Cleft Formation Research Articles

Msx1 Heterozygosity in Mice Enhances Susceptibility to Phenytoin-Induced Hypoxic Stress Causing Cleft Palate.

Cleft palate is among the most frequent congenital defects in humans. While gene-environment multifactorial threshold models have been proposed to explain this cleft palate formation, only a few experimental models have verified this theory. This study aimed to clarify whether gene-environment interaction can cause cleft palate through a combination of specific genetic and environmental factors. Msx1 heterozygosity in mice (Msx1+/-) was selected as a genetic factor since human MSX1 gene mutations may cause nonsyndromic cleft palate. As an environmental factor, hypoxic stress was induced in pregnant mice by administration of the antiepileptic drug phenytoin, a known arrhythmia inducer, during palatal development from embryonic day (E) 11 to E14. Embryos were dissected at E13 for histological analysis or at E17 for recording of the palatal state. Phenytoin administration downregulated cell proliferation in palatal processes in both wild-type and Msx1+/- embryos. Bone morphogenetic protein 4 (Bmp4) expression was slightly downregulated in the anterior palatal process of Msx1+/- embryos. Although Msx1+/- embryos do not show cleft palate under normal conditions, phenytoin administration induced a significantly higher incidence of cleft palate in Msx1+/- embryos compared to wild-type littermates. Our data suggest that cleft palate may occur because of the additive effects of Bmp4 downregulation as a result of Msx1 heterozygosity and decreased cell proliferation upon hypoxic stress. Human carriers of MSX1 mutations may have to take more precautions during pregnancy to avoid exposure to environmental risks.

Botulinum toxin type A as a novel method of preventing cleft lip scar hypertrophy—A literature review

Cleft lip is a congenital development defect. Primary cleft lip repair leads to cleft scar formation. The resulting scar often undergoes hypertrophy, which negatively affects the facial esthetics, function, and patient's mental health. One of the methods used in scar therapy described in recent years is botulinum toxin injections The aim of this work is to present current knowledge about the impact of botulinum toxin A on cleft lip scar appearance and its effect on scar hypertrophy. The literature search was conducted in the English language via the PubMed and Google Scholar databases. The results show injections seem to be a promising method in cleft lip scar management. However, future studies, especially randomized controlled trials, are necessary to assess the effect of BoNT-A compared with placebo and to determine the optimal dosages and injection schemes for BoNT-A treatment in cleft lip patients.

A case of anti‐laminin 332 mucous membrane pemphigoid manifesting as desquamative gingivitis

AbstractAnti‐laminin 332 mucous membrane pemphigoid (MMP) is characterized by circulating anti‐laminin 332 autoantibodies, with a high risk of concurrent malignant neoplasms. We report a case of anti‐laminin 332 MMP manifesting as a desquamative gingivitis. A 45‐year‐old woman experienced painful erythema and occasional bullous lesions on the gingiva despite good oral hygiene and plaque control. Intraoral examination revealed gingival inflammation with desquamation. Biopsy showed subepithelial cleft formation suggesting a subepidermal blister. Direct immunofluorescence revealed the deposition of IgG and IgA in the epithelium. Accordingly, we diagnosed anti‐laminin 332 MMP and treated with systemic corticosteroids. The oral lesion resolved after 3 months.

Scar management in patients after cleft lip repair-Systematic review Cleft lip scar management.

Cleft lip is a commonly occurring congenital development defect. Primary cleft lip repair leads to cleft scar formation. The resulting scar often undergoes hypertrophy, which negatively affects facial esthetics, function, and the patient's mental health. The systematic review presented here was carried out to answer the following question: What cleft lip scar management options exist and how effective are they? The systematic review of the articles on scar management methods in cleft lip patients was done in accordance with the PRISMA checklist. The literature search was conducted via the PubMed and Google Scholar databases. A total of 95 items were obtained. Finally, nine works have been included in the systematic review. Among the obtained works, there is a variety of cleft lip scar management methods. All the presented methods of cleft lip scar management proved to be effective in cleft scar therapy. Cleft lip scar management should be considered as a constant and mandatory element of the treatment plan in cleft patients. It is also worth considering creating detailed protocols of conduct for cases of cleft lip scaring which pay attention to existing needs, prevention/correction and problems of superficiality and depth.

Persistent Hypotony and Annular Ciliochoroidal Detachment After Microhook Ab Interno Trabeculotomy.

