey will enhance our understanding of the feasibility of adopting advanced MIS by a broad range of gastrointestinal surgeons.
Methods
We conducted a descriptive, crosssectional survey of all community general surgeons currently practising in Ontario. Based on a literature review, expert opinion and empirical data, a draft survey was developed. We explored the following issues in the survey: barriers to introducing advanced MIS in a community setting, feasibility of introducing advanced MIS procedures in all community hospitals and prerequisites to be met before a general surgeon in the community undertakes advanced MIS. We also explored the significance of each of the following parameters in successfully introducing and acquiring advanced MIS procedures in a community setting: previous MIS experience of the surgeon, expected volume of procedures, hospital resources, availability of assistants, instruction in advanced MIS and mentoring.
A focus group of 6 local experts reviewed a draft survey for validity and clarity. Consensus was reached on a final draft. A pilot assessment was performed at the 2002 Canadian Association of General Surgeons (CAGS) meeting in London, Ontario, involving 31 general surgeons attending an advanced MIS course. A mailing list was developed using a master list of Canadian surgeons obtained by MD Select. This list was limited to general surgeons practising in Ontario; the list was exported to Microsoft Excel, where it was filtered by appropriate fields to include only practising general surgeons. Three surveys were sent at 3-week intervals to all nonrespondents.
All data from returned surveys was entered into a database in spreadsheet format using Microsoft Excel and was imported into SPSS. We performed a descriptive analysis, and we used the chi-squared or Fisher's exact test for between-group comparisons, with p < 0.05 considered for statistical significance. The data were summarized to establish the factors perceived to be the most significant barriers to performing advanced MIS procedures. These included surgeons' willingness to undertake training or mentoring and their "tolerance" of a learning curve and the instrumentation and resources available. We also established the factors that correlate with successes and failures in the performance of advanced MIS procedures in the community setting.
Results
A total of 475 surveys were mailed, with a response rate of 54.7% (260, 87% men). The majority of respondents were engaged in community surgery (203, 78%), most of whom had been in practice for over 10 years (60%), and 41.4% worked in a community with a population under 100 000.
Few community surgeons in Ontario are currently performing a high volume of advanced MIS (Fig. 1). There were no significant differences by years of practice or sex except for laparoscopic inguinal hernia repair (men: 14.2% v. women: 0%, p = 0.05). A total of 56.7% of surgeons believe they acquired their MIS skills while in surgical practice. Seventy percent believe it is important to acquire further skills in advanced MIS procedures, and 57.6% have attended a course in MIS while in practice (no difference by years of practice or sex). A total of 12.3% of respondents reported performing advanced MIS without formal instruction, and an additional 13.8% would consider this approach in their practice.
According to Ontario surgeons, the most appropriate methods of instruction in advanced MIS for a surgeon in practice are expert mentoring (79.7%), courses (77.2%), a colleague mentor (63.9%), procedural videos (51.5%) and fellowship training (21.4%). Most respondents would accept increased operating time and personal stress during the learning curve for advanced MIS (96.1% and 84.2%, respectively) while some (16.7%) would accept increased procedural complications.
Most surgeons seem to have access to a reasonable range of instrumentation: a 30� laparoscope (90.1%), a spare laparoscope (96%), an endovascular stapler (86.6%), atraumatic forceps (84.8%), long graspers or scissors (85.6%), 2 monitors (57.4%) and video recording capabilities (57.3%).
When asked to assess their surgical team regarding MIS skills, many surgeons responded that they are working with inexperienced assistants (57.6%), inexperienced nurses (54.8%) and inexperienced anaesthetists (43.4%). However, surgeons who reported performing a high annual volume of laparoscopic colorectal surgery (over 10 procedures per year) believe they have an experienced team of nurses, assistants and anaesthetists (Table 1).
The most important barriers to incorporating advanced MIS procedures into surgical practice are shown in Figure 2. Surgeons with less than 10 years in practice differed from their more senior counterparts by ranking untrained nursing staff (7.9% v. 4.2%, p = 0.01) and inexperienced assistants (12% v. 6.2%, p = 0.008) as more important barriers. When surgeons were stratified according to their annual volume of laparoscopic colorectal procedures, those with a low annual volume believed more strongly that they require a mentor than their high-volume counterparts; high-volume surgeons think an inexperienced assistant is a significant barrier to the routine performance of advanced MIS procedures (Table 2).
Discussion
The effectiveness of advanced MIS for gastrointestinal disease will be determined by the feasibility of completing these procedures in a broad range of practice settings. The technical complexity of the MIS operating suite has been recognized, and structured approaches have been suggested to promote efficiency.3,4 The positive impact that a trained laparoscopic team can have on the outcomes of laparoscopic cholecystectomy (LC) has been described.1 See and colleagues demonstrated that urologists are more likely to encounter problems in laparoscopic surgery after an instructional course if they have a variable surgical assistant.5 However, the overall impact of the surgical team on the success of incorporating advanced MIS into surgical practice has been poorly described.
