Monthly Archives: September 2006

Gene Key to Taste bud Development Identified

  • 9/30/2006
  • Chapel Hill, NC
  • staff
  • Sudbury, UK

Scientists have identified a gene that controls the development of taste buds. The gene, SOX2, stimulates stem cells on the surface of the embryonic tongue and in the back of the mouth to transform into taste buds, according to the researchers.

“Not only did we find that SOX2 is crucial for the development of taste buds, but we showed that the amount of SOX2 is just as important,” said Brigid Hogan, Ph.D., chair of the Duke University Medical Center Department of Cell Biology and senior member of the research team.

“If there isn’t enough SOX2 present, or if there is too much, the stem cells will not turn into taste buds.”

The researchers made their discovery in mice, but they believe the same process occurs in humans.

According to the researchers, the findings will help scientists better understand how the behavior of certain stem cells is controlled.

The SOX2 gene is already known to be crucial in controlling whether embryonic stem cells remain undifferentiated and whether stem cells in the brain, eye and inner ear differentiate into specialized nerve cells.

Taste bud cells, much like skin cells, continually slough off and are replaced by new ones.

So the findings provide insights into the interactions between SOX2 and tongue stem cells during embryonic development, as well as into how stem cells continue to operate in adults, the researchers said.

The researchers published the findings in the October 2006 issue of the journal Genes and Development.

Their findings were entirely serendipitous, Hogan said. “In my laboratory, we were studying the role of SOX2 in the development of the lung, esophagus and the gut in embryonic mice.”

“We were quite surprised when we accidentally found the gene’s role to be so pronounced in the developing tongue.”

The particular strain of mice that Hogan and her colleagues use had been developed by Larysa Pevny, Ph.D., a geneticist and developmental neurobiologist at the University of North Carolina at Chapel Hill, who is co-author with Hogan of the journal report.

In engineering her mouse strain for studying stem cells in the nervous system, Pevny combined the SOX2 gene with another gene, derived from jellyfish, and inserted the combination into the animals’ chromosomes.

She selected the added gene for its capacity to produce a special protein, called enhanced green fluorescent protein, that glows green when exposed to ultraviolet light.

“When we shine light on tissue from these animals, any cell that is expressing SOX2 will fluoresce, or light up,” Pevny explained.

“This allows us to directly visualize those areas where SOX2 is active. It is a very powerful tool.”

In their work, Hogan and her colleagues use this fluorescence marker as a tool for tracking the activity of SOX2 in the esophagus, among other sites.

As they worked with the mice, they noticed that specific areas on the tongue and in the back of the mouth lit up, in addition to areas in the esophagus.

Further studies, Hogan said, confirmed that SOX2 was present in high amounts during the development of taste buds.

In another set of experiments, Hogan’s team used another variant of the mouse strain made by Pevny in which the SOX2 gene was altered to produce only low levels of SOX2.

In these animals, the stem cells in the tongue were not transformed into taste buds, she said. Instead, the cells became the “scaly” cells that cover the surface the tongue and help to direct food to the back of the mouth.

The findings could lead to understanding of developmental disorders of the gut caused by mutations in the human SOX2 gene, Hogan said.

For example, babies with such mutations can develop a tracheoesophageal fistula, a condition in which there is an abnormal connection between the windpipe and throat that requires surgery for correction.

Cancer patients receiving chemotherapy or radiation therapy often report the loss of taste during treatments.

These therapies target cells that are dividing, making them effective in killing cancer cells but also causing the unwanted side effect of killing taste buds. When the cancer treatments end, the taste buds gradually return, Hogan said.

September, 2006|Archive|

New cancer drug from Merck to hit markets soon

  • 9/30/2006
  • New Delhi, India
  • staff
  • The Hindu (www.hindu.com)

For patients suffering from head and neck cancer, there is a new hope as a new therapy drug will be soon hitting the market.

The cancer drug, Erbitux, got a clearance from the Drugs Controller General of India yesterday.

