Recent advances in management of acute leukemia

Resident: Roberts

Date: 1/29/10

Author: Chessells

Journal: Arch Dis Child

Year: 2000

Pages: 438-432

Discussion:

Leukemia is a clonal disease resulting from genetic mutations and transformation of a single early progenitor myeloid or lymphoid cell. Despite much research limited understanding of the exact cause is known.

ALL: Over 95 percent of children with ALL achieve remission after three to four weeks of treatment with oral steroids, , weekly IV vincristine and a third drug L-Asparaginase.. If chemotherapy is performed within the first 8 - 10 months from diagnosis, it significantly reduces relapse.

AML: These patients require intense hospital based chemotherapy which produces bone marrow suppression. A therapy that requires upto five courses of treatment and a bone marrow transplant has increased survival rates upwards of 48 percent at seven years.

Relapse: 30 percent with ALL and 45 percent with AML relapse. Those that relapse after the first few months of remission have a good chance at achieving a second remission. If they relapse after two years the chance of cure is almost impossible.

Conclusions: There have been significant improvement in the outlook for children with acute leukemia. There is still room for improvement with conventional chemotherapy and the need for randomized trials. New treatment is needed for relapsed patients due to poor prognosis.

Oral complications in children with cancer

Article title: Oral complications in children with cancer.
Author(s): Childers, Noel K. et al
Journal: Oral Surgery, Oral Medicine, Oral Pathology
Page #s: pp. 41-47
Year: Jan, 1993
Major topic: Oral complications in children with cancer.
Minor topic(s): NA
Type of Article: Summary of research

Main Purpose: To report the results of a 2.5 yr prospective follow-up study on the incidence of oral complications in 214 pediatric patients with cancer.

Overview of method of research: 214 pediatric cancer patients followed over 2.5 yrs at CH Alabama. Biweekly oral exams. 50 healthy control subjects. Patients grouped into the 12 most common malignant diseases and one group labeled “other”. Oral complications were classified by area, size and description. Mean age of pts was 7.4 y.o.

Key points in the article discussion:

I. In the previous ten yrs, it seems that the incidence of oral complications in cancer patients he decreased.
A. This fact may be due to improved chemotherapeutic an radiation protocols.

II. Certain groups experienced statistically significant increased levels of oral complications.
A. These were patients with solid tumors, sarcomas and the types of malignancies that had poorer prognosis.
B. Typically Pt’s in these more severe groups received more severe treatment… makes sense.
C. Routine dental care shown to reduce effects of oral complications.

III. Within the leukemia group.
A. AML had significantly higher incidence of complications including candidiasis
B. AML considered a “risk group”… especially for candidiasis.

IV. Various complications and top three risk groups
A. Mucositis: Sarcoma, AML, Solid tumors
B. Ulcers: AML, Sarcoma, Solid tumors
C: Candida: AML, Sarcoma, Solid tumors
D. Gingivitis: AML, Leukemia, ALL

Assessment of article: One huge limitation of this study was that they weren’t able to control for different treatment modalities. Also, most of the subjects in this study had deficient oral health care which effected results. Further categorization and research is needed.

An update of the etiology and management of xerostomia 1/29/10

Department of Pediatric Dentistry
Resident’s Name:Murphy
Program: Lutheran Medical Center – Providence
An update of the etiology and management of xerostomia
Author(s): Porter, SR, et al
Journal: Oral Surgery Oral Medicine Oral Pathology
Year. Volume (number). Page #’s: Jan 2004. 97:1. 28-41
Major topic: Etiology of xerostomia and is implications
Minor topic(s): Treatments of xerostomia
Overview of method of research: Review article

Findings:
Xerostomia(X), aka dry mouth is the abnormal reduction of saliva. It can be a symptom of certain diseases, or an adverse effect of medications. Causes of X are many, including Sjogrens Symdrome(SS), sarcoidosis, HIV, HCV infection, diabetes, radiation to head and neck, chemotherapy, chronic graft-versus-host disease, medications(to date X has been associated with more than 500 drugs, see link for list below), and trauma.
SS is the second most common autoimmune connective tissue disorder. It is a chronic multisystem immune mediated disorder characterized by inflammation of exocrine glands, which leads to dryness of the eyes and mouth. It can either be a primary or secondary disease. Treatment includes use of interferon alpha(a), corticosteroids, and hydroxychloroquine. SS is currently not very well understood, and has not responded well to immunosuppressive therapy. More research is needed.
Management of Xerostomia
Everything from dietary changes to medicines have been used to try to curtail the symptoms of X. Topical agents such as salivary substitutes, lubricating agents such as gels, mouthwashes, lozenges, pastilles(Salivix, Provalis), mucin sprays(yes) and chewing sugar free gum are all common, economical ways try to improve the symptoms of X. Systemic medicines are also used to treat X. Cholinergic agonists such as pilocarpine and cevimeline are extremely popular drugs used to treat X. Other drugs used are bethanechol, carbacholine, pyridostigmine, and bromhexine. As of right now, Bethanechol and cevmeline are the only drugs that are efficacious in the treatment of drug induced X.
Some alternative method of treating X include electro-stimulation, acupuncture, and dietary supplementation.
Pilocarpine

Key points/Summary: Currently anticholinergic agents hold the most promise and are most appropriate for the treatment of radiation induced X. Greater knowledge of salivary gland disorders must be studied before specific therapies can be developed. For drug induced X, try getting the MD to switch the patient to another drug.

Assessment of Article: Good article. Wasn’t as boring as I thought it would be. Informative. They didn’t really go over any new therapies, which I thought they would. It was just…(more research needed).

Drug List
http://www.drcarpenter.com/Media/PDFs-Documents/DrugsThatCauseXerostemia.pdf

Cancer Dental Treatment Chart

Oral aspects and management of severe graft-vs-host disease in a young patient with Beta-thalassemia: case report

Dan Boboia 1/29/10 Lit. Review

Title: Oral aspects and management of severe graft-vs-host disease in a young patient with Beta-thalassemia: case report
Author: Fonseca et al
Type of Article: Case Report
Past Med Hx.
A 6 y/o Saudi Arabian male was referred to Fred Hutchinson Cancer research Center (FHCRC) in Seattle on 9/94 for evaluation and treatment of Graft-vs-host disease (GVHD). The patient was diagnosed with beta-thalassemia major (bm) at 6 weeks of age and had blood transfusions until he was 12 months of age. He had a transplant in the US at 12 months of age. His mother was the matched donor. Despite having adequate engraftment he presented with several post-op complications including CMV infection, hypertension, and chronic GVHD 82 days s/p transplant. Once he arrived back to Saudi Arabia he received cyclosporine and prednisone for 5 yrs on an irregular schedule due to poor compliance. All primary teeth were removed a few years after his transplant due to gross caries. He had never used fluoride or antibacterial rinses.

Present illness and PE:
At the time of his admission the GVHD involved the skin, eyes, GI tract, and oral cavity. A skin biopsy was active for GVHD. Oral examination revealed compromised mandibular motion. Additionally microstomia as well as perioral scaring and scleroderma made oral hygiene and eating very difficult. Further exam revealed carious lesions on all 4 permanent first molars, as well as crowding, malocclusion, gingivitis, and purulent exudate was observed.
Treatment:
· Intensive OH regimen including rinses of 0.12% chlorhexidine combined with saline, one tuft tooth brush to access posterior area of the mouth
· Daily dexamethasone for 4 weeks
· Intensive physical therapy and oral stimulation exercises
· Ext of all 6 year molars 3 months after admissions
· Pt was d/c back to his country and has a yearly recall at the FHCRC
Discussion:
· Viral, fungal, bacterial infections are the most significant life-threatening head and neck complications in pretransplant patients
· Oral pain and increasing dryness more then 100 days post-transplant are suggestive of the chronic form of GVHD
· This patient had decreased mouth opening causing poor nutrition; his high carb liquid feedings, xerostomia, trismus, and microstomia all contributed to his high caries rate
· Common sequelae of chemoradiation are age dependent; they are more significant in children under 5 years of age and are: tooth agenisis, microdontia, atypical root and crown morphology, hypocalcification, and early apical closure.

