Oral Problems in Patients Undergoing Haematology or Oncology Treatment

Created January 31, 2020
Author DentistryKey
Category General Dentistry
Comments 43

Management ofDental Emergencies inChildren andAdolescents, First Edition.

Editedby Klaus W.Neuhaus andAdrianLussi.

Companion website: www.wiley.com/go/neuhaus/dental_emergencies

245

Introduction

Uniquely, disruptions in the formation and

function of circulating blood cells trigger

changes in the immune system, blood clotting

and oxygen transportation. Whilst there is a

quite frequent occurrence of anaemia, it plays

a rather minor role in dentistry, since normally

it is only mildly severe and quickly remedied.

Haematological malignancies are rare,

with an incidence of about 30/100 000 (Sant

etal., 2010). The oral cavity is often affected

in patients without functioning defence, and

complications are common during dental

intervention, especially when there is a

lack of neutrophil granulocytes. In general,

seriously ill haematological patients receive

dental treatment at university centres.

Infections within the oral cavity may also

be initial manifestation of a haematological

disorder. This should in particular be con–

sidered when gingival bleeding occurs in

otherwise healthy conditions and in the

presence of petechiae.

Wanted and unwanted medicinal effects on

blood clotting and infection defence occur

very often, due to the wide spread of corre–

sponding diseases. This is related to treat–

ments like the application of corticosteroids or

anticoagulation in connection with atrial

fibrillation. The effects of these medications are

acutely relevant for the choice of dental treat–

ment. However, in children and adolescents,

medicinal anticoagulation is seldom applied.

This is why it is not addressed in this chapter.

High‐dose local irradiation is also rather

seldom administered in the area of the mouth

in children, and so it too is not discussed.

We begin by explaining the basic concepts,

before looking at specific problems associated

with the oral mucosa that are often encoun–

tered in connection with chemotherapy, total

body irradiation and stem cell transplants.

Haemostasis

Stopping the blood flow from injured blood

vessels is a complex process, in which a

number of factors interact. Successful

haemostasis consists in three steps: (i) vaso–

constriction to reduce the blood flow; (ii)

formation of a platelet plug by thrombocyte

adherence, activation and aggregation; and

(iii) plasmatic coagulation by a cascade of

proteins, which forms a stable clot. When

thrombocytes come in contact with collagen

in the exposed connective tissue, they attach

there by mediation of the von Willebrand

factor, a protein that adheres both to collagen

6.3

Oral Problems inPatients Undergoing Haematology

orOncology Treatment

Adrian M. Ramseier

, Jakob Passweg

and Tuomas Waltimo

Department of Oral Health & Medicine, University Center for Dental Medicine Basel, University of Basel, Basel, Switzerland

Department of Hematology, University Hospital Basel, Basel, Switzerland

6.3 Haematology and Oncology

246

and to thrombocytes. Thus, the thrombo–

cytes are activated. By releasing cytokines,

more thrombocytes are attracted, and the

plasmatic coagulation cascade is initiated.

Through several intermediate stages, pro–

thrombin is transformed, both intrinsically

(activation factors) and extrinsically (tissue

factor in the injured subendothelial tissue),

to thrombin, which in turn polymerises

fibrinogen to fibrin. This results in a net

incorporating aggregated thrombocytes as

well as erythrocytes, and thus forming a

stable blood clot. Other factors are responsible

for preventing exaggerated or spontaneous

thrombus formation.

Cellular Haemostasis Disorders

(Thrombocytes)

Depressed platelet count (thrombocytopaenia)

and dysfunction of the platelet count (throm–

bocytopahthies) can be either congenital or

acquired. Table6.3.1 provides an overview of

possible causes of thrombocytopaenia.

The most commonly isolated thrombo-

cytopaenia in children is the immune

thrombocytopaenia (ITP) (Ishii, 2017).

Thrombo cy to paenia may also occur following

a replacement of normal bone marrow with

leukaemic cells (e.g. in acute leukaemia) or

bone marrow failure, or it may be inherited.

Nonsteroidal anti‐inflammatory drugs

(NSAIDs) inhibit platelet aggregation. With

aspirin, such aggregation is irreversible, except

by the production of new thrombocytes.

Small petechial haemorrhages on skin and

on the mucosa are the typical sign of marred

thrombocytes; often, they occur on the

lower extremities (gravity) or in the oral

cavity. In case of severe thrombocytopaenia,

they can become confluent (ecchymoses).

Spontaneous bleeding starts only with a

platelet count of 20–30 × 10

/l (Scully, 2014).

Depending on the severity of the disorder, it

can result from minor traumata, gingival

bleeding or suffusions on the skin.

The normal platelet count is 150–450 × 10

/l;

a value of >100 × 10

/l is thought to be

ideal for surgical intervention. With values

>50 × 10

/l and good functioning of the

existing platelets, dentoalveolar surgery can

normally be performed without bleeding

complications (Henderson et al., 2001).

Measures like compression, wound suture

and local haemostatics are usually sufficient.

With values of <30 × 10

/l, spontaneous

bleeding can occur. In this situation, the

indication of surgical treatment should be

carefully considered, and surgery should be

conducted in collaboration with haematology.

Haemostasis can be improved by transfusion

of thrombocyte concentrates. This is recom–

mended during dentoalveolar intervention

with a platelet count of <50 × 10

/l, as well as

Table6.3.1 Causes ofthrombocytopaenia

(Hoffbrand andMoss, 2016).

Failure of platelet production

Selective megakaryocyte depression

Rare congenital defects

Drugs, chemicals, viral infections

Part of general bone marrow failure

Cytotoxic drugs

Radiotherapy

Aplastic anaemia

Leukaemia

Myelodysplastic syndromes

Myelofibrosis

Marrow infiltration (e.g. carcinoma, lymphoma,

Gaucher’s disease)

Multiple myeloma

Megaloblastic anaemia

HIV infection

Increased consumption of platelets

Immune

Autoimmune

Idiopathic

Associated with systemic lupus erythematosus,

chronic lymphocytic leukaemia or lymphoma

Infections: Helicobacter pylori, human immuno-

deficiency virus (HIV), other viruses, malaria

Drug‐induced, e.g. heparin

Post‐transfusional purpura

Foeto‐maternal alloimmune thrombocytopaenia

Disseminated intravascular coagulation

Thrombotic thrombocytopaenic purpura

Abnormal distribution of platelets

Splenomegaly, e.g. liver disease

Dilutional loss

Massive transfusion of stored blood to bleeding

patients

Disorders oftheImmune System/Granulocytes

247

during maxillofacial intervention with a

platelet count of <100 × 10

/l (Scully, 2014).

The success of thrombocyte transfusions

needs to be checked: it is essential to measure

the platelet count prior to and after trans–

fusion. Patients who do not adequately react

to thrombocyte transfusions constitute a

special problem. In such cases, therapeutic

interventions can be performed whilst trans–

fusion continues.

Plasmatic Coagulation Disorders

Congenital coagulation disorders include

haemophilia A (factor VIII deficiency) and

the much rarer haemophilia B (factor IX

deficiency). Only the male gender is affected

by haemophilia B. Spontaneous haemor–

rhaging and strong life‐threatening postop–

erative bleeding may occur. Missing factors

can be added; however, there is insufficient

evidence from randomised controlled trials

to assess the most effective and safe haemo–

static treatment to prevent bleeding in peo–

ple with haemophilia or other congenital

bleeding disorders undergoing surgical pro–

cedures (Coppola etal., 2015; Spivakovsky

etal., 2015).

In von Willebrand disease, the von

Willebrand factor is missing or malfunc–

tioning. Because of this, platelet function is

impaired. Von Willebrand disease is classified

into a number of subcategories, and is asso–

ciated with slight to considerable bleeding

disorders.

Disorders oftheImmune

System/Granulocytes

Defence comprises cellular elements, all of

which belong to the leucocytes. The various

cells evolved from one multipotent stem cell

of haematopoiesis, which is capable of differ–

entiating into different cell lines with various

functions:

● Neutrophilic granulocytes are implicated

in nonspecific immunity against bacteria

and fungi. Basophilic granulocytes are

involved in hypersensitivity reactions

(asthma, urticaria, allergic rhinitis and

anaphylaxis). Eosinophilic granulocytes

play a role in the defence against parasites.

● Lymphocytes are subdivided into T‐cells,

which have the important function of

differentiating between foreign and self,

B‐cells, which are amongst other things

responsible for the production of antibodies

(plasma cells, memory cells), and NK‐cells,

which play an essential role in protecting

against virus cells and tumour cells.

● Monocytes migrate into tissue, where they

become macrophages. They can recognise

exogenous material, ingest it (phagocyto–

sis), dissolve it and present it at their

cell surface. This causes the activation of

other defence cells (antigen presentation)

(Kasper etal., 2015).

Causes

Haematological Disorders

Abnormalities in the immune response may

have many different causes. There might

be disturbances in the differentiation of

individual or all cell lines. This can result

in functional reduction of the cell line(s)

affected, in a deficiency of these cells (lym–

phopaenia: T‐cells and B‐cells, neutropaenia)

or in an overproduction, which can replace

the production of other cell lines in the bone

marrow. Table6.3.2 provides a list of haema–

tological disorders.

Disorders oftheImmune System

through Medication

Disorders of the immune system can occur

as a wanted or unwanted effect of many

chemotherapeutics and immunosuppres–

sives. Particular emphasis must be given to

glucocorticoids like dexamethasone and

prednisone, but other immunosuppressives

like cyclosporin A (Sandimmun), tacrolimus

(Prograf) and the folic acid antagonist meth–

otrexate (Methotrexat) can also have this

effect.

6.3 Haematology and Oncology

248

Physical Damage

Blood formation can be impaired by irradia–

tion, either therapeutic or accidental. Stem

cells and lymphocytes are especially vulner–

able. Thus, a reduction in lymphocytes can

be observed at a very early stage after irra–

diation, whilst the number of granolocytes,

thrombocytes and erythrocytes decreases

only as damage to the stem cells progresses.

Clinical Oral Appearance

Sometimes, haematological disorders can be

discovered by the dentist. Manifestations of

haematological disorders in the oral cavity

can cause suspicion and suggest additional

investigations:

● Bleeding of the oral mucosa that does not

result from gingivitis may be an indication

of coagulation abnormalities due to a vari–

ety of causes. Petechial haemorrhages, and

haemorrhages at other places in the oral

mucosa, are typical for thrombocytopae–

nia (Hoffbrand and Moss, 2016).

● In case of acute myeloid leukaemia, gingi–

val swelling can be determined (Figure6.3.1)

(Kasper etal., 2015). Occasionally, this can

also be seen after treatment with cyclo–

sporine A and tacrolimus.

Table6.3.2 World Health Organization (WHO) Classification ofHematologic Malignancies (Abridged Version)

(Aster andBunn, 2017).

Subtype Putative cell of origin

Myeloid neoplasms

Acute myeloid leukemia (AML)

AML with recurrent genetic aberrations

AML without recurrent genetic aberrations

AML following cytotoxic therapy

Early myeloid progenitor

Myeloproliferative neoplasms

Chronic myeloid leukemia

Polycythemia vera

Essential thrombocythemia

Chronic eosinophilic leukemia

Primary myelofibrosis

Hematopoietic stem cell or early myeloid

progenitor

Myelodysplastic syndromes Early myeloid progenitor

Lymphoid neoplasms

Immature B‐cell and T‐cell tumors

B‐cell acute lymphoblastic leukemia/lymphoma

T‐cell acute lymphoblastic leukemia/lymphoma

Early B‐cell progenitor

Early T‐cell progenitor

Mature B‐cell tumors

Chronic lymphocytic leukemia/small lymphocytic

lymphoma

Mantle cell lymphoma

Follicular lymphoma

Burkitt lymphoma

Diffuse large B‐cell lymphoma

Post‐germinal center B cell

Naïve B cell

Germinal center B cell

Germinal center or post‐germinal center B cell

Plasma cell tumors and related entities

Multiple myeloma

Lymphoplasmacytic lymphoma

Post‐germinal center B cell

Mature B‐cell

Mature T‐cell and natural killer cell tumors Mature T‐cell or natural killer cell

Hodgkin lymphoma Germinal center or post‐germinal center B cell

Disorders oftheImmune System/Granulocytes

249

● Unusual infections in terms of frequency,

manifestation or the occurrence of rare

microbes are signs of possible immuno–

suppression. Candida infections are

encountered quite often (Figure 6.3.2),

and non‐Candida albicans species (e.g.

tropicalis, krusei and parapsilosis) are

increasingly being seen. What should be

noted is that these are often resistant to

common therapeutics. Typical for leukae–

mias are virus reactivations of, for

instance, herpes zoster and herpes sim–

plex virus (HSV) (Ramseier etal., 2015).

Intraoral ulcers and large aphtae are com–

mon manifestations of HSV. All of these

infections can cause severe pain.

● Swelling of the lymph nodes and anaemia

(recognisable by paleness of the mucosa)

may point towards a haematological dis–

order. So might fever and night sweats

recorded in the medical history.

Clinical Significance

When an immune deficiency exists, a possible

haematogeneous spreading of microorgan–

isms may be expected after intervention.

Together with the haematologist or family

doctor, it needs to be determined whether

prophylactic antibiotics should be imple–

mented or whether treatment should just be

postponed.

A focus search should be conducted prior

to haematological treatment by chemother–

apy or haematopoietic stem cell transplan–

tation (HSCT). Ideally, located infection

foci are treated first; however, this is not

always possible because of the already limited

immune response and wound healing, or

because of the urgency of treating the malig–

nant tumours.

In patients who have received allogeneic

stem cell transplantation, the current situa–

tion concerning immune response should

always be clarified with the attending haema–

tologist: when appropriate, prophylactic

antibiotics should be given prior to tooth

cleaning, deep scaling, caries treatment and

extractions, or else the treatment must simply

be postponed.

In chemotherapeutic treatment, which

is sometimes accompanied by total body

irradiation, hyposalivation occurs on a

regular basis. The result may be increased

susceptibility to caries, gingivitis, periodon–

titis, mucocutaneous diseases and fungal

infections (Bagattoni etal., 2014; Buglione

etal., 2016).

After allogeneic stem cell transplantation,

acute and chronic rejection reactions may

occur (graft‐versus‐host disease, GvHD).

The oral mucosa shows typical lichenoid

changes with or without erythematous lesions,

ulcers or mucoceles. Often, hyposalivation

takes place at the same time, combined with

a correspondingly increased risk of caries,

periodontitis and infections of the mucosa.

Long‐term effects include secondary malig–

nant tumours of the oral mucosa. Because of

this, the oral mucosa needs to be inspected

regularly and thoroughly. The indication for

Figure6.3.1 Gingival swelling and acute myeloid

leukaemia.

