NEW BREAST IMAGING MODALITIES

RSNA 2008: New Breast Imaging Modalities Reveal Cancers as Small as a Single Millimeter

December 4, 2008 (Chicago, Illinois) — Two imaging modalities that look at breast cancer activity on a cellular level can pick up occult tumors that are only 1 to 3 mm in size in women with a history of breast cancer, radiologists reported here at the 94th Scientific Assembly and Annual Meeting of the Radiological Society of North America (RSNA 2008).

Results with positron-emission mammography (PEM) were announced by Kathy Schilling, MD, medical director of the Center for Breast Cancer, in Boca Raton, Florida. Results with breast-specific gamma imaging (BSGI) were announced by Rachel F. Brem, MD, professor of radiology and director of the Breast Imaging and Interventional Center at the George Washington University Medical Center, in Washington, DC.

Mammography and ultrasound analyze the anatomic structures of the breast. PEM and BSGI assess cellular activity. PEM measures uptake of fluorodeoxyglucose by breast cancer cells and BSGI uses sestamibi (technicium 99m) uptake to assess cellular activity.

Dr. Schilling presented findings from PEM in 208 patients with breast cancer. The investigators found 189 malignant lesions, of which 176 were visible on PEM, for a sensitivity of 93%.

PEM was able to detect malignancies in 100% of fatty breasts, 93% of dense breasts, and 85% of extremely dense breasts, and in 90% of premenopausal women and 94% of postmenopausal women with breast cancers, whether or not they were taking hormone-replacement therapy.

"There is no hormonal influence on PEM. There is no change it its accuracy," Dr. Schilling said, "and there is no effect of breast density on PEM accuracy."

"PEM can identify 2 mm ductal cancer in situ lesions. These are not visible on conventional mammography," she added. One caution is that PEM is performed while the patient is fasting. That and the glucose-based radiotracer that is used make it unsuitable for diabetic patients, Dr. Schilling cautioned.

PEM is done with the patient seated. "It is a very comfortable procedure," Dr. Schilling commented. The same is true for BSGI, Dr. Brem added.

Dr. Brem presented findings from BSGI in 159 women with at least 1 suspicious or cancerous lesion found on mammography or physical examination. The objective was to determine how often unsuspected occult cancers could be detected in a population already known to have breast cancer.

An additional suspicious lesion was found in 46 women (29%). Lesions were malignant in 14 of 39 (36%) cases biopsied. Nine lesions were in the same breast and 5 were in the contralateral breast. Dr. Brem reported that 73% of women had dense breasts.

The mean size of the occult lesions was 1.16 mm, and the smallest was only 1 mm in size. Half of the occult lesions were smaller than 1 cm.

BSGI is an effective approach for the detection of unsuspected cancers," Dr. Brem said. "It is complementary to ultrasound and uses a lower dose of radiation than PEM."

"PEM delivers the equivalent to approximately 3 mammograms. BSGI is at least half that dose," she said. There are few or no contraindications with BSGI. It can be used in diabetics and in patients with compromised renal function, and there are no weight restrictions or other limitations, Dr. Bream said.

In an interview with Medscape Radiology during RSNA 2008, Society spokesperson Lillian Stern, MD, assistant professor of radiology at Thomas Jefferson University School of Medicine, in Philadelphia, Pennsylvania, commented that PEM and BSGI "are novel ways of looking at breast cancers, looking at cellular activity rather than anatomically or physiologically."

"It's effective in tumors with 'single-file cells' that have no round masses or calcifications that would be visible with conventional imaging," she noted.

"I use BSGI in asymmetrical breasts, where there is less fat in 1 breast.... Most of the time, the results are clearly positive or clearly negative, and we can give the results to the patient immediately."

It will not replace mammography or magnetic resonance imaging (MRI), but I am using MRI less often now," Dr, Stern commented.

Dr. Schilling is a consultant with Johnson and Johnson and Naviscan PET Systems, Inc. Dr. Brem is a board member with Dilon Technologies LLC, manufacturers of a BSGI system. Dr. Stern has disclosed no relevant financial relationships.

RSNA 2008: 94th Scientific Assembly and Annual Meeting of the Radiological Society of North America: Scientific Session VB31-04: Presented December 3, 2008.

HORMONAL TREATMENTS DO NOT IMPAIT COGNITIVE FUNCTION

Hormonal Treatments Do Not Impair Cognitive Function in Women With Breast Cancer

NEW YORK (Reuters Health) Nov 27 - Concern that estrogen depletion in women with breast cancer may contribute to cognitive compromise does not appear to be warranted, at least over the short term, according to a report in the November 1st issue of Cancer.

"Antiestrogen therapy with tamoxifen or aromatase inhibitors did not have any significant effects on cognitive function, and I think it is safe to say that patients needn't worry about cognitive side effects of these medications," Dr. Kerstin Hermelink from Ludwig Maximilian University, Munich, Germany, told Reuters Health.

Dr. Hermelink and colleagues assessed the effects of induced menopause and antiestrogen therapy on cognitive function in 101 women with nonmetastatic, invasive breast cancer.

At about 7 months after the completion of neoadjuvant therapy, the cognitive performance of the overall group, and of all subgroups based on menopausal status and antiestrogen therapy, ranged within or above the test norms on all cognitive tests, the investigators report.

In fact, they say, the effects of induced menopause on cognitive function appeared to be positive in some tests.

"In our study, cognitive compromise was already present before any cancer treatment," Dr. Hermelink explained. "Several other prospective studies have also found pretreatment cognitive dysfunction. Therefore, cognitive compromise in cancer patients must at least in part have other causes than the cancer therapy. We presume that stress might play an important role."

VITAMIN D AGAIN

VDR Polymorphisms Linked With Survival in Advanced NSCLC

NEW YORK (Reuters Health) Nov 26 - Researchers who previously showed that polymorphisms in the vitamin D receptor (VDR) gene and serum vitamin D levels may be linked with survival in early-stage non-small cell lung cancer (NSCLC) have now found that some VDR polymorphisms and haplotypes are associated with better survival in advanced NSCLC as well.

In the Journal of Clinical Oncology published online ahead of print on October 20, Dr. David C. Christiani at the Harvard School of Public Health in Boston and colleagues explain that on the basis of their earlier findings, they theorized that "the variant A allele of the Cdx-2 polymorphism, wild-type C allele of the FokI polymorphism, and the variant T allele of the BsmI polymorphism, either individually or combined in joint effects or haplotypes, would be associated with better survival," as would higher circulating levels of vitamin D.

In their study of 294 patients with advanced NSCLC, there was no difference in survival based on circulating vitamin D levels at a median follow-up of 42 months.

There was, however, an association of the C/C genotype of the FokI polymorphism with improved survival. Specifically, the authors report, "median survival for C/C was 21.4 months, for C/T was 12.1 months, and for T/T was 15.6 months (log-rank p = 0.005)."

The Cdx-2 and BsmI polymorphisms had no significant impact on survival.

However, there was also an association between improved survival and having increasing numbers of protective alleles, with an adjusted hazard ratio of 0.57 for two or more vs one or no protective alleles.

Also, the authors report that compared to the most common haplotype of G-C-T, the G-T-C (Cdx-2-FokI-BsmI) haplotype was associated with worse survival (adjusted hazard ratio, 1.61). They point out that the G-T-C (Cdx-2-FokI-BsmI) haplotype is thought to have lower VDR activity, whereas the C/C genotype of the FokI polymorphism, which was linked with improved survival, is thought to have higher VDR activity.

"Clinical trials are...investigating the addition of vitamin D or vitamin D analogs to the treatment of patients with various cancers, including lung cancer," the authors note, adding, "Investigating these polymorphisms in these clinical trials will be important for associations with treatment outcomes."

A BETTER DRUG FOR ELEVATED URIC ACID

Febuxostat Outperforms Allopurinol in Lowering Urate Levels

NEW YORK (Reuters Health) Nov 28 - The xanthine oxidase inhibitor, febuxostat, lowers serum urate levels to a greater extent than allopurinol in patients with gout, researchers report in the November 15 issue of Arthritis & Rheumatism.

Dr. H. Ralph Schumacher, Jr., of the University of Pennsylvania and VA Medical Center in Philadelphia and colleagues randomized 1072 patients with gout to febuxostat 80 mg, 120 mg or 240 mg once a day, or allopurinol 300 mg or 100 mg (depending upon renal function), or placebo for 28 weeks.

The patients had serum urate levels of at least 8.0 mg/dL, and the primary endpoint was serum urate levels below 6.0 mg/dL (i.e., below saturating level) at the three most recent exams.

Among patients with normal renal function, the primary endpoint was achieved by 48% on febuxostat 80 mg, 65% on 120 mg and 69% on 240 mg, while 22% of patients on allopurinol and none of those on placebo met the endpoint.

Among patients with impaired renal function, 44% of those on febuxostat 80 mg, 45% of those on 120 mg and 60% of those on 240 mg achieved the primary endpoint, while none of the patients on allopurinol did so.