“We got the clearance yesterday. It is an enormous step forward, providing more patients with the potential for a long term benefit,” said Marek Dziki, the Managing Director of Merck Specialities that had also launched last month another cancer drug that treats colon cancer.

He said it is the first and only monoclonal antibody to get an approval for the treatment of head and neck cancer by the US Food and Drug Administration and the European Medicines Agency.

Head and neck cancer is very common in India because of the widespread habit of chewing tobacco and tobacco-related products.

There are an estimated 3.5 million cancer patients in India. Every year around 8,00,000 cases are diagnosed every year, out of which 2,00,000 are head and neck cancer cases.

According to Shyam Agarwal, chairperson of the medical oncology department in Sir Gangaram Hospital, the drug represents an important new option for so many patinets who are fighting head and neck cancer, a seious disease for which there is a tremendous unmet medical need.

“In combination with radiotherapy, the drug provides a significant enhancemet in survival. This is a hallmark development.”

The drug is for all those whose cancer has not spread to other body parts.

“It is the first molecule in 30 years to be approved both in the US as well as in the European Union for the treatment of head and neck cancer,” said Dziki. In the US, it got the clearance in March this year.

Any drug that is sold in India is first cleared by the Drug authority that conducts tests to see whether it would meet the requirements of the population.

September, 2006|Archive|

New cancer drug from Merck to hit markets soon

  • 9/30/2006
  • New Delhi, India
  • staff
  • The Hindu (www.hindu.com)

For patients suffering from head and neck cancer, there is a new hope as a new therapy drug will be soon hitting the market.

The cancer drug, Erbitux, got a clearance from the Drugs Controller General of India yesterday.

“We got the clearance yesterday. It is an enormous step forward, providing more patients with the potential for a long term benefit,” said Marek Dziki, the Managing Director of Merck Specialities that had also launched last month another cancer drug that treats colon cancer.

He said it is the first and only monoclonal antibody to get an approval for the treatment of head and neck cancer by the US Food and Drug Administration and the European Medicines Agency.

Head and neck cancer is very common in India because of the widespread habit of chewing tobacco and tobacco-related products.

There are an estimated 3.5 million cancer patients in India. Every year around 8,00,000 cases are diagnosed every year, out of which 2,00,000 are head and neck cancer cases.

According to Shyam Agarwal, chairperson of the medical oncology department in Sir Gangaram Hospital, the drug represents an important new option for so many patinets who are fighting head and neck cancer, a seious disease for which there is a tremendous unmet medical need.

“In combination with radiotherapy, the drug provides a significant enhancemet in survival. This is a hallmark development.”

The drug is for all those whose cancer has not spread to other body parts.

“It is the first molecule in 30 years to be approved both in the US as well as in the European Union for the treatment of head and neck cancer,” said Dziki. In the US, it got the clearance in March this year.

Any drug that is sold in India is first cleared by the Drug authority that conducts tests to see whether it would meet the requirements of the population.

September, 2006|Archive|

Maryland Doctor Develops Vaccine That Could Fight Cancer

  • 9/30/2006
  • Baltimore, MD
  • staff
  • www.nbc4.com

A Maryland doctor has helped develop a vaccine that could one day help in the fight against certain types of cancer.

The vaccine, which is being tested now, is designed to target cancers of the head and neck.

Doctor Scott Strome at the University of Maryland School of Medicine in Baltimore helped develop the so-called Trojan peptide vaccines.

“It’s given as a shot, with a couple of other drugs that are designed to turn on the immune system,” said Strome.

The vaccines are made of specialized peptides, which are pieces of protiens found in certain cancer cells.

The idea is that when they are injected, they will rev up the patients immune cells. Those cells will then seek out the peptides in the cancer cells and kill them.

Strome likens it to a Trojan horse being used in a surprise attack.

“We use it to kind of sneak into the cell,” said Strome. “It kind of fakes out the body’s immune system to turn on against a protein that we optimistically think will be on the tumor cell itself.”

The survival rate of head and neck cancers is about 50 percent and it’s been that way for about 30 years.

Doctor Strome thinks if the vaccine is effective it may change that.