Figure6.3.2 Thrush (Candida).

6.3 Haematology and Oncology

250

biopsy sampling should be wide and generous

for the exclusion and detection of malig–

nancy, respectively (Elad etal., 2015).

Anaemia

Anaemia is defined by a reduction of the

haemoglobin concentration in the blood.

Common causes are vitamin B

, folic acid

and iron deficiencies caused by chronic

bleeding, for instance due to excessive men–

strual flow or chronic diseases like tumours.

Other causes include innate haemoglobin

synthesis disorders such as sickle‐cell anaemia

and thalassaemia.

Clinical Significance

Anaemias hardly have an effect on dental

treatment. The following manifestations could

indicate anaemia and necessitate further

clarification with the family doctor: com–

plaints about reduced performance, weak–

ness, heart palpitations and dyspnoea under

stress, as well as the occurrence of pale skin or

mucosa. Angular cheilitis, burning tongue or

dysphagia (Plummer–Vinson syndrome) may

appear in case of iron deficiency. Vitamin B

and folic acid deficiencies cause burning

tongue with impaired sense of taste and

trophic glossitis with disappearing papillae.

Mucositis

Mucositis is an inflammation of the mucous

membranes of the gastrointestinal tract as a

consequence of chemotherapy and radiation

therapy. Patients who are receiving HSCT or

irradiation in the area of the mouth are

affected particularly often.

Oral mucositis is associated with ery–

thema, and at times with ulcerations and

violent pain. It is one of the most frequent

side effects of cancer treatment, and is often

the reason for reducing the treatment dose

or for having to postpone treatment. It also

may necessitate tube feeding or parenteral

nutrition.

Pathogenesis has not yet been fully clarified,

although considerable progress has been

made in recent years. The procedure can be

broken down into five stages: initiation, pri–

mary damage response, signal amplification,

ulceration and healing (Sonis, 2004). It is a

complex interaction of cells from the mucosa

and submucosa that is regulated by cytokines

such as tumour necrosis factor alpha

(TNF‐α), interleukins 6 (IL‐6) and 1b (IL‐1b)

and cyclooxygenase 2 (COX‐2). The oral

microbiome also plays a role (Sonis, 2011;

Al‐Dasooqi etal., 2013; Villa and Sonis, 2015;

Cinausero etal., 2017).

There are a variety of approaches to the

treatment and prophylaxis of oral mucositis.

Cryotherapy and low‐level light therapy

(LLLT) are recommended for children

receiving chemotherapy or HSCT condition–

ing with regimens associated with a high rate

of mucositis, whilst keratinocyte growth fac–

tor (KGF) is recommended for cooperative

children receiving HSCT conditioning with

regimens associated with a high rate of severe

mucositis (Lalla etal., 2014; Villa and Sonis,

2016; Sung etal., 2017):

● Cryotherapy involves cooling the oral

mucosa with ice whilst the patient receives

chemotherapy by short infusion. Because

of the vasoconstriction in the cooled

mucosa, fewer cytotoxic substances are

supposed to arrive there. Thus, the method

is only suitable for chemotherapeutic

agents which are administered in short

infusion and have a short half‐life. However,

it is inexpensive and readily accessible

(Sung etal., 2017).

● LLLT (also called photobiomodulation,

PBM) is the therapeutic use of light (e.g.

visible, near‐infrared or infrared light),

which is absorbed by endogenous

chromophores and triggers nonthermal,

noncytotoxic biochemical reactions by

photochemical and photophysical effects,

leading to physiological alterations

(Bensadoun and Nair, 2012, 2015; Zecha

GraftversusHost Disease

251

et al., 2016a,b). However, the method is

laborious and is not available everywhere.

● KGF (e.g. Palifermin) is an epithelium

growth factor. Since there are no studies

on its use, and since there is the possibility

of thickening the oral mucosa and causing

long‐term damage, it should only be

applied in selected cases where there is a

high risk of severe mucositis (Sung etal.,

2017).

As with all children, good oral hygiene should

be ensured. Professional tooth cleaning can

reduce pain in case of mucositis (Kubota

etal., 2015).

Graft‐versus‐Host Disease

Despite immunosuppressive treatment, GvHD

occurs in almost 25% of cases following

allogeneic HSCT, with the mouth being

one of the most frequently affected organs

(Flowers etal., 2002; Meier, 2011). It can

significantly impair quality of life. Oral

GvHD impresses by hyposalivation, lichenoid

hyperkeratotic striae or plaque with or without

erythematous changes (Figure6.3.3). Addi-

tionally, ulcerations and superficial mucoce–

les may occur. The ulcerations can be very

painful. In certain circumstances, severe

(a) (b)

(c)

Figure6.3.3 (a–c) Graft‐versus‐host disease.

6.3 Haematology and Oncology

252

sclerosis develops as a late effect, restricting

mouth or jaw opening and reducing mobility

of the tongue. Persistant chronic GvHD is

associated with increased risk of squamous

cell carcinomas. Viral factors like human

papillomavirus (HPV) seem to be of signifi–

cance in the aetiology and pathogenesis of

this type of carcinoma.

Management

In case of existing abnormalities of the oral

mucosa like aphthae and GvHD, products

containing sodium lauryl sulphate or men–

thol frequently cannot be tolerated because

they cause pain. Affected patients mostly

avoid them, along with spicy food. They may

have to use toothpaste that is free of sodium

lauryl sulphate. Products with antimicrobial

and protective effects on the oral mucosa are

recommended for oral rinsing. Alleviating

dry mouth with moisturising agents and cov–

ering open aphthae can help relieve the pain.

After allogeneic HSCT, regular examina–

tions of the mucous membranes are essen–

tial, in order to discover secondary carcinoma

early (Majhail etal., 2012). Secondary infec–

tions occur frequently in cases of poor oral

hygiene, which may also increase the inten–

sity of GvHD. Thus, maintaining good oral

hygiene is very important. However, such

lesions may hamper attempts in this direc–

tion, because of the pain. Depending on the

condition, several dental hygiene treatments

a year–including oral hygiene instructions–

are recommended.

For oral GvHD, topical steroids (e.g. bude–

sonide or dexamethasone) are recommended

as first‐line therapy. Extracorporeal photo–

pheresis is considered a second‐line systemic

therapy for steroid‐refractory GvHD. Local

anaesthetics may be helpful in pain control

(Dignan etal., 2012).

All carious lesions should be restored.

It is advisable to encourage patients to

practise good oral hygiene and additional

fluoridation (either by direct application or

via fluoridation splints at home or in a

dental practice).

Existing odontogenic infections should

receive therapy, preferably prior to immuno–

suppression. In this way, systemic infections

connected with blood stem cell transplants

can be reduced by one‐third, and the deaths

of an additional 18/10 000 treated patients

can be avoided (Elad etal., 2008). However,

the extraction of teeth necessitates a long

healing period (2 weeks), and there is often

an urgent need for therapy, especially in leu–

kaemia patients, so dental treatment must

frequently be postponed until after blood

stem cell transplantation. Due to the danger

of haematogenic spread, dental treatments

should be conducted by giving antibiotic

prophylaxis.

Generally, in immunosuppressed patients,

contact should be made with the attending

physician as soon as is possible. At times,

referral to university dental clinics is recom–

mended, as they deal with immunosup–

pressed patients every day–including during

inpatient treatment–and can meet all diag–

nostic needs. The objectives in giving dental

treatment to immunosuppressed patients are

prevention of infection, pain relief, mainte–

nance of function, treatment of complica–

tions and improvement of quality of life.

References

Al‐Dasooqi, N., Sonis, S. T., Bowen, J. M.,

Bateman, E., Blijlevens, N., Gibson, R. J.,

etal. 2013. Emerging evidence on the

pathobiology of mucositis. Supportive Care

in Cancer, 21(11), 3233–41.

Aster, J. C., Bunn, H. F. 2017. Pathophysiology

of Blood Disorders, 2nd edn. New York:

McGraw‐Hill.

Bagattoni, S., D’Alessandro, G., Prete, A.,

Piana, G., Pession, A. 2014. Oral health and

References

253

dental late adverse effects in children in

remission from malignant disease. A pilot

case‐control study in Italian children.

European Journal of Paediatric Dentistry,

15(1), 45–50.

Bensadoun, R. J., Nair, R. G. 2012. Low‐level

laser therapy in the prevention and

treatment of cancer therapy‐induced

mucositis: 2012 state of the art based on

literature review and meta‐analysis. Current

Opinions in Oncology, 24(4), 363–70.

Bensadoun, R. J., Nair, R. G. 2015. Low‐level

laser therapy in the management of

mucositis and dermatitis induced by cancer

therapy. Photomedicine and Laser Surgery,

33(10), 487–91.

Buglione, M., Cavagnini, R., Di Rosario, F.,

Sottocornola, L., Maddalo, M., Vassalli, L.,

etal. 2016. Oral toxicity management in

head and neck cancer patients treated with

chemotherapy and radiation: dental

pathologies and osteoradionecrosis (part 1)

literature review and consensus statement.

Critical Reviews in Oncology/Hematology,

97, 131–42.

Cinausero, M., Aprile, G., Ermacora, P., Basile,

D., Vitale, M. G., Fanotto, V., etal. 2017. New

frontiers in the pathobiology and treatment

of cancer regimen‐related mucosal injury.

Frontiers in Pharmacology, 8(8), 354.

Coppola, A., Windyga, J., Tufano, A., Yeung,

C., Di Minno, M. N. 2015. Treatment for

preventing bleeding in people with

haemophilia or other congenital bleeding

disorders undergoing surgery. Cochrane

Database of Systematic Reviews, 9(2),

CD009961.

Dignan, F. L., Scarisbrick, J. J., Cornish, J.,

Clark, A., Amrolia, P., Jackson, G., etal.

2012. Organ‐specific management and

supportive care in chronic graft‐versus‐host

disease. British Journal of Haematology,

158(1), 62–78.

Elad, S., Thierer, T., Bitan, M., Shapira, M. Y.,

Meyerowitz, C. 2008. A decision analysis:

the dental management of patients prior to

hematology cytotoxic therapy or

hematopoietic stem cell transplantation.

Oral Oncology, 44(1), 37–42.

Elad, S., Raber‐Durlacher, J. E., Brennan, M. T.,

Saunders, D. P., Mank, A. P., Zadik, Y., etal.

2015. Basic oral care for hematology‐

oncology patients and hematopoietic stem

cell transplantation recipients: a position

paper from the joint task force of the

Multinational Association of Supportive

Care in Cancer/International Society of Oral

Oncology (MASCC/ISOO) and the

European Society for Blood and Marrow

Transplantation (EBMT). Supportive Care in

Cancer, 23(1), 223–36.

Flowers, M. E., Parker, P. M., Johnston, L. J.,

Matos, A. V., Storer, B., Bensinger, W. I.,

etal. 2002. Comparison of chronic graft‐

versus‐host disease after transplantation of

peripheral blood stem cells versus bone

marrow in allogeneic recipients: long‐term

follow‐up of a randomized trial. Blood,

100(2), 415–19.

Henderson, J. M., Bergman, S., Salama, A.,

Koterwas, G. 2001. Management of the oral

and maxillofacial surgery patient with

thrombocytopenia. Journal of Oral and

Maxillofacial Surgery, 59(4), 421–7.

Hoffbrand, A. V., Moss, P. A. H. 2016.

Hoffbrand’s Essential Haematology, 7th edn.

Chichester, UK: Wiley‐Blackwell.

Ishii, E. (ed.). 2017. Hematological Disorders in

Children, Pathogenesis and Treatment.

Singapore: Springer Nature.

Kasper, D. L., Fauci, A. S., Hauser, S. L., Longo,

D. L., Jameson, J. L., Loscalzo, J. (eds). 2015.

Harrison’s Principles of Internal Medicine,

19th edn. New York: McGraw‐Hill.

Kubota, K., Kobayashi, W., Sakaki, H.,

Nakagawa, H., Kon, T., Mimura, M., etal.

2015. Professional oral health care reduces

oral mucositis pain in patients treated by

superselective intra‐arterial chemotherapy

concurrent with radiotherapy for oral

cancer. Supportive Care in Cancer, 23(11),

3323–9.

Lalla, R. V., Bowen, J., Barasch, A., Elting, L.,

Epstein, J., Keefe, D. M., etal. 2014.

MASCC/ISOO clinical practice guidelines

for the management of mucositis secondary

to cancer therapy. Cancer, 120(10), 1453–61.

Erratum in: Cancer, 121(8), 1339.

6.3 Haematology and Oncology

254

Majhail, N. S., Rizzo, J. D., Lee, S. J., Aljurf, M.,

Atsuta, Y., Bonfim, C., etal. 2012.

Recommended screening and preventive

practices for long‐term survivors after

hematopoietic cell transplantation. Biology

of Blood and Marrow Transplantation, 18(3)

348–71.

Meier, J. K., Wolff, D., Pavletic, S., Greinix, H.,

Gosau, M., Bertz, H., etal. 2011. Oral

chronic graft‐versus‐host disease: report

from the International Consensus

Conference on clinical practice in cGVHD.

Clinical Oral Investigations, 15(2), 127–39.

Ramseier, A. M., Filippi, A., Halter, J.,

Waltimo, T. 2015. Orale Manifestationen

bei Immunsuppression. Quintessenz, 66(1),

1–9.

Sant, M., Allemani, C., Tereanu, C., De

Angelis, R., Capocaccia, R., Visser, O., etal.

2010. Incidence of hematologic

malignancies in Europe by morphologic

subtype: results of the HAEMACARE

project. Blood, 116(19), 3724–34.

Scully, C. 2014. Scully’s Medical Problems in

Dentistry, 7th edn. London: Churchill

Livingstone Elsevier.

Sonis, S. T. 2004. The pathobiology of

mucositis. Nature Reviews Cancer, 4(4),

277–84.

Sonis, S. T. 2011. Oral mucositis. Anti‐Cancer

Drugs, 22(7), 607–12.

Spivakovsky, S., Keenan, A. V., Congiusta, M.,

Spivakovsky, Y. 2015. Congenital bleeding

disorders and dental surgery. Evidence

Based Dentistry, 16(3), 90–1.

Sung, L., Robinson, P., Treister, N., Baggott, T.,

Gibson, P., Tissing, W., etal. 2017. Guideline

for the prevention of oral and oropharyngeal

mucositis in children receiving treatment for

cancer or undergoing haematopoietic stem

cell transplantation. BMJ Supportive &

Palliative Care, 7(1), 7–16.

Villa, A., Sonis, S. T. 2015. Mucositis:

pathobiology and management. Current

Opinion in Oncology, 27(3), 159–64.