Dental care of the Pediatric Cancer Patient 01/29/2010

Resident: J. Hencler
Date: 01/29/2010

Article title: Dental care of the Pediatric Cancer Patient
Author: Marcio A. da Fonseca, DDS, MS
Journal: Pediatric Dentistry-26:1 Pg 53-57

Major topic: Dental care and the pediatric cancer patient
Type of Article: Literature review
Main Purpose: Dental care recommendations

Key points in the article discussion:
Oral/dental infections may complicate or delay cancer tx. Dental consultation on a newly diagnosed patient should be done asap so enough time is available to complete dental tx before cancer therapy begins.

Take a thorough medical hx and consult with PCP/Oncologist. Antibiotic prophylaxis should be considered due to possible lowered immune state or presence of central line, catheter, or port.

Check patient’s hematologic status. Patients with platelet count <20,000 have increased bleeding risk. Elective dental work should be deferred in patients with absolute neutrophil count <1,000. Routine dental tx can be done when ANC >1,000 and platelet count is >50,000. AB prophylaxis should be considered with ANC between 1000 and 2000. Platelet transfusion should be considered when count is between 40,000 and 75,000. Peak concentration of platelets is reached 45-60 mins after transfusion so dental tx should be conducted at this time if possible. During immune suppression all elective dental tx should be avoided.

Aggressive OH should be conducted throughout cancer tx. Patients with poor OH or PD disease can use chlorhexidine rinses daily. The pediatric cancer patient has high caries risk due to nutritional supplements (high carb), fungal rinses with high sucrose such as nystatin, and frequent vomiting (enamel demin).

Dental tx priorities should be infections, EXTs, PD care and souces of infection before tx of caries, RCT permanent teeth, and replacement of defective restorations. SC/RP before cancer tx begins if time allows and EXTs are favorable over pulp therapy. During immune suppression swelling and purulent exudates may not be observed so radiographic exam is important to determine odontogenic infections.

Fixed ortho and space maintainers should be removed in patients with poor OH. Removable appliances may be worn in the patient with good OH.

Partially erupted molars can be a source of infection due to pericoronitis. Overlying gingival should be excised. Loose primary teeth should be left to exfoliate naturally. EXTs ideally should be completed 3 wks before cancer tx initiation. Osteoradionecrosis risk in patients who have undergone radiation to face and have had EXT is elevated and needs to be addressed.

Patient in maintenance phase and prognosis is good, dental procedures can be done routinely. Must still check blood count and need for AB prophylaxis.

Summary of conclusions: Key to maintaining healthy OH during cancer tx is compliance. It is important to educate parent about importance of oral care to minimize discomfort, a healthy diet, potential cariogenicity of pediatric medications and nutritional supplements, and effects of cancer tx on craniofacial growth and dental development. The role of the pediatric dentist in the hematology/oncology team is a very important one.

Assessment of article: Good article. All information is pertinent and useful to a pediatric dentist in clinical situations.

Update in Pediatric Oncology

Resident: Adam J. Bottrill Date: 15JAN10 Region: Providence
Article title: Update in Pediatric Oncology
Author(s): Dunn, Nancy et al.
Journal: Pediatric Oncology
Page #s: pp. 10-19
Year: 1990
Major topic: Pediatric Dentistry
Minor topic(s): None
Type of Article: Topic Summary
Main Purpose: Fortunately, the outlook for children with cancer is improving. This article gives a brief overview of current
Overview of method of research: NA
Key points in the article discussion:

I. Intro:
A. Childhood cancer is still very rare and 85% are either hematological, sarcomas or embryonal tumors (85% of adult cancers are carcinomas). Despite this, it is still the leading cause of death from disease in children under 15y.o. Now, death rate is actually less than half of what it was in 1950.
B. Most children diagnosed with cancer are referred to treatment centers where they are cared for by multi-disciplinary teams. This concentration of care and knowledge has led to massive advancements in knowledge, prognosis indicators and supportive care techniques.

II. Advances in Dx and Tx modalities
A. Tumor Biology
1. Collaborative study participation has lead to numerous histological comparisons, discoveries and prognostic indicator progress.
B. Prognostic Indicators
1. Relatively new phenomena. There were none when no one survived their disease. As more and more children survived, it became apparent that some did better than others. We can now more safely group patients into prognostic risk groups based on these prognostic indicators. Also allows therapy to be more individual.
C. Supportive Care
1. New recommendations WRT to SBE prophylaxis have been developed based on observations and therapies administered to these large groups of kids.
D. Newer Therapeutic Concepts
1. Lately, the interrelationship between surgical, radiation and chemotherapy has been changing. There aren’t many cancers that can be completely removed surgically. Also, early radiation treatment has been playing a smaller role. Chemotherapy is becoming more of the mainstay of treatment in pediatric Pt’s. Bone marrow transplants have become a 4th and commonly used method of treatment.

III. Pediatric Malignancies

A. ALL: 75-80% of childhood leukemias. Most common single malignancy in children. More common in White males age 3-5. Etiology unknown, many theories. Siblings at greater risk and children of parents with chromosomal abnormalities and immunocompromised states at greater risk. Fatigue, bone pain, fever, weight loss, bleeding, pallor, pymphadenopathy or asymptomatic.
1. Dx. made by >25% lymphoblasts in bone marrow.
2. Chemotherapy has provided >95% remission. Overall chance of >5 yr, event-free survival is approx 60%.
3. Usually any bone marrow relapse withing 6 mo. of chemo is sign of poor prognosis.

B. ANLL: 15-20% of leukemias in children. Similar to ALL. But not typically presenting with lymphadenopathy. Gingival hyperplasia more common.
1. Similar treatment to ALL: aggressive chemo, supportive care and CNS prophylaxis. >5yr event-free survival 25-45%. With chemo, up to 60% with bone marrow transplant.

C. CML: Rare in childhood representing <5%>
Assessment of article: Bottom line... too much information to summarize effectively. I barely skimmed the surface and omitted TONS. Maybe someone should call shenanigans on ME.

Indications and complications

Indications for Transplantation

• Nonmalignant diseases
  Inherited metabolic disorders - Adrenoleukodystrophy, Hurler syndrome, metachromatic leukodystrophy, osteopetrosis, and others.
• Inherited immune disorders -Severe combined immunodeficiency, Wiskott-Aldrich syndrome, and others
• Inherited red cell disorders - Pure red cell aplasia, sickle cell disease, beta-thalassemia, and others
• Marrow failure states - Severe aplastic anemia, Fanconi anemia, and others
  Autoimmune diseases (experimental) - Systemic sclerosis, severe systemic juvenile rheumatoid arthritis, lupus, multiple sclerosis, and others

Malignant/premalignant diseases

• Acute lymphoblastic leukemia (ALL)
• Acute myelogenous leukemia (AML)
• Chronic myelogenous leukemia (CML)
• Juvenile myelomonocytic leukemia
• Myelodysplastic syndromes
• Plasma cell disorders
• Hodgkin and non-Hodgkin lymphoma

Complications

• Mucositis: neutropenia seems to have the greatest relationship to mucositis. Great variability in mucositis amongst patients but there seems to be a minimal relationship to drug doses, schedules, duration of treatment, and impairment of renal and hepatic function. It can occur as early as 4-7 days after initiation of conditioning phase and last 10-14 days o. it generally starts with the nonkeratinized surfaces of buccal and lingual mucosa
• Pain management: Young infants frequently need narcotic analgesics. Older children are given paitent controlled analgesics of sedative meds. Local analgesics include viscous lidocaine 2% and dyclonine HCl are effective topical agents. Ice packs and ice pops increase comfort level of patients.
• Oral bleeding: oral manifestations of thrombocytopenia include bruising , petechiae, purpura and oozing of mucosal tissues which can be potentiated by local irritating factors like calculus, plaque, etc. Ulcerations, infections, spontaneous bleeding occurs when platelets are <20000cells/mm3>
• Infections: Candida is the most common oral infection in BMT patients. Nystatin solutions and clotrimazole troches are effective. Ketoconazole, miconozole and flucononazole are ingested and amphotericin B IV is for aggressive treatment. HSV is the main viral pathogen. Patients with a + serotype receive low dose acyclovir up to 28 days post BMT. CMV seropositive patients receive genocidovir for at least 100 days post BMT. Lastly bacterial infections are less common.
• Xerostomia and taste disturbances usually last for a few weeks with the exeption of radiation patients. Salivary flow can be stimulated with sugar free gum or hydration. Avoid coarse foods and spicy foods and consult with a nutritionist.
• Acute GVHD occurs when transplanted T Lymphocytes treat host tissues as foreign causing injury to several parts of the body. Acute GV-HD occurs within the first 100 days post BMT with the median onset at 19 days. Most common oral changes include erythema (dorsal and ventral surface of tongue, floor of mouth) and lichenoid changes. Prevention includes good oral hygiene, steroid rinses, treatment of concurrent infections and topical analgesics.
• Neurotoxicity: Vinblistine and vincristine in the conditioning phase can cause peripheral neuropathy including jaw pain and lower molar toothaches. Treatment is palliative as it disappears after the drugs are discontinued.
  