Adverse event rates were similar across all groups, although diarrhea and dizziness were more frequent in the febuxostat 240 mg group.

"In contrast to allopurinol, febuxostat inhibits both oxidized and reduced forms of xanthine oxidase and has minimal effects on other enzymes of purine and pyrimidine metabolism," Dr. Schumacher explained. However, he noted, "Febuxostat should not be used with allopurinol as other mechanisms are similar."

"The efficacy of febuxostat in subjects with renal impairment is promising and warrants further study," Dr. Schumacher said, but he told Reuters Health that "no other studies are planned that I know."

ACE INHIBITOR AND CCB BETTER COMBINATIN THAN DIURETIC

ACCOMPLISH Published: ACE Inhibitor and CCB Best for Reducing Clinical Events in Hypertensive Patients

December 4, 2008 — The Avoiding Cardiovascular Events in Combination Therapy in Patients Living with Systolic Hypertension (ACCOMPLISH) trial, a large morbidity and mortality study comparing the effects of two forms of antihypertensive combination therapies on major fatal and nonfatal cardiovascular events, is now published in the December 4, 2008 issue of the New England Journal of Medicine [1].

The trial was stopped early because treatment with antihypertensive combination therapy — the angiotensin-converting enzyme (ACE) inhibitor benazepril plus the calcium-channel blocker amlodipine — was more effective than treatment with the ACE inhibitor and diuretic. First presented at the American College of Cardiology 2008 Scientific Sessions in Chicago, IL and reported by heartwire at that time, the results showed that the single-tablet benazepril/amlodipine combination reduced the risk of morbidity and mortality by 20% compared with conventional therapy.

"We have guidelines stating a preference for diuretics as monotherapy or to use diuretics and an ACE inhibitor in combination therapy," lead investigator Dr Kenneth Jamerson (University of Michigan, Ann Arbor) told heartwire. "We now have data that suggest that combination therapy is probably a good initial strategy for high-risk patients, rather than starting with one drug and going slow. Putting patients on either combination doubled their control rate, so combination therapy is something clinicians need to think about, even if they want to keep the diuretic. But the drug that gives superior cardiovascular outcomes is the calcium-channel blocker and ACE inhibitor."

Commenting on the results, Dr Franz Messerli (St Luke's-Roosevelt Hospital, New York), who was not part of the study, said ACCOMPLISH should change the way clinicians treat patients with hypertension.

"This landmark study unequivocally relegates hydrochlorothiazide from first-line to third-line therapy at least in a patient population with similar demographic and clinical features as in ACCOMPLISH," said Messerli. "The issue is not to be taken lightly, since hydrochlorothiazide remains one of the most commonly prescribed antihypertensive drugs. Every year more than 100 million prescriptions of hydrochlorothiazide are written in the US. Almost half of those prescriptions are written for hydrochlorothiazide alone, and the remainder for fixed combinations, mostly with either ACE inhibitors or angiotensin receptor blockers."

High-risk patient population

ACCOMPLISH compared the effects of the two forms of antihypertensive combination therapies on major fatal and nonfatal cardiovascular events in 11,506 men and women aged 55 years or older who had systolic blood pressure ≥ 160 mm Hg. All patients were currently on antihypertensive therapy and had evidence of cardiovascular or renal disease or target-organ damage. Patients enrolled in the trial were obese, with 60% having diabetes mellitus, and nearly all had been treated previously for hypertension.

Despite being treated previously — more than 70% of patients in the trial were currently taking two or more hypertensive agents — just 37.3% of patients had their blood pressure controlled to <>Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC-7). As part of the study protocol, all patients stopped their medication and, without a washout period, were randomized to combination treatment with benazepril plus hydrochlorothiazide or amlodipine plus benazepril.

The study was terminated after a mean follow-up of 36 months. Jamerson noted that patients in both treatment arms received excellent blood-pressure control, with blood pressures of 132/73 mm Hg in the benazepril/amlodipine arm and 133/74 mm Hg in the benazepril/hydrochlorothiazide arm.

Regarding the primary end point, a composite of death from cardiovascular causes, nonfatal myocardial infarction (MI), nonfatal stroke, hospitalization for angina, resuscitation after sudden cardiac arrest, and coronary revascularization, 9.6% of patients in the benazepril/amlodipine arm had an event compared with 11.8% in the benazepril/hydrochlorothiazide arm. This absolute 2.2% benefit translated into a 20% relative reduction in risk.

ACCOMPLISH: Primary and secondary end points

End point	Hazard ratio (95% CI)
Cardiovascular morbidity/mortality*	0.80 (0.72 - 0.90)
Individual components
Cardiovascular mortality	0.80 (0.62 - 1.03)
Fatal and nonfatal MI	0.78 (0.62 - 0.99)
Fatal and nonfatal stroke	0.84 (0.65 - 1.08)
Hospitalization for unstable angina	0.75 (0.50 - 1.10)
Coronary revascularization	0.86 (0.74 - 1.00)
Resuscitation after sudden cardiac arrest	1.75 (0.73 - 4.17)

*Primary end point.

In an editorial accompanying the published study [2], Dr Aram Chobanian (Boston University School of Medicine, MA), who served as chair for the JNC-7 hypertension guidelines, agrees that a recommendation of thiazide-type diuretics as initial therapy for most patients with hypertension needs to be reexamined.

"The results from the many recent studies, including the ACCOMPLISH trial, when considered together, suggest that greater flexibility is now indicated in the choice of the initial drug," writes Chobanian. The drug of choice depends on criteria such as compelling indications or contraindications, as well as coexisting conditions, adverse effects, race, and the clinician's experience, he said.

This increased flexibility, however, "should not negate the importance of diuretics," a cornerstone of antihypertensive therapy for 50 years, stressed Chobanian. In addition, the findings "should not diminish the value of treatment with the combination an ACE inhibitor and a diuretic," an effective combination for lowering blood pressure, as observed in ACCOMPLISH, "that was recently shown to produce major reductions in mortality and morbidity in the very old," noted Chobanian.

In his editorial, Chobanian, like others before him, pointed out that the diuretic used in ACCOMPLISH differed from the diuretic used in the Antihypertensive and Lipid Lowering Treatment to Prevent Heart Attack Trial (ALLHAT). Chlorthalidone, the ALLHAT diuretic, is estimated to be twice as potent as hydrochlorothiazide and to have a longer duration of effect in the 12.5- to 25-mg dose range.

Countering these criticisms, Jamerson said that 90% of clinicians in the US use hydrochlorothiazide, and most of these are using it at doses ranging from 12.5 mg to 25 mg, the dose used in ACCOMPLISH.

"Our message is really simple," said Jamerson. "For the thiazide that most people are using, even if they were able to get the blood pressure down to 130 mm Hg, which most clinicians in the US are not doing, the ACE inhibitor/calcium-channel-blocker combination would still give you better cardiovascular outcomes. For a lot of people, if you're using a combination, this ought to be a strategy to consider."

With doctors using hydrochlorothiazide for hypertension for half a century, Messerli told heartwire that ACCOMPLISH indicates that it is time to turn the page.

BRCA1 HAPLOTYPE AND CHEMOTHERAPY

BRCA1 Haplotype Influences Lung Cancer Chemotherapy

NEW YORK (Reuters Health) Dec 02 - Carriers of certain haplotypes of the BRCA1 gene, which plays a central role in the DNA repair system, do not appear to respond to platinum-based chemotherapy for non-small-cell lung cancer, Korean researchers report in the Journal of Clinical Oncology published online ahead of print.

"Results from this study," senior investigator Dr. Jeong-Seon Ryu told Reuters Health, "show that lung cancer patients with two copies of AACC of BRCA1 do not benefit from platinum doublets -- gemcitabine/platinum, docetaxel/platinum or paclitaxel/platinum -- that are standard regimens worldwide for locally advanced or metastatic non-small-cell lung cancer."

Dr. Ryu of Inha University Hospital, Inchon, and colleagues came to this conclusion after studying the relationship of 4 tagging single-nucleotide BRCA1 polymorphisms and their haplotypes on the outcome of treatment in 300 patients. The five haplotypes studied were AACC, AACA, GCTC, GATC and AATC.

Median survival was 13 months and the researchers did not find any significant associations between any of the tagging polymorphisms and overall survival.

However, patients with two copies of the AACC (wild type) haplotype had significantly shorter survival than those with one or no copy (8.47 versus 14.57 months). This continued to be true after adjustment for factors including weight loss and second-line treatment (hazard ratio, 2.097).

This effect on survival was seen in patient with squamous cell carcinoma but not in those with adenocarcinomas.

"Therefore," concluded Dr. Ryu, "this result suggests that a new strategy is needed for these patients, especially in squamous cell carcinoma."

ΝΕΟΣ ΝΟΜΟΣ

Υπογράφηκε η Κλαδική Σύμβαση Εργασίας απο τον υπουργό Υγείας και την ΟΕΝΓΕ.

