Larynx-Preservation Strategies in the Treatment of Laryngeal Cancer: American Society of Clinical Oncology Clinical Practice Guideline 2017 Update

The American Society of Clinical Oncology has released new guideline recommendations for the use of larynx-preservation strategies in the treatment of laryngeal cancer, which was published in the Journal of Clinical Oncology.

A panel of expert confirmed that the use of a larynx-preservation approach for patients does not compromise survival. Furthermore, there was no larynx-preservation strategy found that offered a survival advantage compared with total laryngectomy and adjuvant therapy. Changes to the previous recommendations involved the use of endoscopic surgical resection in patients with T1 and T2 disease, initial total laryngectomy in patients with T4a disease, and PET imaging for evaluating regional nodes.

According to the new recommendations, patients with T1 or T2 laryngeal cancer should begin treatment with intent to preserve the larynx by using endoscopic resection or radiation therapy. As for patients with T2 or T4 disease, organ-preserving surgery in combination with chemotherapy and radiation (or radiation alone) may preserve the larynx without compromising overall survival. Selected patients with extensive T3 or large T4a lesions or poor laryngeal function prior to treatment are recommended total laryngectomy to achieve better survival rates and quality of life. 

The books "My Voice- a physician's personal experience with throat cancer" and "The Laryngectomee Guide" are available in Turkish (Free).

I am happy to inform you that my  books "The Laryngectomee Guide”  and "My Voice- a physician's personal experience with throat cancer" are available now for FREE download. They were recently published by Turkish Association of Otorhinolaryngology- Head and Neck Surgery and are available on their site. 

The Laryngectomy Guide is available for FREE download in Turkish.

 "My Voice - a physician's personal experience with throat cancer is available for FREE download in Turkish

An Israeli physician helps improve the lives of head and neck cancer patients throughout the Middle East. Jerusalem Post October, 26, 2018.

                          

Clinical Practice Guideline: Evaluation of the Neck Mass in Adults

The American Academy of Otolaryngology-Head and Neck Surgery Foundation has published the "Clinical Practice Guideline: Evaluation of the Neck Mass in Adults." These guidelines includes 12 recommendations how to reduce delays in diagnosis of head and neck squamous cell carcinoma; promote appropriate testing, including imaging, pathologic evaluation, and empiric medical therapies; reduce inappropriate testing; and promote appropriate physical examination when cancer is suspected.

The recommendations include these statements:

·        Clinicians should not routinely prescribe antibiotic therapy for patients with a neck mass unless there are signs and symptoms of bacterial infection.

·        Clinicians should identify patients with a neck mass who are at increased risk for malignancy when the patient lacks a history of infectious etiology and the mass has been present for 2 weeks without significant fluctuation, or the mass is of uncertain duration.

·

·        Clinicians should identify patients with a neck mass who are at increased risk for malignancy based on 1 of these physical examination characteristics: fixation to adjacent tissues, firm consistency, size .1.5 cm, and/or ulceration of overlying skin.

·

·        Clinicians should conduct an initial history and physical examination for all adults with a neck mass to identify those patients with an increased risk for malignancy.

·        For patients with a neck mass who are not at increased risk for malignancy, clinicians or their designees should advise patients of criteria that would trigger the need for additional evaluation. Clinicians or their designees should also document a plan for follow-up to assess resolution or final diagnosis.

·        For patients with a neck mass who are deemed at increased risk for malignancy, clinicians or their designees should explain to the patient the significance of being at increased risk and explain any recommended diagnostic tests.

·        Clinicians should perform, or refer the patient to a clinician who can perform, a targeted physical examination (including visualizing the mucosa of the larynx, base of tongue, and pharynx) for patients with a neck mass deemed at increased risk for malignancy.

·        Clinicians should order neck computed tomography (CT; or magnetic resonance imaging [MRI]) with contrast for patients with a neck mass deemed at increased risk for malignancy.