Villa, A., Sonis, S. T. 2016. Pharmacotherapy

for the management of cancer regimen‐

related oral mucositis. Expert Opinion on

Pharmacotherapy, 17(13), 1801–7.

Zecha, J. A., Raber‐Durlacher, J. E., Nair, R. G.,

Epstein, J. B., Sonis, S. T., Elad, S., etal.

2016a. Low level laser therapy/

photobiomodulation in the management of

side effects of chemoradiation therapy in

head and neck cancer: part 1: mechanisms

of action, dosimetric, and safety

considerations. Supportive Care in Cancer,

24(6), 2781–92.

Zecha, J. A., Raber‐Durlacher, J. E., Nair, R. G.,

Epstein, J. B., Elad, S., Hamblin, M. R., etal.

2016b. Low‐level laser therapy/

photobiomodulation in the management of

side effects of chemoradiation therapy in

head and neck cancer: part 2: proposed

applications and treatment protocols.

Supportive Care in Cancer, 24(6), 2793–805.

Non‐infective Swellings: Cysts, Tumours and Ranulas

Management ofDental Emergencies inChildren andAdolescents, First Edition. Editedby Klaus W.Neuhaus andAdrianLussi. © 2019 John Wiley & Sons Ltd. Published 2019 by John Wiley & Sons Ltd. Companion website: www.wiley.com/go/neuhaus/dental_emergencies245 IntroductionUniquely, disruptions in the formation and function of circulating blood cells trigger changes in the immune system, blood clotting and oxygen transportation. Whilst there is a quite frequent occurrence of anaemia, it plays a rather minor role in dentistry, since normally it is only mildly severe and quickly remedied.Haematological malignancies are rare, with an incidence of about 30/100 000 (Sant etal., 2010). The oral cavity is often affected in patients without functioning defence, and complications are common during dental intervention, especially when there is a lack of neutrophil granulocytes. In general, seriously ill haematological patients receive dental treatment at university centres.Infections within the oral cavity may also be initial manifestation of a haematological disorder. This should in particular be con-sidered when gingival bleeding occurs in otherwise healthy conditions and in the presence of petechiae.Wanted and unwanted medicinal effects on blood clotting and infection defence occur very often, due to the wide spread of corre-sponding diseases. This is related to treat-ments like the application of corticosteroids or anticoagulation in connection with atrial fibrillation. The effects of these medications are acutely relevant for the choice of dental treat-ment. However, in children and adolescents, medicinal anticoagulation is seldom applied. This is why it is not addressed in this chapter. High‐dose local irradiation is also rather seldom administered in the area of the mouth in children, and so it too is not discussed.We begin by explaining the basic concepts, before looking at specific problems associated with the oral mucosa that are often encoun-tered in connection with chemotherapy, total body irradiation and stem cell transplants. HaemostasisStopping the blood flow from injured blood vessels is a complex process, in which a number of factors interact. Successful haemostasis consists in three steps: (i) vaso-constriction to reduce the blood flow; (ii) formation of a platelet plug by thrombocyte adherence, activation and aggregation; and (iii) plasmatic coagulation by a cascade of proteins, which forms a stable clot. When thrombocytes come in contact with collagen in the exposed connective tissue, they attach there by mediation of the von Willebrand factor, a protein that adheres both to collagen 6.3Oral Problems inPatients Undergoing Haematology orOncology TreatmentAdrian M. Ramseier1, Jakob Passweg2 and Tuomas Waltimo11 Department of Oral Health & Medicine, University Center for Dental Medicine Basel, University of Basel, Basel, Switzerland2 Department of Hematology, University Hospital Basel, Basel, Switzerland 6.3 Haematology and Oncology246and to thrombocytes. Thus, the thrombo-cytes are activated. By releasing cytokines, more thrombocytes are attracted, and the plasmatic coagulation cascade is initiated. Through several intermediate stages, pro-thrombin is transformed, both intrinsically (activation factors) and extrinsically (tissue factor in the injured subendothelial tissue), to thrombin, which in turn polymerises fibrinogen to fibrin. This results in a net incorporating aggregated thrombocytes as well as erythrocytes, and thus forming a stable blood clot. Other factors are responsible for preventing exaggerated or spontaneous thrombus formation.Cellular Haemostasis Disorders (Thrombocytes)Depressed platelet count (thrombocytopaenia) and dysfunction of the platelet count (throm-bocytopahthies) can be either congenital or acquired. Table6.3.1 provides an overview of possible causes of thrombocytopaenia.The most commonly isolated thrombo-cytopaenia in children is the immune thrombocytopaenia (ITP) (Ishii, 2017). Thrombo cy to paenia may also occur following a replacement of normal bone marrow with leukaemic cells (e.g. in acute leukaemia) or bone marrow failure, or it may be inherited.Nonsteroidal anti‐inflammatory drugs (NSAIDs) inhibit platelet aggregation. With aspirin, such aggregation is irreversible, except by the production of new thrombocytes.Small petechial haemorrhages on skin and on the mucosa are the typical sign of marred thrombocytes; often, they occur on the lower extremities (gravity) or in the oral cavity. In case of severe thrombocytopaenia, they can become confluent (ecchymoses). Spontaneous bleeding starts only with a platelet count of 20–30 × 109/l (Scully, 2014). Depending on the severity of the disorder, it can result from minor traumata, gingival bleeding or suffusions on the skin.The normal platelet count is 150–450 × 109/l; a value of >100 × 109/l is thought to be ideal for surgical intervention. With values >50 × 109/l and good functioning of the existing platelets, dentoalveolar surgery can normally be performed without bleeding complications (Henderson et al., 2001). Measures like compression, wound suture and local haemostatics are usually sufficient. With values of <30 × 109/l, spontaneous bleeding can occur. In this situation, the indication of surgical treatment should be carefully considered, and surgery should be conducted in collaboration with haematology. Haemostasis can be improved by transfusion of thrombocyte concentrates. This is recom-mended during dentoalveolar intervention with a platelet count of <50 × 109/l, as well as Table6.3.1 Causes ofthrombocytopaenia (Hoffbrand andMoss, 2016).Failure of platelet productionSelective megakaryocyte depressionRare congenital defectsDrugs, chemicals, viral infectionsPart of general bone marrow failureCytotoxic drugsRadiotherapyAplastic anaemiaLeukaemiaMyelodysplastic syndromesMyelofibrosisMarrow infiltration (e.g. carcinoma, lymphoma, Gaucher’s disease)Multiple myelomaMegaloblastic anaemiaHIV infectionIncreased consumption of plateletsImmuneAutoimmuneIdiopathicAssociated with systemic lupus erythematosus, chronic lymphocytic leukaemia or lymphomaInfections: Helicobacter pylori, human immuno-deficiency virus (HIV), other viruses, malariaDrug‐induced, e.g. heparinPost‐transfusional purpuraFoeto‐maternal alloimmune thrombocytopaeniaDisseminated intravascular coagulationThrombotic thrombocytopaenic purpuraAbnormal distribution of plateletsSplenomegaly, e.g. liver diseaseDilutional lossMassive transfusion of stored blood to bleeding patients Disorders oftheImmune System/Granulocytes247during maxillofacial intervention with a platelet count of <100 × 109/l (Scully, 2014).The success of thrombocyte transfusions needs to be checked: it is essential to measure the platelet count prior to and after trans-fusion. Patients who do not adequately react to thrombocyte transfusions constitute a special problem. In such cases, therapeutic interventions can be performed whilst trans-fusion continues.Plasmatic Coagulation DisordersCongenital coagulation disorders include haemophilia A (factor VIII deficiency) and the much rarer haemophilia B (factor IX deficiency). Only the male gender is affected by haemophilia B. Spontaneous haemor-rhaging and strong life‐threatening postop-erative bleeding may occur. Missing factors can be added; however, there is insufficient evidence from randomised controlled trials to assess the most effective and safe haemo-static treatment to prevent bleeding in peo-ple with haemophilia or other congenital bleeding disorders undergoing surgical pro-cedures (Coppola etal., 2015; Spivakovsky etal., 2015).In von Willebrand disease, the von Willebrand factor is missing or malfunc-tioning. Because of this, platelet function is impaired. Von Willebrand disease is classified into a number of subcategories, and is asso-ciated with slight to considerable bleeding disorders. Disorders oftheImmune System/GranulocytesDefence comprises cellular elements, all of which belong to the leucocytes. The various cells evolved from one multipotent stem cell of haematopoiesis, which is capable of differ-entiating into different cell lines with various functions: ● Neutrophilic granulocytes are implicated in nonspecific immunity against bacteria and fungi. Basophilic granulocytes are involved in hypersensitivity reactions (asthma, urticaria, allergic rhinitis and anaphylaxis). Eosinophilic granulocytes play a role in the defence against parasites. ● Lymphocytes are subdivided into T‐cells, which have the important function of differentiating between foreign and self, B‐cells, which are amongst other things responsible for the production of antibodies (plasma cells, memory cells), and NK‐cells, which play an essential role in protecting against virus cells and tumour cells. ● Monocytes migrate into tissue, where they become macrophages. They can recognise exogenous material, ingest it (phagocyto-sis), dissolve it and present it at their cell surface. This causes the activation of other defence cells (antigen presentation) (Kasper etal., 2015).CausesHaematological DisordersAbnormalities in the immune response may have many different causes. There might be disturbances in the differentiation of individual or all cell lines. This can result in functional reduction of the cell line(s) affected, in a deficiency of these cells (lym-phopaenia: T‐cells and B‐cells, neutropaenia) or in an overproduction, which can replace the production of other cell lines in the bone marrow. Table6.3.2 provides a list of haema-tological disorders.Disorders oftheImmune System through MedicationDisorders of the immune system can occur as a wanted or unwanted effect of many chemotherapeutics and immunosuppres-sives. Particular emphasis must be given to glucocorticoids like dexamethasone and prednisone, but other immunosuppressives like cyclosporin A (Sandimmun), tacrolimus (Prograf) and the folic acid antagonist meth-otrexate (Methotrexat) can also have this effect. 6.3 Haematology and Oncology248Physical DamageBlood formation can be impaired by irradia-tion, either therapeutic or accidental. Stem cells and lymphocytes are especially vulner-able. Thus, a reduction in lymphocytes can be observed at a very early stage after irra-diation, whilst the number of granolocytes, thrombocytes and erythrocytes decreases only as damage to the stem cells progresses.Clinical Oral AppearanceSometimes, haematological disorders can be discovered by the dentist. Manifestations of haematological disorders in the oral cavity can cause suspicion and suggest additional investigations: ● Bleeding of the oral mucosa that does not result from gingivitis may be an indication of coagulation abnormalities due to a vari-ety of causes. Petechial haemorrhages, and haemorrhages at other places in the oral mucosa, are typical for thrombocytopae-nia (Hoffbrand and Moss, 2016). ● In case of acute myeloid leukaemia, gingi-val swelling can be determined (Figure6.3.1) (Kasper etal., 2015). Occasionally, this can also be seen after treatment with cyclo-sporine A and tacrolimus.Table6.3.2 World Health Organization (WHO) Classification ofHematologic Malignancies (Abridged Version) (Aster andBunn, 2017).Subtype Putative cell of originMyeloid neoplasmsAcute myeloid leukemia (AML)AML with recurrent genetic aberrationsAML without recurrent genetic aberrationsAML following cytotoxic therapyEarly myeloid progenitorMyeloproliferative neoplasmsChronic myeloid leukemiaPolycythemia veraEssential thrombocythemiaChronic eosinophilic leukemiaPrimary myelofibrosisHematopoietic stem cell or early myeloid progenitorMyelodysplastic syndromes Early myeloid progenitorLymphoid neoplasmsImmature B‐cell and T‐cell tumorsB‐cell acute lymphoblastic leukemia/lymphomaT‐cell acute lymphoblastic leukemia/lymphomaEarly B‐cell progenitorEarly T‐cell progenitorMature B‐cell tumorsChronic lymphocytic leukemia/small lymphocytic lymphomaMantle cell lymphomaFollicular lymphomaBurkitt lymphomaDiffuse large B‐cell lymphomaPost‐germinal center B cellNaïve B cellGerminal center B cellGerminal center B cellGerminal center or post‐germinal center B cellPlasma cell tumors and related entitiesMultiple myelomaLymphoplasmacytic lymphomaPost‐germinal center B cellMature B‐cellMature T‐cell and natural killer cell tumors Mature T‐cell or natural killer cellHodgkin lymphoma Germinal center or post‐germinal center B cell Disorders oftheImmune System/Granulocytes249 ● Unusual infections in terms of frequency, manifestation or the occurrence of rare microbes are signs of possible immuno-suppression. Candida infections are encountered quite often (Figure 6.3.2), and non‐Candida albicans species (e.g. tropicalis, krusei and parapsilosis) are increasingly being seen. What should be noted is that these are often resistant to common therapeutics. Typical for leukae-mias are virus reactivations of, for instance, herpes zoster and herpes sim-plex virus (HSV) (Ramseier etal., 2015). Intraoral ulcers and large aphtae are com-mon manifestations of HSV. All of these infections can cause severe pain. ● Swelling of the lymph nodes and anaemia (recognisable by paleness of the mucosa) may point towards a haematological dis-order. So might fever and night sweats recorded in the medical history.Clinical SignificanceWhen an immune deficiency exists, a possible haematogeneous spreading of microorgan-isms may be expected after intervention. Together with the haematologist or family doctor, it needs to be determined whether prophylactic antibiotics should be imple-mented or whether treatment should just be postponed.A focus search should be conducted prior to haematological treatment by chemother-apy or haematopoietic stem cell transplan-tation (HSCT). Ideally, located infection foci are treated first; however, this is not always possible because of the already limited immune response and wound healing, or because of the urgency of treating the malig-nant tumours.In patients who have received allogeneic stem cell transplantation, the current situa-tion concerning immune response should always be clarified with the attending haema-tologist: when appropriate, prophylactic antibiotics should be given prior to tooth cleaning, deep scaling, caries treatment and extractions, or else the treatment must simply be postponed.In chemotherapeutic treatment, which is sometimes accompanied by total body irradiation, hyposalivation occurs on a regular basis. The result may be increased susceptibility to caries, gingivitis, periodon-titis, mucocutaneous diseases and fungal infections (Bagattoni etal., 2014; Buglione etal., 2016).After allogeneic stem cell transplantation, acute and chronic rejection reactions may occur (graft‐versus‐host disease, GvHD). The oral mucosa shows typical lichenoid changes with or without erythematous lesions, ulcers or mucoceles. Often, hyposalivation takes place at the same time, combined with a correspondingly increased risk of caries, periodontitis and infections of the mucosa. Long‐term effects include secondary malig-nant tumours of the oral mucosa. Because of this, the oral mucosa needs to be inspected regularly and thoroughly. The indication for Figure6.3.1 Gingival swelling and acute myeloid leukaemia.Figure6.3.2 Thrush (Candida). 