Η διάρκεια της σύμβασης είναι μονοετής με αρχή την 1/1/2009 και κατάληξη την 31/12/2009 με σημείο επαναδιαπραγμάτευσης την 1/10/2009. Η ισχύουσα κλαδική σύμβαση θα αποτελέσει και την βάση του νέου ιατρικού μισθολογίου που θα ολοκληρωθεί μέσα στο 2009.Ακολoυθεί το πλήρες κείμενο της Συμφωνίας:

Η νέα κλαδική Συλλογική Σύμβαση Εργασίας προβλέπει:

1. Οι νοσοκομειακοί γιατροί κλάδου ΕΣΥ και ειδικευομένων θα πραγματοποιούν τις απαραίτητες εφημερίες, για την ασφαλή λειτουργία των νοσοκομείων και των Κέντρων Υγείας .

Το πρόγραμμα των εφημεριών αυτών καταρτίζεται σύμφωνα με τις κείμενες διατάξεις.Για τις ανάγκες κατάρτισης του προγράμματος εφημεριών και ομαλής λειτουργίας των νοσοκομείων και των Κέντρων Υγείας δεν θα εφαρμοστούν ελαστικά ωράρια και ελαστικές σχέσεις εργασίας. ‘Όπου στην παρούσα σύμβαση μνημονεύονται οι ειδικευμένοι γιατροί του ΕΣΥ, συμπεριλαμβάνονται και οι οδοντίατροι του ΕΣΥ, καθώς και οι γιατροί ΕΣΥ του Νοσοκομείου Παπαγεωργίου της Θεσσαλονίκης.

2. Το επίσημο ωράριο των νοσοκομειακών γιατρών είναι 7ωρο, συνεχές, πρωινό και 5νθήμερο, από Δευτέρα έως Παρασκευή. Μετά δε από κάθε ενεργό εφημερία παρέχεται στον εργαζόμενο, σε εργάσιμη ημέρα, 24ωρη ανάπαυση, που δεν μεταφέρεται πέρα της μιας εβδομάδος.

3. Το επίδομα βιβλιοθήκης των νοσοκομειακών γιατρών δεν υπόκειται σε φορολόγηση.

4. Οι πρώτες 4 για τους ειδικευμένους νοσοκομειακούς γιατρούς και οι πρώτες 6 για τους ειδικευόμενους γιατρούς, εφημερίες κάθε είδους και κατ΄ επιλογήν του γιατρού, φορολογούνται με ειδικό συντελεστή 20% ή με το εισόδημα. Οι πέραν των 4 πρώτων ή 6 εφημεριών, για τους ειδικευμένους και τους ειδικευόμενους γιατρούς αντίστοιχα, δεν υπόκεινται σε φορολόγηση.

Το 50% του επιδόματος εφημερίας των Διευθυντών γιατρών της Α΄ Ζώνης δεν υπόκειται σε φορολόγηση. Το μέτρο αυτό θα ισχύει μετά την 1/1/09 για τους Συντονιστές Διευθυντές Α΄ Ζώνης. Για τις ανάγκες ερμηνείας της παρούσης, εξομοιούται με Συντονιστή Διευθυντή, κάθε Διευθυντής, που είναι μοναδικός στο Τμήμα του.

5. Αναδιαρθρώνεται η Ιατρική υπηρεσία στη βάση οργανωμένης εξέλιξης των νοσοκομειακών γιατρών μέσα στο σύστημα από τον εισαγωγικό βαθμό του Επιμελητού Β΄ (πύλη εισόδου) μέχρι τον βαθμό του Διευθυντού, σε πολυδιευθυντικό σύστημα.

Από 1/1/09 οι οργανικές θέσεις των γιατρών Κλάδου ΕΣΥ μετονομάζονται σε θέσεις ειδικευμένων γιατρών. Οι υπηρετούντες σήμερα γιατροί διατηρούν τον βαθμό τους.

Η ένταξη και η εξέλιξη των νοσοκομειακών γιατρών στο ΕΣΥ γίνεται εφεξής ως ακολούθως.

α) Κάθε ειδικευμένος γιατρός του ΕΣΥ εξελίσσεται μέχρι τον βαθμό του Διευθυντού, υπό προϋποθέσεις χρόνου προϋπηρεσίας στον κάθε βαθμό, καθώς και σύμφωνα με τα εκπαιδευτικά και επιστημονικά κριτήρια που προβλέπει το αρ. 35 παρ. 6 του Ν. 2519/97, όπως ισχύει. Η αξιολόγηση είναι ατομική και γίνεται κατόπιν αιτήσεως του ενδιαφερομένου.

β) Κάθε θέση που κενούται, προκηρύσσεται από το Νοσοκομείο εντός 1 μηνός υποχρεωτικά. Η διαδικασία για την κάλυψη των κενών ή κενούμενων θέσεων είναι ανοικτή και ενεργείται με τα κριτήρια της παρ. 7 αρ.37 του Ν. 2519/97, όπως ισχύει. Ο επιλεγόμενος γιατρός προσλαμβάνεται στον εισαγωγικό βαθμό του Επιμελητού Β΄ και ακολούθως εξελίσσεται βαθμολογικά μέσα στο σύστημα.

γ) Η παρούσα δεν εφαρμόζεται για την πλήρωση θέσεων που έχουν προκηρυχθεί, μέχρι την ημέρα υπογραφής της και θεωρούνται εξ αυτού του λόγου εκκρεμείς. Τα αρμόδια συμβούλια επιλογής υποχρεούνται εντός τριών μηνών από την υπογραφή της παρούσης να έχουν ολοκληρώσει τις διαδικασίες για την πλήρωση των εκκρεμών θέσεων. Μετά την πάροδο της προθεσμίας αυτής, η ευθύνη ολοκλήρωσης των διαδικασιών για την πλήρωση των εκκρεμών θέσεων, περιέρχεται στα αρμόδια Συμβούλια της παρούσης.

δ) Οι βαθμοί των ειδικευμένων γιατρών είναι : Επιμελητής Β΄, Επιμελητής Α΄και Διευθυντής.

ε) Γιατροί που υπηρετούν στο ΕΣΥ ή Πανεπιστημιακοί γιατροί δύνανται να διεκδικήσουν προκηρυσσόμενη θέση σε άλλο νοσοκομείο και αν επιλεγούν διατηρούν το βαθμό τους. Η αντιστοίχηση βαθμών και τίτλων ΕΣΥ και Πανεπιστημιακών είναι: Λέκτορας με ειδικότητα Επιμελητής Β΄Επίκουρος Καθηγητής Επιμελητής Α΄Καθηγητής Α΄ Βαθμίδας Διευθυντής

Γιατροί οι οποίοι υπηρετούν σε Νοσοκομεία ή Κέντρα Υγείας του ΕΣΥ ή σε Πανεπιστημιακές κλινικές και προσληφθούν σε θέσεις άλλων Νοσοκομείων ή Κέντρων Υγείας, εξελίσσονται στον επόμενο βαθμό με καθυστέρηση 2 (δύο) ετών πέραν των προβλεπομένων, εις ότι αφορά τους Επιμελητές Β΄ και με καθυστέρηση 4 (τεσσάρων) ετών εις ότι αφορά τους Επιμελητές Α΄ . Τα ανωτέρω δεν ισχύουν για γιατρούς που υπηρετούν σε Νοσοκομεία ή Κέντρα Υγείας άγονων περιοχών και προσλαμβάνονται σε οποιοδήποτε Νοσοκομείο ή Κέντρο Υγείας της χώρας. Ομοίως δεν εφαρμόζονται για τους γιατρούς που υπηρετούν σε οποιοδήποτε Νοσοκομείο ή Κέντρο Υγείας άγονων περιοχών.

Οι άγονες περιοχές για τις ανάγκες εφαρμογής και ερμηνείας της παρούσης καθορίζονται με απόφαση του Υπουργού Υγείας και Κοινωνικής Αλληλεγγύης, κατόπιν πρότασης του Εθνικού Κέντρου Επιχειρήσεων Υγείας και της Γενικής Διεύθυνσης Υγείας του Υπουργείου Υγείας και Κοινωνικής Αλληλεγγύης. Οι κατέχοντες τον βαθμό του Διευθυντή δεν δύνανται πλέον να διεκδικήσουν άλλη θέση, αν δεν παρέλθει εξαετία από τη λήψη του βαθμού.

στ) Ο νοσοκομειακός γιατρός δύναται να εξελιχθεί στον επόμενο βαθμό κατόπιν αιτήσεως και αξιολογήσεώς του. Αν η αξιολόγηση είναι αρνητική δικαιούται να ζητήσει επαναξιολόγηση μετά 2 τουλάχιστον χρόνια από την 1η αξιολόγηση του στο συγκεκριμένο βαθμό. Επί νέας αρνητικής αξιολόγησης παραμένει στον ίδιο βαθμό , του απονέμονται οι αποδοχές του επόμενου βαθμού και δικαιούται άλλης αξιολόγησης μετά 5 έτη.