·        Clinicians should perform fine needle aspiration (FNA) instead of open biopsy, or refer the patient to someone who can perform FNA, for patients with a neck mass deemed at increased risk for malignancy when the diagnosis of the neck mass remains uncertain.

·        For patients with a neck mass deemed at increased risk for malignancy, clinicians should continue evaluation and perform additional ancillary tests of patients with a cystic neck mass, as determined by FNA or imaging studies, until a diagnosis is obtained and should not assume that the mass is benign.

Hopefully this guideline will promote the efficient, effective, and accurate diagnostic workup of neck masses to ensure that adults with potentially malignant disease receive prompt diagnosis and intervention to optimize outcomes.

Click here to read the executive summary of the guidelines, click here to read the guidelines and click here to read the plain language summary. 

  

Current laryngectomy-related patient education materials are too difficult for an average adult to understand

A recent study by Wong and colleagues from the Boston University Medical Center found that current laryngectomy-related patient education materials are too difficult for an average American adult to understand.

The authors evaluated laryngectomy-related educational materials from an online search using the validated Patient Education Materials Assessment Tool, calculated reading difficulty, and assessed the correlation between readability, understand-ability, and action ability.

The authors concluded that current laryngectomy-related patient education materials are highly variable in understandability and action ability, and reading difficulty across all formulas also exceeded the eighth-grade reading level of an average American adult.They suggested that future revisions of laryngectomy-related educational materials may be warranted in order for current materials to benefit a wider readership.

Honey use can reduce the incidence of radio/chemotherapy-induced oral mucositis

A recent meta-analysis by Xu et al. showed that, compared with blank control, topical application of honey treatment could reduce the incidence of oral mucositis after radio/chemotherapy (P = 0.003). Honey has also been shown to reduce the level of pain in patients suffering from oral mucositis after radio/chemotherapy.

Although the exact etiology of the prophylactic effect of honey on the management of radio/chemotherapy-induced mucositis is not understood, investigators have proposed several hypotheses. It may act by the following mechanisms: 

1. The sugar content in honey is very high; honey is hygroscopic and readily dehydrates bacteria and other microorganisms, thus demonstrating antimicrobial properties and reducing the severity of oral mucositis. 
2. Honey contains glucose oxidase; this enzyme catalysis the oxidation of glucose to hydrogen peroxide, which has a local antimicrobial effect. 
3. Clinical trials have also confirmed that honey can alleviate wound inflammation and accelerate granulation formation and epithelial crawling, accordingly promoting wound. healing.

Further multi-center randomized controlled trials are needed to support the current evidence.

Cancer Moonshot Report Blue Panel Report 2016

The latest Cancer Moonshot report from a panel of top-tier cancer experts lays out 10 recommendations to speed progress in fighting cancer.

The working groups concentrated on opportunities in seven areas that included: Clinical Trials, enhancing data sharing, cancer Immunology, implementation of science, pediatric cancer, precision prevention and early detection, and tumor evolution and progression.

The list of recommendations from the 28-member panel are:

A. Establish a network for direct patient involvement

B. Create a clinical trials network devoted exclusively to immunotherapy

C. Develop ways to overcome cancer’s resistance to therapy

D. Build a national cancer data ecosystem

E. Intensify research on the major drivers of childhood cancers

F. Minimize cancer treatment’s debilitating side effects

G. Expand use of proven cancer prevention and early detection strategies

H. Mine past patient data to predict future patient outcomes

I. Develop a 3-D cancer atlas

J. Develop new cancer technologies

Gathering information about tumor profiles and treatment outcomes in a linked network of databases would enable more precise knowledge about what works, in whom, and in which types of cancer. This network would also allow patients to “pre-register” for clinical trials, enabling them or their physicians to be contacted if their tumor’s molecular characteristics made them eligible for clinical trials that match their cancer profile. By enabling patients to enroll directly, the network would reach a broader and more diverse.  

Complications rate, length of hospitalization, and readmission after laryngectomy.

