Ljiljana Jankovic

A systematic review of salivary gland hypofunction and xerostomia induced by cancer therapies: prevalence, severity and impact on quality of life

PurposeThis systematic review aimed to assess the literature for prevalence, severity, and impact on quality of life of salivary gland hypofunction and xerostomia induced by cancer therapies.MethodsThe electronic databases of MEDLINE/PubMed and EMBASE were searched for articles published in English since the 1989 NIH Development Consensus Conference on the Oral Complications of Cancer Therapies until 2008 inclusive. Two independent reviewers extracted information regarding study design, study population, interventions, outcome measures, results and conclusions for each article.ResultsThe inclusion criteria were met by 184 articles covering salivary gland hypofunction and xerostomia induced by conventional, 3D conformal radiotherapy or intensity-modulated radiotherapy in head and neck cancer patients, cancer chemotherapy, total body irradiation/hematopoietic stem cell transplantation, radioactive iodine treatment, and immunotherapy.ConclusionsSalivary gland hypofunction and xerostomia are induced by radiotherapy in the head and neck region depending on the cumulative radiation dose to the gland tissue. Treatment focus should be on optimized/new approaches to further reduce the dose to the parotids, and particularly submandibular and minor salivary glands, as these glands are major contributors to moistening of oral tissues. Other cancer treatments also induce salivary gland hypofunction, although to a lesser severity, and in the case of chemotherapy and immunotherapy, the adverse effect is temporary. Fields of sparse literature included pediatric cancer populations, cancer chemotherapy, radioactive iodine treatment, total body irradiation/hematopoietic stem cell transplantation, and immunotherapy.

A systematic review of salivary gland hypofunction and xerostomia induced by cancer therapies: management strategies and economic impact

PurposeThis systematic review aimed to assess the literature for management strategies and economic impact of salivary gland hypofunction and xerostomia induced by cancer therapies and to determine the quality of evidence-based management recommendations.MethodsThe electronic databases of MEDLINE/PubMed and EMBASE were searched for articles published in English since the 1989 NIH Development Consensus Conference on the Oral Complications of Cancer Therapies until 2008 inclusive. For each article, two independent reviewers extracted information regarding study design, study population, interventions, outcome measures, results, and conclusions.ResultsSeventy-two interventional studies met the inclusion criteria. In addition, 49 intensity-modulated radiation therapy (IMRT) studies were included as a management strategy aiming for less salivary gland damage. Management guideline recommendations were drawn up for IMRT, amifostine, muscarinic agonist stimulation, oral mucosal lubricants, acupuncture, and submandibular gland transfer.ConclusionsThere is evidence that salivary gland hypofunction and xerostomia induced by cancer therapies can be prevented or symptoms be minimized to some degree, depending on the type of cancer treatment. Management guideline recommendations are provided for IMRT, amifostine, muscarinic agonist stimulation, oral mucosal lubricants, acupuncture, and submandibular gland transfer. Fields of sparse literature identified included effects of gustatory and masticatory stimulation, specific oral mucosal lubricant formulas, submandibular gland transfer, acupuncture, hyperbaric oxygen treatment, management strategies in pediatric cancer populations, and the economic consequences of salivary gland hypofunction and xerostomia.

Mucositis prevention by improved dental care in acute leukemia patients

Goals of workThe aim of the present study was to evaluate the effects of the intensive dental care protocol in preventing oral complications in acute leukemia patients.Patients and methodsThirty-four patients hospitalized for induction remission therapy for acute leukemia were randomly assigned to one of two groups, whether to receive intensive dental care protocol or not. The intensive dental care group of patients received dental treatment and plaque and calculus removal prior to chemotherapy and supervised oral hygiene measures during chemotherapy. The limited dental care group of patients did not receive prechemotherapy dental care. Groups were comparable in age, sex, and antineoplastic treatment received. Patients were examined after admission to the hospital; at the initiation of the chemotherapy; and 7, 14, 21, and 28 days after initiation of therapy. Positive data about subjective difficulties were taken by anamnesis. Oral hygiene index (OHI) and gingival index (GI) were used to assess the periodontal status of the patients. The severity of mucositis was evaluated according to WHO classification.Main resultsThe results of this study pointed out lower mean values of GI and lower mean values of mucositis score in the intensive dental care group of patients during the whole period of examination. Although the differences in mean values were not statistically significant on most of the examination days, intensive dental care group of patients developed less severe and less painful oral complications compared to the limited dental care group of patients.ConclusionWe conclude that proper dental care and preventive measures both before and during chemotherapy can be beneficial to these patients.