“We treat the cancer and then potentially we can give an adjuvant vaccine, to boost the immune system to make sure it doesn’t come back,” he said. The human trials of the vaccine are just beginning.

Here is more detailed information about the current clinical trial for this vaccine.

Trial:
MAGE-A3/HPV 16 Vaccine for Squamous Cell Carcinoma of the Head and Neck
Sponsored by:
National Institute of Dental and Craniofacial Research (NIDCR)
ClinicalTrials.gov Identifier:
NCT00257738

Purpose:
Squamous Cell Carcinoma of the Head and Neck (SCCHN) is a devastating illness, the treatment of which is associated with significant morbidity. This type of cancer affects 43,000 individuals each year with an estimated survival rate of 50%. A potential treatment alternative for this patient population is the use of peptide-based immunotherapy. This clinical tial will be using a vaccines comprised on the Trojan peptides MAGE-A3 and HPV 16 to treat patients with Squamous Cell Carcinoma of the Head and Neck who have recurrent, progressive or metastatic SCCHN.

Condition:
Squamous Cell Carcinoma of the Head and Neck

Intervention:
Vaccine: MAGE-A3 and HPV 16 Trojan pepti

Study Type: Interventional
Study Design: Treatment, Non-Randomized, Open Label, Dose Comparison, Expanded Access Assignment, Safety/Efficacy Study

Official Title: MAGE-A3/HPV 16 Peptide Based Immunotherapeutic Vaccines for Squamous Cell Carcinoma of the Head and Neck

Further study details as provided by National Institute of Dental and Craniofacial Research (NIDCR):

Primary Outcomes:
Primary Outcome: the number and type of toxicity incidents.;
Secondary Outcomes:; Change in the number of anti-SCCHN T-cells as measured by Elispot.;
Progression-Free survival.;
Survival.;
Toxicity: Maximum grade of each toxicity and percentage of patients experiencing toxicity.;
Response: Response of tumor as measured by CT plus PET scan using the RECIST criteria, and the number of patients who achieve a Complete Response or Partial Response by end of treatment.; Other immunologic considerations: Number of classic and non-classic HLA antigens and the expression level of MAGE-A3 and HPV 16.
Expected Total Enrollment: 90
Study start: November 2005; Expected completion: November 2007
Last follow-up: November 2005; Data entry closure: November 2007

Squamous Cell Carcinoma of the Head and Neck affects 43,000 individuals in the United States annually with an estimated overall survival rate of 50%. In order to improve both the survival rate and quality of life for patients who develop unresectable disease recurrence, new therapeutic alternatives are mandated. One potential treatment alternative for this patient population is the use of peptide-based immunotherapy. Despite the success fo preclinical studies using peptide vaccines, therapeutic responses in patients have been sporadic. The reasons for failure are multifactorial and include problems with patient selection, a limited number of antigenic targets, and an inability to correlate immunologic response with therapeutic efficacy. Specifically, patients with disseminated SCCHN have defects in antigen processing, presentation and effector mechanisms that limit their ability to respond to T cell based immunotherapy. Additionally, a paucity of antigenic peptide epitopes are defined for SCCHN, and immunologic monitoring does not correlate well with clinical response.

Recently several investigators, including our research team, have identified a high prevalance of MAGE-A3 and HPV 16 on SCCHN, and characterized several putative cytolytic and helper epitopes. Addtionally, we have defined a novel method to enhance the immune response to therapeutic peptide vaccines using Trojan complexes composed of CD4 and CD8 T-cell epitopes, connected by furin cleavable linkers.