A recent study by Goepfert and colleagues from the University of Texas MD Anderson Cancer Center, Houston, Texas; found that complications occurred in approximately one-third of patients who had laryngectomy. Complications occurred in 83 patients (34%) and included 3 deaths (1.2%). Wound complications occurred in 53 patients (22%), and 34 were pharyngocutaneous fistulas. Thirty-four patients (14%) were readmitted within 30 days.

These complications were more common in those with poor wound-healing risk factors such as prior smoking and radiation. Length of hospital stay was longer among reconstructed patients. Readmission was associated with low albumin in the serum and postoperative wound complications.

This study highlights the need for improvement in patient care improvement and the need to counsel high-risk patients undergoing laryngectomy. 

Implantation of an Artificial Larynx in a Laryngectomee

Debry et el. from France reported (New England Journal of Medicine 2017; 376:97-98) the implanted for the second time an artificial larynx replacing laryngeal functions. The artificial larynx has two parts implanted in a two-phase procedure. The device contains a titanium tracheal prosthesis with a porous distal end to improve soft-tissue integration and a removable titanium open-ventilation cap that allows the continuous passage of air while protecting the patient’s airway from aspiration. The cap allows the patient to breathe and drink liquids. When the coughing the upper flap opens transiently allowing expulsion of bronchopulmonary secretions.

Following implantation the patient was able to speak at an intelligible whisper, and continued to use a tracheostomy cannula for 18 hours a day. During a 16 months follow-up stenosis did not occur and the device did not interfere with radiotherapy, and the tracheostomy cannula could be closed at will. The patient could breathe and expectorate through the upper airways and maintained adequate arterial blood hemoglobin saturation on ambient air. Additionally, he was able to swallow saliva, although occasional aspiration of food took place. The patient’s ability to smell was restored.

Artificial Larynx

Recent advances in targeted treatment for oral cavity and oropharyngeal cancer

With greater understanding of the cellular changes that cause cancer, newer drugs that specifically target these changes have been developed. Targeted drugs work in a different way than regular chemotherapy agents. They also often have different (and usually less severe) side effects.

Nivolumab (Opdivo®) injection, for intravenous use, was approved by the FDA for the treatment of patients with recurrent or metastatic squamous cell carcinoma of the head and neck (SCCHN) with disease progression on or after platinum-based therapy. Nivolumab is a human immunoglobulin G4 (IgG4) monoclonal antibody that binds to the PD-1 receptor and blocks its interaction with PD-L1 and PD-L2, releasing PD-1 pathway-mediated inhibition of the immune response, including the anti-tumor immune response. Nivolumab treatment was proven in a phase 3 trial to significantly extend overall survival for patients with SCCHN.

Side effects include: fatigue, rash, itching, cough, upper respiratory tract infection, swelling of the extremities, shortness of breath, and muscle pain.

Cetuximab (Erbitux®) is a monoclonal antibody (which is a manufactured version of an immune system protein) that targets epidermal growth factor receptor (EGFR), a protein on the surface of certain cells that helps them grow and divide. Oral cavity and oropharyngeal cancer cells often have more than normal amounts of EGFR. By blocking EGFR, cetuximab can slow or entirely stop cell growth.

Cetuximab can be administered in combination with radiation therapy for some earlier stage cancers. For more advanced cancers, it can be combined with standard chemotherapeutic  drugs such as cisplatin, or it may be used by itself.

Cetuximab is administered by infusion into a vein (IV), generally once a week. Side effect of cetuximab include allergic reaction during the first infusion and skin problems such as an acne-like rash on the face and chest, headache, tiredness, fever, and diarrhea.

Several other drugs that target EGFR are now being studied as well, some of which are already being used to treat other types of cancers.

Extending the life span of tracheoesophageal voice prosthesis (TEP) by oral decontamination that reduces biofilm formation.

Somogyi-Ganss and colleges of the University of Texas MD Anderson Cancer Center, Houston, investigated the patterns of tracheoesophageal voice prosthesis (TEP) and oral colonization with microorganisms, and recorded changes in TEP device life after targeted decontamination between 2003 and 2013. 