Calcitonin gene-related peptide levels in saliva of patients with burning mouth syndrome

Burning mouth syndrome (BMS) is an intraoral burning sensation for which no medical or dental cause can be found. Recent studies suggest that primary neuropathic dysfunction might be involved in the pathogenesis of BMS. Calcitonin gene-related peptide (CGRP) plays an important role in the development of pain and serves as a biological marker of trigeminovascular activation. The aim of this study was to determine the levels of CGRP in the saliva of BMS patients and estimate the trigeminovascular activation in BMS. CGRP levels were measured, by RIA method in 78 BMS patients and 16 healthy subjects. The levels of CGRP were non-significantly decreased in BMS patients in comparison to healthy subjects. These results suggest that trigeminal nerve degeneration may be the underlying cause of BMS.

Prevalence of oral herpes simplex virus reactivation in cancer patients: a comparison of different techniques of viral detection.

BACKGROUND Oral reactivation of latent Herpes simplex virus (HSV) infection may easily occur in cancer patients. Virus reactivation can cause oral mucosa damage, worsen already existing lesions caused by stomatotoxic effect of cancer therapy and, whether symptomatic or asymptomatic, ample spreading and promote viral transmission. METHODS Polymerase chain reaction (PCR), cell-culture and direct immunofluorescence have been used to determine the frequency of oral HSV reactivation in 60 patients undergoing chemotherapy for different malignancies. RESULTS By means of PCR, the presence of viral DNA was detected in 71.7% of patients prior to chemotherapy and in 85.0% after chemotherapy. 33.3% of patients before and 40.0% after chemotherapy were viral-culture positive, while 3.3% of patients before and 11.7% after chemotherapy were positive as shown by direct immunofluorescence. No significant difference in HSV-1 reactivation was found before and after chemotherapy. In addition, no significant difference was found when comparing HSV-1 reactivation in patients with and without mucositis. HSV-2 was not detected in any of the patients. CONCLUSIONS Reactivation of latent HSV is exceptionally frequent in cancer patients. The results of this study suggest that virus reactivation occurs independently of cancer chemotherapy. The potential role of HSV reactivation in oral mucosa damage remains unclear.

Humoral immunity to cow’s milk proteins and gliadin within the etiology of recurrent aphthous ulcers?

OBJECTIVES The goal of this study was to determine the incidence of serum antibodies to gliadin and to cows milk proteins (CMP) using ELISA test, within patients who have recurrent aphthous ulcers (RAU). SUBJECTS AND METHODS Fifty patients with recurrent aphthous ulcers and fifty healthy people were included in this research. Levels of serum IgA and IgG antibodies to gliadin and IgA, IgG and IgE to CMP were determined using ELISA. RESULTS The levels of serum antigliadin IgA and IgG antibodies were not significantly higher in patients with RAU in comparison with the controls (P = 0.937 and P = 0.1854 respectively). The levels of serum anti-CMP IgA, IgG and IgE antibodies were significantly higher in patients with RAU in comparison with the controls (P < 0.005, P < 0.002 and P < 0.001 respectively). In general, the increased humoral (IgA or IgG) immunoreactivity to CMP was found in 32 of 50 patients, while 17 of them showed the increased levels of both IgA and IgG immunoreactivity to CMP. At the same time, 16 out of 50 patients had IgA, IgG and IgE immunoreactivity to CMP. CONCLUSION These results indicate the strong association between high levels of serum anti-CMP IgA, IgG and IgE antibodies and clinical manifestations of recurrent aphthous ulcers.

The role of specific cow's milk proteins in the etiology of recurrent aphthous ulcers.

BACKGROUND Recurrent aphthous ulcerations (RAU), or recurrent aphthous stomatitis, is recognized as one of the most common oral mucosal diseases worldwide. It was noted some connection between immunity to cows milk proteins (CMP) and oral diseases. The goal of this study was to determine the prevalence of the increased levels of serum antibodies to specific cows milk proteins (SCMP), constituents of cheese or of whey, by enzyme-linked immunosorbent assay (ELISA) test, in subjects who have RAU. METHODS Fifty subjects with RAU and 50 healthy people, as controls (C), were included in this research. Levels of serum IgA, IgG, and IgE antibodies to SCMP were determined by ELISA. The statistical analysis of data was performed by Wilcoxon rank sum test with continuity correction. RESULTS The levels of serum anti-SCMP IgA, IgG, and IgE antibodies were significantly higher in subjects with RAU in comparison with controls (P < 0.005). CONCLUSIONS These results indicate the strong association between high levels of serum anti-SCMP IgA, IgG, and IgE antibodies, especially to caseins: α-, β-, and κ-casein from cows milk and clinical manifestations of RAU. Serum immunity to the whey proteins in subjects with RAU was not in so high percentage expressed.