Many outstanding questions need to be addressed to understand the feasibility of completing advanced MIS in varied hospital or practice settings. In addition, more research is required to understand what may constitute a barrier for surgeons who want to include advanced MIS techniques into their surgical practice. Empirically, we believe the determinants for successful introduction of advanced MIS techniques may be included in the following conceptual categories: the current training of the surgeon and their motivation to undergo training in advanced MIS techniques, the human resources available to the surgeon (nursing, assistants, anaesthetists) and the availability and selection of instrumentation and resources (including access to operating rooms).
In this study, we found that most general surgeons currently practising in Ontario are self-taught. Few perform a high volume of advanced MIS, but most plan to introduce advanced MIS procedures into their practice. Although several studies have been published on learning curves for individual MIS procedures, none clearly address the feasibility of introducing advanced MIS procedures into the community.6-8 Marusch and colleagues9 emphasized surgical experience as a requirement to performing advanced MIS procedures without describing how this experience should be acquired or whether there were other limiting factors to routinely performing advanced MIS. Voitk and others7,10 presented learning curves for selected MIS procedures in a community hospital with a group of experienced surgeons. There was limited discussion of the key factors that may affect the characteristics of a learning curve. Simons and colleagues11 addressed learning curves for advanced MIS procedures in previously trained MIS surgeons. Lishman12 outlined his impressions of the requirements for introducing MIS surgery into surgical practice in a discussion that was largely anecdotal and that presented little supporting data. The most appropriate method for introducing new techniques into surgical practice and credentialing surgeons in these techniques has yet to be established. A short course may introduce an advanced MIS procedure and allow a surgeon and his or her team to determine whether it is feasible to adopt the procedure into practice (i.e., human resources, training requirements, administrative support, adequate case volume).13 This course should be followed by a comprehensive approach to teaching that is rational and fulfills the needs of surgeon trainees. This will include determining the needs of surgical teams and providing appropriate education for the nurses, assistants and surgeons. A period of observation and planning at the mentor's institution should be followed by individualized training in MIS skills and a graded approach to training by the mentor for the relevant procedures. There are now training systems available (i.e., Fundamentals in Laparoscopic Surgery) and sophisticated training devices (Virtual Reality Procedural Training: Minimally Invasive Surgery Trainer, Surgical Education Platform) that may facilitate training and evaluation for surgeons in practice. 14,15 Centralized mentoring (mentor's institution) and, finally, mentoring at the surgeon trainee's institution will complete the training program and should allow mentors to complete an appropriate evaluation and credentialing statement.
In this study, respondents indicated that lack of a mentor was an important barrier to overcome in order to introduce advanced MIS into surgical practice (Fig. 2). Currently in Canada, there is no clear mechanism to facilitate access to expert mentors. National experts in MIS must accept the challenge to coordinate and facilitate a new training paradigm that is effective and feasible for surgeons in practice who wish to adopt advanced MIS procedures.
We have shown that recently trained surgeons may be more likely to introduce advanced MIS into practice. This may be a surrogate marker for an increase in advanced MIS occurring at academic training centres. Although this does not give insight into the clinical outcomes achieved by recent graduates, it demonstrates that, as the volume of advanced MIS increases at academic centres where residency training programs are centralized, the competence of graduates in advanced MIS may also increase.
Surgical practice as an advanced MIS surgeon differs dramatically from practice as an open surgeon. There is a distinct role change in the operating room because the surgeon has a greater reliance on his or her surgical team (Table 1, Table 2). Each member of the MIS team plays a more important role than in open surgery, largely due to the increased technical complexity of advanced MIS procedures.3,4,16 As a result, greater consideration must be given to training the entire surgical team in preparation for routine advanced MIS surgery for gastrointestinal disease. 17 There is some evidence that specialized operating room teams lead to increased efficiency and improved job satisfaction, enhancing the recruitment and retention of nurses.18
Our data indicate that the feasibility of incorporating advanced MIS into practice may be determined largely by the surgical team. Inexperience of the surgical team may be the most significant barrier to introducing advanced MIS into practice (Table 1). More importantly, we have shown that the impact of a trained surgical team may not be clearly recognized by surgeons, especially those inexperienced in routine advanced MIS (Table 2). Surgeons seem to emphasize the significance of instrumentation and operating room access in the performance of routine advanced MIS. Despite this, most surgeons report that they have access to a reasonable selection of laparoscopic instrumentation. Further, the impression of restricted operating room access may be an artificial barrier, linked to concerns of reduced throughput during training of the MIS surgical team. The performance of routine advanced MIS by surgeons may require a shift in the traditional surgical paradigm: more technically complex procedures are completed with a marginal increase in operating time to achieve an important benefit for patients (less time in hospital, reduced wound complications and reduced morbidity overall).