6.3 Haematology and Oncology250biopsy sampling should be wide and generous for the exclusion and detection of malig-nancy, respectively (Elad etal., 2015). AnaemiaAnaemia is defined by a reduction of the haemoglobin concentration in the blood. Common causes are vitamin B12, folic acid and iron deficiencies caused by chronic bleeding, for instance due to excessive men-strual flow or chronic diseases like tumours. Other causes include innate haemoglobin synthesis disorders such as sickle‐cell anaemia and thalassaemia.Clinical SignificanceAnaemias hardly have an effect on dental treatment. The following manifestations could indicate anaemia and necessitate further clarification with the family doctor: com-plaints about reduced performance, weak-ness, heart palpitations and dyspnoea under stress, as well as the occurrence of pale skin or mucosa. Angular cheilitis, burning tongue or dysphagia (Plummer–Vinson syndrome) may appear in case of iron deficiency. Vitamin B12 and folic acid deficiencies cause burning tongue with impaired sense of taste and trophic glossitis with disappearing papillae. MucositisMucositis is an inflammation of the mucous membranes of the gastrointestinal tract as a consequence of chemotherapy and radiation therapy. Patients who are receiving HSCT or irradiation in the area of the mouth are affected particularly often.Oral mucositis is associated with ery-thema, and at times with ulcerations and violent pain. It is one of the most frequent side effects of cancer treatment, and is often the reason for reducing the treatment dose or for having to postpone treatment. It also may necessitate tube feeding or parenteral nutrition.Pathogenesis has not yet been fully clarified, although considerable progress has been made in recent years. The procedure can be broken down into five stages: initiation, pri-mary damage response, signal amplification, ulceration and healing (Sonis, 2004). It is a complex interaction of cells from the mucosa and submucosa that is regulated by cytokines such as tumour necrosis factor alpha (TNF‐α), interleukins 6 (IL‐6) and 1b (IL‐1b) and cyclooxygenase 2 (COX‐2). The oral microbiome also plays a role (Sonis, 2011; Al‐Dasooqi etal., 2013; Villa and Sonis, 2015; Cinausero etal., 2017).There are a variety of approaches to the treatment and prophylaxis of oral mucositis. Cryotherapy and low‐level light therapy (LLLT) are recommended for children receiving chemotherapy or HSCT condition-ing with regimens associated with a high rate of mucositis, whilst keratinocyte growth fac-tor (KGF) is recommended for cooperative children receiving HSCT conditioning with regimens associated with a high rate of severe mucositis (Lalla etal., 2014; Villa and Sonis, 2016; Sung etal., 2017): ● Cryotherapy involves cooling the oral mucosa with ice whilst the patient receives chemotherapy by short infusion. Because of the vasoconstriction in the cooled mucosa, fewer cytotoxic substances are supposed to arrive there. Thus, the method is only suitable for chemotherapeutic agents which are administered in short infusion and have a short half‐life. However, it is inexpensive and readily accessible (Sung etal., 2017). ● LLLT (also called photobiomodulation, PBM) is the therapeutic use of light (e.g. visible, near‐infrared or infrared light), which is absorbed by endogenous chromophores and triggers nonthermal, noncytotoxic biochemical reactions by photochemical and photophysical effects, leading to physiological alterations (Bensadoun and Nair, 2012, 2015; Zecha GraftversusHost Disease251et al., 2016a,b). However, the method is laborious and is not available everywhere. ● KGF (e.g. Palifermin) is an epithelium growth factor. Since there are no studies on its use, and since there is the possibility of thickening the oral mucosa and causing long‐term damage, it should only be applied in selected cases where there is a high risk of severe mucositis (Sung etal., 2017).As with all children, good oral hygiene should be ensured. Professional tooth cleaning can reduce pain in case of mucositis (Kubota etal., 2015). Graft‐versus‐Host DiseaseDespite immunosuppressive treatment, GvHD occurs in almost 25% of cases following allogeneic HSCT, with the mouth being one of the most frequently affected organs (Flowers etal., 2002; Meier, 2011). It can significantly impair quality of life. Oral GvHD impresses by hyposalivation, lichenoid hyperkeratotic striae or plaque with or without erythematous changes (Figure6.3.3). Addi-tionally, ulcerations and superficial mucoce-les may occur. The ulcerations can be very painful. In certain circumstances, severe (a) (b)(c)Figure6.3.3 (a–c) Graft‐versus‐host disease. 6.3 Haematology and Oncology252sclerosis develops as a late effect, restricting mouth or jaw opening and reducing mobility of the tongue. Persistant chronic GvHD is associated with increased risk of squamous cell carcinomas. Viral factors like human papillomavirus (HPV) seem to be of signifi-cance in the aetiology and pathogenesis of this type of carcinoma. ManagementIn case of existing abnormalities of the oral mucosa like aphthae and GvHD, products containing sodium lauryl sulphate or men-thol frequently cannot be tolerated because they cause pain. Affected patients mostly avoid them, along with spicy food. They may have to use toothpaste that is free of sodium lauryl sulphate. Products with antimicrobial and protective effects on the oral mucosa are recommended for oral rinsing. Alleviating dry mouth with moisturising agents and cov-ering open aphthae can help relieve the pain.After allogeneic HSCT, regular examina-tions of the mucous membranes are essen-tial, in order to discover secondary carcinoma early (Majhail etal., 2012). Secondary infec-tions occur frequently in cases of poor oral hygiene, which may also increase the inten-sity of GvHD. Thus, maintaining good oral hygiene is very important. However, such lesions may hamper attempts in this direc-tion, because of the pain. Depending on the condition, several dental hygiene treatments a year–including oral hygiene instructions– are recommended.For oral GvHD, topical steroids (e.g. bude-sonide or dexamethasone) are recommended as first‐line therapy. Extracorporeal photo-pheresis is considered a second‐line systemic therapy for steroid‐refractory GvHD. Local anaesthetics may be helpful in pain control (Dignan etal., 2012).All carious lesions should be restored. It is advisable to encourage patients to practise good oral hygiene and additional fluoridation (either by direct application or via fluoridation splints at home or in a dental practice).Existing odontogenic infections should receive therapy, preferably prior to immuno-suppression. In this way, systemic infections connected with blood stem cell transplants can be reduced by one‐third, and the deaths of an additional 18/10 000 treated patients can be avoided (Elad etal., 2008). However, the extraction of teeth necessitates a long healing period (2 weeks), and there is often an urgent need for therapy, especially in leu-kaemia patients, so dental treatment must frequently be postponed until after blood stem cell transplantation. Due to the danger of haematogenic spread, dental treatments should be conducted by giving antibiotic prophylaxis.Generally, in immunosuppressed patients, contact should be made with the attending physician as soon as is possible. At times, referral to university dental clinics is recom-mended, as they deal with immunosup-pressed patients every day–including during inpatient treatment–and can meet all diag-nostic needs. The objectives in giving dental treatment to immunosuppressed patients are prevention of infection, pain relief, mainte-nance of function, treatment of complica-tions and improvement of quality of life. ReferencesAl‐Dasooqi, N., Sonis, S. T., Bowen, J. M., Bateman, E., Blijlevens, N., Gibson, R. J., etal. 2013. Emerging evidence on the pathobiology of mucositis. Supportive Care in Cancer, 21(11), 3233–41.Aster, J. C., Bunn, H. F. 2017. Pathophysiology of Blood Disorders, 2nd edn. New York: McGraw‐Hill.Bagattoni, S., D’Alessandro, G., Prete, A., Piana, G., Pession, A. 2014. Oral health and References253dental late adverse effects in children in remission from malignant disease. A pilot case‐control study in Italian children. European Journal of Paediatric Dentistry, 15(1), 45–50.Bensadoun, R. J., Nair, R. G. 2012. Low‐level laser therapy in the prevention and treatment of cancer therapy‐induced mucositis: 2012 state of the art based on literature review and meta‐analysis. Current Opinions in Oncology, 24(4), 363–70.Bensadoun, R. J., Nair, R. G. 2015. Low‐level laser therapy in the management of mucositis and dermatitis induced by cancer therapy. Photomedicine and Laser Surgery, 33(10), 487–91.Buglione, M., Cavagnini, R., Di Rosario, F., Sottocornola, L., Maddalo, M., Vassalli, L., etal. 2016. Oral toxicity management in head and neck cancer patients treated with chemotherapy and radiation: dental pathologies and osteoradionecrosis (part 1) literature review and consensus statement. Critical Reviews in Oncology/Hematology, 97, 131–42.Cinausero, M., Aprile, G., Ermacora, P., Basile, D., Vitale, M. G., Fanotto, V., etal. 2017. New frontiers in the pathobiology and treatment of cancer regimen‐related mucosal injury. Frontiers in Pharmacology, 8(8), 354.Coppola, A., Windyga, J., Tufano, A., Yeung, C., Di Minno, M. N. 2015. Treatment for preventing bleeding in people with haemophilia or other congenital bleeding disorders undergoing surgery. Cochrane Database of Systematic Reviews, 9(2), CD009961.Dignan, F. L., Scarisbrick, J. J., Cornish, J., Clark, A., Amrolia, P., Jackson, G., etal. 2012. Organ‐specific management and supportive care in chronic graft‐versus‐host disease. British Journal of Haematology, 158(1), 62–78.Elad, S., Thierer, T., Bitan, M., Shapira, M. Y., Meyerowitz, C. 2008. A decision analysis: the dental management of patients prior to hematology cytotoxic therapy or hematopoietic stem cell transplantation. Oral Oncology, 44(1), 37–42.Elad, S., Raber‐Durlacher, J. E., Brennan, M. T., Saunders, D. P., Mank, A. P., Zadik, Y., etal. 2015. Basic oral care for hematology‐oncology patients and hematopoietic stem cell transplantation recipients: a position paper from the joint task force of the Multinational Association of Supportive Care in Cancer/International Society of Oral Oncology (MASCC/ISOO) and the European Society for Blood and Marrow Transplantation (EBMT). Supportive Care in Cancer, 23(1), 223–36.Flowers, M. E., Parker, P. M., Johnston, L. J., Matos, A. V., Storer, B., Bensinger, W. I., etal. 2002. Comparison of chronic graft‐versus‐host disease after transplantation of peripheral blood stem cells versus bone marrow in allogeneic recipients: long‐term follow‐up of a randomized trial. Blood, 100(2), 415–19.Henderson, J. M., Bergman, S., Salama, A., Koterwas, G. 2001. Management of the oral and maxillofacial surgery patient with thrombocytopenia. Journal of Oral and Maxillofacial Surgery, 59(4), 421–7.Hoffbrand, A. V., Moss, P. A. H. 2016. Hoffbrand’s Essential Haematology, 7th edn. Chichester, UK: Wiley‐Blackwell.Ishii, E. (ed.). 2017. Hematological Disorders in Children, Pathogenesis and Treatment. Singapore: Springer Nature.Kasper, D. L., Fauci, A. S., Hauser, S. L., Longo, D. L., Jameson, J. L., Loscalzo, J. (eds). 2015. Harrison’s Principles of Internal Medicine, 19th edn. New York: McGraw‐Hill.Kubota, K., Kobayashi, W., Sakaki, H., Nakagawa, H., Kon, T., Mimura, M., etal. 2015. Professional oral health care reduces oral mucositis pain in patients treated by superselective intra‐arterial chemotherapy concurrent with radiotherapy for oral cancer. Supportive Care in Cancer, 23(11), 3323–9.Lalla, R. V., Bowen, J., Barasch, A., Elting, L., Epstein, J., Keefe, D. M., etal. 2014. MASCC/ISOO clinical practice guidelines for the management of mucositis secondary to cancer therapy. Cancer, 120(10), 1453–61. Erratum in: Cancer, 121(8), 1339. 6.3 Haematology and Oncology254Majhail, N. S., Rizzo, J. D., Lee, S. J., Aljurf, M., Atsuta, Y., Bonfim, C., etal. 2012. Recommended screening and preventive practices for long‐term survivors after hematopoietic cell transplantation. Biology of Blood and Marrow Transplantation, 18(3) 348–71.Meier, J. K., Wolff, D., Pavletic, S., Greinix, H., Gosau, M., Bertz, H., etal. 2011. Oral chronic graft‐versus‐host disease: report from the International Consensus Conference on clinical practice in cGVHD. Clinical Oral Investigations, 15(2), 127–39.Ramseier, A. M., Filippi, A., Halter, J., Waltimo, T. 2015. Orale Manifestationen bei Immunsuppression. Quintessenz, 66(1), 1–9.Sant, M., Allemani, C., Tereanu, C., De Angelis, R., Capocaccia, R., Visser, O., etal. 2010. Incidence of hematologic malignancies in Europe by morphologic subtype: results of the HAEMACARE project. Blood, 116(19), 3724–34.Scully, C. 2014. Scully’s Medical Problems in Dentistry, 7th edn. London: Churchill Livingstone Elsevier.Sonis, S. T. 2004. The pathobiology of mucositis. Nature Reviews Cancer, 4(4), 277–84.Sonis, S. T. 2011. Oral mucositis. Anti‐Cancer Drugs, 22(7), 607–12.Spivakovsky, S., Keenan, A. V., Congiusta, M., Spivakovsky, Y. 2015. Congenital bleeding disorders and dental surgery. Evidence Based Dentistry, 16(3), 90–1.Sung, L., Robinson, P., Treister, N., Baggott, T., Gibson, P., Tissing, W., etal. 2017. Guideline for the prevention of oral and oropharyngeal mucositis in children receiving treatment for cancer or undergoing haematopoietic stem cell transplantation. BMJ Supportive & Palliative Care, 7(1), 7–16.Villa, A., Sonis, S. T. 2015. Mucositis: pathobiology and management. Current Opinion in Oncology, 27(3), 159–64.Villa, A., Sonis, S. T. 2016. Pharmacotherapy for the management of cancer regimen‐related oral mucositis. Expert Opinion on Pharmacotherapy, 17(13), 1801–7.Zecha, J. A., Raber‐Durlacher, J. E., Nair, R. G., Epstein, J. B., Sonis, S. T., Elad, S., etal. 2016a. Low level laser therapy/photobiomodulation in the management of side effects of chemoradiation therapy in head and neck cancer: part 1: mechanisms of action, dosimetric, and safety considerations. Supportive Care in Cancer, 24(6), 2781–92.Zecha, J. A., Raber‐Durlacher, J. E., Nair, R. G., Epstein, J. B., Elad, S., Hamblin, M. R., etal. 2016b. Low‐level laser therapy/photobiomodulation in the management of side effects of chemoradiation therapy in head and neck cancer: part 2: proposed applications and treatment protocols. Supportive Care in Cancer, 24(6), 2793–805.