In order to define the feasability and safety of these agents in combination with GM-CSF and montanide ISA 51 for the immunotherapy of SCCHN, in this proposed trial, we will screen patients for immunologic competence based on specific eligibility criteria including both antigen and HLA-A2 expression on tumors. In registered patients, we will test the ability of two novel Trojan peptide complexes, composed of MAGE-A3 and human papilloma virus 16 (HPV 16) epitopes, to stimulate antigen-specific CD 4 and CD 8 T-cell responses. Finally, we will correlate immunologic reponse with cell dose and the generation of both HPV 16 and MAGE-A3 antigen loss and HLA-A2 loss variants on tumors by evaluating patients for: 1) Changes in tumor size by both physical measurement and CT plus PET measurement; 2) Determining what proportions of individuals who achieve a complete response (CR), partial response (PR), or have stable disease (SD); 3) Progression-free survival; 4) Survival. Successful completion of this clinical trial will result in the development of a strong foundation for a Phase II/III clinical trial using HPV 16 and MAGE-A3 Trojan peptides for the immunotherapy of SCCHN.

Eligibility

Ages Eligible for Study: 18 Years – 80 Years, Genders Eligible for Study: Both

Criteria
Inclusion Criteria:
1. Biopsy-proven progressive, recurrent or metastatic Squamous Cell Carcinoma of the Head and Neck.
2. Biopsy-proven Squamous Cell Carcinoma of the Head and Neck which the patient is unwilling to have treated with surgery, chemotherapy or radiation therapy.
3. Age greater than or equal to 18 – 80 years of age.
4. ALL of the following: HLA-A2 positive tumor and HLA-A2 positive peripheral blood lymphocytes.
5. One or more of the following: MAGE-A3 positive tumor HPV 16 positive tumor or both.
6. Laboratory values: Alkaline Phosphastase of less than or equal to 3 times the upper limit of normal, AST less than or equal to 3 times the upper limit of normal, Creatinine less than or equal to 1.5 times the upper limit or normal, and Hemoglobin greater tha or equal to 9.0 mg/dL.
7. Patients must be capable of understanding the investigational nature of this study, the potential risks and benefits, and capable of providing valid informed consent.
8. The subject must be willing to return to the University of Maryland Medical Center for treatment and study-related follow up procedures and testing.
9. Life expectance of greater than or equal to 7 months.
10. Willingness to provide blood and tumor specimens and complete the imaging studies as required by the protocol.
11. A tumor that is biopsy accessible.

Exclusion Criteria:

1. ECOG performance status of 3 or 4.
2. ANY of the following: Known H.I.V. infection; other circumstances that in the opinion of the study physician renders the patient a poor candidate for this trial (e.g. concurrent use of systemic immunosuppressants or an immunocompromising condition).Patients with ANY malignant or metastatic Squamous Cell Carcinoma mass or lesion with the Central Nervous System [CNS] (e.g. Intraparenchymal- brain, Intracordal/Spinal Canal, Bony masses or lesions with extension into the CNS. AND Patients with ANY malignant or metastatic mass or lesion, or volume of a mass or lesion in a location that in the judgement of the Investigator, may significantly impair the health of or threaten the patients’ life should an inflammatory response occur.
3. Any of the following: Pregnant women; Nursing women unwilling to stop breastfeeding; men or women of childbearing potential who are unwilling to employ adequate contraception.
4. Any of the following prior therapies: Chemotherapy less than or equal to 4 weeks prior to registration; Immunotherapy less than or equal to 4 weeks prior to registration; Radiation Therapy less than or equal to 4 weeks prior to registration; Biologic therapy less than or equal to 4 weeks prior to registration; Immunotherapy less than oe equal to 4 weeks prior to registration.
5. Other concurrent chemotherapy, immunotherapy, radiotherapy or any ancillary treatment considered investigational.
6. Either of the following: Other active cancer requiring therapy to control the disease; A history of other malignancy less than or equal to 3 years (except for adequately treated basal cell carcinoma and squamous cell carcinoma of the skin, prostate cancer or carcinoma of the cervix).
7. Pre-treatment Hemoglobin of less than or equal to 9 mg/dL.