  

Pediatric Bone Marrow transplantation: oral complications and recommendations for care

Department of Pediatric Dentistry
Lutheran Medical Center

Name: Craig Elice Date: January 22, 2010
Article title: Pediatric Bone Marrow transplantation: oral complications and recommendations for care.
Author(s): da Fonseca MA.
Journal: Pediatric Dentistry 20 (7)
Volume (number): 20(7) 386-94
Month, Year: 1998
Major topic: Bone Marrow transplant, oral complications
Type of Article: Review of Literature
Main Purpose: The article provided an overview of Bone Marrow Transplant and the importance of a detailed oral examination prior to transplant and then to review oral complications and recommendations for treatment
Findings: Pretreatment goals are to identify, eliminate, and prevent problems that will cause the transplant to be less successful. The medical history should yield information on the disease, time of onset, modalities of the treatment received so far and complications. Surgeries, hospitalizations, ER visits, past episodes of infection, current hematologic status, allergies, meds and review of systems. Information about the transplant should include the type of transplant, donor preparation regimen, graft vs. host disease prophylaxis. The patient and family should be informed of the high sucrose level of some of the meds like nystatin, and clotrimazole troches . the patients central venous line needs antibiotic coverage due to the increased risk of infection.

Hematologic status focuses on platelet status and absolute neutrophil count. Thrombocytopenia occurs with platelets at <100000 cells/mm3. Moderate risk of bleeding occurs when platelets are <50000 cells/mm3. Neutropenia is when ANC <1500 cells/mm3 and elective dental treatment is contra indicated when ANC <100 cells/mm3.

Dental history and examination is necessary. Radiographs should be exposed as part of the screening. OHI and oral rehabilitation should be accomplished pre BMT as the patient will not be able to receive any dental procedures for up to one year post BMT. A cleaning , scaling as well as restoration of caries should occur ASAP with procedures that have moderate success like pulpotomies, and pulpectomies being contraindicated. Loose primary teeth should be allowed to exfoliate naturally, Wisdom teeth should be extracted if patient is at an appropriate age, Orthodontic appliances should be removed OH consists of toothbrushing with fluoridated toothpaste, and flossing should be done as tolerated. Oral rinses are effective (Na Bicarbonate, saline, and sterile water) are effective at cleaning and keeping tissues moist. Hydrogen peroxide can irritate and cause super infection. Chlorhexidine rinse is indicated, but long-term use is discouraged due to altered taste, high alcohol content, and possibility of super infection.

Education is critical. The importance of OH and preventing infection is discussed as it improves the transplant outcome. Disuss dietary habits, potential effects of some of the meds, and the effects of chemotherapy and radiation on the craniofacial growth and development and dental structures with the patient.

Oral complications can occur from conditioning regimen (7-10 days prior to transplant) to early ingraftment period (up to 30 days post BMT). It includes the following:
Mucositis: neutropenia seems to have the greatest relationship to mucositis. Great variability in mucositis amongst patients but there seems to be a minimal relationship to drug doses, schedules, duration of treatment, and impairment of renal and hepatic function. It can occur as early as 4-7 days after initiation of conditioning phase and last 10-14 days o. it generally starts with the nonkeratinized surfaces of buccal and lingual mucosa

Pain management: Young infants frequently need narcotic analgesics. Older children are given paitent controlled analgesics of sedative meds. Local analgesics include viscous lidocaine 2% and dyclonine HCl are effective topical agents. Ice packs and ice pops increase comfort level of patients,

OH as noted.

Oral bleeding: oral manifestations of thrombocytopenia include bruising , petechiae, purpura and oozing of mucosal tissues which can be potentiated by local irritating factors like calculus, plaque, etc. Ulcerations, infections, spontaneous bleeding occurs when platelets are <20000cells/mm3 or less. Platelet transfusion may be necessary. Topical therapies like moist gauze pressure packs, ice packs, and topical hemostatic agents shold be tried first.

Infections: Candida is the most common oral infection in BMT patients. Nystatin solutions and clotrimazole troches are effective. Ketoconazole, miconozole and flucononazole are ingested and amphotericin B IV is for aggressive treatment. HSV is the main viral pathogen. Patients with a + serotype receive low dose acyclovir up to 28 days post BMT. CMV seropositive patients receive genocidovir for at least 100 days post BMT. Lastly bacterial infections are less common.

Xerostomia and taste disturbances usually last for a few weeks with the exception of radiation patients. Salivary flow can be stimulated with sugar free gum or hydration. Avoid coarse foods and spicy foods and consult with a nutritionist.

Acute GVHD occurs when transplanted T Lymphocytes treat host tissues as foreign causing injury to several parts of the body. Acute GV-HD occurs within the first 100 days post BMT with the median onset at 19 days. Most common oral changes include erythema (dorsal and ventral surface of tongue, floor of mouth) and lichenoid changes. Prevention includes good oral hygiene, steroid rinses, treatment of concurrent infections and topical analgesics.

Neurotoxicity: Vinblistine and vincristine in the conditioning phase can cause peripheral neuropathy including jaw pain and lower molar toothaches. Treatment is palliative as it disappears after the drugs are discontinued.
Key points/Summary: The pediatric dentist is an important part of the transplant team. We are best consulted during the pretherapy phase when oral disease is eliminated and the patient can attain an optimal state of dental health. Dental health is important to improve the chances of a successful outcome to the transplant
Assessment of article: Good article which I believe provides up to date information regarding the role of the pediatric dentist in providing care to this patient. .

Chemoradiation therapy

Resident’s Name: Joanne Lewis Date: January 22, 2010

Article title: Chemoradiation therapy: effect on dental development

Author(s): Curt Goho, DDS

Journal: Pediatric Dentistry: Jan/Feb 1993 – Volume 15, Number 1

Type of Article: Scientific article

Main Purpose: to provide an overview of the effects of chemoradiation therapy on dental development.

Key points/Summary: Radiation – sufficiently high radiation doses cause ameloblast and ondontoblast death – can result in complete tooth agenesis; partially formed teeth have remaining development halted, with tooth and/or root agenesis. Lower radiation doses cause sublethal changes; odontoblasts are most susceptible to low-dose radiation just before initiating dentin matrix formation => localized dental defects seen as niches in the dentin or wavy, irregular dentinoenamel junction, with enamel hypoplasias over the defective dentin and shortened, thin, tapered roots. Chemotherapy – can easily damage odontoblasts and ameloblasts that are in susceptible phases of the cell cycle (M or S) => tooth agenesis, thin, tapered roots.

Assessment of article: Good article – very interesting.

Management of oral complications associated with cancer therapy in pediatric patients

Department of Pediatric Dentistry
Lutheran Medical Center

Resident’s Name: Brian Schmid Date: 1/22/10
Article title: Management of oral complications associated with cancer therapy in pediatric patients
Author(s): Anne R Simon, Michael Roberts
Journal: Journal of Dentistry for Children
Month, Year: 1991
Major topic: cancer therapy-related oral complications
Type of Article: Review
Findings: Cancer is the second most cause of childhood morbidity in the US. Increased and often successful therapies have also increased the related morbidities such as oral complications. These problems are especially important for children with increased nutritional needs, also oral complications from cancer therapies is 3x more common in children than adults. The complications are due to a combination of factors including size, location and intensity of radioactive dose.