Two subgroups were evaluated: (1) patients with microbial analysis of the TEP and the mouth were analyzed to identify patterns of common contamination, and (2) patients who were prescribed targeted oral decontamination with topical or oral antimicrobials on the basis of the microbial analysis of the VP were analyzed to evaluate effects on device life.

Among 42 patients, 3 patients had only fungal, 5 only bacterial, and 33 had colonization with multiple species of fungi and bacteria. In the TEP-oral micro-flora subgroup (n = 15), 7 had common microorganisms in the mouth and on the TEP. Among the decontamination subgroup (n = 23), 6 patients received broad spectrum rinse, 16 anti-fungal agents and 13 antibiotics, or a combination thereof. After targeted decontamination, the median device life of prostheses improved from 7.89 to 10.82 weeks (p = 0.260). The majority of patients with a short TEP device life in this pilot had colonization with multiple species of bacteria and fungi. TEPs rarely had fungal contamination alone (3 %), and non-Candida albicans species were more common than expected. For these reasons, the investigators explored the use of targeted decontamination regimens that were associated with 1.4-fold improvement in TEP duration.

These findings suggest that reducing the colonization of TEPs by microorganisms can extend their useful lifespan.

Association was found between Hepatitis C and Head and Neck Cancers.

Hepatitis C virus (HCV) infection is associated with liver cancer (hepatocellular carcinoma) and non-Hodgkin's lymphoma. After noting that many of their patients with head and Neck Cancers (HNCs) also have HCV infection, Mahale and colleagues of MD Anderson Cancer Center, Houston, TX, investigated whether such anassociation actually exists. In patients seen between 2004 to 2014.

The investigators compared 409 patients with HNCs to 694 with smoking-associated (lung, esophagus, or bladder) cancers seen between 2004 to 2014. The prevalence of HCV infection was higher in oropharyngeal cancer patients (14.0%) , and especially in HPV-positive ones (16.9%), and non oropharyngeal HNC patients (20.0%) than in control subjects (6.5%). A statistically significant association of HCV infection was found with non oropharyngeal (except nasopharyngeal) HNCs and HPV-positive oropharyngeal cancers.

The authors concluded that further studies are required to explore the possible interaction between HCV and HPV, and the association between HCV and other HPV-related malignancies.

Immunotherapy of HPV induced head and neck cancer (HNC)

Immunotherapy of HPV induced  HNC represents a new treatment approach that might allow clinicians to use conventional treatment at lower doses, and reduce treatment-related toxicity. Therapy is directed at  the oncoproteins E6 and E7 that are expressed by tumor cells.

Prophylactic vaccination against HPV  induces antigen-specific B cells that can  prevent initial infections. In contrast, therapeutic vaccines generate CD8+ HPV-specific T cell immune response against E6 and E7 oncoproteins. 

Their role in prevention of HPV-related oropharyngeal cancers is currently being evaluated, with one trial showing promising results.

Several vaccination therapies are under investigation in HPV-associated HNC. DNA vaccines produce non-living antigens able to induce cytotoxic T cell, and Th and B cell immunity. Several DNA vaccine trials targeting HPV are being tested in cervical cancer.

Peptide  vaccines incorporate amino acid sequences that are synthesized to form an immunogenic peptide molecule representing the specific epitope of a tumor-associated antigens that binds onto human leukocyte antigen. (http://www.ncbi.nlm.nih.gov/pubmed/14647479). Several peptide vaccines are under evaluation in HPV+ HNC..

Vaccination strategies involving Dendritic cells are also currently being assessed in HPV+ HNC. Activated DCs cells are injected back into the patient 5to kill the cancer (http://www.ncbi.nlm.nih.gov/pubmed/26351330). Several bacterial HPV vaccines targeting E6 and E7 have been developed. 

Finally, adoptive T-cell transfer (ACT) might be a promising immunotherapy strategy for HPV HNC; it involves harvesting and ex vivo expansion of the patient’s own tumor antigen specific T-cells. Subsequently, T-cells are re-introduced to the patient, with the view to enhance immunity and improve anticancer immune response.

