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Old 01-23-2007, 02:31 PM
Dross Dross is offline
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Default Surgery and adjuvant therapy may work for pancreatic cancer

Massimo Raimondo, M.D.
Professor of Medicine
Mayo Clinic
Jacksonville, Florida

Once the diagnosis of pancreatic cancer is reached, every patient should be made aware of the specific type of cancer being diagnosed including the stage of the disease (meaning the extent of the disease: early, locally advanced, metastatic or end stage). Patients with pancreatic cancer should know what questions to ask based on their individual characteristics and current overall medical status.

The medical oncologist can advise patients regarding the standard chemotherapy agent(s) and consider experimental drugs and protocols when necessary. This may involve referral to tertiary care medical center with particular interest in pancreatic diseases. The medical oncologist can also coordinate the care for the patient who may have developed chronic pain, malnutrition & weight loss, depression by involving other medical doctors that will help alleviate symptoms usually associated with pancreatic cancer.

When patients with a presumed diagnosis of pancreatic cancer are seen, the goal is to rapidly secure the diagnosis and the stage of the disease. To reach this purpose, It is suggested that a dedicated pancreatic magnetic resonance imaging (MRI) in conjunction with an endoscopic ultrasound (EUS) are done. The MRI, performed by radiologists, gives a panoramic view of the pancreas tumor or mass outlining the extent of the disease meaning possible involvement of nearby vital organs or blood vessels. This is considered “staging of the disease.” EUS, performed by advanced endoscopists, serves as a complementary test to the MRI for staging. The advantage of EUS is to be able to perform an ultrasound guided (real-time) biopsy of the tumor for tissue diagnosis.

Routine blood work along with liver chemistry are also performed including one of the most common serum tumor marker called CA 19-9, which is used as prognostic markers. This is a blood work that is frequently elevated in pancreatic cancer patients. This marker has a prognostic role implying that its reduction after treatment signifies disease remission. An increasing level signifies lack of response and/or disease recurrence.

Ninety-five per cent of patients presenting with solid pancreatic cancer will have a tumor originating from the exocrine portion of the gland responsible for the production of digestive enzymes and bicarbonate. The most common form is the ductal adenocarcinoma. Rarer forms are the acinar cell carcinoma and the pancreatoblastoma. Five per cent of the solid tumors originate from the portion of the gland responsible for making hormones, such as insulin. Those are called pancreatic neuroendocrine tumors. The first line of treatment for both ductal adenocarcinoma and neuroendocrine tumors is surgery, if feasible. Depending on the stage of the disease, they may require adjuvant radiation and/or chemotherapy.

One of the most common serum markers is CA19-9. This is a blood work that is frequently elevated in pancreatic cancer patients. This marker has a prognostic role implying that its reduction after treatment signifies disease remission. An increasing level signifies lack of response and/or disease recurrence.

Computed tomography (CT scan) and/or Magnetic Resonance Imaging (MRI) of the pancreas are the two most common imaging modalities performed to follow up patients with pancreatic cancer after treatment. These tests are non invasive and accurate to follow disease regression or progression. Endoscopic ultrasound (EUS) is usually considered to obtain tissue diagnosis for abnormalities noted on CT/MRI concerning for recurrence. EUS is also considered in those patients with constant pain because it allows to perform a nerve block (called Celiac Plexus Neurolysis).

In the United States, the first line of treatment for locally advanced or metastatic pancreatic cancer is Gemzar (gemcitabine) either alone or in combination with Capecitabine. In Europe, oncologists usually recommend 5-Fluoro Uracile containing chemotherapy or Gemzar (gemcitabine).

The most important factor to determine whether to recommend adjuvant therapy for early stage pancreatic cancer is the presence of “positive margin” at the time of surgery. In other words, at the time of surgery and after the resection of the primary pancreatic tumor has been performed, there is still microscopic evidence of cancer at the resection margins. This assessment is made by the pathologist either at the time of surgery or shortly thereafter. Chemotherapy is usually recommended in Europe. In USA, chemotherapy is usually associated with radiation treatment.

When treating pancreatic cancer, physicians concentrate their attention on the eradication of the tumor. If this is not feasible by surgery alone, radiation and chemotherapy are the other modalities used. Most, if not all patients with pancreatic cancer, will develop pancreatic insufficiency with various degrees of maldigestion, primarily of fat. This can contribute to weight loss or inability to gain weight. Therefore, it is of paramount importance that physician treating pancreatic cancer patients include pancreatic enzyme supplementation in their medical regimen.

Various preparations are available in the market. On average, every patient should take 2 or 3 tablets (with at least 20,000 Units of lipase) in conjunction with each meal. These tablets will allow patients to digest nutrients (particularly fat), maintain their weight and hopefully stabilize their energy level.

Positive margins refer to the presence of tumor cells at the edge of the resection, i.e. tumor cells remain in the patient near the tumor site after the tumor has been removed. If obvious tumor was left behind in the patient after surgery, then it is called an R2 resection. If the presence of tumor cells at the margin is only found upon microscopic examination, then it is called an R1 resection. The concern with positive margins is recurrence of the tumor at the site of surgery.

In the largest single-institution retrospective study to date, researchers at Mayo Clinic Cancer Center have shown that giving patients both radiation and chemotherapy after completely removing invasive pancreatic cancer may improve overall survival rates.

The study's lead author, a radiation oncology resident in Rochester, Michele Corsini, M.D., presented the findings at the 2007 Gastrointestinal Cancers Symposium. The American Cancer Society reports that while the incidence of pancreatic cancer has decreased over the last few years, it remains the fourth most common cause of cancer-related death.