Location and Contact Information

Please refer to this study by ClinicalTrials.gov identifier NCT00257738

Scott E Strome, MD 410-328-5828 sstrome@smail.umaryland.edu

Maryland
University of Maryland School of Medicine, Baltimore, Maryland, 21201-1619, United States; Recruiting
Scott E Strome, MD 410-328-5828 sstrome@smail.umaryland.edu
Scott E Strome, MD, Principal Investigator

Study chairs or principal investigators
Scott E Strome, MD, Principal Investigator, University of Maryland School of Medicine

More Information:

Study ID Numbers: NIDCR-15324
Last Updated: July 13, 2006
Record first received: November 21, 2005
ClinicalTrials.gov Identifier: NCT00257738
Health Authority: United States: Food and Drug Administration
ClinicalTrials.gov processed this record on 2006-09-29

September, 2006|Archive|

Endoscopic Retrograde Dilation of Completely Occlusive Esophageal Strictures

  • 9/28/2006
  • New York, NY
  • Alejandro Garcia et al.
  • Ann Thorac Surg 2006;82:1240-1243

Backgoround:
Completely occlusive esophageal strictures may develop after head and neck radiotherapy or esophagectomy with gastric or colonic interposition. Major surgical intervention may be required to restore alimentary tract patency when endoscopic lumen reconstitution is not feasible by routine antegrade endoscopy. Retrograde endoscopic lumen identification and dilation is a useful method to reestablish alimentary tract patency, thereby avoiding surgical intervention.

Methods:
Patients requiring endoscopic dilation for completely occlusive esophageal strictures were identified by the gastroenterology, thoracic, and head and neck services. Retrograde access was obtained by balloon dilation of either a jejunostomy or gastrostomy tract, and an endoscope was passed to the area of stricture. Antegrade and retrograde endoscopy were performed simultaneously. A guidewire was passed either retrograde or antegrade under direct endoscopic visualization, followed by antegrade Savary dilation under fluoroscopic guidance.

Results:
From 2003 to 2006, 9 patients were identified with completely occlusive esophageal strictures requiring retrograde lumen identification and dilation. Stricture developed in 6 patients after radiotherapy for head and neck cancer and in 3 after esophagectomy with either gastric or colonic interposition for esophageal cancer. Endoscopic dilation was successful in all patients, without perforation.

Conclusions:
Retrograde endoscopic lumen identification and dilation is an option to reestablish lumen patency of completely occlusive esophageal strictures after esophagectomy with gastric or colonic interposition or after head and neck chemoradiotherapy.

Authors:
Alejandro Garcia, BA1, Raja M. Flores, MD1, Mark Schattner, MD2, Dennis Kraus, MD3, Manjit S. Bains, MD1, Richard J. Wong, MD3, Nabil Rizk, MD1, Arnold Markowitz, MD2, Hans Gerdes, MD2, Moshe Shike, MD2

Authors’ affiliations:
1 Division of Thoracic Surgery, Memorial Sloan-Kettering Cancer Center, New York, New York

2 Division of Gastroenterology, Memorial Sloan-Kettering Cancer Center, New York, New York

3 Division of Head and Neck Surgery, Memorial Sloan-Kettering Cancer Center, New York, New York

September, 2006|Archive|

Tumor and lymph node lymphangiogenesis—impact on cancer metastasis

  • 9/28/2006
  • Zurich, Switzerland
  • Nadja E. Tobler and Michael Detmar
  • Journal of Leukocyte Biology. 2006;80:691-696

The extent of lymph node (LN) metastasis is a major determinant for the staging and the prognosis of most human malignancies and often guides therapeutic decisions. Although the clinical significance of LN involvement is well documented, little has been known about the molecular mechanisms that promote tumor spread via lymphatic vessels to sentinel and distal LN and beyond.

However, recent discoveries have identified novel lymphatic-specific markers, and the newly discovered lymphangiogenesis factors vascular endothelial growth factor-C (VEGF-C) and VEGF-D were found to promote tumor-associated lymphatic vessel growth in mouse tumor models, leading to enhanced tumor spread to sentinel LN.

Our recent findings indicate that VEGF-A also acts as a potent tumor lymphangiogenesis factor that promotes lymphatic tumor spread. VEGF-A overexpressing primary tumors induced sentinel LN lymphangiogenesis even before metastasizing and maintained their lymphangiogenic activity after metastasis to draining LN.