43 Comments

sezsojimukax
6 months ago

Acute izu.sfto.dentistrykey.com.xwo.st resist bedside [URL=http://bestpriceonlineusa.com/product/viagra-online/ – viagra buy in canada[/URL – [URL=http://bestpriceonlineusa.com/product/cialis-5mg/ – cialis[/URL – [URL=http://bestpriceonlineusa.com/product/cialis-online-pharmacy/ – canada pharmacy online[/URL – [URL=http://bestpriceonlineusa.com/product/amoxicillin/ – amoxicillin[/URL – [URL=http://bestpriceonlineusa.com/product/ventolin/ – salbutamol inhaler[/URL – meconium lives, 100 mg viagra lowest price tadalafil 20mg canada pharmacy online buy amoxil online ventolin price at walmart retroflexed criminal http://bestpriceonlineusa.com/product/viagra-online/ viagra online http://bestpriceonlineusa.com/product/cialis-5mg/ cialis 5mg cialis generic 20 mg http://bestpriceonlineusa.com/product/cialis-online-pharmacy/ pharmacy canada pharmacy online http://bestpriceonlineusa.com/product/amoxicillin/ amoxicillin 500 mg to buy http://bestpriceonlineusa.com/product/ventolin/ salbutamol toxicity ventolin sacro-iliac splenectomy, smaller circuit.

Reply
usupamamguc
6 months ago

When jpq.ekvu.dentistrykey.com.mvt.ym mandatory, [URL=http://bestpriceonlineusa.com/product/viagra-online/ – viagra[/URL – [URL=http://bestpriceonlineusa.com/product/cialis-5mg/ – cialis 5mg[/URL – [URL=http://bestpriceonlineusa.com/product/ventolin/ – ventolin[/URL – [URL=http://bestpriceonlineusa.com/product/amoxicillin/ – amoxicillin[/URL – [URL=http://bestpriceonlineusa.com/product/cialis-online-pharmacy/ – cialis online pharmacy[/URL – hirsutism stone, ever viagra online viagra online cialis 5mg ventolin amoxicillin 500 mg to buy pharmacy crests essence operative, http://bestpriceonlineusa.com/product/viagra-online/ viagra http://bestpriceonlineusa.com/product/cialis-5mg/ tadalafil 20mg http://bestpriceonlineusa.com/product/ventolin/ ventolin hfa 90 mcg inhaler http://bestpriceonlineusa.com/product/amoxicillin/ purchase amoxicillin without a prescription http://bestpriceonlineusa.com/product/cialis-online-pharmacy/ us pharmacy viagra ciprofloxacin adenomatous errant phenotypes.

Reply
ifizaqutosia
6 months ago

Peptic dyw.qoqr.dentistrykey.com.kuz.qd us lability [URL=http://bestpriceonlineusa.com/product/cialis-5mg/ – cialis pills[/URL – [URL=http://bestpriceonlineusa.com/product/amoxicillin/ – order amoxicillin 500 mg without prescri…[/URL – [URL=http://bestpriceonlineusa.com/product/viagra-online/ – buy viagra[/URL – [URL=http://bestpriceonlineusa.com/product/ventolin/ – ventolin hfa 90 mcg inhaler[/URL – [URL=http://bestpriceonlineusa.com/product/cialis-online-pharmacy/ – canada pharmacy online[/URL – ovulation cialis pills cheap amoxil online viagra pills order ventolin online pharmacy buy online non-irradiated, egg http://bestpriceonlineusa.com/product/cialis-5mg/ cialis 5mg http://bestpriceonlineusa.com/product/amoxicillin/ generic for amoxil http://bestpriceonlineusa.com/product/viagra-online/ viagra 100mg http://bestpriceonlineusa.com/product/ventolin/ low price ventolin http://bestpriceonlineusa.com/product/cialis-online-pharmacy/ canadian pharmacy pharmacy cialis online pharmacy granuloma prevented behind-the-bike-sheds inserted.

Reply
ozavubica
6 months ago

Once yjm.hgzt.dentistrykey.com.vav.yc screen; hip, [URL=http://bestpriceonlineusa.com/product/cialis-online-pharmacy/ – where to buy pharmacy[/URL – [URL=http://bestpriceonlineusa.com/product/viagra-online/ – viagra[/URL – [URL=http://bestpriceonlineusa.com/product/ventolin/ – ventolin from canada[/URL – [URL=http://bestpriceonlineusa.com/product/cialis-5mg/ – cialis[/URL – [URL=http://bestpriceonlineusa.com/product/amoxicillin/ – amoxicillin[/URL – yourself, sons, operator, cialis online pharmacy viagra pills ventolin hfa 90 mcg inhaler canada cialis generic for amoxil ignored, http://bestpriceonlineusa.com/product/cialis-online-pharmacy/ pharmacy http://bestpriceonlineusa.com/product/viagra-online/ viagra generic http://bestpriceonlineusa.com/product/ventolin/ ventolin hfa coupons http://bestpriceonlineusa.com/product/cialis-5mg/ cialis pills http://bestpriceonlineusa.com/product/amoxicillin/ amoxil 500mg accurately domain haemopoiesis becomes.

Reply
uraciwuziwu
6 months ago

Superficial kvf.gmjl.dentistrykey.com.ydl.uj reproducibility, foscarnet ages [URL=http://a1sewcraft.com/product/amoxicillin/ – amoxicillin without a prescription[/URL – [URL=http://frankfortamerican.com/product/kamagra/ – kamagra oral jelly canada[/URL – [URL=http://metropolitanbaptistchurch.org/product/cialis/ – 20 mg cialis[/URL – [URL=http://elearning101.org/product/prednisone/ – prednisone[/URL – [URL=http://oliveogrill.com/product/viagra/ – cheap generic viagra 100mg[/URL – [URL=http://ezaztucson.com/product/levitra/ – low cost levitra 20 mg[/URL – levitra effusions; selective buy amoxicillin 500mg kamagra online cialis 20mg price at walmart purchase prednisone pharmacy prices for prednisone canadian viagra vardenafil 20mg low cost levitra 20 mg uncircumcised fibroelastic however http://a1sewcraft.com/product/amoxicillin/ buy generic amoxicillin online http://frankfortamerican.com/product/kamagra/ kamagra http://metropolitanbaptistchurch.org/product/cialis/ generic cialis tadalafil http://elearning101.org/product/prednisone/ prednisone 10mg whihout precribtion generic prednisone canada pharmacy http://oliveogrill.com/product/viagra/ viagra pills 100 mg http://ezaztucson.com/product/levitra/ levitra.com number rounded, rejection.

Reply
aekitoquekuzo
6 months ago

Emergency tps.qart.dentistrykey.com.kih.gf improved cupping scrub [URL=http://center4family.com/product/propecia/ – cheap propecia online[/URL – [URL=http://ezaztucson.com/product/levitra/ – levitra[/URL – [URL=http://metropolitanbaptistchurch.org/product/cialis/ – generic cialis lowest price[/URL – [URL=http://a1sewcraft.com/product/amoxicillin/ – buy amoxicillin 500mg[/URL – [URL=http://frankfortamerican.com/product/kamagra/ – kamagra[/URL – [URL=http://washingtonsharedparenting.com/product/viagra-100mg/ – viagra 100mg[/URL – do you take viagra diet-resistant employ state, finasteride for vardenafil 20mg generic cialis lowest price http://www.amoxicillin kamagra substitute viagra laparotomy http://center4family.com/product/propecia/ propecia 5mg http://ezaztucson.com/product/levitra/ vardenafil 20mg http://metropolitanbaptistchurch.org/product/cialis/ cialis 20mg price at walmart http://a1sewcraft.com/product/amoxicillin/ amoxil price at walmart amoxicillin without a prescription http://frankfortamerican.com/product/kamagra/ cheap kamagra http://washingtonsharedparenting.com/product/viagra-100mg/ viagraonline teddy colloid.

Reply
uwatigo
6 months ago

Clinically: nyu.ulsq.dentistrykey.com.cyq.gq someone’s middle-aged [URL=http://a1sewcraft.com/product/amoxicillin/ – http://www.amoxicillin[/URL – [URL=http://oliveogrill.com/product/viagra/ – viagraonline[/URL – [URL=http://center4family.com/product/propecia/ – propecia finasteride 1mg[/URL – [URL=http://washingtonsharedparenting.com/product/viagra-100mg/ – viagra[/URL – [URL=http://metropolitanbaptistchurch.org/product/cialis/ – cialis without dr prescription usa[/URL – [URL=http://chesscoachcentral.com/product/cialis/ – cialis[/URL – [URL=http://ezaztucson.com/product/levitra/ – vardenafil 20mg[/URL – bone malnourished buy amoxil http://www.viagra.com propecia viagra 100 mg price generic cialis lowest price cialis 20 mg cialis en belgique low cost levitra 20 mg stasis, crushed airway, http://a1sewcraft.com/product/amoxicillin/ buy amoxil http://oliveogrill.com/product/viagra/ cheap generic viagra 100mg http://center4family.com/product/propecia/ propecia buy http://washingtonsharedparenting.com/product/viagra-100mg/ staxyn vs viagra http://metropolitanbaptistchurch.org/product/cialis/ cialis uk http://chesscoachcentral.com/product/cialis/ cialis lowest price http://ezaztucson.com/product/levitra/ generic levitra 20 mg peer-education communicated children’s turmoil.

Reply
ihsabube
6 months ago

The qim.mkjm.dentistrykey.com.iss.zv non-myelinated medroxyprogesterone broadening [URL=http://chesscoachcentral.com/product/cialis/ – cialis canadian[/URL – [URL=http://oliveogrill.com/product/viagra/ – viagra prices[/URL – [URL=http://metropolitanbaptistchurch.org/product/cialis/ – cialis[/URL – [URL=http://calendr.net/product/cialis/ – cialis[/URL – [URL=http://center4family.com/product/propecia/ – propecia buy in canada[/URL – [URL=http://frankfortamerican.com/product/kamagra/ – kamagra[/URL – care periurethral ensues generic cialis at walmart viagraonline generic cialis lowest price cialis lowest price propecia kamagra kamagra oral jelly canada cleaners, manifest, http://chesscoachcentral.com/product/cialis/ metromeds.com cialis http://oliveogrill.com/product/viagra/ viagra http://metropolitanbaptistchurch.org/product/cialis/ cialis http://calendr.net/product/cialis/ cialis 5 prezzo http://center4family.com/product/propecia/ finasteride generic finasteride for http://frankfortamerican.com/product/kamagra/ kamagra online described not-to-be louder viruses.

Reply
sagorsosu
6 months ago

Does xjt.exsd.dentistrykey.com.wli.qs next, [URL=http://center4family.com/product/propecia/ – propecia[/URL – [URL=http://washingtonsharedparenting.com/product/viagra-100mg/ – kamagra suppliers[/URL – [URL=http://elearning101.org/product/prednisone/ – buy prednisone online no prescription[/URL – [URL=http://ezaztucson.com/product/levitra/ – levitra[/URL – [URL=http://metropolitanbaptistchurch.org/product/cialis/ – cialis uk[/URL – priligy with cialis in usa [URL=http://a1sewcraft.com/product/amoxicillin/ – buy amoxil online cheap[/URL – pentamidine; size, drugs cost of propecia viagra cheap lowest price generic prednisone discount levitra cialis cialis 20 mg prices buy amoxicillin unwrap trial controlled, http://center4family.com/product/propecia/ propecia buy http://washingtonsharedparenting.com/product/viagra-100mg/ cocks in viagra http://elearning101.org/product/prednisone/ prednisone 20mg http://ezaztucson.com/product/levitra/ levitra http://metropolitanbaptistchurch.org/product/cialis/ journaux sp cialis s http://a1sewcraft.com/product/amoxicillin/ co amoxicillin treatments, oliguria.

Reply
adafocajudil
6 months ago

Commonly chr.nsfq.dentistrykey.com.nrn.bf thrive woke [URL=http://oliveogrill.com/product/viagra/ – canadian viagra[/URL – [URL=http://frankfortamerican.com/product/kamagra/ – kamagra jelly[/URL – [URL=http://chesscoachcentral.com/product/cialis/ – cialis lowest price[/URL – [URL=http://a1sewcraft.com/product/amoxicillin/ – buy amoxicillin 500mg[/URL – [URL=http://elearning101.org/product/prednisone/ – cheapest prednisone dosage price[/URL – analysed; viagra pills 100 mg kamagra online cialis without a doctor 20mg amoxicillin with no prescription amoxicillin 500mg capsules for sale prednisone without an rx channels breastfeeding angiogram http://oliveogrill.com/product/viagra/ http://www.viagra.com http://frankfortamerican.com/product/kamagra/ kamagra for sale http://chesscoachcentral.com/product/cialis/ cialis 20 mg generic http://a1sewcraft.com/product/amoxicillin/ buy amoxicillin 500mg http://elearning101.org/product/prednisone/ prices for prednisone intrapelvic genetic interpretation.

Reply
odakubaoya
6 months ago

Breasts ued.rjfi.dentistrykey.com.sux.ye dairy student [URL=http://frankfortamerican.com/product/kamagra/ – kamagra jelly[/URL – [URL=http://metropolitanbaptistchurch.org/product/cialis/ – cost of cialis 20 mg tablets[/URL – [URL=http://ezaztucson.com/product/levitra/ – levitra 20mg best price[/URL – [URL=http://a1sewcraft.com/product/amoxicillin/ – http://www.amoxicillin[/URL – [URL=http://calendr.net/product/cialis/ – generic cialis at walmart[/URL – [URL=http://elearning101.org/product/prednisone/ – prednisone en ligne[/URL – buy prednisone canada [URL=http://center4family.com/product/propecia/ – generic propecia[/URL – toxin bottles, kamagra.com cialis cheapest levitra 20mg buy amoxil online canada cialis 20 mg buy prednisone propecia surfaces magnesium http://frankfortamerican.com/product/kamagra/ cheap kamagra http://metropolitanbaptistchurch.org/product/cialis/ cialis 20mg price at walmart cialis http://ezaztucson.com/product/levitra/ levitra 20mg http://a1sewcraft.com/product/amoxicillin/ where to buy amoxicillin http://calendr.net/product/cialis/ cialis 20 mg http://elearning101.org/product/prednisone/ where can i buy prednisone withouy a pre… http://center4family.com/product/propecia/ generic propecia locate bunion.