MUCOSITIS: the most common oral complication of cancer therapy. It is closely related to toxicity of chemotherapeutic agents and their effect on the rapidly multiplying basal epithelial cells. The nadir of the neutrophil count also coincides with the most extreme mucositis. Symptoms include: burning sensation, dryness, tingling of the lips and severe pain. This can lead to malnutrition, dehydration and premature cessation of cancer therapy. The most common treatment is “Magic Mouthwash” whose original recipe included hydrocortisone, tetracycline, nystatin and diphenhydramine, although many variations are also used. Chlorhexidine is now widely used but contains no analgesic agent.

INFECTIONS: Oral fungal infections, such as Candida, occur most commonly on the buccal mucosa, tongue, gingiva and pharynx. This is treated with antifungals such as Nystatin, clotrimidazole etc which may come in mouthrinse, lozenge or pill form. Chlorhexidine has also shown success but should NOT be used in conjunction with Nystatin; this combination will inactivate both substances. The troches and pastilles often contain cariogenic substrates and their use should always be followed by excellent oral hygiene instruction. Oral bacterial infections are often secondary to severe mucositis and should be cultured before antibiotics are prescribed. Herpes simplex virus is the most common viral infection correlated with chemotherapy and bone marrow transplant. Acyclovir is the treatment of choice, IV for the more serious cases.

XEROSTOMIA: Temporary or permanent salivary gland destruction is common when radiation is directed at the head and neck. Synthetic salivary substitutes and stimulation of normal salivary flow are essential.

BLEEDING COMPLICATIONS: The amount of bleeding is directly related to the amount of thrombocytopenia and is exacerbated by poor oral hygiene. Platelet infusions are required when topical techniques fail.

Key points/Summary: The oral health care needs of the pediatric cancer patient are broad, read up.

Assessment of article: A nice summation of oral health complications but more detail is needed if you’re going to be treating any patients in this population.

Micrognathia after radiation therapy for childhood facial tumors

Department of Pediatric Dentistry

Lutheran Medical Center

Date: 01/22/2010

Article title: Micrognathia after radiation therapy for childhood facial tumors

Author(s): Kaste SC, Hopkins KP

Journal: Oral Surg Oral Med Oral Path

Volume (number): 77:95-99

Month, Year: 1994

Major topic: Affect of radiation therapy on oral structures

Minor topics: Dental management of pts under radiation therapy

Type of Article: 2 cases and long-term follow-up

Main Purpose: Educate readers on the consequences of radiation therapy

Overview of method of research: Review of current treatment modalities and case review

Findings: Radiation-induced dental effects include maxillary and mandibular hypoplasia, tooth or root dwarifsm, anodontia, caries and altered tooth eruption patterns. Additionally, radiation causes osteocyte death, microvascualr injury, periosteal damage and fibrous replacement of marrow spaces with all affect bone growth and development. The impact and severity of these treatments are depend on the child’s age at time of therapy, the radiation dose, and anatomical location of treatment.

Radiation doses of 10Gy and 30Gy have been shown to permanently damage ameloblasts. And studies have shown that does in excess of 20 Gy can result in significant bone and growth disturbance, regardless of age. It is particularly damaging if therapy in done during times of significant patient growth.

Knowing the late effects of radiation treatment to oral (or near oral) structures can aid clinicians in anticipatory guidance and help them better manage patients and improve their quality of life.

Key points/Summary :

Case 1:

4yr old boy with an extra-abdominal desmoid tumor on the palate. He received 32 Gy in addition to chemotherapy. Lateral Ceph at the time of treatment revealed a “normal” skeletal relationship of the maxilla and mandible.

At age 6, mandiblar lysis, root agenesis and stunting of root development of radiographically evident.

At age 12, radiographs revealed over-retained primary teeth, and displaced permanent molars. Significant mandibular micrognathia was present and overjet with severe.

At age 17 micrognathia was apparent and microdontia of all permanent 2nd molars was present. The crowns of the 3rd molars were displaced high in the ramus.

Case 2:

5 year old with embryonal rhabdomyosarcoma arising in the right nasopharynx. Threated with 35Gy and chemotherapy.

At age 15 he showed generalized root stunting, malposition of maxillary teeth and significant maxillary hypoplasia with facial disproportion. Some anodontia was also present.

Assessment of article: Very interesting. This would be a very interesting and challenging population to treat. The article never addressed what, if any, dental treatment was offered to these patients. That would be interesting to know, since the article suggested that dentists could improve the patient quality of life through proper management.

Recognizing Cancer in Children 01/22/2010

Resident: J. Hencler
Date: 01/22/2010

Article title: Recognizing Cancer in Children
Author(s): William H. Schultz
Journal: Journal of the American Academy of Physician Assistants
Volume #2; Number 5; Pg 338-352
Year: 1989

Major topic: Cancer in children

Type of Article: Review of current information

Main Purpose:
Increase the practitioner’s awareness of childhood cancer to aid in better diagnosis

Overview of method of research: Review of current information

Background and discussion:
An estimated 6500 cancers are diagnosed each yr in children, most common of which are leukemia, lymphomas, or brain tumors.
Etiology: Common cancers in children involve tissues that are not in direct contact with the environment. Genetic predisposition is more important in causing cancer in children than are environmental agents. (Table 1) Disorders with preexisting chromosomal aberrations, such as Down syndrome and Bloom syndrome, are associated with a high risk of leukemia. Also, a few childhood cancers are inherited such as retinoblastoma.
Diagnosis: The clinical features of childhood cancer are not obvious because signs and symptoms are usually nonspecific. Diagnosis is often delayed because major complaints are usually attributed to minor causes. Lymph node enlargement, fever, weakness, weight loss, cough, and shortness of breath are common symptoms associated with infectious diseases but are also cardinal features of malignancies. (Table 2) Even though most pediatric tumors have already metastasized before diagnosis, early detection of an asymptomatic tumor enhances the child’s prognosis.
Management: Emotional support for family should be provided. Children treated at pediatric cancer centers with state of the art protocols have a higher disease free survival rate than do children treated elsewhere. Supportive care must be provided to manage the acute complications of aggressive cancer therapy. These may include erythrocyte/platelet transfusion and broad spectrum antibiotics. Infections are the leading cause of death in children with cancer. Patients undergoing cancer therapy should not be vaccinated with live virus preparations.

Common Childhood Malignancies:

1. Acute Leukemia: Hematologic malignancies including leukemia and lymphomas, comprise the majority of cancers seen in children. Leukemia arises in the bone marrow and is a cancer of the leukocytes and progresses to bone marrow dysfunction and infiltration of tissues. A triad of anemia, neutropenia, and thrombocytopenia is a common consequence of dysfunctional bone marrow. Hematologic manifestations of leukemia are due to bone marrow replacement with malignant cells. Significant bone pain results when the marrow cavity becomes packed with leukemic cells. (Table 3) Erythrocyte mass and oxygen carrying capacity of the blood is decreased resulting in fatigue, irritability, pallor, tachycardia, and dyspnea. Acute lymphocytic leukemia is the most prevalent childhood leukemia. Bone marrow aspiration is the definitive test for leukemia. Before starting therapy a spinal tap is done to determine any CNS involvement. Most protocols call for 3 years of therapy. Bone marrow transplant may be required during therapy.

2. Brain Tumors: CNS tumors are the second most common childhood cancer. The clinical features of most childhood brain tumors are due to increased intracranial pressure caused by spinal fluid obstruction. (Table 4) Older children may have history of morning headache, vomiting, dizziness, or change in behavior. CT scan and MRI are the most specific tests to determine intracranial neoplasm. Surgical resection and irradiation therapy are the treatment for childhood brain tumors.

3. Lymphomas: Lymphomas are a diverse group of cancers of the immune system. Included in this group of lymphoid cancers are Hodgkin’s disease (HD) and non-Hodgkin’s lymphoma (NHL). Progressive cervical lymph node enlargement without associated symptoms is the most common early clinical manifestation of HD in children. Painless hard lymph nodes frequently represent metastatic cancer. In NHL, the gastrointestinal tract and mediastinum are primary disease sites more often than peripheral lymph nodes. Diagnosis of lymphoma is based upon histologic examination of involved tissues. Treatment of localized, early stage HD may consist of radiation alone but more advanced disease may require either involved-field or extended-field radiation combined with multiagent chemotherapy. NHL must be regarded as microscopically disseminated at diagnosis and always requires chemotherapy. The diagnosis for children with abdominal tumors is more favorable when complete excision is possible.