ζ) Δικαίωμα αίτησης για αξιολόγηση έχει ο Επιμελητής Β΄ μετά από 7 χρόνια στον βαθμό . Ο Επιμελητής Α΄ έχει δικαίωμα αξιολόγησης μετά από 8 έτη στον βαθμό ή 15 χρόνια στο ΕΣΥ από τα οποία, τα 5 χρόνια στον βαθμό του Επιμελητή Α΄ και στην ίδια θέση, χωρίς αρνητικές αξιολογήσεις στον προηγούμενο βαθμό, σε εφαρμογή της παρούσης.Από την κύρωση της παρούσης με νόμο και την έναρξη ισχύος του, παύει η απονομή του τίτλου του Αναπλ. Διευθυντή.

Οι υπηρετούντες κατά τη δημοσίευση της παρούσης Επιμελητές Α΄ που πληρούν τις νόμιμες προϋποθέσεις και όλοι οι σημερινοί Αναπλ. Διευθυντές, εντός της επόμενης 2ετίας, έχουν δικαίωμα να αξιολογηθούν, κατόπιν αίτησής τους, για τον βαθμό του Διευθυντή, κατά ειδικότητα και κατά σειρά αρχαιότητος στον βαθμό του Επιμελητή Α΄, ανά Νοσοκομείο και τα Κέντρα Υγείας του και σε ποσοστό 25% κάθε εξάμηνο. Το τελευταίο 6μηνο του 2010, μαζί με τους εναπομείναντες της παραγράφου αυτής, έχουν δικαίωμα να αξιολογηθούν και όσοι στο μεσοδιάστημα εξασφάλισαν τις προϋποθέσεις.

η) Όταν σε ένα τμήμα υπηρετούν περισσότεροι από ένας Διευθυντής, εκλέγεται ένας ως Συντονιστής Διευθυντής με 4ετή θητεία. Σε περίπτωση που δεν εκδηλώνεται ενδιαφέρον, ορίζεται, ο Συντονιστής, από τον Διοικητή του νοσοκομείου. Οι υπηρετούντες κατά την έναρξη ισχύος της παρούσης σε οργανική θέση Διευθυντές, καθίστανται Συντονιστές Διευθυντές, μέχρις αποχωρήσεώς τους για οιοδήποτε λόγο.

θ) Και στην Α΄ Ζώνη εφημερεύουν οι Διευθυντές σε ενεργό ή άλλου είδους εφημερία. Απαλλάσσονται της υποχρέωσης αυτής στην Α΄ Ζώνη οι Συντονιστές Διευθυντές ή Διευθυντές τμημάτων όπου δεν υπηρετεί άλλος Διευθυντής.

ι) Εκλεκτορικά Σώματα.

Α – Συμβούλιο προσλήψεων – κρίσεων σε ανοιχτές προκηρύξεις

Τα μέλη του Συμβουλίου προσλήψεων-κρίσεων σε ανοιχτές προκηρύξεις, είναι τα εξής :

1. Ο Διοικητής του Νοσοκομείου ως Πρόεδρος του Συμβουλίου με Αναπληρωτή του τον Διευθυντή Ιατρικής Υπηρεσίας και σε περίπτωση που ο τελευταίος δεν είναι γιατρός κλάδου ΕΣΥ, από τον Υποδιοικητή του Νοσοκομείου.

2. Ο Πρόεδρος του Επιστημονικού Συμβουλίου που αναπληρώνεται από τον νόμιμο αντικαταστάτη του, εφόσον είναι γιατροί κλάδου ΕΣΥ. Σε περίπτωση που δεν συντρέχει η προϋπόθεση αυτή, αντικαθίστανται από τον αρχαιότερο σε προϋπηρεσία γιατρό κλάδου ΕΣΥ του νοσοκομείου.

3. Ο Διευθυντής του αντίστοιχου Τομέα που αναπληρώνεται από τον νόμιμο αντικαταστάτη του εφόσον είναι γιατροί κλάδου ΕΣΥ. Σε περίπτωση που δεν συντρέχει η προϋπόθεση αυτή, αντικαθίστανται από τον αρχαιότερο σε προϋπηρεσία γιατρό κλάδου ΕΣΥ του οικείου τομέα.

4. Ο Συντονιστής Διευθυντής του οικείου τμήματος που αναπληρώνεται από τον νόμιμο αντικαταστάτη του, εφόσον είναι γιατροί κλάδου ΕΣΥ. Σε περίπτωση που δεν συντρέχει η προϋπόθεση αυτή, αντικαθίστανται από τους αρχαιότερους σε προϋπηρεσία γιατρούς κλάδου ΕΣΥ του τμήματος.

5. Ο Εκπρόσωπος των Επιμελητών Α΄ στο Επιστημονικό Συμβούλιο κι εφόσον δεν είναι γιατρός κλάδου ΕΣΥ ο αρχαιότερος σε προϋπηρεσία Επιμελητής Α΄ ιατρός κλάδου ΕΣΥ του νοσοκομείου, που αναπληρώνεται από τον αρχαιότερο Επιμελητή Α΄, ιατρό κλάδου ΕΣΥ,της ίδιας με την κρινόμενη θέση, ειδικότητας.Οι 4ος και 5ος κριτές είναι συγχρόνως και εισηγητές οι οποίοι υποχρεώνονται να καταθέσουν τις εισηγήσεις τους σε 1 ½ μήνα από το πέρας της προκήρυξης. Ενστάσεις υποβάλλονται εντός 20 ημερών από την κατάθεση των εισηγήσεων. Οι ενστάσεις απαντώνται εντός 15 ημερών και το Συμβούλιο συνεδριάζει και αποφασίζει σε διάστημα 15 ημερών από την τελευταία ημερομηνία απάντησης των ενστάσεων.

Έδρα του Συμβουλίου είναι το Νοσοκομείο που προκηρύσσει τη θέση.

Β – Συμβούλιο Αξιολόγησης προς εξέλιξη των υπηρετούντων γιατρών του ΕΣΥ

Το Συμβούλιο αυτό, είναι η Γενική Συνέλευση του, αντίστοιχου προς τον αξιολογούμενο, τομέα και απαρτίζεται κάθε φορά από τους ειδικευμένους μονίμους γιατρούς του ΕΣΥ του Νοσοκομείου και Κ. Υγείας του από τον βαθμό του αξιολογούμενου και επάνω. Η Συνέλευση συγκαλείται υποχρεωτικά από τον Διοικητή του Νοσοκομείου ή από τον νόμιμο αναπληρωτή του και είναι σε απαρτία αν παρίσταται το 50% των εχόντων δικαίωμα συμμετοχής για τον κάθε βαθμό. Επί μη απαρτίας η συνέλευση επαναλαμβάνεται μέσα σε μία εβδομάδα με νόμιμη απαρτία το 30% των εχόντων δικαίωμα συμμετοχής. Επί νέας ελλείψεως απαρτίας η συνέλευση επαναλαμβάνεται μετά 7 ημέρες και θεωρείται ότι βρίσκεται σε απαρτία, ανεξάρτητα από τον αριθμό των παρόντων ιατρών. Θετική θεωρείται η ατομική αξιολόγηση εφόσον συγκεντρώνει το 50% + 1 των ψήφων των παρόντων. Η ψηφοφορία είναι φανερή.

Το πρώτο 15νθήμερο κάθε έτους ορίζονται από τη Συνέλευση του Τομέα, ένας (1) εισηγητής με τον αναπληρωματικό του για κάθε ειδικότητα και επί ελλείψεώς της από συναφή ειδικότητα. Δεύτερος εισηγητής είναι ο εκάστοτε Συντονιστής Διευθυντής ή μοναδικός Διευθυντής του τμήματος του αξιολογούμενου με τον αναπληρωτή του και σε περίπτωση που ελλείπει ο αρχαιότερος γιατρός κλάδου ΕΣΥ του τμήματος.Αξιολογήσεις γίνονται 2 φορές το χρόνο.Οι εισηγητές λαμβάνουν μέχρι 31 Ιανουαρίου κάθε έτους τους φακέλους των γιατρών, που είναι υποψήφιοι για αξιολόγηση. Σε ένα μήνα από τη λήψη των φακέλων οι εισηγητές καταθέτουν την εισήγησή τους στη Γραμματεία του Τομέα.

Η Γραμματεία μέσα σε 5 ημέρες επιδίδει τις εισηγήσεις στους υποψηφίους γιατρούς, οι οποίο δικαιούνται να υποβάλουν ένσταση σε προθεσμία 15 ημερών.Μέσα σε 15 ημέρες από την εκπνοή της προθεσμίας ένστασης , απαντώνται οι ενστάσεις και σε 15 ημέρες ο Διευθυντής του Τομέα καλεί την αντίστοιχη συνέλευση του Τομέα. Η συνέλευση αφού ακούσει τις εισηγήσεις , τις ενστάσεις και τις απαντήσεις από τους εισηγητές, καθώς και κάθε σχετική διευκρίνιση αυτών, αποφασίζει αιτιολογημένα.Οι εισηγητές λαμβάνουν 2η φορά στο ίδιο έτος τους φακέλους των ενδιαφερομένων γιατρών μέχρι 31/7 και ακολουθείται ή ίδια διαδικασία που περιγράφεται ανωτέρω.Η πρώτη διαδικασία αξιολόγησης μετά τη δημοσίευση του παρόντος δύναται να αρχίσει ένα μήνα αργότερα από τα προβλεπόμενα.