Pancreatic cancer, which has a very poor prognosis, killed more than 32,000 people in the United States last year. "We are constantly looking for ways to improve the prognosis of patients with cancers such as this," says Robert Miller, M.D., co-primary investigator and a radiation oncologist at Mayo Clinic. "Our findings show that surgery should be complemented by both radiation and chemotherapy for best results."

In the study, the team of surgeons, oncologists and radiation oncologists from Mayo's Arizona and Minnesota campuses examined the records of 472 consecutively-treated patients. The patients all had surgery with negative margins (some healthy tissue cut out around the cancerous cells), between 1975 and 2005, to remove pancreatic adenocarcinoma. They excluded patients who had metastatic cancer, tumors that could not be removed or were not removed entirely (positive surgical margins), or indolent (slow growing) tumor types.

Ultimately 454 patients were included in the final comparison of patients who received adjuvant therapy with those who had not. More than half (274) received concurrent radiation and chemotherapy following surgery and 50 percent survived two years, with 28 percent surviving at least five years. The researchers report more than one-third (180) received no additional therapy after surgery, and the comparative survival rates were significantly less, at 39 percent and 17 percent in two and five years, respectively.

Additional chemotherapy after concurrent radiation and chemotherapy seemed to have an even greater effect on survival (61 percent and 34 percent survived two and five years), but only 28 patients received that combination, not enough for the researchers to draw a firm conclusion about its effectiveness.

Drs. Miller and Corsini and their fellow researchers think these findings are important to clinicians worldwide. "While long-term outcomes with pancreatic cancer are generally poor," Dr. Corsini says, "our findings show that including both chemotherapy and radiation following surgery may significantly improve patient survival rates." Mayo currently uses a treatment strategy for most patients that includes a combination of radiation and chemotherapy after surgery.

Does the Starting Time of Chemo After Surgery Matter?

It has generally been assumed as to the timing of the start of chemotherapy, that it should begin after the immediate effects of surgery have been weathered by the patient, and when the patient is well enough to begin to accept the side-effects of the chemo.

But, does this timing have more significance than is generally believed?

Sueda and associates from Hiroshima University in Japan reviewed the records of 104 patients who received chemotherapy after potentially curable surgery in pancreatic cancer, dividing the patients into two groups: those who began the chemo more than or less than 20 days after the day of the pancreatic cancer surgery.

They found that those who had received the chemotherapy earlier in the process had significantly better 5-year survival rates (52% vs. 26%). One note is that the early chemo group tended to have had fewer after-surgery complications. So, might these surgical complications be a tell all that the later group was not as predisposed to survival?

[url]http://www.ncbi.nlm.nih.gov/pubmed/23178955

Last edited by gdpawel : 02-15-2013 at 07:48 PM. Reason: corrected url address
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Old 02-19-2011, 10:21 AM
gdpawel gdpawel is offline
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Default Surgical Specimen Is the Personalized Part of Personalized Cancer Medicine

In this dawning era of molecular medicine, surgeons and pathologists are playing a more pivotal role in cancer medicine. They are the custodians of the specimens and therefore the molecules that represent the personalized part of personalized cancer medicine. Surgeons will continue to cure cancer with greater success rates through earlier detection and excision, but as the custodiams of the tissue, they will also be central to improving cancer management through molecularly targeted interventions.

Ann Surg Oncol. 2009 August; 16(8): 2079–2080.
Published online 2009 May 27. doi: 10.1245/s10434-009-0526-1. PMCID: PMC2711907

© Society of Surgical Oncology 2009

The Surgical Specimen Is the Personalized Part of Personalized Cancer Medicine

Carolyn C. Compton, MD, PhD

Office of Biorepositories and Biospecimen Research, National Cancer Institute, Bethesda, MD USA
Carolyn C. Compton, Email: [email]comptcar@mail.nih.gov[/email]

Received March 15, 2009

As a pathologist, I have been evaluating cancer resection specimens throughout my career and have come to have a deep appreciation of the challenges of surgical oncology. Happily for patients, surgeons cure cancer on a fairly regular basis by excising it with expert technique and detailed knowledge of human anatomy and tumor biology. The tissue resected by the surgeon and analyzed by the pathologist is the source of crucial information that, in turn, informs the decisions and actions of our medical oncology colleagues.

As cancer medicine looks forward to a new era of molecularly defined cancer subtypes and targeted therapies, however, the role of both surgeon and pathologist is evolving to require an ever greater degree of professional attention towards the surgical resection specimen. It is the surgically resected tissue that possesses the molecular information needed to define the specific molecular characteristics of the patient’s tumor, the specific therapies to which the tumor would be expected to respond, and even the specific risks of adverse reactions to given therapies predicted by the patient’s genetic make-up. This molecular information forms the basis of the “personalized” approaches envisioned for cancer patients in an age of molecular medicine. The professional responsibility to assure that the specimen’s molecular composition and integrity are safeguarded is shared by both the surgeon and the pathologist. Current momentum towards molecular medicine is rapidly elevating this professional responsibility to one of the most important aspects of cancer patient care.