It is hopeful that these novel immunotherapy strategies of HPV positive HNC will improve patient outcome.

History of smoking and long term outcome in head and neck cancer patients.

A new study by Peterson and colleagues investigated associations between a history of tobacco use and survival outcomes. The researchers from  the Department of Otolaryngology, University of Michigan Medical School, Ann Arbor, Michigan surveyed 687 previously untreated patients with cancer of the oral cavity (n = 271), oropharynx (n = 257), larynx (n = 135), or hypopharynx (n = 24). They explored the associations of tobacco use intensity (packs/day), duration (years of use), and timing before diagnosis with overall survival, disease-specific survival, and recurrence-free survival.

The study showed that cigarette use duration, timing, and intensity were significant predictors for all adverse outcomes. Never smoking and pack-years were not significantly associated with outcomes after adjustment for prognostic factors, such as stage, comorbidities, and human papillomavirus (HPV) status, which were strongly associated with clinical outcomes.

The authors concluded that their findings confirm the association between smoking history and survival and the importance of clinical variables in evaluating smoking as a prognostic factor. They also stated that timing, intensity, and duration of cigarette use should be considered with other prognostic factors when considering risk stratification for treatment planning.

Laryngeal Carcinoma patients’ outcomes can be improved by adding Cetuximab to radiotherapy

Laryngeal preservation and laryngectomy-free survival of patients with hypopharyngeal or laryngeal carcinoma, can be improved by addition of cetuximab to radiotherapy according to a recent study published by  Bonner et al. from the University of Alabama at Birmingham.

The authors examined the rates of laryngeal preservation and laryngectomy-free survival in a randomized trial involving patients with cancer of the larynx or hypopharynx. A total of 168 patients from 73 centers in the US and 14 other countries were randomized to cetuximab and radiotherapy (CRT; 90 patients) or radiotherapy alone (78 patients).

The researchers found the rates of laryngeal preservation (no need for laryngectomy) were 87.9 and 85.7% for CRT and radiotherapy alone, respectively, at two years. Median overall survival was 27 months in the CRT group and 21 months in the radiotherapy-alone group. There were no differences observed in overall quality of life, need for a feeding tube, or speech.

Sexual and non-sexual transmission of Human Papilloma Virus (HPV)

Human papillomavirus (HPV), is the most common sexually transmitted disease in the US and responsible for around 5% of cancers worldwide, most notably cervical and throat cancer. The virus can spread through sexual contact but non sexual transmission is also possible. A study by Myers et al. suggests that non sexual transfer can occur because HPV is resistant to many surface disinfectants and hand sanitizers that are alcohol based.

A report by Dahlstrom et al. has provided further evidence that HPV is not restricted to sexual intercourse and can also be spread via mouth-to-genital and mouth-to-mouth contact, with individuals who use tobacco being at the highest risk for infection.

Fakhry et al. demonstrated statistically significant relationships between current tobacco use and oral HPV-16 infection. This association may be due to the fact that smokers are more likely to have mouth ulcers and chronic inflammation that allows the virus to enter the oral mucosa and persist there. Because tobacco use may make HPV infections less likely to clear, smokers may have a higher risk of eventually developing oropharyngeal cancers. 

Understanding how HPV is transmitted is important because it can helps identify those who are most at risk for HPV infection and how they can protect themselves and their partners.

Combined effects of smoking and HPV16 in oropharyngeal cancer

A new study explored the effects of joint exposure impacts of smoking and HPV infection on oropharyngeal cancer risk. Specifically, the investigators studied if smoking confers any additional risk to HPV-positive oropharyngeal cancer.

Anantharamanet al.  examined the interaction between smoking and HPV16 in 1904 cancer patients and 3024 control from two large European multi-center studies. They observed that both smoking and HPV seropositivity were independently associated with oropharyngeal cancer. The joint association of smoking and HPV infection was additive suggesting they act as independent risk factors for oropharyngeal cancer.