Training of an MIS surgical team must include training for all team members in conjunction with the procedural training of the surgeon. If this challenge is met, it will be feasible for advanced MIS to be successfully performed on a wide scale by a variety of surgeons. If this challenge is not met, we predict that only select teams will complete routine advanced MIS in the surgical management of gastrointestinal disease through specialization or regionalization.
Acknowledgements: We thank the Surgical Outcomes Research Committee for assisting with data entry.
Competing interests: Dr. Birch has received speaker fees from Bard and consulting fees from Johnson & Johnson/Ethicon Endo-Surgery.
[Reference]
References
1. Kenyon TA, Lenker MP, Bax TW, et al. Cost and benefit of the trained laparoscopic team. A comparative study of a designated nursing team vs a nontrained team. Surg Endosc 1997;11:812-4.
2. Chan SW, Hensman C, Waxman BP, et al. Technical developments and a team approach leads to an improved outcome: lessons learnt implementing laparoscopic splenectomy. ANZ J Surg 2002;72:523-7.
3. Herron DM, Gagner M, Kenyon TL, et al. The minimally invasive surgical suite enters the 21st century. A discussion of critical design elements. Surg Endosc 2001;15: 415-22.
4. Kenyon TA, Urbach DR, Speer JB, et al. Dedicated minimally invasive surgery suites increase operating room efficiency. Surg Endosc 2001;15:1140-3.
5. See WA, Cooper CS, Fisher RJ. Predictors of laparoscopic complications after formal training in laparoscopic surgery. JAMA 1993;270:2689-92.
6. Occelli B, Narducci F, Lanvin D, et al. Learning curves for transperitoneal laparoscopic and extraperitoneal endoscopic paraaortic lymphadenectomy. J Am Assoc Gynecol Laparosc 2000;7:51-3.
7. Voitk AJ. The learning curve in laparoscopic inguinal hernia repair for the community general surgeon. Can J Surg 1998; 41:446-50.
8. Perino A, Cucinella G, Venezia R, et al. Total laparoscopic hysterectomy versus total abdominal hysterectomy: an assessment of the learning curve in a prospective randomized study. Hum Reprod 1999;14:2996-9.
9. Marusch F, Gastinger I, Schneider C, et al. Experience as a factor influencing the indications for laparoscopic colorectal surgery and the results. Surg Endosc 2001; 15:116-20.
10. Voitk A, Joffe J. Alvarez, Rosenthal G. Factors contributing to laparoscopic failure during the learning curve for laparoscopic Nissen fundoplication in a community hospital. J Laparoendosc Adv Surg Tech A 1999;9:243-8.
11. Simons AJ, Athone GJ, Ortega AE, et al. Laparoscopic assisted colectomy learning curve. Dis Colon Rectum 1995;38:600-3.
12. Lishman IV. Laparoscopic surgery in peripheral hospitals. Aust Fam Physician 1994;23:383-93.
13. Birch DW, Sample C, Gupta R. The impact of a comprehensive course in advanced minimal access surgery on surgeon practice. Can J Surg 2007;50:9-12.
14. Chaudhry A, Sutton C, Wood J, et al. Learning rate for laparoscopic surgical skills on MIST VR, a virtual reality simulator: quality of human-computer interface. Ann R Coll Surg Engl 1999;81:281-6.
15. Peters JH, Fried GM, Swanstrom LL, et al. Development and validation of a comprehensive program of education and assessment of the basic fundamentals of laparoscopic surgery. Surgery 2004;135: 21-7.
16. Seus JD, Wood T. Reaping maximum benefits from minimally invasive surgery. J Healthc Mater Manage 1994;12:20-4.
17. Winer WK. The role of the operating room staff in operative laparoscopy. J Am Assoc Gynecol Laparosc 1993;1:86-8.
18. Sprengel AD. Snell WE, Boissoneau R. Specialty surgical teams. Results of a study. AORN J 1993;58:1170-80.
[Author Affiliation]
Daniel W. Birch, MD;* Monali Misra, MD;[dagger] Forough Farrokhyar, PhD[dagger]
[Author Affiliation]
From the *Centre for the Advancement of Minimally Invasive Surgery, Royal Alexandra Hospital, the Department of Surgery, University of Alberta, Edmonton, Alta. and the [dagger]Department of Surgery, Hamilton Health Sciences, McMaster University, Hamilton, Ont.
Presented at the 2004 Annual Meeting of Society of American Gastrointestinal and Endoscopic Surgeons, Denver, Colorado.