Currently, however, safeguarding the molecular integrity or documenting surgical variables that impact the molecular composition of the resection specimen is not widely considered to be primary aspects of the surgeon’s professional responsibility. Manipulations of the tissue within the surgical procedure itself may have dramatic effects on the molecular make-up of that tissue. However, these manipulations are neither recorded nor controlled when and where possible. Variables such as anesthesia type and duration, drugs administered preoperatively and intraoperatively, and devascularization/ischemia time for the resected tissue may dramatically alter molecular profiles and/or molecular integrity. Once successfully resected, the specimen may spend varying amounts of time at room temperature in the surgical suite and/or holding unit before being delivered to Pathology, which may further alter the molecular composition and quality of the tissue.

Without the surgeon’s extension of professional responsibility to the resected tissue to control, when feasible, and track such variables, the advantages of personalized adjuvant approaches may be lost to the patient. In molecular medicine, the resected tissue becomes the major determinant of all downstream therapy. Therefore, the care of the specimen must be addressed co-equally with the care of the patient. This elevated bar for ensuring tissue integrity and molecular quality also must be addressed by pathologists. The fresh specimen will need to be overseen by the pathologist with the same immediacy and professional attention. More than ever, surgeons and pathologists will be required to work together closely to achieve the goal of meeting the new standards of “specimen care” required for molecular analysis.

Our knowledge about the affects of iatrogenic variables such as surgical manipulation, intraoperative drug delivery, and pathological handling on the molecular profiles that reflect the biology in resected tissues is growing rapidly.1–5 Postoperative tissue ischemia time, for example, has been shown to alter gene and protein expression profiles within minutes following surgical excision in colectomy specimens and prostatectomy specimens.1–3 Not surprisingly, even before resection has been completed, intraoperative manipulations have been shown to markedly alter gene transcription levels during radical prostatectomies.4 The effects of different peri- and intraoperative variables on molecular profiles in different types of tissues are just beginning to be understood, but it is clear that surgeons and pathologists alike contribute significantly to the final molecular composition and integrity of the resected tissue.5

Procedures that maximize specimen quality respect the fact that resected tissues are vital and biologically reactive. Until they are fixed or frozen, biospecimens are viable and capable of reacting to physiological stress. They are a living part of the patient from which they come and are responsive to changes in temperature, perfusion, oxygenation, and other physiological and biochemical variables, both pre- and intraoperatively as well as postoperatively. Typically, once a tumor is successfully resected, the surgeon’s attention turns to patient and relatively little is directed towards the specimen. Unless an intraoperative consultation such as a frozen section is requested and the specimen is immediately addressed for this purpose, it may sit unattended for varying periods of time before being prepared for delivery to the pathology laboratory. The conditions of delivery itself may vary, as may the immediacy of the specimen handling once it has arrived in the pathology laboratory. Furthermore, some of the newer surgical techniques, such as robotically assisted prostate resections, may further compromise the quality of the resection specimen if it is allowed to remain in the operative site at body temperature for significant amounts of time after devascularization.

In this emerging age of molecular medicine, a new level of awareness of and attention to “the state of the specimen” will be required by surgeons, operating room staff, pathologists, and pathology staff. All play essential roles in the series of events leading up to stabilization of the tissue that impact its molecular make-up and molecular integrity. Surgeons are the initiators and controllers of many of these events and therefore represent the “gatekeepers.” The powerful molecular analysis technologies now at our disposal and the increasingly sensitive and specific analysis platforms under development provide us with unprecedented abilities to define the molecular features of cells and tissues. However, they also pose new risks by providing us with the ability to derive the wrong answer with even greater speed and accuracy unless the analytes are of high quality and are derived from high-quality specimens. It is our joint professional responsibility to follow procedures that will ensure the quality of the biospecimen and to document the specimen handling history for the patient’s record.

In this dawning era of molecular medicine, where a hard-won understanding of the molecular details of cancer is leading to more powerful and accurate diagnostics and therapeutics, I foresee surgeons and pathologists playing a new and more pivotal role in cancer medicine. They are the custodians of the specimens and therefore the molecules that represent the personalized part of personalized medicine. Surgeons will continue to cure cancer with greater success rates through earlier detection and excision; but as the custodians of the tissue, they will also be central to improving cancer management through molecularly targeted interventions.

References

1. Spruessel A, Steimenn G, Jung M, Lee SA, Carr T, Fentz A-K, et al. Tissue ischemia time affects gene and protein expression patterns within minutes following surgical excision. BioTechniques. 2004;30:1030–7.

2. Dash A, Maine IP, Varambally S, Shen R, Chinnaiyan AM, Rubin MA. Changes in differential gene expression because of warm ischemia time of radical prostatectomy specimens. Am J Pathol. 2002;161:1743–8.

3. Lin DW, Coleman IM, Hawley S, Huang CY, Dumpit R, Gifford D, et al. Influence of surgical manipulation on prostate gene expression: implications for molecular correlates of treatment effects and disease prognosis. J Clin Oncol. 2006;23:3763–70.

4. Schlomm T, Näkel E, Lübke A, Buness A, Chun FK-H, Steuber T, et al. Marked gene transcript level alterations occur early during radical protatectomy. Eur Urol. 2008;53:333–46.

5. Signoretti S, Bratslavsky G, Waldman FM, Reuter VE, Haaga J, Merino M, et al. Tissue-based research in kidney cancer: current challenges and future directions. Clin Cancer Res. 2008;14:3699–705.
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Old 02-19-2011, 10:22 AM
gdpawel gdpawel is offline
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Default Personalized Cancer Medicine Is Here, Now

As we enter the era of "personalized" medicine, it is time to take a fresh look at how we evaluate treatments for cancer patients. More emphasis is needed matching treatment to the patient. Patients would certainly have a better chance of success had their cancer been chemo-sensitive rather than chemo-resistant, where it is more apparent that chemotherapy improves the survival of patients, and where identifying the most effective chemotherapy would be more likely to improve survival.