Our recent studies showed that primary human melanomas that later metastasized were characterized by increased lymphangiogenesis and that the degree of tumor lymphangiogenesis can serve as a novel predictor of LN metastasis and overall patient survival, independently of tumor thickness. Tumor lymphangiogenesis also significantly predicted the presence of sentinel LN metastases at the time of surgical excision of the primary melanoma. Together, these findings suggest that tumor lymphangiogenesis actively contributes to cancer dissemination, that blockade of lymphatic vessel growth might inhibit tumor metastasis to LN, and that the extent of tumor-associated lymphangiogenesis could serve as a novel, prognostic parameter for the metastatic risk of human cancers.

Authors’ affiliation:
Institute of Pharmaceutical Sciences, Swiss Federal Institute of Technology, ETH Zurich, Switzerland

September, 2006|Archive|

Cephalon Gets FDA Approval for Fentora

  • 9/28/2006
  • Frazer, PA
  • staff
  • Chron.com

Drug maker Cephalon Inc. has received Food and Drug Administration approval to market its cancer pain treatment Fentora.

The company expects to launch the drug in October. Cephalon said late Monday the drug is the first oral cancer-pain reliever that is absorbed directly into the blood stream via the cheek lining.

Conventional short-acting oral opioids are swallowed and absorbed in the gastrointestinal tract, which can take up to 30 to 45 minutes to take effect.

Fentora is currently indicated for those cancer patients who are already receiving and are tolerant to opioid therapy for breakthrough pain, a common component of chronic pain characterized by its rapid onset, intensity and relatively short duration. An estimated 800,000 cancer patients will experience breakthrough pain this year, based on data reported by the American Cancer Society.

“Our longer-term clinical strategy is focused on developing Fentora for patients with breakthrough pain associated with other conditions, including neuropathic pain and back pain,” said Frank Baldino, Cephalon chairman and chief executive, in a statement.

Cephalon will manufacture Fentora in five dosage strengths _ 100, 200, 400, 600 and 800 micrograms.

Under an agreement, the FDA approval allows Barr Laboratories to launch a generic version of Actiq, the painkiller Fentora is meant to replace.

September, 2006|Archive|

Optimal sampling site for mucosal candidosis in oral cancer patients is the labial sulcus

  • 9/28/2006
  • Reading, United Kingdom
  • Riina Rautemaa et al.
  • J. Med Microbiol 55 (2006), 1447-1451

Traditional sampling methods for the diagnosis of oral candidosis in head and neck cancer patients, i.e. saliva collection or tongue scrapings, are often impossible to perform.

The aim was to determine the optimal sampling method. Eighteen oral cancer patients and five control subjects were sampled semi-quantitatively from the labial sulcus, dorsum of the tongue, dental plaque and saliva for cultivation of yeasts. The patients were examined prior to all cancer treatment (n=5), or 2–4 weeks (n=5) or 8–12 weeks (n=8) post-operatively.

The incidence of Candida was found to increase from 40 % at the control and pre-operative level up to 73 % 8–12 weeks post-operatively. Candida albicans was found to be the only species until 4 weeks post-operatively. Thereafter, the incidence of species other than C. albicans was 38 %.

The most sensitive sampling site was found to be the vestibular sulcus, from which all culture-positive cases could be confirmed. Tongue surface scraping was found to be more sensitive than saliva collection in detecting Candida. All sampling methods and sites were equally sensitive in detecting the different Candida species. Dental plaque was found to have the highest density of Candida colonization, and was thus found to be the most significant source of Candida infection, which emphasizes the role of dental care in these patients.