Some patients with NHL possessed immunoreactivity to gliadin and to cow’s milk proteins

Non-Hodgkin lymphoma (NHL) represents heterogeneous group of diseases either B, or T cell origin. In order to assess whether food antigens contribute to the imbalance of immune response, the aim of this work was screening the sera of patients with (mostly) B cell NHL, and of people with non-malignant health disorders (NMD), as well as of healthy people for their immunoreactivity to food constituent gliadin, and to cow’s milk proteins. Data obtained by ELISA tests show the existence of the enhanced immunoreactivity to food antigens in some NHL patients, as well as in some people with NMD. The high degree of coincidence in the presence of enhanced levels of immune complexes in circulation (CIC) and of immunoreactivity with gliadin in immunofixation (after the serum protein electrophoresis in agarose gel in veronal buffer, at pH 8.6) especially in NHL patients points that some antigliadin immunoreactivity unrevealed in ELISA tests could be hidden in CIC. This, only in the presence of malignant genotype, as well as the enhanced levels of CIC in some of NHL patients could both, at least partially contribute to the persistent non-specific support of disease. They call for the new research of the clinical importance of both, the elevated humoral immunity to food antigens (gluten, cow’s milk proteins) for the course of this very severe hematological disease.

Good tolerance to goat's milk in patients with recurrent aphthous ulcers with increased immunoreactivity to cow's milk proteins.

BACKGROUND Recurrent aphthous ulcers (RAU) represent a very common, but poorly understood mucosal disorder. The connection between immunity to cows milk proteins (CMP) and oral diseases was noted earlier. The goal of this study was to determine the prevalence of the increased levels of serum antibodies to goats milk proteins (GMP), by enzyme-linked immunosorbent assay (ELISA) test, in subjects who have RAU and proven increased immunity to CMP. METHODS Fifty subjects with RAU (36 with proven increased immunity to CMP and 14 without this increased immunity) were included in this research. Levels of serum IgA, IgG, and IgE antibodies to the same quantity of the examined antigens were determined by ELISA. The statistical analysis of data was performed by Wilcoxon rank-sum test and Mann-Whitney test. RESULTS The levels of serum antifresh cows milk IgA, IgG, and IgE antibodies were significantly higher than the levels of serum antifresh goats milk, in subjects with RAU with proven increased immunoreactivity to CMP (P = 0.0003; P < 0.0001; P < 0.0001). CONCLUSIONS These results indicate that patients with RAU with increased immunity to CMP could consider the use of goats milk as the alternative protein source.

Circulating immune complexes, immunoglobulin G, salivary proteins and salivary immunoglobulin A in patients with Sjögren's syndrome

INTRODUCTION Sjögrens syndrome (SS) is a chronic autoimmune disorder, with its major clinical manifestations resulting from changes in exocrine glands. OBJECTIVE The aim of this study was to evaluate serum concentrations of circulating immune complexes (CIC) and immunoglobulin G (IgG), and salivary proteins (SP) and salivary immunoglobulin A (slgA) in 40 patients with SS, and to correlate these values among themselves, as well as with the unstimulated salivary flow rate (USFR) and the duration of disease. METHODS The total of 40 patients were included in this research. CIC was determined using the solution of polyethylene glycol and IgG with the standard procedure of radial immunodiffusion. SP was investigated by the method of Lowry and slgA was separated from the whole saliva using the method of immune chromatography. RESULTS The values of most of the studied parameters exceeded the normal range in a high degree: CIC 72.5%, IgG 70%, SP 80%. The concentrations of CIC were significantly higher in the patients with the duration of disease less than 10 years. With the decrease of USFR, the concentration of slgA and IgG were increased with statistical significance. CONCLUSION The increased prevalence of abnormal values of CIC, IgG and SP indicate that the patients with SS have developed a higher level of immune reactivity. These results could be useful in diagnosis and disease activity monitoring.