Findings presented at the 41st Annual Meeting of the European Society for Clinical Investigation in Uppsala, Sweden and the Annual Meeting of the American Assoication for Cancer Research (AACR) in San Diego, CA concluded that "functional profiling" with cell-based assays is relevant for the study of both "conventional" and "targeted" anti-neoplastic drug agents (anti-tumor and anti-angiogenic activity) in primary cultures of "fresh" human tumors.

Cell-based Assays with "cell-death" endpoints can show disease-specific drug activity, are useful clinical and research tools for "conventional" and "targeted" drugs, and provide unique information complementary to that provided by "molecular" tests. There have been more than 25 peer-reviewed publications showing significant correlations between cell-death assay results and patient response and survival.

Many patients are treated not only with a "targeted" therapy drug like Tarceva, Avastin, or Iressa, but with a combination of chemotherapy drugs. Therefore, existing DNA or RNA sequences or expression of individual proteins often examine only one compenent of a much larger, interactive process. The oncologist might need to administer several chemotherapy drugs at varying doses because tumor cells express survival factors with a wide degree of individual cell variability.

There is a tactic of using biopsied cells to predict which cancer treatments will work best for the patient, by taking pieces of live "fresh" tumor tissue, applying different chemotherapy treatments to it, and examining the results to see which drug or combination of drugs does the best job killing the tumor cells. A cell-based assay test with "functional profiling," using a cell-death endpoint, can help see what treatments will not have the best opportunity of being successful (resistant) and identify drugs that have the best opportunity of being successful (sensitive).

Funtional profiling measures the response of the tumor cells to drug exposure. Following this exposure, they measure both cell metabolism and cell morphology. The integrated effect of the drugs on the whole cell, resulting in a cellular response to the drug, measuring the interaction of the entire genome. No matter which genes are being affected, functional profiling is measuring them through the surrogate of measuring if the cell is alive or dead.

For example, the epidermal growth factor receptor (EGFR) is a protein on the surface of a cell. EGFR-inhibiting drugs certainly do target specific genes, but even knowing what genes the drugs target doesn't tell you the whole story. Both Iressa and Tarceva target EGFR protein-tyrosine kinases. But all the EGFR mutation or amplificaton studies can tell us is whether or not the cells are potentially susceptible to this mechanism of attack. They don't tell you if Iressa is better or worse than Tarceva or other drugs which may target this. There are differences. The drugs have to get inside the cells in order to target anything. So, in different tumors, either Iressa or Tarceva might get in better or worse than the other. And the drugs may also be inactivated at different rates, also contributing to sensitivity versus resistance.

As an example of this testing, researchers have tested how well a pancreatic cancer patient can be treated successfully with a combination of drugs commonly used to fight lung, pancreatic, breast, and colorectal cancers. The pre-test can report prospectively to a physician specifically which chemotherapy agent would benefit a cancer patient. Drug sensitivity profiles differ significantly among cancer patients even when diagnosed with the same cancer.

The funtional profiling technique makes the statistically significant association between prospectively reported test results and patient survival. It can correlate test results that are obtained in the lab and reported to physicians prior to patient treatment, with significantly longer or shorter overall patient survival depending upon whether the drug was found to be effective or ineffective at killing the patient's tumor cells in the laboratory.

This could help solve the problem of knowing which patients can tolerate costly new treatments and their harmful side effects. These "smart" drugs are a really exciting element of cancer medicine, but do not work for everyone, and a pre-test to determine the efficacy of these drugs in a patient could be the first crucial step in personalizing treatment to the individual.

Literature Citation:

Functional profiling with cell culture-based assays for kinase and anti-angiogenic agents Eur J Clin Invest 37 (suppl. 1):60, 2007

Functional Profiling of Human Tumors in Primary Culture: A Platform for Drug Discovery and Therapy Selection (AACR: Apr 2008-AB-1546)
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Old 07-12-2011, 11:37 PM
gdpawel gdpawel is offline
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Default The Surgical Oncologist

Surgeons are trained not only in the evaluation and management of patients with malignancy, but in the evaluation and management of patients with benign disease as well. Many surgeons have a large number of patients in their practice with benign conditions (i.e. cysts). Many patients will never need an operation.

The role of the surgeon is to perform the workup, often an ultrasound and/or needle biopsy, and then determine if cancer is present or not. Once cancer is diagnosed, the surgeon will work with the medical oncologist and radiation oncologist as a team to decide in a multidisciplinary fashion what the best adjuvant treatment is, if needed.

For decades, any surgeon was considered competent to exercise all surgical skills, including cancer surgery. Indeed, while most surgeons may be acceptably competent, the specialty of surgical oncology is increasingly important. The surgical oncologist is most often the first specialist to see a patient before other oncologic specialists.

Surgical procedures for cancer are often complex and technically demanding. Studies have shown that patients have better outcomes, the lowest complications and death rates when they are treated by experienced surgical oncologists. In addition, cutting-edge techniques can often provide superior results over tried-and-true methods that have been around for many years.

Surgical oncologists are clinical scientists with knowledge of and experience in cancer surgery that come from additional training, limitation of the scope of general surgical practice, familiarity with the biology and natural history of cancers, and the role of the other oncologic specialties in their diagnosis and management.

Some researchers believe the reason for better survival for patients who could undergo complete resection without any tumor left behind is that these tumors are biologically less aggressive and would do better regardless of the type of treatment they receive, and that the removal of lymph nodes at the time of surgery may additionally contribute to a better outcome.