Accepted for publication Apr. 19, 2005
Correspondence to: Dr. Daniel W. Birch, Royal Alexandra Hospital, 10240 Kingsway, Edmonton AB T5H 3V9; fax 780 735-4771; dbirch@ualberta.ca
The U.S. drew the Ivory Coast 0-0 at a four-nation Hong Kong warm-up tournament for the Beijing Olympics on Wednesday.
The Netherlands, considered a leading contender for gold in Beijing, was to play Cameroon later Wednesday at the Hong Kong Stadium.
The Ivory Coast dominated the first half but failed to convert. Kafoumba Coulibaly had two shots on goal late in the half but U.S. goalkeeper Brad Guzan caught both.
The United States seized the momentum briefly in the second half before the Ivory Coast carved out some promising later chances without finishing. Sekou Cisse's strike from near the edge of the area produced another good save by Guzan.
The U.S. will play Cameroon on Saturday and the Ivory Coast will play the Netherlands.
LOS ANGELES (AP) — Director Michael Bay promises that the third "Transformers" movie is way better than the second.
The 46-year-old's pride was bruised after part two of the franchise, 2009's "Transformers: Revenge of the Fallen," did a bang-up job at the box office (bringing in more than $400 million domestically) but was roundly beat-up by critics. Rolling Stone's Peter Travers said the movie was so "beyond bad, it carves out its own category of godawfulness." It also won the Razzie that year for worst director, worst script and worst film.
Now, Bay is back with "Transformers: Dark of the Moon," which opens in IMAX 3-D on Tuesday night and goes wide at midnight Wednesday. When asked to describe the new movie, Bay said, "it's a lot better than No. 2."
"This one is much more of a mystery," he said, sitting at a shady outdoor table on the Paramount lot. "It's really epic in scope, it's got more heart. It's kind of back down to basics. Movie two, we kind of went off on a tangent."
That tangent brought Sam Witwicky (Shia LaBeouf) and his giant robot friends and foes to Egypt, where he and the noble Autobots fought to save humankind — and the Earth and the sun — from the evil Decepticons. LaBeouf said the second film was "just far too complicated," but volume three is "simple enough to be able to enjoy. ... It's without a doubt our best film."
Besides a more straightforward plot, "Transformers: Dark of the Moon" introduces new cast members Frances McDormand, John Malkovich, Patrick Dempsey, Ken Jeong and Victoria's Secret model Rosie Hungtington-Whiteley, who replaces Megan Fox as Sam's love interest. (Bay told GQ magazine that executive producer Steven Spielberg demanded he fire Fox after she compared Bay to Hitler.)
"Dark of the Moon" also introduces a whole new dimension as Bay's first 3-D film. Though he didn't initially embrace the technology, the film lent itself to 3-D "because just the size differential between robots and humans," the director said. "You can really feel it."
Shooting in 3-D affected his filming style, requiring longer shots and wider frames. It's more expensive and more time consuming, but ultimately Bay found he enjoyed "sculpting with space" and pushing the boundaries of the technology.
He shot more than half the footage with 3-D cameras, including soaring images captured by wing-suited stuntmen flying off of high-rise buildings. "We were able to strap that camera on things that it's never been on before," he said. "You look at it and you just know it's real. You can't fake that stuff."
Only 10 to 15 percent of the movie is completely computer generated. The remaining footage was carefully converted from flat images to dimensional ones by a team of more than 5,000 artists who spent a year on the project. Even Spielberg gave the 3-D his thumbs-up, Bay said. "Spielberg said to me, 'This is the best 3-D I've ever seen,'" the director proudly recalled. "And, you know, he doesn't blow smoke."
"Transformers: Dark of the Moon" opens with the historic American moon landing, which ends up being more than an exploratory mission advancing the U.S. space program and national pride. It turns out a Cybertronian spaceship crash-landed there, and the astronauts are there to investigate.
Like the second "Transformers" flick, this story spans the globe, from China to Africa to Angkor Wat. The film has its world premiere this week in Moscow, which became a billion-dollar movie market in 2010. The last "Transformers" was China's biggest box-office hit to date. Bay said international test screenings of No. 3 have impressed audiences so far, and he makes his movies for audiences, not critics.
"Honestly, they've had a field day making fun of me, but people go to my movies in droves," Bay said. "You can't do movies for critics. You've got to do movies that you like and you feel in your gut and hopefully the audience likes."
This time, the sprawling story culminates with skyscrapers toppling on Chicago's Michigan Avenue. Peter Cullen, who voices lead Autobot Optimus Prime, said Bay was like the chief of his own army during the making of "Transformers." ''I compare him to Norman Schwarzkopf, you know, Stormin' Norman. Here's a guy in charge of this massive undertaking, and he gets it done," said the veteran voice actor.