4. Neuroblastoma (Nb): Arises from neural crest tissues of the sympathetic nervous system and demonstrates a diversity of primary sites from the base of the skull to deep in the pelvis. Most occur in the retroperitoneal area. Nb is the most frequently discovered malignant tumor in infants. Children diagnoses after the age of 2 do much worse than those who are younger at diagnosis. Nb frequently causes nonspecific symptoms that sometimes mimic common pediatric illnesses. Vanillylmandelic acid and homovanillic acid are metabolites whose levels are elevated in Nb and can be easily measured in the urine for diagnostic purposes. Total surgical excision of localized tumor can achieve a 2 year survival rate greater than 80%. Unfortunately most Nb is widespread at diagnosis. Post operative chemotherapy and irradiation may shrink an unresectable tumor.

5. Wilms’ Tumor (WT): Is a primary malignancy of mixed histologic features occurring in the kidney. It is the most common abdominal neoplasm in children. WT is often discovered when the child’s abdomen enlarges or an abdominal mass is found. Symptoms include malaise, constipation, anorexia, or fever. It is usually palpated unilaterally but a small percentage of cases involve both kidneys. Treatment protocol may include radiotherapy, adjunctive chemotherapy, or surgical nephrectomy depending on staging.

6. Osteosarcoma (Os): Is a relatively rare bone cancer that affects adolescents. The tumor usually arises in the long bones in the metaphyseal region, where growth is more active. The femur, tibia and humerus are frequent sites of primary tumor involvement, with most originating around the knee. A Common symptom of Os is pain and swelling at the primary site. Histologic examination of tissue obtained with an open biopsy confirms the diagnosis. With the ability to identify intramedullary tumor extension, more conservative surgical approaches can be tried, such as cross-bone amputations and “limb sparing” procedures. Adjunctive chemotherapy for Os is a common treatment protocol.

Fortunately, cancer in children is rare. Early diagnosis and appropriate referral is so important and may greatly improve prognosis.

Assessment of article:
Good article. May be a little outdated at 21 years old but still relevant to the pediatric dentist who should have some knowledge of the cancer types that commonly affect our patient population.

Update on new treatments and developments in childhood brain tumors 1/22/10

Department of Pediatric Dentistry
Resident’s Name: Murphy Program: Lutheran Medical Center - Providence
Article title: Update on new treatments and developments in childhood brain tumors
Author(s): Partap, Sonia, Paul Graham Fisher.
Journal: Current Opinions on Pediatrics
Year. Volume (number). Page #’s: 2007. 19. 670-674
Major topic: Various type of brain cancers in children, their symptoms, and treatments.
Minor topic(s): New ideologies for treatment
Main Purpose: To review brain tumors occurring in children, discuss their current treatment options, and analyze new options.
Overview of method of research: n/a
Findings: Primary central nervous system tumors are the second most common cancer in children with 3,400 new cases each year(hematological malignancies are the first). This article discusses three types of brain tumors, their symptoms, prognosis, treatment options, survival rates, and newest research findings.

Medulloblastoma
Medulloblastoma’s account for 40% of pediatric posterior fossa CNS tumors. They arise in the cerebellum, especially in the vermis. It is theorized that they are derived from external granule cells. Incidence is around 5 years old, but can occur in older children. The tumor presents as a large mass effect in the posterior fossa. Children often have symptoms such as nausea/vomiting, headache, and papilledema. These all are from increased intracranial pressure congruent with ataxia. The severity of the tumor is broken down into either average risk or high risk, depending on if there are metastases or not.

Treatment Options for MB
Surgical Removal
This is the first step, with the goal being removing the intracranial pressure and as much as the disease as possible, depending on the level of risk. Total removal of the tumor shows the best survival rates(DUH). Complications areising from removal of the tumor include cerebellar mutism, which is also known as posterios fossa syndrome. Children that develop this usually do so 1-2 days post op and have rapid onset of emotional lability, mutism, and high pitched crying. This resolves on it’s own, however long term issues with speech and cognitive deficits remain.

Radiation and Chemo
While craniospinal radiation(CSRT) is imperative for the treatment of MB, it is associated with neurocognitive effects and endocrinopathies. For years, any pt. W/ MB was treated w/ 36Gy to the craniospinal axis, and 18-24Gy to the posterior fossa. Recently, children with average risk MB have been treated with 23.4Gy to the CSA, and a boost to the posterior fossa. 36Gy remains the standard of care for high-risk children. When used in conjunction w/ CSRT, chemo improves overall survival rate than just chemo alone. The treatment regiment usually includes either cyclophosophamide, vincristine, cisplatin, or lomustine. Less toxicity has been seen w/ lomustine as opposed to cyclophosphamide. Survival rates with this treatment are around 81%(w/ 23.4 Gy). Long term monitoring for hearing, fertility, endocrinopathies, and secondary malignancies are needed, especially when comparing pt’s who receive high amounts of cyclo and less cisplatin and vincristine.

Future Directions
Advances in molecular biology broaden our understanding of correlations between MB subtypes, their features, and their relation to outcomes with respect to how they were treated. For example, a newly found histological subtype, ERBB2 carries a worse prognosis, which can help to dictate proper treatment. As our knowledge of MB precursor cells expands w/ the use of mouse models, new interventions may materialize to help inhibit the progression of MB before it begins.

Ependymoma
EM is the third most common CNS tumor in children. 50% of the kids with this are younger than five. EM often arises from the remnants of the ependymal lining located in the ventricular system of the posterior fossa. EM can cause hydrocephaly and symptoms of intracranial pressure. Pt’s usually present w/ seizures and motor/sensory complaints. EM carries a high risk of recurrence and metastasis.

Treatment Options for EM
Surgical Removal
Total surgical resection is an important prognostic factor for EM. However, only half of children with EM are long term survivors.

Radiation/Chemo
Radiation is standard when the tumor has communicated with the ventricular system, despite it’s detrimental effects on the developing brain. Chemo is ineffective. Sad stuff.

Future Directions
Scientists are attempting to identify a potential biological and therapeutic marker as a prognosticator for EM. Human telomere reverse transcriptase(hTERT), which aids in uncontrolled cell growth, was found in 87 tumors. Tumors tht were hTERT neg had a 5 year survival rate of 84%, while hTERT pos. was 41%.
Advances in stem cell research show promise in trying to find new treatments for EM.

Brainstem Glioma
(All of these are unbelievably bad, but this guy is depressingly terrible)BG represents 8-10% of all pediatric CNS tumors. Prognosis is dismal. Usual age of onset is 7, and median survival time ranges form 9-11 MONTHS. Only 20% last beyond 1 year. Children present with weakness, hemiparesis, ataxia, and difficult with lateral gaze. MRI’s are usually used in the diagnosis, showing obscuration of the pons, and engulfment of the basilar artery.

Treatment Options.
Surgery/Radiation/Chemo
Due to their location and extent in the pons, resection is not possible. The standard of treatment for BG is high levels of radiation. 54Gy is given in 30 daily fractions of 1.8Gy over 6 weeks. This improves survival and also reduces or temporarily stabilizes tumor size, giving the child a better quality of life. SO far, increasing radiation rates, using chemo, and combined therapies show no improvement in survival rate. They tried to use cyclosporine A to breach the blood brain barrier to provide intracerebral chemo, however this study was suspended because it was making kids seize and severly altering their mental status.

Future Directions
So far, progress has been slow. There has been promising data with tipifarnib in adults. More research is needed…obviously.

Brain Tumors as Secondary Malignancies
As the treatment for most pedicatric cancers improve, more people are living longer. The cure rate for ALL, the most common childhood cancer is 80%. The risk for secondary malignancies rises steadily 30 years after the initial treatment, at a % of 10.85%. The long term affects of radiation is also of great importance. Screening of pituitary function in teenager pt.s treated with CNS radiation is paramount due to the lack of adequate hormone levels that place the child at risk for physical and cognitive disabilities. Children treated w/ radiation have increased risk of brain tumors, stroke(6.4% in leukemia surviors and 29% in brain tumor survivors), and CVA’s. The 5 year survival rate is 70%. Clinicians need to shift their focus to include the complete assessment of the treatment, not just irradicating the disease.
Key points/Summary:
Brain tumors are still largely a mystery for clinicians. While surgery, chemo, and radiation work(to some extent) the long term affects can kill a pt. Just as easily as the original tumor.