Surgery is an integral part of the multimodality treatment of many cancers.

The line of reasoning frequently used to explain the value of surgery included five points.

First, surgery is thought to remove resistant clones of tumor cells and thus decrease the likelihood of the early onset of drug resistance.

Second, the removal of large masses likely to be associated with poorly vascularized areas of tumor improves the probability of delivering adequate drug doses to the remaining cancer cells.

Third, the higher growth fraction in better vascularized small masses enhanced the effect of chemotherapy.

Fourth, smaller masses required fewer cycles of chemotherapy and thus decreased the likelihood of drug resistance.

Fifth, removal of bulky disease enhances the immune system. Patients who present with a large mass are suffering because of that mass and they need that tumor out to relieve symptoms and to save life due to symptoms. It's important to deal with the bulk.

Sources:
Mayo Clinic
American Board of Surgeons
Society of Surgical Oncology

Surgery is the "gold standard" against which other treatments are measured. There is no better way to eliminate a cancer than total removal.
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Last edited by gdpawel : 02-21-2013 at 04:00 PM. Reason: additional info
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Old 09-13-2011, 04:12 PM
gdpawel gdpawel is offline
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Default Many Patients With Operable Pancreatic Cancer are Not Offered Surgical Treatment

Analysis of data from the largest cancer database in the country has shown that a significant proportion of patients with operable pancreatic cancer are not being offered surgical treatment, even though an operation is the only potential cure for this type of cancer.

Researchers from the National Cancer Database (NCDB) released their comments on this groundbreaking study that found that 38.2 percent of patients with early-stage pancreatic cancer were not offered a surgical procedure as a treatment.

"As surgeons, the message we have been sending for many years is that surgical treatment for early-stage pancreatic cancer can have a positive impact on survival and quality of life. This study suggests, however, that the percentage of patients who should have an operation but don't get it, is alarmingly high," according to Mark S. Talamonti, MD, FACS, chief of the division of surgical oncology, Feinberg School of Medicine, Northwestern University, Chicago, IL, and co-researcher of the study.

Dr. Talamonti believes patients are not being offered an operation because of nihilism and skepticism on the part of medical professionals, including some surgeons, who question whether patients with pancreatic cancer can benefit from any treatment at all.

"For physicians who trained before the 1980s and 1990s when studies started to show some improvement in survival and quality of life from treatment for pancreatic cancer, the general idea was that there was no effective treatment for the disease. While this is a very formidable disease with considerable medical challenges, the reality is that not everybody has to die. Many patients do benefit by having the appropriate operation by sufficiently experienced surgeons in high-volume medical centers," Dr. Talamonti said.

"The pessimistic attitude toward pancreatic cancer and pancreatic cancer surgery is based on outdated data," explained Karl Bilimoria, MD, a research fellow at the American College of Surgeons (ACS) and Department of Surgery, Feinberg School of Medicine, Northwestern University, focusing on surgical oncologic outcomes and lead author of the study.

"Pancreatic cancer had terrible outcomes in the 1960s. The mortality and complications associated with surgical procedures for pancreatic cancer and the lack of effective systemic therapies made the short-term and long-term outlook for patients rather dismal. But there have been improvements over the last 30 to 40 years, to the point where postoperative mortality is less than 3 percent in many hospitals, and long-term survival rates are now about 30 percent after surgical resection for Stage I disease," Dr. Bilimoria added.

"We need to get the message out to the gatekeepers -- the primary care and internal medicine physicians, gastroenterologists, and medical oncologists who see these patients before they are referred to surgeons -- that it's better to operate than not to operate," Dr. Talamonti said.

Data for the study were obtained from the National Cancer Data Base (NCDB), which is maintained by the American College of Surgeons Commission on Cancer (CoC). The NCDB accounts for more than 75 percent of all cancers treated in the United States each year. The database includes information on more than 20 million patients with cancer who have been cared for at 1,440 hospitals in this country.

NCDB researchers examined data on 292,565 patients with pancreatic cancer. From 1995 to 2004, they studied 9,559 patients with Stage I disease who were potential candidates for an operation. Stage I pancreatic cancer is confined to the pancreas itself, and it typically occurs in 10 percent to 15 percent of patients initially diagnosed with pancreatic cancer, according to Dr. Bilimoria.

Although overall utilization of surgical procedures for pancreatic cancer increased during the period of the study by 14 percent, only 28.6 percent of patients actually underwent an operation. Of the remaining patients who did not have an operation, 51.7 percent did not have a documented or identifiable reason why they did not have the procedure. A total of 38.2 percent of patients were not offered an operation, and 13.5 percent did not undergo a procedure for unknown reasons.

Although the study could not fully explore why patients with operable cancer did not have a surgical procedure, it did at least identify some common underlying factors -- advanced age, race, socioeconomic status, and insurance status. Patients who were not offered an operation tended to be about 6 years older than those who had one -- 71.7 years versus 65.1 years on average. Patients also were less likely to have an operation if they were African American, had lower annual incomes or less education, and were covered by Medicare or Medicaid.

A surgical procedure also was not offered to many patients whose tumor was located in the head or the body of the pancreas. "This finding goes back to a previous perception that the Whipple procedure [also known as pancreatoduodenectomy, during which surgeons remove the head of the pancreas, the first portion of the small intestine (duodenum), part of the bile duct, and sometimes a portion of the stomach] was worse than the disease. But over the last 10 to 15 years, there have been unequivocal data that the operation is associated with improvement in quality of life and survival when done by experienced surgeons. The thought may still exist that the operation is a bad thing to subject patients to, even though the data show that is just not true," said Dr. Talamonti.