Despite a history of action-packed box-office juggernauts, Bay said with the longer shots and 3-D action scenes, "this one really tops myself."
LaBeouf said pride also had a lot to do with it. "Everybody just fired on another level on this movie," he said. "We all have a lot of pride, you know. And so everybody came to really play this time."
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Online: http://www.transformersmovie.com/
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Sandy Cohen can be reached at www.twitter.com/APSandy
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AP Entertainment Writer Derrik J. Lang contributed to this report.
With Roger Federer sitting out, Switzerland lost a doubles match to Italy in a Davis Cup playoff and had its lead cut to 2-1.
Simone Bolelli and Potito Starace beat Marco Chiudinelli and Stanislas Wawrinka 6-2, 6-4, 7-6 (3) Saturday.
In Thursday's draw, Federer was selected to team with Wawrinka, reviving the team that won the Olympic doubles title last year. But Switzerland captain Severin Luthi decided to rest Federer in favor of the 117th-ranked Chiudinelli.
The Swiss team said the change was purely tactical, and that there was no problem with Federer, who watched from the front row.
Federer can seal the tie with a win over Andreas Seppi in the first of Sunday's reverse singles matches.
The winner will return to the World Group next year.
Abstract: Carcinoembryonic antigen (CEA) was first identified over 30 years ago as a marker of malignant colonic cells, but has since been shown to be expressed by a range of normal epithelial cells. Moreover, CEA is one member of a larger gene family and shares structural homology with other family molecules. Despite this confused picture, CEA is now known to function in several biological roles, including cell-cell adhesion. Its use in the diagnostic setting has also changed over the years, where in routine immunohistochemistry, monoclonal antibodies to CEA are useful in aiding diagnosis when used as part of a panel. Here, recent advances in understanding the biological role(s) that CEA and CEA-related antigens may play in cell adhesion are highlighted, together with results from molecular studies that illustrate how structure can influence the choice of CEA antibodies for use in both the research and diagnostic laboratory.
Key words: Carcinoembryonic antigen. Cell adhesion. Neoplasms. Tumor markers, biological.
Introduction
Carcinoembryonic antigen (CEA) was first described by Gold and Freedman in 1965(1,2) as a high-molecularweight glycoprotein found in colonic tumours and fetal colon but not in normal adult colon. With the development of more sensitive immunoassays, however, raised circulating CEA was also found in cases of breast, lung and ovarian tumours, and in cases of alcoholic cirrhosis.3 Despite this, CEA continues to be of interest as a multifunctional glycoprotein capable of acting as a Ca^sup 2+^-independent homophilic and heterophilic cell-cell adhesion molecule.4,5 It plays a role in diagnostic pathology and continues to be studied as a molecule involved in metastasis and carcinogenesis. Here, the major advances which have been made in understanding CEA and CEA-related antigens are covered, including molecular study of its gene structure, how this relates to the expressed protein, and how the specificity of antibodies to CEA may be affected by the expression of homologous CEA family members.
Molecular structure
In mature form, CEA is a glycoprotein with a molecular weight (MW) of approximately 180 kDa. The protein component has an MW of 78 kDa and the majority of the molecule is carbohydrate, comprising mannose, galactose, N-acetylglucosamine, fucose and neuraminic (sialic) acid.3,6,7
It has long been recognised that CEA is a member of the immunoglobulin gene superfamily.3 This diverse family includes major histocompatibility antigens, together with cell adhesion molecules such as ICAM-1, NCAM and LFA1.8 The common structure of the immunoglobulin gene superfamily is thought to have evolved from a single ancestral unit - the proteaseresistant immunoglobulin fold - which has undergone divergence and duplication.9
The CEA gene family is clustered on chromosome 19q, within a 1.2 Mb region,lo and can be divided into two subgroups: the CEA subgroup and the pregnancyspecific glycoprotein (PSG) subgroup (Fig. 1). Within each, there is a highly conserved region of 70-90% similarity in the N-domain exons. This conservation is significantly lower (50-60%0)7 between the subgroups. The CEA gene subgroup consists of CEA and the cross-relating genes coding for non-specific crossreacting antigen (NCA) 50/90, biliary glycoproteins (BGP) and other active genes.7 The primary structure of complementary DNA (cDNA) sequences of CEA and the genes of CEArelated family members have been established.11-14 There is a close correlation between exon expression and the domain structure, with the first exon encoding the 5'-untranslated region and the first two-thirds of the leader peptide10,,4 (Fig. 2). Comparative analysis of the cDNA transcripts for CEA and NCA-50 shows that there is a high sequence homology between the two molecules. There are major differences within the 3'-untranslated region, which can be utilised in the design of specific probes for use in in situ hybridisation (ISH) and the polymerase chain reaction (PCR).'1's However, the presence of an NCA-like 3'-untranslated region may present specificity problems.14
ISH is a powerful tool for the study of gene expression and for the localisation of messenger RNA (mRNA) within cells. Using such techniques, there appears to be a relationship between mRNA expression of CEA and protein distribution. 16-20 Several studies21-23 have found that CEA mRNA expression is under both transcriptional control mechanisms, such as gene methylation, and post-translational mechanisms, such as glycosylation and several regulatory elements which bind multiple nuclear binding factors. Hauk and Stanners23 also showed that CEA and NCA mRNA expression differed in a transfected cell line (CaCo-2) when stimulated by interferon-gamma (IFN-gamma). Such observations are important when considering the biological roles) that CEA and CEA-related gene products may play.