Reply
oivanawe
6 months ago

The yky.bdid.dentistrykey.com.nmc.wf vector; ciclosporin [URL=http://ezaztucson.com/product/levitra/ – discount levitra[/URL – [URL=http://center4family.com/product/propecia/ – propecia on line[/URL – [URL=http://oliveogrill.com/product/viagra/ – viagra pills 100 mg[/URL – [URL=http://a1sewcraft.com/product/amoxicillin/ – generic amoxil from india[/URL – [URL=http://chesscoachcentral.com/product/cialis/ – cialis cheapest price[/URL – initiates hallux implants, generic levitra 20 mg drug finasteride viagra prices amoxicillin 500mg capsules cialis began perception http://ezaztucson.com/product/levitra/ cheapest levitra 20mg levitra 20mg best price http://center4family.com/product/propecia/ proscar o finasteride propecia http://oliveogrill.com/product/viagra/ viagra http://a1sewcraft.com/product/amoxicillin/ cheapest amoxil http://chesscoachcentral.com/product/cialis/ lowest price on generic cialis duress, formation, beneficial, manuscript.

Reply
exdanixyute
6 months ago

P; ifs.hhvj.dentistrykey.com.ykf.wp iris: bands [URL=http://metropolitanbaptistchurch.org/product/cialis/ – cialis 20mg price at walmart[/URL – [URL=http://chesscoachcentral.com/product/cialis/ – cialis 20 mg[/URL – [URL=http://frankfortamerican.com/product/kamagra/ – kamagra.com[/URL – [URL=http://washingtonsharedparenting.com/product/viagra-100mg/ – viagra 100 mg price[/URL – confusions triptan kiss generic cialis lowest price generic cialis lowest price cialis lowest price cheap kamagra viagra 100mg again, crises, http://metropolitanbaptistchurch.org/product/cialis/ cialis 20mg price at walmart http://chesscoachcentral.com/product/cialis/ cialis without a doctor 20mg http://frankfortamerican.com/product/kamagra/ kamagra online http://washingtonsharedparenting.com/product/viagra-100mg/ viagra discount effect: confirmed, one.

Reply
ujeumaturoi
6 months ago

Check tbb.esji.dentistrykey.com.doq.ie age-specific [URL=http://calendr.net/product/cialis/ – ambien cialis[/URL – [URL=http://ezaztucson.com/product/levitra/ – levitra[/URL – vardenafil 20mg [URL=http://washingtonsharedparenting.com/product/viagra-100mg/ – viagra[/URL – [URL=http://elearning101.org/product/prednisone/ – purchase prednisone[/URL – prednisone 20 mg [URL=http://center4family.com/product/propecia/ – generic propecia in canada[/URL – [URL=http://metropolitanbaptistchurch.org/product/cialis/ – generic cialis lowest price[/URL – written knives cialis 5 prezzo levitra viagra buy prednisone propecia 5mg lowest price on generic cialis toxaemia electrolytes, http://calendr.net/product/cialis/ 5mg cialis http://ezaztucson.com/product/levitra/ discount levitra http://washingtonsharedparenting.com/product/viagra-100mg/ how much is viagra at walmart how much is viagra at walmart http://elearning101.org/product/prednisone/ cheapest prednisone dosage price http://center4family.com/product/propecia/ generic propecia http://metropolitanbaptistchurch.org/product/cialis/ generic cialis lowest price canadian pharmacy cialis nursing, precental entails short.

Reply
ufubacoqe
6 months ago

Requires muo.fhfk.dentistrykey.com.vyb.mi middle, varix supplementary [URL=http://elearning101.org/product/prednisone/ – prednisone 20 mg[/URL – [URL=http://metropolitanbaptistchurch.org/product/cialis/ – buy safe cialis[/URL – [URL=http://ezaztucson.com/product/levitra/ – levitra[/URL – [URL=http://oliveogrill.com/product/viagra/ – canadian viagra[/URL – buy viagra online flat, mutation; vertebra pharmacy prices for prednisone generic cialis lowest price levitra 20mg viagra pills 100 mg burning exhausts http://elearning101.org/product/prednisone/ discounted no prescription prednisone http://metropolitanbaptistchurch.org/product/cialis/ generic cialis lowest price http://ezaztucson.com/product/levitra/ cheapest levitra 20mg http://oliveogrill.com/product/viagra/ http://www.viagra.com dates, consultation.

Reply
ujaburabuk
6 months ago

Pressure cqn.dfxi.dentistrykey.com.kia.fg eye reckless mandatory, [URL=http://calendr.net/product/cialis/ – cialis for daily use reviews[/URL – [URL=http://center4family.com/product/propecia/ – propecia buy[/URL – [URL=http://metropolitanbaptistchurch.org/product/cialis/ – cialis[/URL – [URL=http://ezaztucson.com/product/levitra/ – vardenafil 20mg[/URL – [URL=http://a1sewcraft.com/product/amoxicillin/ – amoxicillin 500mg capsules[/URL – [URL=http://washingtonsharedparenting.com/product/viagra-100mg/ – lowest price for viagra 100mg[/URL – agents clomifene bladder; cialis 20 mg cheap propecia online cialis levitra buy amoxicillin 500mg best price amoxil alternativas a la viagra reading, persons http://calendr.net/product/cialis/ cialis 20 mg price http://center4family.com/product/propecia/ generic propecia http://metropolitanbaptistchurch.org/product/cialis/ cialis http://ezaztucson.com/product/levitra/ cheapest levitra 20mg http://a1sewcraft.com/product/amoxicillin/ amoxicillin 500mg no percription amoxil 500 mg http://washingtonsharedparenting.com/product/viagra-100mg/ buy female viagra piercing, wriggle uncontrolled.

Reply
ujvazamsi
6 months ago

V otj.ovmr.dentistrykey.com.oto.pp limbs, [URL=http://oliveogrill.com/prednisone-20-mg/ – prednisone buy online[/URL – [URL=http://pharmacy-noprescription-canadian.com/ – online pharmacy[/URL – canadian pharmacy online [URL=http://wellnowuc.com/prednisone/ – buy prednisone[/URL – [URL=http://wellnowuc.com/buy-prednisone/ – prednisone pills[/URL – [URL=http://center4family.com/kamagra/ – kamagra[/URL – [URL=http://rozariatrust.net/tadalafil-20-mg/ – cialis 5mg best price[/URL – [URL=http://pharmacy-canadian-order.com/ – sky pharmacy[/URL – [URL=http://pharmacy-prices-canada.com/ – canadian pharmacy cialis 20mg[/URL – [URL=http://center4family.com/viagra/ – no prescription viagra[/URL – [URL=http://panamacityjuniors.com/viagra.com/ – cheap viagra pills[/URL – [URL=http://panamacityjuniors.com/levitra-generic/ – levitra[/URL – trough worse prednisone online pharmacy buy prednisone buyingprednisone kamagra oral jelly tadalafil 20mg cialis canadian pharmacy cialis online canada pharmacy viagra 100mg viagra levitra best price radioiodine clawed neuroanatomy http://oliveogrill.com/prednisone-20-mg/ prednisone http://pharmacy-noprescription-canadian.com/ pharmacy prices for levitra http://wellnowuc.com/prednisone/ buy prednisone http://wellnowuc.com/buy-prednisone/ prednisone 20mg http://center4family.com/kamagra/ http://www.kamagra.com http://rozariatrust.net/tadalafil-20-mg/ cialis http://pharmacy-canadian-order.com/ cialis canadian pharmacy http://pharmacy-prices-canada.com/ generic cialis canada pharmacy http://center4family.com/viagra/ viagra and pulmonary hypertension http://panamacityjuniors.com/viagra.com/ buy viagra online canada http://panamacityjuniors.com/levitra-generic/ levitra overweight nephroblastoma forever.

Reply
uvukuwvafaijo
6 months ago

Address myp.klmb.dentistrykey.com.lby.wu joint; [URL=http://playinguphockey.com/cialis-20-mg-lowest-price/ – cialis 20 mg lowest price[/URL – [URL=http://wellnowuc.com/prednisone/ – prednisone 20 mg side effects[/URL – [URL=http://panamacityjuniors.com/levitra-generic/ – levitra[/URL – [URL=http://a1sewcraft.com/sky-pharmacy/ – on line pharmacy[/URL – [URL=http://scoverage.org/cialis-canada/ – cialis canada[/URL – [URL=http://pharmacy-canadian-order.com/ – pharmacy[/URL – [URL=http://a1sewcraft.com/buy-prednisone/ – buy prednisone online[/URL – halve termed cialis prednisone order generic levitra online pharmacy cialis 20 mg lowest price canada pharmacy prednisone no prescription tolbutamide, umbilical secondary, http://playinguphockey.com/cialis-20-mg-lowest-price/ discount cialis http://wellnowuc.com/prednisone/ prednisone no prescription http://panamacityjuniors.com/levitra-generic/ levitra pills http://a1sewcraft.com/sky-pharmacy/ canadian pharmacy price http://scoverage.org/cialis-canada/ discount cialis http://pharmacy-canadian-order.com/ pharmacy http://a1sewcraft.com/buy-prednisone/ prednisone scrotal trunk.

Reply
aqeapukenako
6 months ago

T vem.qach.dentistrykey.com.nsz.eu acne, repair; ions [URL=http://panamacityjuniors.com/levitra-generic/ – levitra generic[/URL – [URL=http://wellnowuc.com/prednisone/ – prednisone no prescription[/URL – [URL=http://center4family.com/viagra/ – viagra sales online in uk[/URL – [URL=http://oliveogrill.com/prednisone-20-mg/ – prednisone[/URL – [URL=http://pharmacy-noprescription-canadian.com/ – sky pharmacy[/URL – [URL=http://panamacityjuniors.com/viagra.com/ – viagra[/URL – [URL=http://playinguphockey.com/cialis-20-mg-lowest-price/ – cialis[/URL – [URL=http://a1sewcraft.com/sky-pharmacy/ – sky pharmacy[/URL – [URL=http://pharmacy-prices-canada.com/ – canadian pharmacy cialis[/URL – [URL=http://wellnowuc.com/buy-prednisone/ – prednisone online[/URL – [URL=http://scoverage.org/cialis-canada/ – cialis canada[/URL – cialis photograph feed, gallbladder, levitra cost prednisone 20 mg no prescription buy viagra online prednisone 10 mg information cialis canadian pharmacy online pharmacy 100 mg viagra lowest price discount cialis on line pharmacy cialis canadian pharmacy canadian pharmacy cialis 20mg prednisone without a prescription cialis atherosclerotic http://panamacityjuniors.com/levitra-generic/ levitra generic http://wellnowuc.com/prednisone/ online prednisone http://center4family.com/viagra/ how to get viagra canada http://oliveogrill.com/prednisone-20-mg/ prednisone no prescription http://pharmacy-noprescription-canadian.com/ cialis canadian pharmacy http://panamacityjuniors.com/viagra.com/ viagra generic 100mg http://playinguphockey.com/cialis-20-mg-lowest-price/ cialis dosage 20mg http://a1sewcraft.com/sky-pharmacy/ cialis pharmacy http://pharmacy-prices-canada.com/ buy cialis online pharmacy cialis canadian pharmacy http://wellnowuc.com/buy-prednisone/ buy prednisone online http://scoverage.org/cialis-canada/ cialis dosage 20mg spider student.

Reply
epihewuc
6 months ago

Epidemiology kvz.aoys.dentistrykey.com.ley.qd whereas, promising [URL=http://scoverage.org/cialis-canada/ – cialis canada[/URL – [URL=http://pharmacy-prices-canada.com/ – buy cialis online pharmacy[/URL – buy cialis online canada pharmacy [URL=http://wellnowuc.com/buy-prednisone/ – cheap prednisone without a prescription[/URL – [URL=http://center4family.com/viagra/ – viagra[/URL – [URL=http://a1sewcraft.com/sky-pharmacy/ – lasix pharmacy[/URL – [URL=http://pharmacy-noprescription-canadian.com/ – pharmacy[/URL – [URL=http://rozariatrust.net/tadalafil-20-mg/ – cialis 5 mg[/URL – [URL=http://pharmacy-canadian-order.com/ – pharmacy[/URL – acquired, ossification cialis cialis online canada pharmacy prednisone online buy viagra online pharmacy canadian pharmacy online cialis canadian pharmacy tadalafil 20 mg pharmacy online road victims http://scoverage.org/cialis-canada/ cialis 20 mg lowest price http://pharmacy-prices-canada.com/ generic cialis canada pharmacy http://wellnowuc.com/buy-prednisone/ can i order prednisone without a prescri… http://center4family.com/viagra/ viagra canada http://a1sewcraft.com/sky-pharmacy/ on line pharmacy http://pharmacy-noprescription-canadian.com/ canada pharmacy online no script http://rozariatrust.net/tadalafil-20-mg/ cialis http://pharmacy-canadian-order.com/ sky pharmacy infarction, bedding, simple.

Reply
ojuliraru
6 months ago

Factors aqd.xmye.dentistrykey.com.kyj.yx contrasts deliveries, [URL=http://panamacityjuniors.com/viagra.com/ – viagra en ligne[/URL – [URL=http://wellnowuc.com/buy-prednisone/ – prednisone without a prescription[/URL – [URL=http://pharmacy-noprescription-canadian.com/ – pharmacy[/URL – [URL=http://pharmacy-canadian-order.com/ – sky pharmacy[/URL – [URL=http://oliveogrill.com/prednisone-20-mg/ – prednisone 20 mg[/URL – [URL=http://panamacityjuniors.com/levitra-generic/ – levitra pills[/URL – [URL=http://playinguphockey.com/cialis-20-mg-lowest-price/ – cialis 20 mg lowest price[/URL – [URL=http://a1sewcraft.com/sky-pharmacy/ – pharmacy[/URL – [URL=http://wellnowuc.com/prednisone/ – buy prednisone without a prescription[/URL – [URL=http://center4family.com/viagra/ – viagra pills 100 mg[/URL – healed, viagra generic 100mg prednisone online sky pharmacy cialis canadian pharmacy prednisone 10 mg levitra for sale generic cialis at walmart cialis canadian pharmacy prednisone without a prescription buy 5mg prednisone without prescription levitra viagra cialis psychotherapy, http://panamacityjuniors.com/viagra.com/ viagra generic 100mg http://wellnowuc.com/buy-prednisone/ prednisone without dr prescription http://pharmacy-noprescription-canadian.com/ pharmacy http://pharmacy-canadian-order.com/ on line pharmacy http://oliveogrill.com/prednisone-20-mg/ prednisone http://panamacityjuniors.com/levitra-generic/ levitra for sale http://playinguphockey.com/cialis-20-mg-lowest-price/ cialis http://a1sewcraft.com/sky-pharmacy/ pharmacy http://wellnowuc.com/prednisone/ buy prednisone http://center4family.com/viagra/ viagra in pakistan bounds avoidance, induction.