The American College of Surgeons is beginning to explore how it may respond to findings from this study. "ACS is looking at not just the Whipple procedure but cancer surgery in general to make sure segments of our population are not underserved and that the information that is disseminated about surgical treatment for pancreatic cancer is accurate," Dr. Talamonti, said. "It is imperative to get the information out that patients who need and qualify for this surgical approach are offered the operation."

"Pancreatic cancer surgeons should continue to give lectures about the efficacy of this type of surgery and treatment for pancreatic cancer to improve the medical community's opinion of what surgeons can do for patients with pancreatic cancer in 2007," Dr. Bilimoria, said.

Pancreatic cancer is the fourth leading cause of death due to cancer in this country. The American Cancer Society estimates that in 2007 more than 37,000 individuals will be diagnosed with pancreatic cancer and more than 33,000 will die from the disease.

A complete report of these research findings entitled "National Failure to Operate on Early-Stage Pancreatic Cancer" appeared in an issue of Annals of Surgery. Other authors of the study include David J. Bentrem, MD, FACS (Northwestern University, Chicago, IL); Clifford Y. Ko, MD, FACS (University of California, Los Angeles, and VA Greater Los Angeles); Andrew K. Stewart, MA (American College of Surgeons Commission on Cancer); and David P. Winchester, MD, FACS (American College of Surgeons).

The study was supported by the American College of Surgeons Clinical Scholars in Residence program and a research grant from the Northwestern University Department of Surgery.

The American College of Surgeons is a scientific and educational organization of surgeons that was founded in 1913 to raise the standards of surgical practice and to improve the care of the surgical patient. The College is dedicated to the ethical and competent practice of surgery. Its achievements have significantly influenced the course of scientific surgery in America and have established it as an important advocate for all surgical patients. The College has more than 71,000 members and is the largest organization of surgeons in the world.

For more information, visit [url]http://www.facs.org/.
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Old 01-21-2013, 05:31 PM
gdpawel gdpawel is offline
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Default Laboratory Oncology

Larry Weisenthal, M.D., PhD.
Medical and Laboratory Director
Weisenthal Cancer Group
Huntington Beach, California

The tumor holds the key to a patient's clinical outcome and survival. Each specimen must be individualized. Performing cell function analysis deserves the same degree of professional time and attention as major extirpative or debulking surgery or radiotherapy.

All sorts of specimens, from nice, sterile, viable sugar-cubed size pieces of tumor tissue from a sterile site to mucinous, contaminated low viability specimens from inside the colon lumen to several liters of bloody fluid to fried liver (from electrocautery biopsies of liver tumors) to small needle biopsies to bone marrow and blood specimens.

For solid tumors, testing is done with three-dimensional (3D) clusters (microclusters). It takes a lot of work to glean viable tumor cells and get a quantitative yield and separate tumor cells from normal and dead cells and get rid of mucin and what is called "brain matrix" from specimens of glioblastoma, and then to isolate the viable cell clusters from the discohesive, single cells and so on. Two specimens are seldom alike.

Not infrequently though, patients have a fairly major, invasive surgery primarily to get tumor for testing, so failure (an inevaluable assay) is not an option. Going after a surgical/biopsy specimen has a role in eliminating ineffective agents and avoid unnecessary toxicity and in directing "correct" therapy.

There would be a huge advantage to the patient to receive a "positive/sensitive" drug, compared to a "negative/resistant" drug. The time and energy required to conduct an excisional biopsy pales in comparison to the time, energy and lost opportunities associated with months of ineffective, toxic therapy.

Reliable, sensitive and specific cell-death endpoints are needed in a functional cytometric profiling assay. At least three different cell-death endpoints are used for every specimen (of the five that are immediately at disposal). You've got to make sure that the signal that is being measured is really from tumor and not normal cells and different endpoints have different advantages and disadvantages, depending on the type of specimen.

In certain instances, one cell-death endpoint is biologically more valid than another. When you get the same result with multiple endpoints, there is confidence in the results. When there is disagreement, and there is no readily understandable reason for the disagreement, much more caution is done in using this information for treatment recommendations.

Functional cytometric profiling is not a simple, turn-key solution. It is more a professional service, more than a simple laboratory test. It is sometimes thought of as a practicing the specialty of "Laboratory Oncology." I am an early member of an emerging new medical specialty, which I refer to as Laboratory Oncology. The function of the laboratory oncologist is to utilize available forms of laboratory testing of tumor biopsies to best individualize (personalize) cancer treatment with drugs, radiation, and/or surgery.

These forms of laboratory testing are based on multiple approaches, including traditional anatomic pathology, molecular genetics, and cell biology (typically through the application of cell culture methodologies). The importance of Laboratory Oncology is that there is an exploding growth in the number of anti-cancer drugs, which tend to be of only partial and unpredictable efficacy, which are often toxic, and which are extremely expensive. There is a huge need for existing and improved methodologies to best match treatment to the patient.
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Old 02-15-2013, 07:44 PM
gdpawel gdpawel is offline
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Default About the CA 19-9 Biomarker in Pancreatic Cancer

Andrea Wang-Gillam, M.D., PhD.
Assistant Professor of Medicine
Division of Oncology
Section of Medical Oncology
Washington University School of Medicine

What is learned from the CA 19-9 test for pancreatic cancer and how accurate is it?