Γ – Συμβούλιο επιλογής Συντονιστών Διευθυντών

Το Συμβούλιο αποτελείται από τους Διευθυντές και τους Συντονιστές Διευθυντές του οικείου Τομέα. Εισηγητές είναι ο Πρόεδρος του Επιστημονικού Συμβουλίου και ο Διευθυντής της Ιατρικής Υπηρεσίας. Και οι δύο αναπληρώνονται από τους νόμιμους αναπληρωτές τους.
Δικαίωμα υποψηφιότητας έχουν οι Διευθυντές του ίδιου τμήματος. Η επιλογή γίνεται μεταξύ των αιτούντων και οι εισηγητές υποβάλλουν τις εισηγήσεις τους εντός 15 ημερών από τη λήψη των φακέλων. Τυχόν ενστάσεις υποβάλλονται εντός 15 ημερών από την κοινοποίηση των εισηγήσεων. Οι εισηγητές απαντούν εντός 15 ημερών από την παραλαβή των ενστάσεων. Το Συμβούλιο επιλογής συγκαλείται υποχρεωτικά από τον Διευθυντή του Τομέα, γιατρό κλάδου ΕΣΥ, εντός 15 ημερών από τις απαντήσεις επί των ενστάσεων. Σε περίπτωση που ο Διευθυντής του Τομέα δεν είναι γιατρός κλάδου ΕΣΥ, το Συμβούλιο συγκαλείται από τον αρχαιότερο Διευθυντή Τμήματος, γιατρό κλάδου ΕΣΥ.΄Οπου ως εκλεκτορικά σώματα αναφέρονται η Γενική Συνέλευση του Τομέα ή μέρος αυτής, σε νοσοκομεία όπου υπάρχουν Πανεπιστημιακές Κλινικές δεν καλούνται και δεν συμμετέχουν με οποιονδήποτε τρόπο (ούτε στον υπολογισμό της απαρτίας) οι Πανεπιστημιακοί γιατροί. Στην περίπτωση αυτή το Συμβούλιο Επιλογής, που αποτελείται αποκλειστικά από γιατρούς κλάδου ΕΣΥ, συγκαλείται από τον Διοικητή του Νοσοκομείου ή τον νόμιμο αναπληρωτή του.

ια) Νοσοκομειακοί γιατροί που συνταξιοδοτούνται υποχρεωτικά μέχρι 31/12/2009 τους χορηγούνται οι αποδοχές του επόμενου βαθμού και δεν κρίνονται.

ιβ) Τα 2 πρώτα χρόνια (έως 31 – 12 – 2010) οι νέες προσλήψεις αφορούν γιατρούς που δεν υπηρετούν στο ΕΣΥ . Ως εκ τούτου υπηρετούντες γιατροί στο ΕΣΥ και μέχρι 31/12/2010 δεν μπορούν να διεκδικήσουν άλλη θέση στο ΕΣΥ εκτός και εάν παραιτηθούν, μέχρι τη λήξη της εκάστοτε προκήρυξης.

6. Κατά τη χρονική διάρκεια της Συλλογικής Σύμβασης και μάλιστα στο πρώτο εξάμηνο θα προσληφθούν, στο πλαίσιο της παρούσης, 2000 νέοι γιατροί σε οργανικές θέσεις ( εξ αυτών τουλάχιστον 1.500 ειδικευμένοι, σε οργανικές θέσεις Επιμελητών Β΄), στις οποίες δεν περιλαμβάνονται όσες έχουν προκηρυχθεί μέχρι την υπογραφή της παρούσης ή θα κενωθούν λόγω συνταξιοδοτήσεων.

Ο καθορισμός των αναγκών των προσλήψεων θα γίνεται από κοινή επιτροπή του Υπουργείου Υγείας και της ΟΕΝΓΕ για να προτιμώνται τα υποστελεχωμένα τμήματα ώστε την 1/7/09 να μην υπάρχουν γιατροί που θα υποχρεώνονται να κάνουν περισσότερες από 7 ενεργείς εφημερίες το μήνα ή 11 (έντεκα) εφημερίες παντός τύπου. Ρητά προβλέπεται η απαγόρευση μετατροπής των ενεργών εφημεριών, σε εφημερίες ετοιμότητας.Θέσεις που προκηρύσσονται εκτός κοινής Επιτροπής Υπουργείου Υγείας – ΟΕΝΓΕ δεν υπολογίζονται στις ανωτέρω 2.000 περιγραφόμενες. Η συνεχόμενη για δύο φορές άγονη διαδικασία για την κάλυψη μιας θέσης, δε συνεπάγεται την απώλεια της πίστωσης για την κάλυψή της.Η κοινή αυτή Επιτροπή θα προτείνει κατά τη διάρκεια της συλλογικής σύμβασης λειτουργία Τμημάτων Επειγόντων Περιστατικών και νέα πρότυπα εφημέρευσης.

7. ΜΙΣΘΟΛΟΓΙΟ:

Από 1/1/2009 στο ισχύον μισθολόγιο των Νοσοκομειακών γιατρών παρέχονται οι εξής αυξήσεις κατά βαθμό:
α) Ειδικευόμενος: Αυξάνεται ο Β.Μ κατά 210 € και το Νοσοκομειακό επίδομα κατά 90 €.

β) Επιμελητής Β΄ : Αυξάνεται ο Β.Μ κατά 300 €.

γ) Επιμελητής Α΄ : Αυξάνεται ο Β.Μ κατά 360 €.

δ) Διευθυντής : Αυξάνεται ο Β.Μ κατά 420 €.

Μετά από συζήτηση εντός αυστηρά των χρονικών ορίων της Σύμβασης, εφαρμόζεται Νέο Ειδικό Ιατρικό Μισθολόγιο που η πρώτη φάση ξεκινάει με την υπογραφή της Συλλογικής Σύμβασης και τις ανωτέρω αυξήσεις και στο καταληκτικό επίπεδο θα προσαρμόζεται προοδευτικά στις προτάσεις των θεσμικών εκπροσώπων των νοσοκομειακών γιατρών.Ο τρόπος υπολογισμού του ωρομισθίου των ιατρικών εφημεριών θα προσεγγίσει την επόμενη 3ετία, τον τρόπο υπολογισμού των υπερωριών των Δημοσίων Υπαλλήλων.

8. Από δημοσιεύσεως της παρούσης καταργείται το εδάφιο 2 της παραγράφου 9 του άρθρου 45, του ν.3205/2003. Η διάρκεια της συλλογικής Σύμβασης και κατά άρθρα 1, 6 και 7 είναι ετήσια από 1/1/09 έως 31/ 12/09.

Έναρξη διαλόγου για την κατάρτιση της επόμενης Συλλογικής Σύμβασης ορίζεται η 15η Οκτωβρίου του 2009.Οι διατάξεις της παρούσης είναι ειδικές και κατισχύουν κάθε αντίθετης διάταξης.

9. Μεταβατική διάταξη

Δεν επαναπροκηρύσσονται οι θέσεις γιατρών που υπηρετούν στο ΕΣΥ ως επιμελητές Α΄, Β΄, και Γ΄ με πενταετή θητεία και δεν έχουν μονιμοποιηθεί κατά την έναρξη ισχύος της παρούσης.

Με τη συμπλήρωση της πενταετίας οι γιατροί που κατέχουν τις θέσεις αυτές κρίνονται ατομικά με βάση τα κριτήρια του άρθρου 35 παρ.6 ν. 2519/ 1997, όπως ισχύει και εφόσον η κρίση τους είναι επιτυχής, μονιμοποιούνται. Αρμόδιο για την κρίση τους είναι το Συμβούλιο της παρούσης για την εξέλιξη των υπηρετούντων γιατρών ΕΣΥ. Αν η κρίση δεν είναι επιτυχής τότε οι θέσεις κενούνται και επαναπροκηρύσσονται. Στην περίπτωση αυτή ισχύουν όσα αναφέρονται στην παρούσα για την προκήρυξη και πλήρωση των κενών θέσεων.

CANCER STEM-CELL MODEL DOES NOT APPLY TO MELANOMA

Cancer Stem-Cell Model May Need to Be Reassessed

December 3, 2008 — One of the hottest new theories in cancer — that the disease is propagated by a handful of rogue cancer stem cells — might need to be reassessed for many cancers in light of new findings with melanoma that suggest that these propagator cells are more common than has previously been supposed.

Previous studies have suggested that only 1 in 1 million melanoma cells have the ability to run wild, exhibiting the kind of unchecked proliferation that leads to new tumors. However, a new study conducted with a different assay system suggests that as many as 1 in 4 melanoma cells are tumorigenic.

The new finding is the cover article of the December 4 issue of Nature.

"The question of whether cells with tumorigenic potential are common or rare within human cancers has fundamental implications for therapy," the researchers comment.