The deduced amino acid sequences of CEA and CEA-related proteins show that CEA is synthesised as a precursor of 702 amino acids, comprising a leader peptide of 34 amino acids and a mature CEA peptide of 668 amino acids.10,4 The mature peptide is divided into structural domains based on three internal repeat regions. These are referred to as N, A1B1, A2B2 and A3B3 domains.7.10 The Fifth CD Workshop (Boston, 1993) assigned all CEA-related antigens to CD66, CEA being assigned CD66e.
The carbohydrate moieties of CEA and CEA-related antigens may be involved in cell-cell adhesion. It has been proposed that the CEA family of antigens, particularly those associated with neutrophils (e.g. NCA [CD66c]), act as presenter molecules of oligosaccharide structures.24,25 A high proportion of the carbohydrate moiety is in the form of.>acetylglucosamine, consistent with the attachment of Lewis-type antigens, which act as ligands to the selectin family of adhesion molecules.26-29 The CEA-related antigen BGP is also associated with neutrophils, and the V domain of BGPc binds to CD66-classified antibodies. This domain also mediates homotypic adhesion of the Chinese hamster ovarian cell line (CHO-BGPc) transfectants in a temperature-dependent manner.3
CEA and cell adhesion
Together with integrins, cadherins, selectins and CD44, the immunoglobulin superfamily is recognised as a group of cell adhesion molecules.31 Most cell adhesion molecule interactions are accompanied bv the transmission of signals regulating differentiation or proliferation, and allow the exchange of information mediated by other cellular components.8,32,33 Although these molecules display a diversity of functions involved with immunity and in the control of the behaviour of cells in various tissues, they share the common feature of being recognition molecules at the cell surface.34
It has been suggested that CEA plays a role in cell recognition and in the regulation of cellular interactions. Benchimol et al.35 proposed a model of the role CEA may play during the malignant transformation of colonocytes, where overexpression of CEA leads to the disruption of normal intercellular forces at both the lateral and basal surfaces, due to the reduction in strength of other adhesion molecules. This results in an undermining of the single-layer configuration seen in the normal colonic crypt. With the over-production of CEA further down the crypt, an embryonic, multilayered configuration is assumed which, together with cellular division and further genetic insult, could develop into overt malignancy.
In the colon and elsewhere, CEA is expressed along the apical border of normal epithelial cells. In well-differentiated tumour cells, there is a reported increase in CEA expression along both lateral and basal surfaces, with cytoplasmic CEA expressed in poorly differentiated cells.36-38 In vitro studies have shown an increase in cellular CEA with the loss of polarisation.39
Dysregulation of CEA-related antigen expression has been confirmed in colorectal adenomas. Scheller et al. investigated the mRNA transcript expression of BGP CGM2 and NCA in 22 colorectal adenomas, and compared it with their respective normal mucosa. BGP and CGM2 mRNA levels were down-regulated in 20 and 18 adenomas, respectively, when compared to normal mucosa. NCA mRNA was increased by up to 2.4fold in 11 adenomas, when compared to their normal mucosa. This early dysregulation in colorectal tumourigenesis suggests importance in the development of the malignant phenotype.
In cell-cell adhesion, CEA and NCA are Ca^sup 2+^-independent, homophilic and heterophilic adhesion molecules.4,5 Oikawa et al.4 found that the N-domain of NCA and the CEA family member CGM6(7) (CD66b) mediated heterotypic cell adhesion. Domain-specific antibodies inhibited homophilic cell-cell adhesion in colorectal carcinoma cell lines where the epitopes within N and A3B3 domains were reported to be responsible for CEA-CEA binding. The involvement of N and a repeated loop of the A3B3 domain in homophilic adhesion by CEA was confirmed by Kuwahara et al.40 The same antibodies failed to inhibit cell adhesion to type IV collagen and laminin.41
CEA is involved in cell-extracellular matrix (ECM) adhesion of the colonic carcinoma cell line SW1222.(42) This cell line binds to type I collagen through a receptor which recognises the Arg-Gly-Asp (RGD) tripeptide sequence.43 Cell adhesion to type I collagen matrix was inhibited by a panel of monoclonal antibodies to the 180 kDa CEA and other members of the CEA family. However, the same antibodies failed to inhibit adhesion to type I collagen in another CEAexpressing carcinoma cell line (LS 174T). This cell line does not adhere to collagen via the RGD-recognising receptor, and both cell lines failed to adhere to CEA itself. It was proposed that CEA and the RGD-recognising receptor cooperate in cell adhesion to collagen and regulate the functional activity of the SW1222 collagen receptor.