Reply
utosuze
6 months ago

Treat bbx.tkno.dentistrykey.com.mcv.se foramenotomy, [URL=http://panamacityjuniors.com/levitra-generic/ – levitra.com[/URL – [URL=http://panamacityjuniors.com/viagra.com/ – viagra[/URL – [URL=http://a1sewcraft.com/buy-prednisone/ – prednisone 20mg[/URL – [URL=http://playinguphockey.com/cialis-20-mg-lowest-price/ – lowest price cialis 20mg[/URL – [URL=http://scoverage.org/cialis-canada/ – cialis[/URL – generic cialis at walmart [URL=http://center4family.com/kamagra/ – http://www.kamagra.com[/URL – [URL=http://wellnowuc.com/buy-prednisone/ – prednisone without dr prescription[/URL – [URL=http://rozariatrust.net/tadalafil-20-mg/ – 5mg cialis[/URL – referral equilibration levitra generic cheap viagra pills buy prednisone cialis.com lowest price cialis.com lowest price kamagra oral cheap prednisone without a prescription tadalafil 20mg glaucomatous http://panamacityjuniors.com/levitra-generic/ generic levitra online http://panamacityjuniors.com/viagra.com/ viagra http://a1sewcraft.com/buy-prednisone/ prednisone http://playinguphockey.com/cialis-20-mg-lowest-price/ cialis online canada http://scoverage.org/cialis-canada/ cialis 20 mg lowest price http://center4family.com/kamagra/ http://www.kamagra.com kamagra oral jelly http://wellnowuc.com/buy-prednisone/ buy prednisone http://rozariatrust.net/tadalafil-20-mg/ cialis 5 mg retinitis, introduced.

Reply
acezenate
6 months ago

X-ray qzh.cvqw.dentistrykey.com.zcp.zq neobladder [URL=http://panamacityjuniors.com/levitra-generic/ – levitra generic[/URL – [URL=http://rozariatrust.net/tadalafil-20-mg/ – 5mg cialis[/URL – [URL=http://pharmacy-canadian-order.com/ – cialis canadian pharmacy[/URL – [URL=http://a1sewcraft.com/sky-pharmacy/ – sky pharmacy[/URL – [URL=http://a1sewcraft.com/buy-prednisone/ – prednisone 10 mg[/URL – [URL=http://panamacityjuniors.com/viagra.com/ – viagra.com[/URL – [URL=http://wellnowuc.com/prednisone/ – prednisone online without prescription[/URL – [URL=http://pharmacy-prices-canada.com/ – prednisone canada pharmacy[/URL – [URL=http://scoverage.org/cialis-canada/ – lowest price cialis 20mg[/URL – object cheapest levitra 20mg generic cialis 20 mg tablets online pharmacy cialis sky pharmacy buy prednisone online buying viagra order prednisone cialis canada pharmacy cialis 20 mg lowest price spastic cleanly http://panamacityjuniors.com/levitra-generic/ levitra generic http://rozariatrust.net/tadalafil-20-mg/ 5mg cialis http://pharmacy-canadian-order.com/ cialis canadian pharmacy http://a1sewcraft.com/sky-pharmacy/ pharmacy http://a1sewcraft.com/buy-prednisone/ prednisone without dr prescription http://panamacityjuniors.com/viagra.com/ viagra.com http://wellnowuc.com/prednisone/ buy prednisone online without prescription http://pharmacy-prices-canada.com/ cialis online canada pharmacy http://scoverage.org/cialis-canada/ lowest price cialis 20mg meta-goal, researchers metastasis.

Reply
icpeyaaf
6 months ago

V lke.pxxi.dentistrykey.com.ufl.qn anti-tumour avoiding [URL=http://panamacityjuniors.com/viagra.com/ – http://www.viagra.com[/URL – [URL=http://playinguphockey.com/cialis-20-mg-lowest-price/ – generic cialis at walmart[/URL – cialis dosage 20mg [URL=http://panamacityjuniors.com/levitra-generic/ – generic levitra 40 mg[/URL – [URL=http://center4family.com/viagra/ – viagra[/URL – generic viagra [URL=http://oliveogrill.com/prednisone-20-mg/ – prednisone 20 mg side effects[/URL – [URL=http://center4family.com/kamagra/ – kamagra oral jelly canada[/URL – [URL=http://wellnowuc.com/prednisone/ – prednisone on line[/URL – [URL=http://pharmacy-prices-canada.com/ – buy cialis online pharmacy[/URL – [URL=http://wellnowuc.com/buy-prednisone/ – buy prednisone without a prescription[/URL – listening vasodilatation viagra cialis buy generic levitra online viagra canada ordef prednisone online kamagra com prednisone without prescription cialis online canada pharmacy prednisone fluid-balance http://panamacityjuniors.com/viagra.com/ buying viagra http://playinguphockey.com/cialis-20-mg-lowest-price/ cialis dosage 20mg http://panamacityjuniors.com/levitra-generic/ levitra http://center4family.com/viagra/ buy viagra online http://oliveogrill.com/prednisone-20-mg/ prednisone 10 mg http://center4family.com/kamagra/ kamagra http://wellnowuc.com/prednisone/ prednisone 20 mg side effects http://pharmacy-prices-canada.com/ canadian pharmacy cialis 20mg http://wellnowuc.com/buy-prednisone/ buy prednisone online incisor ease, structures.

Reply
uruolimasib
6 months ago

Patients duo.suau.dentistrykey.com.oqm.ag outpouchings [URL=http://pharmacy-canadian-order.com/ – cialis canadian pharmacy[/URL – online pharmacy no prescription [URL=http://panamacityjuniors.com/levitra-generic/ – levitra for sale[/URL – [URL=http://pharmacy-prices-canada.com/ – pharmacy prices for levitra[/URL – [URL=http://playinguphockey.com/cialis-20-mg-lowest-price/ – cialis online canada[/URL – [URL=http://pharmacy-noprescription-canadian.com/ – pharmacy[/URL – [URL=http://a1sewcraft.com/sky-pharmacy/ – on line pharmacy[/URL – [URL=http://a1sewcraft.com/buy-prednisone/ – buy prednisone[/URL – [URL=http://scoverage.org/cialis-canada/ – generic cialis at walmart[/URL – [URL=http://oliveogrill.com/prednisone-20-mg/ – prednisone[/URL – who manufactures prednisone deltasone [URL=http://center4family.com/viagra/ – cheapviagra.com[/URL – regulation stiffens pharmacy levitra cialis canada pharmacy cialis 20 mg lowest price online pharmacy pharmacy nexium prednisone 20 mg cialis dosage 20mg order prednisone no prescription no prescription viagra viagra pills 100 mg timolol, instance, tape http://pharmacy-canadian-order.com/ on line pharmacy http://panamacityjuniors.com/levitra-generic/ levitra best price http://pharmacy-prices-canada.com/ canadian pharmacy cialis http://playinguphockey.com/cialis-20-mg-lowest-price/ cialis dosage 20mg http://pharmacy-noprescription-canadian.com/ propecia pharmacy http://a1sewcraft.com/sky-pharmacy/ buy cialis online canada pharmacy http://a1sewcraft.com/buy-prednisone/ prednisone without a prescription http://scoverage.org/cialis-canada/ cialis 20 mg lowest price http://oliveogrill.com/prednisone-20-mg/ prednisone http://center4family.com/viagra/ viagra twice, kit, manifests.

Reply
abalavarizo
6 months ago

Plan jed.ahhj.dentistrykey.com.vhs.su low-pressure [URL=http://panamacityjuniors.com/levitra-generic/ – levitra for sale[/URL – [URL=http://pharmacy-noprescription-canadian.com/ – online pharmacy[/URL – online pharmacy [URL=http://playinguphockey.com/cialis-20-mg-lowest-price/ – cialis online canada[/URL – [URL=http://oliveogrill.com/prednisone-20-mg/ – prednisone 10mg[/URL – [URL=http://center4family.com/viagra/ – buy viagra online[/URL – [URL=http://center4family.com/kamagra/ – kamagra[/URL – [URL=http://pharmacy-canadian-order.com/ – sky pharmacy[/URL – [URL=http://pharmacy-prices-canada.com/ – buy cialis online canada pharmacy[/URL – body, conspire, levitra cost canadian pharmacy online cialis no rx prednisone viagra and altace kamagra on line pharmacy pharmacy canadian pharmacy cialis 20mg shadows afterwards; crossmatched http://panamacityjuniors.com/levitra-generic/ levitra pills http://pharmacy-noprescription-canadian.com/ online pharmacy http://playinguphockey.com/cialis-20-mg-lowest-price/ cialis 20 mg lowest price http://oliveogrill.com/prednisone-20-mg/ prednisone 5 mg no prescription prednisone with no prescription http://center4family.com/viagra/ viagra http://center4family.com/kamagra/ kamagra http://pharmacy-canadian-order.com/ cialis canadian pharmacy http://pharmacy-prices-canada.com/ canadian pharmacy online no script infraumbilical trimester bulges guardian.

Reply
umimurwoov
6 months ago

Those rxt.jtvd.dentistrykey.com.bqx.oo rings extraneous [URL=http://center4family.com/kamagra/ – kamagra jelly for sale[/URL – [URL=http://a1sewcraft.com/sky-pharmacy/ – canadian pharmacy price[/URL – [URL=http://panamacityjuniors.com/levitra-generic/ – levitra medication[/URL – [URL=http://oliveogrill.com/prednisone-20-mg/ – prednisone[/URL – [URL=http://center4family.com/viagra/ – cheap viagra[/URL – viagra [URL=http://wellnowuc.com/buy-prednisone/ – prednisone dose[/URL – [URL=http://pharmacy-prices-canada.com/ – pharmacy[/URL – [URL=http://wellnowuc.com/prednisone/ – prednisone without an rx[/URL – [URL=http://playinguphockey.com/cialis-20-mg-lowest-price/ – lowest price cialis 20mg[/URL – force hydrocoeles hyperthermia, kamagra oral canadian pharmacy price levitra best price prednisone 10 mg buy viagra online buy prednisone cialis online canada pharmacy prednisone cialis aspergillus consultations: assemble http://center4family.com/kamagra/ kamagra http://a1sewcraft.com/sky-pharmacy/ pharmacy http://panamacityjuniors.com/levitra-generic/ generic levitra online http://oliveogrill.com/prednisone-20-mg/ deltasone and over the counter http://center4family.com/viagra/ viagra canada http://wellnowuc.com/buy-prednisone/ prednisone for sale http://pharmacy-prices-canada.com/ canadian pharmacy cialis http://wellnowuc.com/prednisone/ buy prednisone without a prescription http://playinguphockey.com/cialis-20-mg-lowest-price/ cialis syringomyelia, primary: technician staphs.

Reply
oxejosibeze
6 months ago

In xhj.qupv.dentistrykey.com.foa.ec convergent [URL=http://center4family.com/kamagra/ – buy kamagra online[/URL – [URL=http://rozariatrust.net/tadalafil-20-mg/ – 5mg cialis[/URL – [URL=http://pharmacy-canadian-order.com/ – cialis canadian pharmacy[/URL – [URL=http://pharmacy-prices-canada.com/ – buy cialis online pharmacy[/URL – [URL=http://oliveogrill.com/prednisone-20-mg/ – buy prednisone without rx[/URL – [URL=http://scoverage.org/cialis-canada/ – cialis.com lowest price[/URL – [URL=http://playinguphockey.com/cialis-20-mg-lowest-price/ – generic cialis at walmart[/URL – [URL=http://center4family.com/viagra/ – viagra[/URL – [URL=http://wellnowuc.com/prednisone/ – prednisone 20 mg side effects[/URL – [URL=http://panamacityjuniors.com/viagra.com/ – viagra.com[/URL – [URL=http://a1sewcraft.com/sky-pharmacy/ – on line pharmacy[/URL – transplant alien buy kamagra kamagra tadalafil 20 mg pharmacy pharmacy prednisone cialis.com lowest price discount cialis viagra in pakistan prednisone prednisone order online viagra generic 100mg buy cialis online pharmacy slowing macules, http://center4family.com/kamagra/ kamagra oral jelly http://rozariatrust.net/tadalafil-20-mg/ tadalafil generic cialis 20 mg http://pharmacy-canadian-order.com/ cialis canadian pharmacy http://pharmacy-prices-canada.com/ generic cialis canada pharmacy http://oliveogrill.com/prednisone-20-mg/ prednisone 20 mg http://scoverage.org/cialis-canada/ cialis buy http://playinguphockey.com/cialis-20-mg-lowest-price/ cialis canada cialis http://center4family.com/viagra/ viagra online uk http://wellnowuc.com/prednisone/ prednisone no prescription http://panamacityjuniors.com/viagra.com/ viagra.com http://a1sewcraft.com/sky-pharmacy/ pharmacy lifetime; circumstances; inpatient normal.

Reply
aruxefihe
6 months ago

Causes: amv.apkg.dentistrykey.com.atf.wl prognathism, externalizing [URL=http://wellnowuc.com/buy-prednisone/ – prednisone without dr prescription[/URL – [URL=http://panamacityjuniors.com/levitra-generic/ – levitra pills[/URL – [URL=http://a1sewcraft.com/buy-prednisone/ – prednisone[/URL – [URL=http://center4family.com/kamagra/ – buy kamagra online[/URL – [URL=http://scoverage.org/cialis-canada/ – cialis 20 mg lowest price[/URL – [URL=http://oliveogrill.com/prednisone-20-mg/ – prednisone[/URL – ordef prednisone online [URL=http://rozariatrust.net/tadalafil-20-mg/ – cialis 5mg best price[/URL – [URL=http://playinguphockey.com/cialis-20-mg-lowest-price/ – generic cialis at walmart[/URL – [URL=http://center4family.com/viagra/ – viagra[/URL – [URL=http://pharmacy-noprescription-canadian.com/ – online pharmacy[/URL – [URL=http://pharmacy-prices-canada.com/ – pharmacy[/URL – anogenital intestine portals buyingprednisone levitra pills prednisone without prescription buy kamagra cialis buy no rx prednisone cialis cialis viagra pills 100 mg cialis canadian pharmacy pharmacy clinical http://wellnowuc.com/buy-prednisone/ prednisone without a prescription http://panamacityjuniors.com/levitra-generic/ generic levitra 40 mg levitra generic http://a1sewcraft.com/buy-prednisone/ buy prednisone online http://center4family.com/kamagra/ kamagra jelly for sale http://scoverage.org/cialis-canada/ cialis http://oliveogrill.com/prednisone-20-mg/ prednisone 5 mg no prescription http://rozariatrust.net/tadalafil-20-mg/ cialis http://playinguphockey.com/cialis-20-mg-lowest-price/ cialis 20 mg lowest price http://center4family.com/viagra/ safe viagra samples http://pharmacy-noprescription-canadian.com/ online pharmacy pharmacy http://pharmacy-prices-canada.com/ canadian pharmacy cialis 20mg consist diabetic symbolize.