Authors:
Riina Rautemaa1,2,3, Peter Rusanen1,4, Malcolm Richardson1,3 and Jukka H. Meurman2,4

Authors’ affiliations:
1 Department of Bacteriology and Immunology, Haartman Institute, University of Helsinki, Helsinki, Finland

2 Department of Oral and Maxillofacial Diseases, Helsinki University Central Hospital (HUCH), Helsinki, Finland

3 Microbiology Unit of Helsinki University Central Hospital (HUCH) Laboratory Diagnostics, Helsinki, Finland

4 Institute of Dentistry, University of Helsinki, Helsinki, Finland

September, 2006|Archive|

Smokeless Tobacco and Cancer Risk

  • 9/27/2006
  • Scottsdale, AZ
  • Richard Johnson
  • www.market-day.net

There are two types of smokeless tobacco–snuff and chewing tobacco. Snuff,a finely ground or shredded tobacco, is packaged as dry, moist, or insachets (tea bag-like pouches). Typically, the user places a pinch or dipbetween the cheek and gum. Chewing tobacco is available in loose leaf, plug(plug-firm and plug-moist), or twist forms, with the user putting a wad oftobacco inside the cheek. Smokeless tobacco is sometimes called “spit” or”spitting” tobacco because people spit out the tobacco juices and saliva that build up in the mouth.

Chewing tobacco and snuff contain 28 carcinogens (cancer-causing agents).The most harmful carcinogens in smokeless tobacco are the tobacco-specific nitrosamines (TSNAs). They are formed during the growing, curing, fermenting, and aging of tobacco. TSNAs have been detected in some smokeless tobacco products at levels many times higher than levels of other types of nitrosamines that are allowed in foods, such as bacon and beer.

Other cancer-causing substances in smokeless tobacco include N-nitrosaminoacids, volatile N-nitrosamines, benzo(a)pyrene, volatile aldehydes,formaldehyde, acetaldehyde, crotonaldehyde, hydrazine, arsenic, nickel,cadmium, benzopyrene, and polonium-210.

All tobacco, including smokeless tobacco, contains nicotine, which is addictive. The amount of nicotine absorbed from smokeless tobacco is 3 to 4 times the amount delivered by a cigarette. Nicotine is absorbed more slowly from smokeless tobacco than from cigarettes, but more nicotine per dose is absorbed from smokeless tobacco than from cigarettes. Also, the nicotine stays in the bloodstream for a longer time.

Smokeless tobacco users increase their risk for cancer of the oral cavity. Oral cancer can include cancer of the lip, tongue, cheeks, gums, and the floor and roof of the mouth.

People who use oral snuff for a long time have a much greater risk for cancer of the cheek and gum than people who do not use smokeless tobacco.

The possible increased risk for other types of cancer from smokeless tobacco is being studied.

Some of the other effects of smokeless tobacco use include addiction to nicotine, oral leukoplakia (white mouth lesions that can become cancerous), gum disease, and gum recession (when the gum pulls away from the teeth).Possible increased risks for heart disease, diabetes, and reproductive problems are being studied.

In 1986, the Surgeon General concluded that the use of smokeless tobacco “is not a safe substitute for smoking cigarettes. It can cause cancer and a number of non-cancerous conditions and can lead to nicotine addiction and dependence.” Since 1991, NCI has officially recommended that the public avoid and discontinue the use of all tobacco products, including smokeless tobacco. NCI also recognizes that nitrosamines, found in tobacco products,are not safe at any level. The accumulated scientific evidence does not support changing this position.

Because all tobacco use causes disease and addiction, NCI recommends that tobacco use be avoided and discontinued. Several non-tobacco methods have been shown to be effective for quitting cigarettes. These methods include pharmacotherapies such as nicotine replacement therapy and bupropion SR,individual and group counseling, and telephone quitlines

September, 2006|Archive|

No Relationship Between Head And Neck Cancer Tumor Site And Location Of Swallowing Dysfunction

  • 9/26/2006
  • Toronto, Ontario, Canada
  • Benjamin S. Bleir, MD et al.
  • MedicalNewsToday.com

Over the past twenty years there has been a significant shift from surgery towards chemoradiation therapy as primary treatment for certain head and neck cancers. While primary chemoradiation allows many patients to avoid surgery and its concurring postoperative complications, it may be associated with significant post-treatment dysphagia, or difficulty in swallowing, which can be debilitating and potentially lethal.