An additional observation was that the prevalence of oropharyngeal cancer increases with smoking for both HPV16-positive and HPV16-negative persons. 

The authors concluded that the impact of smoking on HPV16-positive oropharyngeal cancer highlights the continued need for smoking cessation programs for primary prevention of head and neck cancer.

Good dental hygiene may reduce the risk of head and neck cancers

Daily tooth brushing and annual dentist visits may reduce the risk of head and neck cancers by a small margin, according to a recent study by Hashin et al. of the department of preventive medicine at Icahn School of Medicine at Mount Sinai in New York.

The researchers combined data from 13 past studies including a total of almost 9,000 oropharyngeal, hypopharyngeal, and pharyngeal cancer patients and more than 12,000 comparison subjects without cancer. The studies were done in the Americas, Europe and Japan. In all of them, oral hygiene was assessed based on gum disease or bleeding, missing teeth, daily tooth brushing, visiting a dentist at least once per year and whether a person wore dentures.

Individuals with fewer than five missing teeth, annual dentist visits, daily tooth brushing and no gum disease had lower risk than others of having head and neck cancer. Wearing dentures was not related to cancer risk. 

The indicators of oral hygiene/health used in the study are all connected with chronic irritation to the head and neck and are indicative of tooth wear, mechanical trauma, and general health maintenance.

The authors conclude that good oral hygiene, as characterized by few missing teeth, annual dentist visits, and daily tooth brushing, may modestly reduce the risk of head and neck cancer.

Acupuncture can help head and neck cancer patients' pain, dry mouth, lymphedema, neuropathy, tirednes, and nausea

Acupuncture can help head and neck cancer with managing some physical and emotional problems such as pain, feeling sick, and anxiety. It can also help individuals relax and improve their overall feeling of wellbeing.

Acupuncture is helpful in relieving some symptoms of cancer and the side effects of cancer treatment. It has sown to work in relieving chemotherapy related sickness, tiredness and cancer related pain.

Needling a variety of trigger and painful points, percutaneous electrical nerve stimulation, and osteo-puncture, along with whole body energetic acupuncture support, are approaches available to the acupuncturists.

Acupuncture is used to treat a wide range of pain conditions and some other symptoms. Some of the condition that acupuncture can be helpful that relate to head and neck cancer include:

• Acute and chronic pain control
• Dry mouth after radiation
• Muscle spasms, tremors, tics, contractures
• Peripheral neuropathy (after chemotherapy)
• Lymphedema after radiation (preliminary studies only)
• Anxiety, fright, panic
• Cancer and chemotherapy related tiredness
• Certain functional gastro-intestinal disorders (nausea and vomiting, esophageal spasm, hyperacidity, etc.)
• Headache, migraine, vertigo, tinnitus
• Cervical and lumbar spine syndromes and frozen shoulder
• Insomnia
• Anorexia
• Constipation  

Acupuncture performed by professionally qualified practitioners is generally very safe and has few side effects. Read more at Medical  issues in head and neck cancer section.

American Cancer Society key recommendations for head and neck cancer (HNC) survivorship care

The American Cancer Society published key recommendations for head and neck cancer (HNC) survivorship care. These are important recommendations that can improve patients’ care that includes surveillance for HNC recurrence, Assessment and management of physical and psychosocial long-term and late effects of HNC and its treatment (i.e. GERD, aspiration, fatigue, lymphedema, hypothyroidism, oral and dental care, taste problems, muscle dysfunction, speech and hearing ), psychological issues (Distress/depression/anxiety) , and nutrition.

To read the recommendations go to 

http://dribrook.blogspot.com/p/americancancer-society-key.html

Risk factors for pharyngocutaneous fistula after laryngectomy

Pharyngocutaneous fistula (PCF) is the most common surgical complication after total laryngectomy. Controversy still remains regarding the multiple risk factors implicated.