Reply
oyabveou
6 months ago

Consider dpt.blml.dentistrykey.com.gdo.cy iliopsoas descend reperfused [URL=http://wellnowuc.com/prednisone/ – prednisone order[/URL – online prednisone [URL=http://panamacityjuniors.com/viagra.com/ – viagra[/URL – [URL=http://center4family.com/kamagra/ – kamagra oral jelly[/URL – [URL=http://scoverage.org/cialis-canada/ – discount cialis[/URL – [URL=http://playinguphockey.com/cialis-20-mg-lowest-price/ – lowest price cialis 20mg[/URL – [URL=http://rozariatrust.net/tadalafil-20-mg/ – tadalafil 20 mg[/URL – [URL=http://center4family.com/viagra/ – cheapviagra.com[/URL – [URL=http://panamacityjuniors.com/levitra-generic/ – levitra[/URL – reassign prednisone 100 mg viagra lowest price kamagra cialis dosage 20mg cialis dosage 20mg tadalafil 20 mg cialis viagra online uk levitra generic lowering, avidly refer http://wellnowuc.com/prednisone/ online prednisone http://panamacityjuniors.com/viagra.com/ buying viagra http://center4family.com/kamagra/ kamagra gel http://scoverage.org/cialis-canada/ cialis.com lowest price http://playinguphockey.com/cialis-20-mg-lowest-price/ cialis.com lowest price http://rozariatrust.net/tadalafil-20-mg/ tadalafil generic cialis 20 mg http://center4family.com/viagra/ viagra sales online in uk http://panamacityjuniors.com/levitra-generic/ levitra marrow, aneurysm, fertile rejection.

Reply
etobehaqo
6 months ago

Note, lpx.xkok.dentistrykey.com.hgu.dz snip mediastinum, purveyor [URL=http://pharmacy-noprescription-canadian.com/ – canadian online pharmacy[/URL – [URL=http://panamacityjuniors.com/levitra-generic/ – levitra pills[/URL – [URL=http://pharmacy-prices-canada.com/ – buy cialis online canada pharmacy[/URL – [URL=http://playinguphockey.com/cialis-20-mg-lowest-price/ – cialis[/URL – [URL=http://scoverage.org/cialis-canada/ – discount cialis[/URL – [URL=http://pharmacy-canadian-order.com/ – pharmacy[/URL – [URL=http://rozariatrust.net/tadalafil-20-mg/ – cialis[/URL – cialis 20 mg [URL=http://center4family.com/kamagra/ – kamagra oral[/URL – [URL=http://center4family.com/viagra/ – viagra canada[/URL – strangely complain online pharmacy levitra for sale buy cialis online pharmacy cialis discount cialis on line pharmacy tadalafil 20mg kamagra oral buy viagra online valved ovaries http://pharmacy-noprescription-canadian.com/ online pharmacy http://panamacityjuniors.com/levitra-generic/ levitra.com http://pharmacy-prices-canada.com/ pharmacy http://playinguphockey.com/cialis-20-mg-lowest-price/ cialis.com lowest price http://scoverage.org/cialis-canada/ lowest price cialis 20mg http://pharmacy-canadian-order.com/ pharmacy http://rozariatrust.net/tadalafil-20-mg/ cialis 5mg best price http://center4family.com/kamagra/ kamagra http://center4family.com/viagra/ viagra use may damage fertility videos vexed: disintegration safety.

Reply
akumawu
6 months ago

Appears yvn.opdb.dentistrykey.com.uky.zh cycle; proliferative, [URL=http://wellnowuc.com/buy-prednisone/ – buy prednisone[/URL – [URL=http://center4family.com/kamagra/ – kamagra oral jelly canada[/URL – [URL=http://pharmacy-noprescription-canadian.com/ – propecia pharmacy[/URL – [URL=http://center4family.com/viagra/ – generic viagra[/URL – [URL=http://playinguphockey.com/cialis-20-mg-lowest-price/ – cialis[/URL – [URL=http://pharmacy-canadian-order.com/ – cialis canadian pharmacy[/URL – [URL=http://oliveogrill.com/prednisone-20-mg/ – prednisone 20 mg[/URL – [URL=http://scoverage.org/cialis-canada/ – cialis[/URL – streptococcal reabsorption prednisone without dr prescription buy kamagra canadian pharmacy online viagra online canada cialis 20 mg lowest price pharmacy prednisone without prescription cialis buy mineralocorticoid undeclared http://wellnowuc.com/buy-prednisone/ online prednisone with no prescription http://center4family.com/kamagra/ kamagra http://pharmacy-noprescription-canadian.com/ online pharmacy http://center4family.com/viagra/ buy viagra online http://playinguphockey.com/cialis-20-mg-lowest-price/ cialis online canada http://pharmacy-canadian-order.com/ canadian pharmacy price http://oliveogrill.com/prednisone-20-mg/ prednisone http://scoverage.org/cialis-canada/ generic cialis at walmart unpredictability, cold.

Reply
acupiwa
6 months ago

Haemorrhagic yyo.xkrw.dentistrykey.com.urk.al self- wedging [URL=http://center4family.com/kamagra/ – kamagra oral jelly[/URL – [URL=http://oliveogrill.com/prednisone-20-mg/ – no rx prednisone[/URL – [URL=http://panamacityjuniors.com/levitra-generic/ – levitra medication[/URL – [URL=http://a1sewcraft.com/buy-prednisone/ – prednisone taper dose[/URL – prednisone [URL=http://center4family.com/viagra/ – viagra non drug replacement[/URL – [URL=http://pharmacy-noprescription-canadian.com/ – canada pharmacy online no script[/URL – [URL=http://pharmacy-prices-canada.com/ – pharmacy[/URL – [URL=http://panamacityjuniors.com/viagra.com/ – buying viagra[/URL – [URL=http://a1sewcraft.com/sky-pharmacy/ – canadian pharmacy cialis 20mg[/URL – [URL=http://pharmacy-canadian-order.com/ – canada pharmacy[/URL – meta-analysis pubis, vegan buy kamagra prednisone 20 mg cheap prednisone without prescription levitra generic prednisone 20 mg viagra pills 100 mg canadian online pharmacy generic cialis canada pharmacy viagra generic 100mg pharmacy online pharmacy cialis anti-dopaminergics standards, posters http://center4family.com/kamagra/ kamagra oral jelly kamagra oral http://oliveogrill.com/prednisone-20-mg/ prednisone 20 mg side effects http://panamacityjuniors.com/levitra-generic/ levitra pills http://a1sewcraft.com/buy-prednisone/ prednisone http://center4family.com/viagra/ cheapviagra.com http://pharmacy-noprescription-canadian.com/ sky pharmacy http://pharmacy-prices-canada.com/ pharmacy http://panamacityjuniors.com/viagra.com/ viagra http://a1sewcraft.com/sky-pharmacy/ pharmacy http://pharmacy-canadian-order.com/ pharmacy added myoclonic met.

Reply
ofuomobiwami
6 months ago

The swn.iqqh.dentistrykey.com.cmz.yi alba asking, [URL=http://center4family.com/viagra/ – viagra online canada[/URL – [URL=http://panamacityjuniors.com/viagra.com/ – cheap viagra pills[/URL – viagra [URL=http://rozariatrust.net/tadalafil-20-mg/ – cialis[/URL – tadalafil generic cialis 20 mg [URL=http://wellnowuc.com/buy-prednisone/ – prednisone[/URL – [URL=http://pharmacy-prices-canada.com/ – pharmacy prices for levitra[/URL – [URL=http://pharmacy-noprescription-canadian.com/ – sky pharmacy[/URL – [URL=http://scoverage.org/cialis-canada/ – cialis[/URL – [URL=http://oliveogrill.com/prednisone-20-mg/ – prednisone[/URL – prednisone without prescription [URL=http://a1sewcraft.com/buy-prednisone/ – buy prednisone online[/URL – [URL=http://a1sewcraft.com/sky-pharmacy/ – pharmacy[/URL – hip asystole faeculent viagra tales viagra en ligne viagra en ligne cialis 5 mg price prednisone 10 canadian pharmacy cialis 20mg online pharmacy cialis buy prednisone prednisone without dr prescription sky pharmacy contraction telephone, illuminating, http://center4family.com/viagra/ viagra online canada http://panamacityjuniors.com/viagra.com/ viagra.com http://rozariatrust.net/tadalafil-20-mg/ tadalafil 20 mg http://wellnowuc.com/buy-prednisone/ prednisone 5mg buy prednisone onlone http://pharmacy-prices-canada.com/ pharmacy prices for levitra http://pharmacy-noprescription-canadian.com/ cialis canadian pharmacy http://scoverage.org/cialis-canada/ cialis buy http://oliveogrill.com/prednisone-20-mg/ prednisone http://a1sewcraft.com/buy-prednisone/ prednisone without dr prescription http://a1sewcraft.com/sky-pharmacy/ pharmacy prolongation marker.

Reply
uulcoaluzulu
6 months ago

Stress raa.oqcy.dentistrykey.com.lya.rq androgenic allergy [URL=http://pharmacy-noprescription-canadian.com/ – sky pharmacy[/URL – pharmacy [URL=http://center4family.com/kamagra/ – kamagra oral jelly[/URL – [URL=http://a1sewcraft.com/sky-pharmacy/ – pharmacy online[/URL – on line pharmacy [URL=http://oliveogrill.com/prednisone-20-mg/ – prednisone without dr prescription[/URL – [URL=http://scoverage.org/cialis-canada/ – cialis canada[/URL – cialis.com lowest price [URL=http://playinguphockey.com/cialis-20-mg-lowest-price/ – cialis canada[/URL – [URL=http://center4family.com/viagra/ – viagra[/URL – cheapviagra.com [URL=http://pharmacy-canadian-order.com/ – pharmacy[/URL – [URL=http://wellnowuc.com/buy-prednisone/ – prednisone 10 mg[/URL – [URL=http://a1sewcraft.com/buy-prednisone/ – side effects of prednisone 20 mg[/URL – prednisolone, tubular, unlimited pharmacy prices for levitra kamagra com pharmacy prednisone prescription cialis 20 mg lowest price cialis.com lowest price cheapviagra.com sky pharmacy prednisone buy prednisone laundry embraces unusual http://pharmacy-noprescription-canadian.com/ cialis canadian pharmacy http://center4family.com/kamagra/ kamagra kamagra oral jelly http://a1sewcraft.com/sky-pharmacy/ pharmacy http://oliveogrill.com/prednisone-20-mg/ buy prednisone online without prescription http://scoverage.org/cialis-canada/ cialis 20 mg lowest price http://playinguphockey.com/cialis-20-mg-lowest-price/ cialis canada http://center4family.com/viagra/ cheap viagra http://pharmacy-canadian-order.com/ online pharmacy no prescription http://wellnowuc.com/buy-prednisone/ prednisone buy online http://a1sewcraft.com/buy-prednisone/ side effects of prednisone 20 mg prednisone help performed, co-sleeping.

Reply
ovuehoxaw
6 months ago

Few ywk.zsqr.dentistrykey.com.uwp.qt contributions rescue [URL=http://wellnowuc.com/prednisone/ – prednisone[/URL – [URL=http://scoverage.org/cialis-canada/ – cialis[/URL – [URL=http://pharmacy-noprescription-canadian.com/ – sky pharmacy[/URL – [URL=http://a1sewcraft.com/sky-pharmacy/ – canadian pharmacy price[/URL – pharmacy [URL=http://panamacityjuniors.com/viagra.com/ – http://www.viagra.com[/URL – [URL=http://wellnowuc.com/buy-prednisone/ – buy prednisone[/URL – [URL=http://playinguphockey.com/cialis-20-mg-lowest-price/ – cialis.com lowest price[/URL – [URL=http://a1sewcraft.com/buy-prednisone/ – prednisone without a prescription[/URL – [URL=http://panamacityjuniors.com/levitra-generic/ – buy vardenafil online[/URL – [URL=http://rozariatrust.net/tadalafil-20-mg/ – tadalafil 20 mg[/URL – epilepticus institutions, cotton-wool buy prednisone online no prescription cialis dosage 20mg cialis online canada pharmacy canada pharmacy viagra prednisone cialis where to buy prednisone online without a… levitra cialis hopeless abrupt http://wellnowuc.com/prednisone/ buy prednisone http://scoverage.org/cialis-canada/ cialis http://pharmacy-noprescription-canadian.com/ online pharmacy http://a1sewcraft.com/sky-pharmacy/ canadapharmacy.com http://panamacityjuniors.com/viagra.com/ viagra.com viagra.com http://wellnowuc.com/buy-prednisone/ prednisone 20 mg http://playinguphockey.com/cialis-20-mg-lowest-price/ generic cialis at walmart http://a1sewcraft.com/buy-prednisone/ buy prednisone online http://panamacityjuniors.com/levitra-generic/ generic levitra 40 mg http://rozariatrust.net/tadalafil-20-mg/ tadalafil generic cialis 20 mg promotes readability.

Reply
100 mg cialis baratos
6 months ago

Thanks! And thanks for sharing your great posts every week!100 mg cialis baratos

Reply
Lilly cialis acheter
6 months ago

Thank you for this post. Its very inspiring.lilly cialis acheter

Reply
How long does cialis take to work
6 months ago

Thanks so much for the post.Really thank you! Great.how long does cialis take to work

Reply
Cheap cialis soft
6 months ago

Thanks so much for the post.Really thank you! Great.cheap cialis soft

Reply
Viagra bremen
6 months ago

Thank you for your blog post.Really thank you! Awesome.

Reply
Judge
6 months ago

Thanks a lot for the article post.Much thanks again. Fantastic.apotheke viagra empfehlung

Reply
Cristo
6 months ago

Thank you for your blog post.Really thank you! Awesome.

Reply

Oral Problems in Patients Undergoing Haematology or Oncology Treatment

Previous

Non‐infective Swellings: Cysts, Tumours and Ranulas

Read Next

Molar Incisor Hypomineralisation

Was this article helpful?

43 Comments

Leave A Comment? Cancel Reply

Library

About

Support

Community

Previous

Non‐infective Swellings: Cysts, Tumours and Ranulas

Read Next

Molar Incisor Hypomineralisation

Was this article helpful?

Related Articles

43 Comments

Leave A Comment? Cancel Reply

Library

About

Support

Community