If tumorigenic cells represent small minority populations, as suggested by evidence supporting the cancer stem-cell model, then it could be possible to develop improved anticancer therapies that would kill only these cancer stem cells, rather than all of the cancer, including the large bulk of nontumorigenic cancer cells. However, if these cancer stem cells are common, then it will not be possible to treat cancer more effectively by focusing on small minority subpopulations of cells, they write.

Existing Model Does Not Apply to Melanoma

The latest study, conducted by researchers at the University of Michigan, used a new assay system to detect tumorigenic cancer cells in mouse transplants. Previous studies have used the NOD/SCID mouse model in which the immune system is severely impaired but not completely inoperative; although these mice lack T and B cells, they still possess natural killer cells, which attack and destroy many of the transplanted cancer cells, the researchers explain.

Hence, the researchers developed a new model (NOD/SCID mice lacking the interleukin-2 gamma receptor), in which the natural killer cells and the T and B cells were eliminated. Under these more permissive conditions, approximately 25% of unselected melanoma cells from 12 different patients formed tumors, the researchers report. These included cells from primary and metastatic melanomas obtained directly from the patients. In single-cell transplants, an average of 27% of unselected melanoma cells from 4 different patients formed tumors, they add.

The researchers believe that the difference between their results and those obtained previously can be explained by the natural killer cells, which wiped out many of the transplanted cancer cells in the older mouse model. "The assay on which the field is based misses most of the cancer cells that can proliferate to form tumors," said lead researcher Sean Morrison, PhD, director of the Center for Stem Cell Biology at the University of Michigan Life Sciences Institute, in Ann Arbor.

The new finding does not invalidate the cancer stem-cell model, the researchers emphasized in a press release. Cancer stem cells likely do exist, but they are "probably much more common than people have been estimating," Dr. Morrison commented in the statement.

"I think the cancer stem-cell model will, in the end, hold up for some cancers," Dr. Morrison said. "But other cancers, like melanoma, probably won't follow a cancer stem-cell model at all. The field will have to be reassessed after more time is spent optimizing the methods used to detect cancer stem cells."

"People were looking to the cancer stem-cell model as an exciting new source for the development of life-saving cures for advanced melanoma," commented coauthor Timothy Johnson, MD, director of the Multidisciplinary Melanoma Program at the University of Michigan Comprehensive Cancer Center. "Unfortunately, our results show that melanoma does not strictly follow this model."

"So we'll need to redirect our scientific efforts and remain focused on the fundamental biological processes underlying the growth of melanomas in humans," Dr. Johnson added. "As we pursue new treatments for advanced melanoma, we'll have to consider that a high proportion of cancer cells may need to be killed."

CAROTID ENDARTERECTOMY BETTER THAN STENTING IN SYMPTOMATIC PATIENTS

Lower Stroke and Death Rates With Carotid Endarterectomy vs Carotid Stenting

December 3, 2008 (Worcester, Massachusetts) — A large study comparing carotid endarterectomy and carotid artery stenting showed the less invasive interventional approach resulted in higher in-hospital mortality and postoperative stroke rates as well as more expensive hospital costs [1].

Among symptomatic patients with carotid artery stenosis, for example, there was a fourfold increased risk of in-hospital mortality and a twofold increased risk of postoperative stroke compared with the surgical approach, report investigators.

"These observations indicate that the anticipated forthcoming results of randomized controlled trials will be of critical importance in determining the future applicability of carotid artery stenting in patients with carotid artery stenosis," writes first author Dr James McPhee (University of Massachusetts Medical School) and colleagues in the December 2008 issue of the Journal of Vascular Surgery.

Those studies include the National Institutes of Health (NIH)–sponsored Carotid Revascularization Endarterectomy vs Stenting Trial (CREST) and International Carotid Stenting Study (ICSS). CREST investigators completed enrollment this past summer and results are expected in 2009. The study includes 2511 asymptomatic and symptomatic patients who are not at high risk for surgery, whereas the ICSS study is a head-to-head comparison of carotid stenting and endarterectomy in approximately 1700 asymptomatic patients with carotid stenosis.

Many Studies and Different Results

In addition to the anticipated CREST and ICSS studies, a number of head-to-head comparisons between carotid artery stenting and endarterectomy have been published in recent years. Conflicting data from clinical trials, however, as well as from single-center and population-based studies, have created some controversy about the indications for carotid stenting.

Two carotid-artery stenting studies--the Stent-Supported Percutaneous Angioplasty of the Carotid Artery versus Endarterectomy (SPACE) [2] and Endarterectomy versus Angioplasty in Patients with Symptomatic Severe Carotid Stenosis (EVA-3S) [3] were published in 2006, and both showed stenting to be inferior to endarterectomy.

These findings, which one interventionalist previously described as an "earthquake" in the field of carotid stenting, contrasted with data from the Stenting and Angioplasty with Protection in Patients at High Risk for Endarterectomy (SAPPHIRE) trial, a study that compared carotid stenting using distal embolic protection with carotid endarterectomy in patients at high surgical risk [4]. Based on the findings from SAPPHIRE, the Food and Drug Administration approved the use of carotid stenting in patients with high-grade symptomatic stenosis who are at high operative risk.

In this analysis, McPhee and colleagues sought to compare clinical outcomes and resource utilization with the two treatment approaches for carotid artery stenosis on the national level. They obtained 2005 discharge data, the first year a code was available for carotid stenting, from a database of 20% of all nonfederal hospitals in the US.

In this one-year period, an estimated 135 701 patients underwent either carotid endarterectomy or stenting, and a majority of these individuals, more than 122 000, underwent carotid endarterectomy. In addition, most patients undergoing revascularization were asymptomatic. Of the 10 496 symptomatic patients revascularized, 9380 received carotid endarterectomy and 1116 underwent carotid stenting.

Results showed higher in-hospital and postoperative stroke rates among those undergoing carotid stenting. The mortality difference between the two treatment arms was more pronounced among symptomatic patients, as was the cost of the procedure and length of hospital stay.

Postoperative Outcomes and Resource Utilization by Endarterectomy and Stenting

Outcome	Carotid endarterectomy	Carotid artery stenting	p
All patients
In-hospital mortality, %	0.57	1.1	0.004
Postoperative stroke, %	1.1	1.8	0.0004
Length of stay, median (range), d	2 (0–117)	1 (0–66)	<0.0001>
Total hospital charges, median, $	17 658	30 396	<0.0001>
Asymptomatic carotid artery stenosis patients (n=122 986)
In-hospital mortality, %	0.38	0.57	0.18
Postoperative stroke, %	0.88	1.6	0.001
Length of stay, median (range), d	1 (0–110)	1 (0–53)	<0.0001>
Total hospital charges, median, $	16 956	28 853	<0.0001>
Symptomatic carotid artery stenosis patients (n=10 495)
In-hospital mortality, %	1.4	4.6	0.0002
Postoperative stroke, %	2.5	4.1	0.15
Length of stay, median (range), d	4 (1–67)	5 (0–66)	<0.0001>
Total hospital charges, median, $	29 894	49 535	<0.0001>

Investigators said the new data are not an indictment of carotid artery stenting, but its role needs to be better defined (eg, in asymptomatic vs symptomatic patients), and future studies will help to do this. Over time, they expect the treatment gap between the two approaches to narrow, particularly as operators gain technical experience and future trials identify patient populations for the different procedures.

Speaking with heartwire, senior investigator Dr Mohammed Eslami (University of Massachusetts Medical School), who performs stenting, said it is a procedure that needs to be performed cautiously and selectively.

"If you have an asymptomatic patient coming to you for a carotid stenting procedure, and that patient dies, there is something wrong with that," he said.

In May 2007, the US Centers for Medicare and Medicaid Services (CMS) said it would not expand Medicare coverage of carotid stenting to asymptomatic subjects or to subjects with less severe blockages, a decision it reiterated this past October.

TRANFUSIONS AND THROMBOTIC EVENTS IN CANCER PATIENTS

Transfusions Linked to Venous, Arterial Thrombotic Events in Cancer Patients

December 2, 2008 — In patients hospitalized with cancer, red blood cell (RBC) and platelet transfusions are associated with an increased risk for venous and arterial thrombotic events, according to the results of a retrospective cohort study reported in the November 24 issue of the Archives of Internal Medicine.

"Anemia is frequent in patients with cancer, but there are concerns regarding treatment with erythropoiesis-stimulating agents," write Alok A. Khorana, MD, from the University of Rochester in Rochester, New York, and colleagues. "Blood transfusions are commonly used as an alternative, but with little data regarding outcomes."

Using the discharge database of the University HealthSystem Consortium, the investigators examined the associations between transfusions and venous thromboembolism, arterial thromboembolism, and mortality rates in hospitalized patients with cancer. The study sample included 504,208 hospitalizations of cancer patients at 60 US medical centers between 1995 and 2003.