CA 19-9 is a blood test which is used to monitor pancreatic cancer recurrence and treatment response. CA19-9 levels are affected by both cancer and benign conditions. For example, elevated CA19-9 is seen in patients with biliary obstruction, inflammation or ascite. Moreover, about 10% patients with pancreatic cancer have normal CA19-9 levels. Because of the above mentioned reasons, we don’t make clinical decisions based solely on CA 19-9 levels.

What is the current status of biomarker development for pancreatic cancer?

Biomarkers in cancer can be used for early detection or to predict clinical outcomes or treatment responses. Although the field of biomarker research has been very active, we haven’t yet identified reliable biomarkers for pancreatic cancer early detection or treatment response. However, CA 19-9 has been used to monitor tumor recurrence and treatment response.

How frequently will tests be performed on a metastatic pancreatic cancer patient to track progress?

To monitor treatment response, we rely on patients’ clinical symptoms, tumor markers (CA 19-9) and radiographic imaging (CT or MRI). In most cases, patients can tell you if treatment is working or not based on his/her cancer-related symptoms. I generally check tumor markers every month and do an imaging study every two months.

The CA 19-9 can be influenced by other conditions, so a rising CA 19-9 level will not necessarily suggest treatment failure. Oncologists rely heavily on any changes in tumor size seen on the CT or MRI. If there is a meaningful change, commonly defined by an enlargement of tumors by 20% or the presence of a new tumor, then the treatment is considered to be ineffective, and other treatment options should be considered.

How often will a metastatic pancreatic cancer patient see the oncologist?

Patients with metastatic pancreatic cancer should be initially evaluated by an oncologist for treatment options. The frequency of oncology visits following that initial visit depends on the patients’ physical well-being and what type of chemotherapy they receive.

In the past, gemcitabine was the only chemotherapy agent available for patients with newly diagnosed metastatic pancreatic cancer. More recently, other chemotherapy regimens including FOLFIRINOX (5FU, oxaliplatin and irinotecan) and gemcitabine plus nab-paclitaxel have shown survival benefit compared to gemcitabine alone.

Very commonly, I see patients on chemotherapy every 2-4 weeks.

Chemosensitivity testing can predict response in pancreatic cancer

[url]http://cancerfocus.org/forum/showthread.php?t=3477
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Old 02-22-2013, 03:07 AM
gdpawel gdpawel is offline
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Default Treatment of Pancreatic Cancer: Is FOLFIRINOX Worth It?

FOLFIRINOX Versus Gemcitabine for Metastatic Pancreatic Cancer
Conroy T, Desseigne F, Ychou M, et al

N Engl J Med. 2011;364:1817-1825

Study Summary

Gemcitabine has long been the standard of care for treatment of advanced pancreatic cancer. Numerous randomized clinical trials conducted in the past 2 decades have attempted to build upon single-agent therapy. For the most part, gemcitabine-based doublets have not shown substantial improvements in survival, although the gemcitabine-erlotinib combination has received US Food and Drug Administration approval as the first-line indication. In this article, investigators from France report on the utility of an aggressive regimen combining gemcitabine given in standard doses with both oxaliplatin and irinotecan (the FOLFIRINOX regimen). The study was a randomized phase 2 trial that was subsequently expanded to phase 3 design, in which 342 patients were randomly assigned to gemcitabine or FOLFIRINOX.

All of the study endpoints favored FOLFIRINOX: overall survival (11.1 vs 6.8 months), progression-free survival (6.4 vs 3.3 months) and response rates (31.6% vs 9.4%). Incidences of grade 3 or 4 neutropenia, febrile neutropenia, thrombocytopenia, diarrhea, and sensory neuropathy as well as grade 2 alopecia were significantly higher in the FOLFIRINOX arm. At 6 months, 31% of the patients in the FOLFIRINOX group had definitive reductions in their scores on the Quality of Life scale vs 66% in the gemcitabine group, suggesting that despite increased adverse events, patients receiving FOLFIRINOX had a better quality of life.

Viewpoint

This is the first study to show substantial improvements in survival in advanced pancreatic cancer. It is unfortunate, however, that this gain occurs with an aggressive multichemotherapy regimen rather than with the addition of targeted therapy as many had hoped for. Although the efficacy of the regimen is clear and substantial, concerns about toxicity and tolerability are ongoing. Anecdotally, many oncologists are empirically reducing starting doses for this regimen, especially of irinotecan. The use of growth factor support should also reduce the risk for febrile neutropenia. Careful patient selection is exceedingly important: Patients who are younger, wishing to seek more aggressive treatment, and who have an excellent performance status are the best candidates for FOLFIRINOX.

Citation: Alok A. Khorana. Treatment of Pancreatic Cancer: Is FOLFIRINOX Worth It? Medscape. Jun 06, 2011

[url]http://www.medscape.com/medline/abstract/21561347
[url]http://www.nejm.org/doi/pdf/10.1056/NEJMoa1011923
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Old 02-23-2013, 04:39 PM
gdpawel gdpawel is offline
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Default Reoperation for locally recurrent or metastatic pancreatic ductal adenocarcinoma

Selective Reoperation for Locally Recurrent or Metastatic Pancreatic Ductal Adenocarcinoma Following Primary Pancreatic Resection was published in September 2012 issue of the Journal of Gastointestinal Surgery by Katz et al.

The researchers looked at the value of additional surgery upon finding a later recurrence of pancreatic cancer metastases in patients who had already had a Whipple-type procedure for adenocarcinoma of the pancreas.