Assessment of Article: Good article. Very informative. Although I’m definitely depressed after reading it.

Lit Review Assignment Dan Boboia and Joanne

Chemotherapy:
Hypodontia
Root abnormalities
Amelogenesis imperfecta
Microdontia of bicuspid teeth
Tendency toward thinning of roots with an enlarged pulp chamber

Radiotherapy Short:
Damage to epithelial surfaces
Mucositis
Intraoral soft tissue ulceration
Taste disorders
Oralpharyngeal mucositis

Radiotherapy Long:
Xerostomia
Caries
Root tip blunting and shortening
incomplete calcification of teeth
premature closure of apices
delayed or arrested tooth development
comprised trismus
abnormal occlusal relationships
facial deformities

Stuff we already Know by Dan and Joanne

Dan Boboia & Joanne Lewis


Chemotherapy Long term:
Hypodontia
Root abnormalities
Amelogenesis imperfecta
Microdontia of bicuspid teeth
Tendency toward thinning of roots with an enlarged pulp chamber

Radiotherapy Short:
Damage to epithelial surfaces
Intraoral soft tissue ulceration
Taste disorders
Oralpharyngeal mucositis



Radiotherapy Long:
Xerostomia
Caries
Root tip blunting and shortening
incomplete calcification of teeth
premature closure of apices
delayed or arrested tooth development
comprised trismus
abnormal occlusal relationships
facial deformities

Oral Complications in Children with Cancer

Dan Boboia 1/22/10 Lit. Review

Title: Oral Complications in Children with Cancer

Author: Childers et al

Main Purpose: To determine the incidence of oral complications in 214 pediatric patients with cancer at Children’s Hospital of Alabama.

Methods / Results: Final study sample comprised 214 pediatric cancer patients; median age was 6 years; Incidence of each oral complication is given in table 1. Incidence of ulcers ranked highest, followed by gingivitis. Children with sarcomas had more ulcers and Candida infections then those with leukemia. There was a 5 x higher rate of gingivitis then in patients with sarcoma. Candida infections in children with solid tumors were four times more then in patients with leukemia.

Conclusion:
Oral complications are a frequent cause of morbidity in children with cancers. There are also certain cancers in which certain oral complications are seen more often. Prevention could be more effective my identifying the risk groups and developing treatment strategies.

Dental Management of the Renal Transplant Patient

Department of Pediatric Dentistry
Lutheran Medical Center

Name: Craig Elice Date: January 15, 2010
Article title: Dental Management of the Renal Transplant Patient
Author(s): Rhodus NL, Little JW
Journal: Compend Contin Educ Dent
Volume (number): 14(4)
Month, Year:
Major topic: Renal Transplant, dental management
Type of Article: Review of Literature
Main Purpose: The article reviewed the indications, process, systemic and oral complications and management of dental patients receiving a kidney transplant
Findings: Indications for renal transplant include chronic renal disease or end-stage renal disease (ERSD). Along with the deterioration of the nephrons comes hypertension, diabetes, congestive heart failure, infections, urinary tract obstructions, hypercalcemia and elevated potassium which all require medical management. Problems managing these issues leads to hemodialysis. Renal transplantation can free the patient from dialysis, but has a host of problems along with it such as graft rejection, chronic immunosuppression, susceptibility to infections, and poor wound healing. Oral complications may include gingivitis, desquamation, and ulceration of the oral mucosa. Oral candidiasis, and HSV I are common. Cyclosporine, azathioprine, prednisone and ALG are common immunosuppressive medications which have many adverse effects. Cyclosporine can cause severe kidney and liver changes, hypertension,, anemia, and bleeding problems as well as gingival hyperplasia, hirsutism, and various cancers of the skin. Azithioprine causes bone marrow suppression increasing the risk of infection and excessive bleeding from anemia, thrombocytopenia, and leucopenia. ALG also causes hemolysis, leukopenia, thrombocytopenia, and tumor development as well as infections. Prednisone acts as an anti-inflammatory agent which has side effects including hypertension, diabetes mellitus, osteoporosis, impaired healing and psychoses. Dental management focuses on elimination of infection by restoring or extracting teeth and disease prevention such as good oral hygiene, antimicrobial mouthwashes, and professional dental cleanings and fluoride applications. Consultation with the physician is important to determine degree of renal dysfunction and the need for antibiotics to prevent infective endocarditis. The need for antibiotics is controversial and is best determined by a physician consult. The dentist should avoid drugs metabolized or excreted by the kidney. Management of these patients can be divided into two phases. The first phase occurs immediately posttransplant when complications and rejection are most likely. Only emergency dental care is provided, while routine dental care is contraindicated. The second phase a.k.a. the stable phase often requires antibiotic prophylaxis. Due to the altered oral flora, the type of antibiotic is uncertain. Patients are at increased risk of infections from the environment therefore infection control procedures are necessary. Patients are susceptible to HBV, HIV, CMV, Epstein Barr, etc. In addition to post-operative infections, the dentist must be wary of risks of excessive bleeding and adverse reactions to physical and emotional stress. Anticoagulants and high doses of prednisone are common medications. If the level of anticoagulation is greater than 2 and a half times the normal PT, the medication dosage should be reduced. Depending of the procedure, it may take 3-4 days of reduced dosage to improve the PT. Avoidance of drugs metabolized or excreted by the kidneys is important. Local anesthetics and antibiotics like penicillin, erythromycin, amoxicillin, and clindamycin are generally safe. Aminoglycosides and tetracycline should not be prescribed as well as aspirin and phenacetin. Analgesics like acetaminophen, codeine, are safe. Patients taking steroids need a physician consult to determine the necessity for a change in dose. Patients on a chronic 5mg dose of prednisone may need to double or triple their normal dose the morning of, and 1 hour preop. Taking a patients blood pressure prior to dental treatment is probably good practice because one of the side effects of cyclosporine is hypertension. Signs of over-immunosuppression include recurrent HSV infections, herpes zoster, candidiasis, large slow to heal aphthous ulcers and infrequently lymphoma, Kaposi’ sarcoma, and hairy leukoplakia.
Key points/Summary: Medical consultation is necessary to establish the following: current status of patient, degree of immunosuppression and if graft rejection is present, need for prophylactic antibiotics, need for steroid supplementation, need to alter anticoagulation dosage, presence of hypertension, current status of renal function, and medications that should be avoided. Dental management should focus on removal of infection and good dental health through oral hygiene practices, cleanings, and fluoride.
Assessment of article: Good article but I think it is dated.

Renal disease

Resident’s Name: Joanne Lewis Date: January 15, 2010

Chapter 23: Renal Disease (The Handbook of Pediatric Dentistry)

Definitions:

Renal Insufficiency – damage past the point of compensation; impaired ability to maintain the internal invironment.

Renal Failure – reduction in glomerular filtration rate; normal homeostasis cannot be maintained.

End-Stage Renal Disease (ESRD) – chronic, irreversible, progressive disease; most common causes are diabetes mellitus, hypertension and chronic glomerulonephritis.

Medical Treatment of ESRD:

Dialysis – peritoneal dialysis or hemodialysis

Renal Transplantation

Oral Manifestations of ESRD

- Malodor

- Metallic taste

- Xerostomia

- Glossitis

- Increased deposition of calculus

- Low caries

- Tooth erosion (due to vomiting)

Prophylactic Antibiotics Prior to Dental Treatment

AHA guidelines do not address prophylactic antibiotic use in ESRD and renal transplant patients. In patients with recent placement of a shunt (<6>

Dental Management During Renal Therapy and Before Transplantation

Stabilize or eliminate existing and potential sources of oral infection.

OH training.

Radiographic exam to look for changes in bone.

Xerostomia? Taking any meds high in sucrose?

Consult with physician.

More aggressive treatment (ext. vs. pulp therapy/endo) may be indicated – dental infections during immunosuppression can have significant impact on medical therapy.

Ortho – only if OH is excellent.

Extractions – at least 7-10 days prior to transplant.