Dedivitiset al. surveyed the literature up to December 2013. The risk factors analyzed were age, sex, smoking habit, alcohol use, comorbidity, preoperative hemoglobin level, blood transfusion, preoperative tracheotomy, previous radiotherapy and chemoradiotherapy, primary tumor site, T classification, cartilage invasion, tumor grade, surgical margins, suture material, second layer of suture, reconstruction, tracheoesophageal prosthesis, and neck dissection. Of the 311 studies that were evaluated 63 met the inclusion criteria.

The author found that the risk factors for PCF were: chronic obstructive pulmonary disease (COPD), previous hemoglobin < 12.5 g/dL, blood transfusion, previous radio or chemotherapy, advanced primary tumor, suprglotic subsite, hypopharyngeal tumor site, positive surgical margins, and the performance of neck dissection.

Liang et al. who performed meta-analysis on on 16 studies found that tumor ssubsite, T stage, previous radiotherapy, postoperative hemoglobin < 12.5 g/dL, and surgical margins were the risk factors associated with the development of PCF.

Recognition of these factors can assist clinicians in expecting and treating PCF.

MRI of a pharyngocutaneous fistula after laryngopharyngectomy, and radial forearm free flap

Can proton pump inhibitors (PPI) cause dementia?

Proton pump inhibitors (PPIs) are widely used by head and neck cancer patients (including laryngectomees). PPIs have been shown to be potentially involved in cognitive decline including dementia. The use of PPIs has also been associated with chronic renal disease, and myocardial infarction.

A prospective cohort study from Germany evaluated 73 679 individuals 75 years of age or older that were treated with PPIs (omeprazole, pantoprazole, lansoprazole, esomeprazole, or rabeprazole) from 2004 to 2011. Those receiving regular PPI medication had a significantly increased risk of incident dementia compared with the patients not receiving PPI medication. This finding is supported by recent analyses on primary data and is in line with mouse models in which the use of PPIs increased the levels of β-amyloid in the brains of mice. 

A significant association of previous and current PPI use with vitamin B12 deficiency was found in a previous study in a population-based sample. Vitamin B12 deficiency has been shown to be associated with cognitive decline. In another study, PPIs were observed to enhance β-amyloid (Aβ) levels in the brains of mice by affecting the enzymes β- and γ-secretase. However, the underlying mechanism by which PPIs might influence the development of dementia is yet to be determined.

The authors concluded that avoidance of PPI medication may prevent the development of dementia. Randomized, prospective clinical trials are needed to examine this connection in more detail. 

Vocal cords grown from human cells

Laboratory grown vocal cord tissue that produces realistic sounds is a step toward creating new vocal cords for patients suffering from diseases such as cancer or injuries that damage their voice. Vocal cords that produce voice sounds have been grown in the laboratory from human cells. Details of the research are reported in the journal Science Translational Medicine.

Investigators from the University of Wisconsin in Madison harvested connective tissue and lining cells from the vocal cords of four patients whose voice boxes had been removed for medical reasons, and one human cadaver. They grew those cells onto scaffolds that produced strong elastic tissue similar to the one in the natural voice box.  After two weeks of allowing the cells to grow in the laboratory, the cells assemble into layers that resembled the structure of healthy vocal cords.

To test the freshly-grown tissue folds, scientists implanted them into one side of voice boxes taken from dogs, and attached them to an artificial windpipe and blew humidified air through them. When air was blown over the tissue it vibrated, producing sounds that had the same characteristics as those made by natural dog vocal cords. High speed digital imaging showed that the cords vibrated like natural tissue too. In follow-up studies using mice the transplants tissue were not rejected during a three months follow-up.  It is unlikely that replacement voice boxes will be created from vocal cord tissue from patients with cancer.  However, vocal cords could be created from stem cells that are turned into muscle and lining cells to form the cords.

Laboratory grown replacements for damaged vocal cords are still years away and more research is needed in animals to show that they work well and do not provoke an immune response, and the process must be performed with clinical grade cells before the implants can be tried in humans.

Normal vocal cords