During treatment, radiation is typically given over a wide field which encompasses both the primary tumor and its associated lymphatic drainage. As a consequence, structures vital to swallowing are subjected to high doses of radiation which may result in complications such as silent aspiration and feeding tube dependence. The addition of chemotherapy to radiation provides a synergistic effect which has been shown to further improve locoregional control. While chemotherapeutic agents act as radiosensitizers and thereby increasing tumor control rates, they also result in increased acute toxicity as well as late complications secondary to collateral injury to surrounding healthy tissue.

A team of scientists from Philadelphia, PA have conducted a study to identify which stages of swallow function are differentially affected by chemoradiation treatment for head and neck cancer, to describe the incidence of long term complications including clinical pneumonia and prolonged feeding tube dependence, and to correlate the clinical variables to the modified barium swallow findings. The authors of the study, “Post Chemoradiation Dysphagia” are Benjamin S. Bleier MD, Marc S. Levine MD, Rosemarie Mick PhD, Stephen E. Rubesin MD, Stephen Z. Sack MD, PhD, Kibwei McKinney BA, and Natasha Mirza, MD. They are presenting their findings at the 110th Annual Meeting & OTO EXPO of the American Academy of Otolaryngology-Head and Neck Surgery Foundation, being held September 17-20, 2006, at the Metro Toronto Convention Centre, Toronto, Canada.

Methodology:

A retrospective review of 30 patients treated at an academic, tertiary care referral medical center between 1996 and 2005 was conducted. All patients completed a modified barium swallow study after presenting with dysphagia following primary radiation therapy with or without concomitant chemotherapy for Stage I-IV squamous cell carcinoma of the oral cavity, oropharynx, nasopharynx, and larynx. Patients were excluded from the study if they had any prior history of radiotherapy, primary tumor resection except neck dissection, or any other head and neck lesions. None of the patients had documented dysphagia prior to radiotherapy.

Results:

Pharyngoesophagrams were analyzed for 21 separate criteria by one of three attending gastrointestinal radiologists and experienced speech-language pathologists. The most common abnormalities included laryngeal penetration, impaired epiglottic tilt, and abnormal pharyngeal contraction. The least common abnormalities included impaired cricopharyngeal opening, and soft palatal atrophy.

A Fisher’s exact test was used to correlate several clinical variables to modified barium swallow findings. No significant relationship was found between pharyngoesophagram abnormalities and a history of neck dissection, tumor stage, or patient age. Duration from radiotherapy to modified barium swallow also had no significant impact on swallow findings.

Conclusions:

The research team found no significant relationship between primary tumor site and location of swallow dysfunction. The researchers did note that while patients with oral and oropharyngeal lesions demonstrated abnormalities throughout the swallowing cascade, all patients with laryngeal lesions had normal function in the oral phase of swallow. The study also demonstrated abnormal epiglottic inversion and laryngeal penetration to be the most common problems in post radiation patients who had treatment for oropharyngeal and pharyngeal malignancies.

The next most frequent problem identified in the study was abnormal pharyngeal contraction. Functional disturbances in this area manifest as abnormalities in clearance of swallowed boluses from the pharynx. Weakness or incoordination in this pharyngeal contraction sequence results in portions of the bolus remaining in the pharynx at the end of the swallow. Both the oropharyngeal and laryngeal group suffered from this pharyngeal muscle hypomobility. While the relatively normal oral swallowing apparatus in patients with laryngeal lesions may relate to the use of parotid and oral cavity sparing radiotherapy techniques, further studies with larger patient populations are needed to truly understand the significance of these findings.

The study also suggests that close follow up of these patients with a modified barium swallow early in the post treatment period may help identify sites of swallowing impairment. This may in turn help reduce subsequent morbidity form pneumonias and long term feeding tube dependence.

Authors:
Benjamin S. Bleier MD, Marc S. Levine MD, Rosemarie Mick PhD, Stephen E. Rubesin MD, Stephen Z. Sack MD, PhD, Kibwei McKinney BA, and Natasha Mirza, MD

September, 2006|Archive|