Of the patients examined in this analysis, 70,542 (14.0%) received at least 1 RBC transfusion and 15,237 (3.0%) received at least 1 platelet transfusion. Venous thromboembolism occurred in 7.2% of patients receiving RBC transfusions and arterial thromboembolism in 5.2%. These rates were significantly greater than the rates of 3.8% and 3.1%, respectively, seen in patients who did not receive transfusions (P < .001).

An increased risk for venous thromboembolism was independently linked to RBC transfusion (odds ratio [OR], 1.60; 95% confidence interval [CI], 1.53 - 1.67) and platelet transfusion (OR, 1.20; 95% CI, 1.11 - 1.29), based on multivariate analysis. Similar results were seen with arterial thromboembolism (OR for RBC transfusion, 1.53; 95% CI, 1.46 - 1.61; and OR for platelet transfusion, 1.55; 95% CI, 1.40 - 1.71; P < .001 for each). Transfusions were also associated with a higher risk for death during hospitalization (OR for RBC transfusion, 1.34; 95% CI, 1.29 - 1.38; and OR for platelet transfusion, 2.40; 2.27 - 2.52; P < .001).

"Both RBC and platelet transfusions are associated with increased risks of venous and arterial thrombotic events and mortality in hospitalized patients with cancer," the study authors write. "Further investigation is necessary to determine whether this relationship is causal."

Limitations of this study include reliance on administrative coding; inability to identify patients concomitantly receiving erythropoiesis-stimulating agents as part of outpatient therapy, which is a potential confounding factor; lack of data regarding compliance with appropriate thromboprophylaxis; inability to determine the time of administration of transfusion in relationship to the development of thromboembolic events or to identify patients admitted with venous thromboembolism who subsequently needed transfusions; and the possibility that anemia is a marker for aggressive tumor biology, more intensive chemotherapy, or "sicker" patients.

"Controversy exists regarding the treatment of anemia in cancer with ESAs [erythropoiesis-stimulating agents] because of potential adverse effects, including thromboembolism and worsened survival," the study authors write. "Data presented herein suggest caution in using transfusions as an alternative to ESAs because these may carry a similar risk of adverse thrombotic and survival outcomes. These findings suggest that rigorous studies evaluating the risks and benefits of blood transfusion in patients with cancer are necessary."

Arch Intern Med. 2008;168:2377-2381.

ROLE FOR PET FOR MANY CANCER TYPES

Impact of PET Scanning Consistent Across All Cancer Types

December 2, 2008 — Scanning with positron emission tomography (PET) scanning has an impact on the intended management of patients with cancer in approximately one third of cases, and new data suggest that this impact is consistent across all cancer types.

The results come from the National Oncologic PET Registry (NOPR), and the latest data are reported in the December issue of the Journal of Nuclear Medicine.

"Although the effectiveness of PET may differ somewhat between individual cancers, it's in the same ballpark," says coauthor Barry Siegel, MD, professor of radiology at Mallinckrodt Institute of Radiology in St. Louis, Missouri. "This result was a little unexpected, but it leads us to believe that a continual parsing of PET's usefulness, cancer by cancer and indication by indication, for purposes of reimbursement does not make clinical sense."

At present in the United States, the Centers for Medicare & Medicaid Services (CMS) restricts the reimbursement of PET scans for only 9 cancer types. The cancers that are covered include non–small-cell lung cancer, esophageal cancer, colorectal cancer, head and neck cancer, lymphoma and melanoma (all for diagnosis, staging, and restaging), breast cancer (for restaging and treatment monitoring), thyroid cancer (for restaging under very specific circumstances), and cervical cancer (for initial staging if conventional imaging result is negative for extrapelvic metastasis).

NOPR was launched in 2006 in response to a proposal from the CMS to expand coverage for PET to other cancers. In this registry, patients are covered under the CMS evidence development program to undergo PET scans for many other cancers and indications, including cancers of the ovary, uterus, prostate, pancreas, stomach, kidney, and bladder. The latest results show that PET has a similar impact across all of these cancer types. Although there was some variation, particularly a high impact on multiple myeloma, the differences across the cancer types were not statistically significant, and overall there was an impact in 38% of cases.

"We found that it did not vary significantly, and that the changes in treatment plans for rare cancers — such as stomach cancer — clustered around the same one-third mark as the more common cancers," said lead author Bruce Hillner, MD, professor of medicine at Virginia Commonwealth University in Richmond. "As a result, we believe that the coverage for PET in the staging, restaging and detection of recurrent cancer should be handled the same across the board," he said in a statement.

"The data from NOPR as well as from other studies, the totality of the PET literature in cancer, show that it is a very effective tool for imaging in cancer, and that it should be approved broadly," Dr. Siegel said in an interview with Medscape Oncology. There is no restriction on the use of computed tomography or magnetic resonance imaging by cancer type, he pointed out, and the use of PET scanning across all cancer types "is just as logical," he added.

"Basically, what we were trying to do is to inform CMS policy," he explained. "We wanted to collect data to show that, if you were thinking of picking and choosing, then you should cover this cancer and maybe not this one, but the truth of the matter is that when you look at the data it's hard to say what to include or exclude," he said. "Our recommendation is to include all cancers. PET is as mature a cancer imaging tool as CT and MRI, and I just don't understand why we don't have a level playing field."

The CMS is expected to decide on the reimbursement of PET scans in other cancers soon. A draft is expected on January 10, 2009, and after another public comment period, the final National Coverage Determination will be made on April 9, 2009.

Dr. Siegel told Medscape Oncology that he was cautiously optimistic. "Our sense is that the CMS has a good understanding of our data, and I think there will be some additional coverage, and I have my fingers crossed for global coverage."

Changes in Intended Management After PET Scans

The latest report assessed the impact of PET for 18 cancer types, none of which are currently on the list for CMS reimbursement. This study looked at 3 distinct indications: initial staging, restaging, and detection of suspected recurrence. Only patients who had pathologically confirmed cancer were included; hence, this study excluded the use of PET for diagnosis. It also excluded patients in whom PET was being used to monitor response to chemotherapy or radiotherapy (this indication has also been studied in NOPR, and results have recently been published online in Cancer).

Table. Impact of PET Scanning on Intended Management of Cancer

Type of Cancer	No. of PET Scans	% Cases With Change in Intended Management
Prostate	5309	35.1
Ovary	4509	41.4
Bladder	3578	37.8
Pancreas	3314	39
Stomach	2025	36.9
Small-cell lung cancer	2983	41.2
Kidney	2877	35.8
Uterus	2869	36.5
Myeloma	1784	48.7
Connective tissue	1350	36.4
Nonmelanoma skin	1057	31.4
Liver and intrahepatic bile ducts	1038	42.9
Cervix	984	32.7
Gallbladder	806	39.7
Other female genitalia	709	37.1
Thyroid	629	35.6
All other	4042	36.6
TOTAL	40,863	38.0

As a result of seeing the PET scans, clinicians changed their intended management of the cancer as follows:

• From nontreatment to treatment in 30% of cases
• From treatment to nontreatment in 8% of cases
• Change in goal from curative to palliative (or vice versa) in 14% of cases
• Change to supportive care or observation in 15.1% of cases
• Major change (eg, from surgery to chemotherapy) in 8.6% of cases
• Minor change (eg, addition or deletion of a mode of therapy) in 23.3% of cases

"We believe that the NOPR results show the impact of PET to be strikingly consistent for a wide range of cancers," the researchers conclude. "Accordingly, the use of PET in management for patients with known cancer should not be restricted by cancer type or testing indication."

Several recent publications have confirmed and validated these findings, Dr. Siegel commented to Medscape Oncology. In particular, several multicenter prospective trials have been conducted in Australia (J Nucl Med. 2008;49:1451-1457, 1593-1600) that provide "very strong process validation" of our data from the registry, he said.

NO ROLE FOR mTOR INHIBITORS IN PANCREATIC CANCER

J Clin Oncol. 2008 Dec 1. [Epub ahead of print]

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Oral mTOR Inhibitor Everolimus in Patients With Gemcitabine-Refractory Metastatic Pancreatic Cancer.

Wolpin BM, Hezel AF, Abrams T, Blaszkowsky LS, Meyerhardt JA, Chan JA, Enzinger PC, Allen B, Clark JW, Ryan DP, Fuchs CS.

Department of Medical Oncology, Dana-Farber Cancer Institute, Department of Medicine, Brigham and Women's Hospital, Division of Hematology/Oncology, Massachusetts General Hospital, and Harvard Medical School, Boston, MA.