This included about 5% of those who had earlier had this surgery. Their conclusion was that surgery for a recurrence of especially a solitary lung tumor appeared to offer survival advantage.

J Gastrointest Surg. 2012 Sep;16(9):1696-704. doi: 10.1007/s11605-012-1912-8. Epub 2012 May 30.

Selective reoperation for locally recurrent or metastatic pancreatic ductal adenocarcinoma following primary pancreatic resection.

Thomas RM, Truty MJ, Nogueras-Gonzalez GM, Fleming JB, Vauthey JN, Pisters PW, Lee JE, Rice DC, Hofstetter WL, Wolff RA, Varadhachary GR, Wang H, Katz MH.

Department of Surgical Oncology, Unit 444, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX 77030, USA.

Abstract

BACKGROUND:

Resection of certain recurrent malignancies can prolong survival, but resection of recurrent pancreatic ductal adenocarcinoma is typically contraindicated because of poor outcomes.

METHODS:

All patients from 1992 to 2010 with recurrent pancreatic cancer after intended surgical cure were retrospectively evaluated. Clinicopathologic features were compared from patients who did and did not undergo subsequent reoperation with curative intent to identify factors associated with prolonged survival.

RESULTS:

Twenty-one of 426 patients (5 %) with recurrent pancreatic cancer underwent potentially curative reoperation for solitary local-regional (n = 7) or distant (n = 14) recurrence. The median disease-free interval after initial resection among reoperative patients was longer for those with lung or local-regional recurrence (52.4 and 41.1 months, respectively) than for those with liver recurrence (7.6 months, p = 0.006). The median interval between reoperation and second recurrence was longer in patients with lung recurrence (median not reached) than with liver or local-regional recurrence (6 and 9 months, respectively, p = 0.023). Reoperative patients with an initial disease-free interval >20 months had a longer median survival than those who did not (92.3 versus 31.3 months, respectively; p = 0.033).

CONCLUSION:

Patients with a solitary pulmonary recurrence of pancreatic cancer after a prolonged disease-free interval should be considered for reoperation, as they are more likely to benefit from resection versus other sites of solitary recurrence.

PMID: 22644446 [PubMed - indexed for MEDLINE]

[url]http://www.ncbi.nlm.nih.gov/pubmed/22644446
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Old 03-12-2013, 03:44 PM
gdpawel gdpawel is offline
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Default "Watchful Waiting" With Non-Functioning Pancreatic Neuroendocrine Tumors

According to Dale O’Brien, M.D., neuroendocrine tumors can roughly be divided into functioning and non-functioning categories. The functioning tumors produce an abundance of a given hormone such that the clinical effects of this overabundance can be observed or felt by physicians and/or patients. Non-functioning neuroendocrine tumors produce no hormone, or produce such hormones in sub-clinical quantity, or produce hormones which are not presently known and in which there is no apparent clinical effect.

Surgical researchers from the Mayo Clinic in the journal Surgery have published their results of a decade long study based on comparing non-surgical “watchful waiting” of almost eighty patients with small non-functioning pancreatic neuroendocrine tumors with the outcomes of 56 patients who were treated with surgery. Subjects were included in the study if their tumor was less than four centimeters in diameter without any apparent metastases or other evidence of spread.

They found that the watchful observation approach was worth advocating when interval radiographic studies show no or small growth or change of a solitary pancreatic neuroendocrine tumor, which they observed was quite frequent.

Surgery. 2012 Dec;152(6):965-74. doi: 10.1016/j.surg.2012.08.038. Epub 2012 Oct 24.

Small, nonfunctioning, asymptomatic pancreatic neuroendocrine tumors (PNETs): role for nonoperative management.

Lee LC, Grant CS, Salomao DR, Fletcher JG, Takahashi N, Fidler JL, Levy MJ, Huebner M.

Department of Surgery, Division of Gastroenterologic and General Surgery, Mayo Clinic, Rochester, MN 55905, USA.

Abstract

BACKGROUND:

Controversy exists regarding the optimal management of incidentally discovered, small pancreatic neuroendocrine tumors (PNETs). Our aim was to review the outcomes of patients who underwent nonoperative and operative management.

METHODS:

We retrospectively reviewed patients with nonfunctioning PNETs at our institution from January 1, 2000 to June 30, 2011. Patients were included if the tumor was sporadic and <4 cm without radiographic evidence of local invasion or metastases.

RESULTS:

Nonoperative patients (n = 77, median age, 67 years; range, 31-94) had a median tumor size of 1.0 cm (range, 0.3-3.2). Mean follow-up (F/U) was 45 months (max. 153 months). Median tumor size did not change throughout F/U; there was no disease progression or disease specific mortality. In the operative group (n = 56, median age, 60 years; range, 27-82), median neoplasm size was 1.8 cm (range, 0.5-3.6). Mean F/U was 52 months (max. 138 months). A total of 46% of the operative patients had some type of complication, more than half due to a clinically significant pancreatic leak. No recurrence or disease specific mortality was seen in the operative group, including 5 patients with positive lymph nodes.

CONCLUSION:

Small nonfunctioning PNETs usually exhibit minimal or no growth over many years. Nonoperative management may be advocated when serial imaging demonstrates minimal or no growth without suspicious features.

Libutti SK, Inabnet WB 3rd. Surgery. 2012 Dec; 152(6):975-6.

PMID: 23102679 [PubMed - indexed for MEDLINE]

[url]http://www.ncbi.nlm.nih.gov/pubmed/23102679
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