Dental care should be done soon after dialysis; avoid the day before dialysis.

Dental Management After Transplantation

Defer all elective procedures during immunosuppression periods.

Increased risk of oral malignancy – monitor.

Ortho – may start or resume after at least a 2 year disease-free survival.

Factors affecting cyclosporine-induced gingival overgrowth in pediatric renal transplant recipients.

Resident: Adam J. Bottrill
Date: 15JAN10
Region: Providence
Article title: Factors affecting cyclosporine-induced gingival overgrowth in pediatric renal transplant recipients.
Author(s): Karpinia, Katherine DMD et al.
Journal: Pediatric Dentistry
Page #s: pp. 450-455
Year: 1996
Major topic: Cyclosporine-induced gingival overgrowth
Minor topic(s): Pediatric renal transplant patients
Type of Article: Summary of research

Main Purpose: To study the occurrence of gingival overgrowth in children after kidney transplantation and to investigate the relationship of gingival overgrowth (GO) to medical and dental parameters.

Overview of method of research: 49 transplant patients taking cyclosporine were evaluated for a number of different characteristics.

Key points in the article discussion:

A. General
1. CsA is used with organ recipients to prevent graft rejection.
2. Taken via oral or IV.
3. absorbed by gut and metabolized by the liver enzymes of the cytochrome P450 system.
4. Blood CsA levels >200 ng/mL is associated with various side effects.
5. GO first reported in 1983.
6. Recently reported that adults with >400 ng/mL have significantly greater risk of GO.
7. Though much has been reported on adults with CsA associated GO, not much out there on children and adolescents.


























B. Hypothesis:
1. The immunosuppressant drug CsA, as used in pediatric renal transplant patients, contributes to the clinical manifestation of GO.
2. Specific aims:
a. document the presence of GO in children with kidney transplants via exam
b. associate documented GO with blood trough levels of CsA
c. document the gingival health status of subjects exhibiting GO, compared with subjects without GO
d. detect relationships between medication and GO

C. Method:
1. 1992-1993: 49 subjects from 5.9-18.6 y.o.
2. 19 received cadaveric kidneys and 30 had living relative donors
3. All subjects were allowed routine dental care.
4. Inclusion Criteria
a. Hx of kidney transplant
b. CsA immunosuppressive therapy
5. Exam
a. CsA levels
b. Plaque and calculus (present vs not present)
c. Gingival index (normal, mild, moderate, severe)
d. Gingival width
e. Probing depth
f. Gingival overgrowth (present or not, per tooth)

D. Results and Discussion
1. Overall, subjects’ OH was fair. No subject was completely plaque-free.
2. This study found that 77.5% of pediatric patients meeting inclusion criteria exhibited GO at exam.
3. All those on CsA >3mo showed GO
4. In contrast with recent reports, this study found the prevalence of GO in children larger than recently reported adult CsA-induced GO.
5. This papillary and marginal GO yielding firm, nodular, or granular growth has been found with CsA, phenytoin, sodium valproate, primidone, CCB’s nifedipine, verapamil, diltiaze and nitrendipine.
6. GO frequency was NOT significantly associated with plaque, gingival index, calculus OR CsA levels.
7. The single most critical factor in GO occurrence was increased TIME of CsA therapy.














Assessment of article: Keep in mind these results are based on very specific inclusion criteria. Shenanigans?... you decide.

Dental Considerations for the patient w/ Renal disease receiving hemodialysis 1/15/10

Murphy January 15, 2010
Article Title: Dental Considerations for the patient w/ Renal disease receiving hemodialysis

Authors: DeRossi DMD, Scott. Michael Glickman, DMD
Journal: JADA
Volume: Jan 1996

Major Topic: Renal Disease and its dental complications
Minor Topic: Renal Disease treatments and complications

Type of Article: Review of disease/treatment options
Main Purpose: Review of how to treat a patient receiving dialysis
Overview of Method of Research: Review of current (1996) literature for dental management of pt’s w/ renal disease.

Findings: About 8 million people in the US are affected by some type of kidney disease. ESRD is a chronic, progressive disease that causes the destruction of nephrons, the kidney’s functional unit. Once destroyed, nephrons do not regenerate. Some things to think of when treating a patient with kidney disease include excessive bleeding, hypertension, anemia, drug intolerance and synergism, increased susceptibility to infection, and various oral manifestations. With renal failure, many of the changes that occur happen over a period of time and are ameliorated by different types of treatment, from dietary changes, to transplants, to medications, to dialysis. There are two types of dialysis, peritoneal dialysis which is essentially ambulatory treatment, and hemodialysis, which is done in the hospital, and is much more common in the US than peritoneal dialysis. Arteriovenus shunts and fistulas are often placed to allow access to the patient’s bloodstream. During treatment, pt’s receive anticoagulants to facilitate blood exchange and to maintain patency.
Around 90% of patients with renal disease show some type of oral manifestation. Patients may complain of/have
-bad breath/metallic breath
-xerostomia
-mucosal pallor
-uremic stomatitis
-painful ulcerations on the ventral tongue surface and anterior mucosal surfaces
-decrease in caries(due to the inhibition of bacteria from highly uremic saliva…very common in children)
-erosion from frequent regurg.
One oral sign that becomes more evident as the late stage of disease approaches is renal osteodystrophy. The increase in urinary excretion of phosphates decrease urine calcium excretions, causing exaggerated release of calcium from bone. This can present as a
-ground glass appearance of bone
-loss of lamina dura
-radiolucent giant cell lesions
-bone loss
-metastatic soft tissue calcifications
-tooth mobility/tooth drift
-malocclusion
-enamel hypoplasia
-pulp stones/calcification
-delayed/altered eruption
Patients on peritoneal dialysis don’t pose any contraindications to dental tx. Hemodialysis pt’s however, do.

Key Point/Summary
Things to consider….
Before Tx
-consult w/ nephrologists for recent coag values and possible AB coverage
-eval hyper/hypotension
-do not take BP in same arm that access is in
-Find out underlying cause of RD
-Obtain CBC to eval for anemia
-Determine presence f uremic symptoms
-Get X-Rays to eval for osteodystrophy
-Determine type of vascular access
-Determine dialysis cycle
-Consider AB coverage and anti anxiety meds
-Review the meds the pt is taking and assess any oral implications(nifedipine)


During TX
-Thorough exam
-eliminate all infection
-use adjunctive hemostatic aids
-make sure pt is comfy
-allow pt breaks to move around
After Tx
-use post procedure hemostatic agents
-review home care
-possible xerostomia therapy
-post op AB
-adjust meds for RD dosage
Patients are best treated on the morning after they receive dialysis. The MOST important thing to keep in mind with these patients is the risk of infection. The mortality rate with these patients is high due to their lowered immune response…45%. ANY dental procedure that may produce bleeding should be covered w/ AB’s….yes you too Dr. Adam!! The best AB to use is vancomycin, but it’s wicked expensive and isn’t practical. Other options are amox 3g PO 1 hour before proc., or clinda 300mg PO 1 hour pre op, the 150mg 6 hours after initial dose.

Assessment of article: Lots of relevant good info on RD. Having a close family member who lived with it for almost 11 years, I know how tough it can be…on everyone. Try to be aware of not only the patients, but also their caregivers and family as well. It sucks. No other way to say it.

Oral changes associated with end-stage liver disease and liver transplantation: implications and dental management

Kris Hendricks January 15, 2010

Article Title: Oral changes associated with end-stage liver disease and liver transplantation: implications for dental management.

Authors: W. Kim Seow, R.W> Shepherd, T.H. Ong

Journal: Journal of Dentistry for Children

Volume: Nov-Dec 1991

Major Topic: Liver Disease and its dental complications

Minor Topic: Oral Pathology

Type of Article: Informative with Case studies

Main Purpose: The study investigates a group of children with end-stage liver disease with particular reference to the oral manifestations of the disease, as well as the complications associated with liver transplantation.

Overview of Method of Research: Review of current (1991) literature for medical and dental live disease management in children. Case study also.