PURPOSE: The PI3K/Akt/mTOR pathway is activated in the majority of pancreatic cancers, and inhibition of this pathway has antitumor effects in preclinical studies. We performed a multi-institutional, single-arm, phase II study of RAD001(everolimus), an oral inhibitor of mTOR, in patients who experienced treatment failure on first-line therapy with gemcitabine. PATIENTS AND METHODS: Thirty-three patients with gemcitabine-refractory, metastatic pancreatic cancer were treated continuously with RAD001 at 10 mg daily. Prior treatment with fluorouracil in the perioperative setting was allowed. Patients were observed for toxicity, treatment response, and survival. RESULTS: Treatment with single-agent RAD001 was well-tolerated; the most common adverse events were mild hyperglycemia and thrombocytopenia. No patients were removed from the study because of drug-related adverse events. No complete or partial treatment responses were noted, and only seven patients (21%) had stable disease at the first restaging scans performed at 2 months. Median progression-free survival and overall survival were 1.8 months and 4.5 months, respectively. One patient (3%) had a biochemical response, defined as >/= 50% reduction in serum CA19-9. CONCLUSION: Although well-tolerated, RAD001 administered as a single-agent had minimal clinical activity in patients with gemcitabine-refractory, metastatic pancreatic cancer. Future studies in metastatic pancreatic cancer should assess the combination of mTOR inhibitors with other agents and/or examine inhibitors of other components of the PI3K/Akt/mTOR pathway.

ALIMTA IN PERITONEAL MESOTHELIOMA

Lung Cancer. 2008 Nov 28. [Epub ahead of print]

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Malignant peritoneal mesothelioma-Results from the International Expanded Access Program using pemetrexed alone or in combination with a platinum agent.

Carteni G, Manegold C, Garcia GM, Siena S, Zielinski CC, Amadori D, Liu Y, Blatter J, Visseren-Grul C, Stahel R.

Cardarelli Hospital, Medical Oncology, Via Cardarelli 9, 80100 Naples, Italy.

AIM: Peritoneal mesothelioma (PM) has rarely been studied. The Expanded Access Program (EAP) provided access to 109 patients with PM. METHODS: This was a nonrandomized, open-label study conducted in chemo-naïve or previously treated patients with PM not amenable to curative surgery. Patients received pemetrexed (PEM) 500mg/m(2) alone or with cisplatin (CIS) 75mg/m(2) or carboplatin (CARBO) AUC 5 every 21 days, supplemented with standard vitamin B(12), folate, and dexamethasone. RESULTS: Response rates (95% CI) for PEM, PEM/CIS, and PEM/CARBO were 12.5% (3.5, 29.0), 20.0% (7.7, 38.6), and 24.1% (10.3, 43.5), respectively. Median survival for PEM was 10.3 months. One-year survival rates for PEM/CIS and PEM were 57.4% (95% CI: 10.3, 100) and 41.5% (95% CI: 4.6, 78.4), respectively, and were not available for PEM/CARBO. Anemia was the most common serious adverse event (6.4%). Neutropenia (34.6%) was the most frequent CTC grade 3 or 4 toxicity reported. CONCLUDING STATEMENT: PEM with or without a platinum agent was both active and well tolerated in patients with peritoneal mesothelioma.

IXABEPILONE TAKES NEGATIVE RECOMMENDATION FROM EMEA

Recommendation for refusal of marketing authorization for ixabepilone

24.11.08

Category: Scientific News

EMEA adopts negative opinion for treatment of metastatic or locally advanced breast cancer

On 20 November 2008, the European Medicines Agency (EMEA) Committee for Medicinal Products for Human Use (CHMP) adopted a negative opinion of the marketing authorization for ixabepilone (2 mg/ml powder and solvent for concentrate for solution for infusion) intended to treat locally advanced or metastatic breast cancer, and recommended that it be refused. The company applying for authorization, Bristol-Myers Squibb Pharma EEIG, may request a re-examination within 15 days of receiving notification of this negative opinion.

Ixabepilone was expected to be used either in combination with capecitabine or on its own, and after previous cytotoxic treatment had failed,.

Ixabepilone is a cytotoxic medicine that belongs to epothilones and is expected to block the ability of cells to modify the internal skeleton that they need to divide and multiply. Ixabepilone is also expected to affect non-cancer cells such as nerve cells, which could cause side effects.

Ixabepilone has been examined in three main studies involving women with locally advanced or metastatic breast cancer and who had already been treated with a number of other anticancer medicines.

The first study looked at ixabepilone given on its own to 128 women, but did not compare it with any other treatment. The main measure of effectiveness was the number of patients whose cancer responded to treatment.

The other two studies compared the effects of capecitabine given on its own with the effects of ixabepilone given in combination with capecitabine in a total of 1,973 women. The main measures of effectiveness were time to progression and overall survival.

The CHMP recommended that ixabepilone be refused marketing authorization because it was concerned that ixabepilone’s benefits in terms of increasing time to progression and the very small increase in survival rates did not outweigh concerns over the medicine’s safety. In particular, the Committee was concerned over neuropathy, which was a severe and common side effect in patients taking the medicine.

The company informed the CHMP that there were no consequences for patients currently included in clinical trials or for compassionate-use programs with ixabepilone.

The EMEA review began on 25 October 2007 with an active review time of 203 days.

STROMAL GENE SIGNATURES HAS PROGNOSTIC ROLE

N Engl J Med. 2008 Nov 27;359(22):2313-2323.

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Stromal Gene Signatures in Large-B-Cell Lymphomas.

Lenz G, Wright G, Dave SS, Xiao W, Powell J, Zhao H, Xu W, Tan B, Goldschmidt N, Iqbal J, Vose J, Bast M, Fu K, Weisenburger DD, Greiner TC, Armitage JO, Kyle A, May L, Gascoyne RD, Connors JM, Troen G, Holte H, Kvaloy S, Dierickx D, Verhoef G, Delabie J, Smeland EB, Jares P, Martinez A, Lopez-Guillermo A, Montserrat E, Campo E, Braziel RM, Miller TP, Rimsza LM, Cook JR, Pohlman B, Sweetenham J, Tubbs RR, Fisher RI, Hartmann E, Rosenwald A, Ott G, Muller-Hermelink HK, Wrench D, Lister TA, Jaffe ES, Wilson WH, Chan WC, Staudt LM; the Lymphoma/Leukemia Molecular Profiling Project.

The affiliations of the authors are listed in the Appendix.

BACKGROUND: The addition of rituximab to combination chemotherapy with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP), or R-CHOP, has significantly improved the survival of patients with diffuse large-B-cell lymphoma. Whether gene-expression signatures correlate with survival after treatment of diffuse large-B-cell lymphoma is unclear. METHODS: We profiled gene expression in pretreatment biopsy specimens from 181 patients with diffuse large-B-cell lymphoma who received CHOP and 233 patients with this disease who received R-CHOP. A multivariate gene-expression-based survival-predictor model derived from a training group was tested in a validation group. RESULTS: A multivariate model created from three gene-expression signatures - termed "germinal-center B-cell," "stromal-1," and "stromal-2" - predicted survival both in patients who received CHOP and patients who received R-CHOP. The prognostically favorable stromal-1 signature reflected extracellular-matrix deposition and histiocytic infiltration. By contrast, the prognostically unfavorable stromal-2 signature reflected tumor blood-vessel density. CONCLUSIONS: Survival after treatment of diffuse large-B-cell lymphoma is influenced by differences in immune cells, fibrosis, and angiogenesis in the tumor microenvironment. Copyright 2008 Massachusetts Medical Society.

BRITISH ARE SMART

UK NICE Recommends Erlotinib Use in NSCLC After Price Reduction

December 1, 2008 — Erlotinib (Tarceva, Roche) is now recommended for use in the second-line treatment of non-small-cell lung cancer (NSCLC) by the National Institute for Health and Clinical Excellence (NICE) in the United Kingdom. This means that this use of the drug is now covered by the UK National Health Service. The decision was reached after lengthy deliberations on cost effectiveness, and only after the manufacturer offered to supply the drug at a discounted price.

Details of the deliberations are outlined by NICE researchers in a special report published online November 27 in Lancet Oncology; the final appraisal is available on the NICE website.

The current standard second-line treatment of NSCLC is intravenous docetaxel. The proposal to use oral erlotinib in its place was hampered by a lack of evidence from a direct comparison between the 2 drugs. Instead, data and estimates from several different trials were used, some of which compared docetaxel to best supportive care. The manufacturer argued that these data showed that erlotinib was at least as effective as docetaxel in terms of overall survival, and was better in terms of time to progression and, hence, progression-free survival, but the Committee was not convinced.

A key factor in the cost-effectiveness analysis, according to the NICE researchers, was the risk for severe febrile neutropenia (grade 3 or 4), which is associated with docetaxel therapy but not with erlotinib. When the cost of treating this adverse effect was included in the analysis, the difference between the 2 drugs was roughly £1000 per patient.

"The Committee concluded that the benefits to quality of life of oral administration and lower adverse events were not sufficient to consider erlotinib cost effective without an equivalent overall survival and progression-free survival relative to docetaxel," the NICE researchers write.

At this point, the manufacturer proposed a scheme to equalize costs between the 2 drugs for the UK National Health Service. This scheme discounts the list price of erlotinib to equalize overall treatment costs (including administration, adverse events, and monitoring costs) for those patients who are eligible for docetaxel.

The Committee considered this proposal to be acceptable and issued the recommendation.

Roche has agreed to continue with this discount until results from an ongoing trial, known as TITAN, become available. This trial is comparing erlotinib with chemotherapy (docetaxel or pemetrexed) as second-line therapy for advanced NSCLC, and the results should resolve the uncertainties over survival.