Use of CEA in diagnosis
Groups interested in using interferons (IFNs) as adjuvants in immunoscintigraphy and immunotherapy trials have identified CEA as a molecule for subsequent monoclonal antibody targeting.44 CEA expression is enhanced by IFN-gamma in cell lines derived from colon45 and lung46 carcinoma. Guadagni et al.47 found that the most responsive of the cell lines tested by IFN-y treatment were the moderately differentiated cell lines, where there was a 300-400% increase in cellular CEA content and an increase from 30-40% to greater than 80% in its cell-surface expression, as measured by flow cytometry. With one exception, those cell lines which did not constitutively express CEA were not stimulated to produce CEA by IFN-gamma treatment. Similarly, expression of CEA in patients diagnosed with gastrointestinal carcinoma is enhanced in a dose-dependent manner following intramuscular injection of IFN-alpha2, whereas CEA expression in samples of normal colonic mucosa remains low.45
For some considerable time, radiolabelled antibodies to CEA have been used in imaging tumours and localising them prior to surgery.48 However, nonspecificity and lack of characterisation in this first generation of antibodies resulted in a limited ability to resolve intrahepatic lesions, as high uptake by normal liver tissue complicated the images.49 Using internationally recognised criteria (see below), a second generation of monoclonal antibodies to CEA have been identified and are undergoing evaluation for tumour imaging and immunotherapy.50-54 Experimental models using mice that are transgenic for human CEA have been proposed.55
Despite its demise as the marker of malignancy, CEA continues to be of some value in the diagnosis and prognosis of cancer.56,57 In colorectal tumours, preoperative serum CEA levels assist in the evaluation of Duke's stage C carcinoma,58 and when used in conjunction with flow cytometry, help to predict the prognosis of patients with Duke's stage B2 and Duke's stage C carcinomas.59 In addition, a significantly higher preoperative level of serum CEA is found in patients with non-resectable tumours.60
Cellular and tissue distribution of CEA can also be useful61-63 and its staining pattern used to predict metastatic potential64 and lymph node status.65 As part of a panel of antibodies, CEA can prove useful in determining the primary site of metastatic adenocarcinoma.66,67 Similarly, in tumours of the extrahepatic biliary tract, the cellular localisation of CEA can identify foci of malignant cells.3738 PCR can be used to detect micrometastasis in specimens of bone.45
On fine-needle biopsy samples, polyclonal anti-CEA can be useful in differentiating atypical variants of hepatocellular carcinoma from metastatic tumour.68 However, because of its lack of specificity and ability to cross-react with CEA-related antigens, the polyclonal antibody was not recommended in other studies.69,70 Absorption with tissue extracts, irrespective of the source of tissue, reduces this cross-reactivity with CEA-related antigens.71 The absorption process, however, has never been standardised, with different authors recommending absorption by various tissue preparations and using different absorption procedures.71,72
Initially, monoclonal antibodies were thought to provide a means of achieving CEA specificity. Characterisation of available antibodies to CEA by an international group showed, however, that only those directed against certain domains of the CEA molecule were specific.73 This was confirmed by other groups,50,52,74-76 and has helped to classify monoclonal antibodies according to recognised standards. Fully characterised monoclonal antibodies to CEA remain important when used for diagnostic purposes. For example, in the differentiation of mesothelioma from adenocarcinoma, CEA is consistently found to be the most useful marker to identify adenocarcinoma, although the use of CEA-specific antibodies remains paramount70,77,78 especially when used as part of an antibody panel on processed tissue following heat-mediated antigen retrieval.79
Conclusions
The capacity of the CEA family of genes to undergo splice variation and post-translational change gives rise to a group of complex glycoproteins. Such variety allows the potential for CEA and CEA-related antigens to participate in many facets of cell growth and development, as well as in carcinogenesis. Well-characterised antibodies are now available and are used for both clinical and diagnostic purposes. CEA, therefore, and the CEA family of related antigens continue to provide valuable insights into carcinogenesis and are of value in diagnosis.