Findings:

• All patients presented with enamel defects and some degree of gingival and enamel staining.
• Good oral hygiene lessens gingival hypertrophy in post-transplant patients
• High concentration topical fluoride applications are not recommended due to compromised metabolism
• Postoperative antibiotic coverage with Pen VK is recommended due to weakened immune system.
• Bleeding tests must be performed prior to any surgical treatment and all deficiencies should be treated prior to or during procedures, including IV infusion of fresh frozen plasma and Vit. K.
• Special anesthetic consideration due to decreased liver function. Usually isoflurane is the general anesthetic of choice.

Key Point/Summary

• End-stage liver disease causes nutrition deficiences due to poor absorption of fats and fat soluble vitamins such as A,D,E,K
• Vit. K deficiencies lead to bleeding tendencies
• Osteopenia, and rachitic skeletal changes as a result of poor vit D metabolism
• Transplant is the preferred treatment
• Post-transplant patients are usually immuno-suppressed with cyclosporin ( at least they were 20 years ago)
• Oral manifestations are green staining on teeth, enamel hypoplasia, gingival staining and cyclosporin induced gingival hypertrophy.
• Histologic and anatomical studies reveal that post-transplant enamel formation is normal. For example a tooth root may be stained and malformed until transplanation and then continue in a normal fashion thereafter.
• In this sample, gingival staining often continued post-transplant, even when billirubin levels were well controlled.
• Gingival hypertrophy increased with time after cyclosporin treatment.

Assessment of article: Good article. May be outdated, but it was interesting and informative without taking it beyond the scope of what a dentist needs to know.

The dental status of children with chronic renal failure

Resident: Hencler
Date: 01/15/2009

Article title: The dental status of children with chronic renal failure (CRF)

Author(s): Wolff, Stark, Sarnat, Binderman, Eisenstein, Drukker
Journal: The International Journal Of Pediatric Nephrology
Volume #6; Number 2; Page #127-132
Year: 1985

Major topic: Dental status and CRF

Type of Article: Clinical observation

Main Purpose:
Investigate the dental status of children with CRF to determine the prevalence and range of changes in dental structures and correlating these changes with metabolic disturbances, secondary to the uremic state, known to affect bone structure and development.

Overview of method of research:
Examined 30 children between 3-17 year old, 18 boys and 12 girls. Patients were divided into three groups according to their therapeutic regimens: (1) 15 on conservative therapy (2) 9 children on dialysis (3) 6 children who had undergone successful kidney transplantation. Eleven had primary dentition, 7 mixed, and 12 with permanent dentition. Hospital charts were reviewed for clinical and laboratory data. Every patient was evaluated for eruption age, enamel hypoplasia or hypocalcification, intrinsic staining, caries rate, gingival condition, and oral hygiene.

Findings:
• Dental Age and Eruption Age: Results demonstrate delay in both dental and eruption age for the 3 groups. Although some degree of retardation was found in both dental parameters, the delay in eruption was minimal, whereas retardation of dental age approached that in bone age.
• Enamel Defects: Location of the enamel defects clearly corresponded to the age at which renal function deteriorated and substantial biochemical disturbances occurred, namely, acidosis, hypocalcemia, hyperphosphatemia, and a rise in alkaline phosphate. There was a high incidence of enamel defects found in the CRF patients in this study.
• Intrinsic Discoloration: Found in the teeth of 9 patients. All cases of discoloration were found in parts of the teeth that developed postnatally. Discoloration was diffuse.
• Oral Hygiene and Gingival Condition: The patients in this study were compared to healthy patients with regards to OH and the gingiva. The authors found that both the OH and gingival indices were both higher for CRF patients in this study when compared to healthy patients.
• Caries: Measuring DMFT and comparing to healthy children, the results demonstrate a marked “protective” effect of CRF, especially in the younger age groups. The authors found a very low caries prevalence.
• Changes in the Jawbones: Absence of lamina dura (LD) was found in 6 and 3 showed loss of cortical borders of the mandibular canal (CBMC) and ground glass appearance of the bone structure. Radiographic changes were most frequent in the dialysis group.

Key points in the article discussion:
The 30 children with CRF clearly differed from a normal childhood population in all dental parameters examined. It appears that in CRF, development of the teeth is less sensitive to metabolic disturbances than that of bone. The degree of retardation was found to be a function of age at onset and duration of CRF and possibly also of steroid therapy in transplanted patients. The patients in this study had a very high incidence of enamel defects, in the form of hypoplasia and hypocalcification. Although the enamel defects have been attributed to hypocalcemia and Vit D deficiency, the authors were unable to relate them to any specific biochemical disturbance or therapeutic regimen. The increased incidence to staining with increasing severity of renal failure seems to be caused by pigments excreted by the kidneys. The poor condition of the gingiva in CRF patients appears to result from poor OH and high incidence of calculus. Poor OH reflects chronic ill health and tendency of parents to be more lax with these children. Reduced caries prevalence in uremic patients is surprising because to the poor OH and commonly recommended dietary regimens (low protein and high carb) for CRF patients. 4 explanations are as follows: (1) most of these patients suffer from anorexia and probably consume less food between meals reducing caries risk, (2) Recommended high fat diet reduce surface tension of the enamel that may lower plaque formation, (3) High salivary phosphate concentration found in uremia may facilitate remineralization of potential carious lesions, and (4) most importantly, the high salivary concentration of urea. Urea and it’s degradation products are both bacteriocidal and alkaline and is a highly effective agent for the prevention of caries. Radiographic changes of the jawbones are known to accompany other bone changes in CRF. Absence of the dental LD has been described in uremic patients. In dialysed patients, loss of LD was more common than loss of CBMC, whereas in transplanted patients the reverse was true because the LD is part of the liable alveolar bone whereas CBMC on the other hand belongs to the more stable basal bone. A ground glass appearance of jawbones is a finding of calcium metabolism disorders and hyperparathyroidism. The lower incidence of this finding in this study may reflect a shorter period of renal failure.

Summary of conclusions:
This study demonstrates that the metabolic defects associated with CRF do affect the development and structure of the teeth and alveolar bone. The nature and extent of these changes are a function of the age of onset of CRF and it’s duration. Despite low caries incidence, the finding of poor OH and resultant gingival changes suggests need for counseling and OHI. Antibiotic prophylaxis is very important when treating patients taking immunosuppressive treatment following kidney transplantation.

Assessment of article:
Good article, relevant to the pediatric dentist. Children with CRF will require special dental management including possible antibiotic prophylaxis and consults with PCP and nephrologists.

A review of liver transplantation for the dentist and guidelines for dental management

LUTHERAN MEDICAL CENTER
Dental Residency Program
Literature Review Form

Resident: Boboia Date: 1/15/10
Article title: A review of liver transplantation for the dentist and guidelines for dental management
Author(s): Glassman et all
Journal: Special Care in Dentistry
Volume #; Number; Page #s): 13:2
Year: 1993
Introduction : The major goal of dental intervention before and after liver transplantation is the prevention of bacteremia from an oral source that could lead to systemic infection. In addition there are many pre- and post-transplant issues that should be addressed in order for the dentist to properly and safely render treatment.
Dental Protocol prior to liver transplant:
• Obtain proper medical dental history
• Prioritize dental problems. Those most likely to cause pain, bleeding, infection, or bacteremia in the next 12 months should receive the highest priority.
• PT/PTT, platelet count, and bleeding time should be known prior to performing any procedures which will cause bleeding. A PT time less then 16 seconds requires no transfusions, anything higher will. Platelet count less then 50,000 will require platelet replacement. In additition, minimize bleeding through topical hemostatic agents, pressure packs, etc. Swallowed blood is also an issue because it’s a source of protein that may not be easily metabolized
• Acites – contact physician regarding use of AB prophylaxis or refer to AHA guidelines
• Caution when using drugs such as acetaminophen, local anesthetics, narcotics, etc. since most are metabolized by the liver

Dental protocol after liver transplant:
• Obtain all current medical history
• Thorough dental exam
• Prioritize dental problems. Those most likely to cause pain, bleeding, infection, or bacteremia in the next 12 months should receive the highest priority.
• AB prophylaxis when necessary
• Steroid supplementation when appropriate
• OH procedures; stress use of floss to prevent cyclosporine induced gingival hyperplasia and other dental pathology. Remove local irritants
• Caution when using drugs such as acetaminophen, local anesthetics, narcotics, etc. since most are metabolized by the liver