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[Author Affiliation]
P. MAXWELL
Immunocytochemistry and Molecular Pathology Laboratory, Institute of Pathology, Royal Group of Hospitals Trust, Belfast BT12 6BA, Northern Ireland, UK
(Accepted 9 April 1999)
During November each year it has become normal practice for menacross the nation to sprout strange and interesting moustaches inthe interests of fundraising.
Movember, as the phenomenon is known, aims to raise vital fundsand awareness for men's health, specifically prostate cancer andother cancers that affect men.
The male members of the team at The Home Partnership inChelmsford took up the challenge for 2011, calling themselves TeamTash Factor.
They are proud to confirm that they raised a total of Pounds2,775 for this cause.
Team Tash Factor would like to say a massive thank you toeveryone who donated, helping to change the face of men's health.
Pictured from left are: Steve Burnside, Merrick Allen, ScottMason and Lee McGoldrick.
An allegedly intoxicated teen motorist smashed into a police car during a chase and one of the two officers in the cruiser was killed, authorities said Saturday.
The second officer was hospitalized in stable condition.
The officers had joined the pursuit of an SUV whose driver ran a red light and then failed to stop for police late Friday, officials said. The SUV struck the passenger side of their police car.
Police said the driver of the SUV, described as a 16-year-old who did not have a driver's license, tried to run but was soon captured. He was treated at a hospital for minor injuries and taken into custody for questioning. No charges had been filed as of noon Saturday, police said.
Authorities identified the slain officer as Isabel Nazario, an 18-year veteran whose sister and fiance also are on the police force.
"This is the second officer that we've had killed this year. It's a very difficult time," Police Commissioner Charles Ramsey said late Friday.
Defending champion Olympiakos has fired Brazilian coach Zico following poor results in the Greek league.
Two losses in a row and a goalless draw at Kavala has helped rival Panathinaikos extend its lead from two to seven points. After 18 of 30 rounds, Panathinaikos has 47 points against 40 for Olympiakos.
Olympiakos said on its Web site Tuesday that it named former player Bozidar Bandovic as new coach.
Zico has been at Olympiakos since September. He replaced Temuri Ketsbaia, who was fired after 85 days in charge _ also for poor results.
Olympiakos reached the round of 16 in the Champions League and hosts French club Bordeaux in the first leg on Feb. 23.
Asian stocks turned in another shaky performance Thursday, with Japan's market notching its seventh straight loss, as worries about the pace of economic recovery continued to hold investors back.
The weakness followed more losses on Wall Street overnight, with many of the region's markets fluctuating in a narrow range in thin trade. Crude oil prices rose modestly after a spectacular plunge in recent days to trade near $61 a barrel.
Global markets have been grinding lower over the last week after economic evidence, notably unemployment figures in the U.S. and Europe, suggested any rebound in growth could be feeble and take longer that investors expected.
Earnings season, which kicked off Wednesday with a narrower-than-expected loss from U.S. aluminum maker Alcoa, will likely help shape the direction of equities markets in the coming weeks.
"Reality is coming back into the market and now you're seeing investors locking in profits after the euphoria in June," said Clive McDonnell, Sinagpore-based head of Asia strategy at BNP Paribas Securities. "I wouldn't describe investor sentiment as fragile, but it's certainly coming down from the euphoric highs we saw earlier."
In Japan, the Nikkei 225 stock average lost 129.69 points, or 1.4 percent, to 9,291.06 after the yen strengthened to its highest point in almost five months this week. That weighed on the broader market, with major exporters like Toyota and Sony losing between 2 percent and 3 percent.
Hong Kong's Hang Seng rose 69.52, or 0.4 percent, to 17,790.59 in choppy trade, while South Korea's Kospi benchmark was virtually flat with a loss of just 0.13 point.
In Australia, the main stock measure edged down 0.1 percent as the country's unemployment rate rose to a six-year high of 5.8 percent in June, showing that companies continued to shed workers despite the government's massive stimulus spending
Elsewhere, India's Sensex recovered to add 0.1 percent. Shanghai's index gained 1.4 percent.
Incessant worries about the scope of any economic recovery led Wall Street to a lackluster finish overnight. Adding to the downbeat mood were mixed forecast for the global economy from the International Monetary Fund as well as another sharp fall in commodity prices.
The Dow Jones industrials ended up 14.81, or 0.2 percent, to 8,178.41, but the broader Standard & Poor's 500 index fell 1.47, or 0.2 percent, to 879.56.
Wall Street futures pointed to a modestly higher open Thursday. Dow futures were up 52 points, or 0.6 percent, at 8,168 and S&P futures gained 7.1, or 0.8 percent, to 880.80.
Benchmark crude for August delivery was up 66 cents to $60.80. On Wednesday, the contract fell more than 4 percent, or $2.79.
The dollar rebounded to 93.52 yen from 92.71 yen after sliding in recent days. The euro was higher at $1.3956 from $1.3880.