To report persistent hypotony after μLOT, a minimally invasive glaucoma surgery (MIGS). This observational case series included 4 consecutive cases (3 men, 1 woman; mean age, 48.8±15.1 y) of persistent hypotony that developed after μLOT between May 2015 and March 2018. The patients' data and surgical results were obtained from the medical charts. All patients had open-angle glaucoma (2 juvenile, 1 primary, and 1 pigmentary) and were myopic (axial lengths, >24 mm). Two patients had undergone previous refractive surgery. μLOT alone was performed in 2 cases and combined with cataract surgery in 2 cases. In all cases, hypotony below 5 mm Hg was recorded 1 day postoperatively and sustained. In all cases, ultrasound biomicroscopy showed an annular CCD; communication between the anterior chamber and suprachoroidal space was detected in 3 of 4 cases. The hypotony resolved in 3 of the 4 cases from 2 to 8 months postoperatively, that is, spontaneously in 2 cases (cases 1 and 4) and after sulfur hexafluoride gas injection into the anterior chamber in 1 case (case 2). CCD resolution accompanied remarkedly high intraocular pressure, which required filtration surgeries. The incidence of persistent hypotony was 0.7% (4/547 eyes). After MIGS, persistent hypotony because of CCD rarely occurs. Increased uveoscleral outflow because of LOT or creation of a cyclodialysis cleft by traction of the pectinate ligament can be a mechanism of CCD development. Young age and myopia can be risks for cyclodialysis cleft formation and hypotony maculopathy after MIGS.

A LCMS-based untargeted lipidomics analysis of cleft palate in mouse

BackgroundRecent studies have shown that lipid metabolism was abnormal during the formation of cleft palate. However, the composition of these lipid species remains unclear. ObjectiveAims of this study were to identify the lipid species components and reveal the key lipid metabolic disorders in cleft palate formation. MethodsThe pregnant mice were divided into experimental group exposed to all-trans retinoic acid (RA-treated group) (n = 12) and control group (n = 12) at embryonic gestation day 10.5 (E0.5). The component of the palatal tissue metabolome was analyzed using a LCMS-based nontargeted lipidomics approach. Multivariate statistical analysis was then carried out to assess the differences between the RA-treated group and the control group. ResultsTwenty-nine lipid species were found to discriminate between RA-treated and control embryos. Among them, 28 lipid species increased and 1 lipid species decreased in the RA-treated group. Among these lipids, 13 were triglycerides, 9 were PEs, 3 were PCs, 2 were PSs, 2 were DGs. Further analysis of the number of carbons and unsaturated bond of triglycerides showed that TGs with high unsaturated bonds constituted a higher fraction in the RA-treated group. A higher amount of triglycerides containing 52, 54, 56, 58, 60 carbons, and 1 to 8 unsaturated bonds. Of note, under RA treatment, TG 50:1, 52:2, 56:6and 60:8 became the most prominent. ConclusionLipid metabolism is significantly different in the formation of cleft palate induced by RA, and the unsaturated triglycerides increased in the RA-treated group may play an important role in the formation of cleft palate.

The Effect of Buccal Fat Pad Graft in the Palatoplasty and the Risk Factor of Postoperative Palatal Fistula.

The aim of this study was to evaluate the effect of buccal fat pad (BFP) in the palatoplasty and to investigate the risk factors associated with postoperative palatal fistula formation. Sixty-five cleft palate patients were enrolled for this study. Clinical data regarding sex, age, type of cleft, surgical technique, the ratio of cleft width, and BFP graft were collected. The ratio of cleft width was measured and calculated using preoperative clinical photographs. In 36 patients, the BFP was harvested and grafted on the cleft palate to prevent palatal fistula formation. The patients were followed up, the incidence of fistula formation was investigated, and the risk factors related with the fistula were evaluated. Four patients had postoperative palatal fistula and were not BFP grafted during operation. The BFP graft and ratio of cleft width are significant factors in palatal fistula formation (P = .035, .003). There was a significant difference in the ratio of cleft width between the normal and fistula groups (P = .006). In the logistic regression analysis, there was significant association between high ratio of cleft width and palatal fistula formation in the no BFP group (odds ratio; 11.15, P = .036). The ratio of cleft width and BFP graft was a significant factor in palatal fistula formation. The BFP graft is a reliable procedure to prevent palatal fistula formation and increase the success of palatoplasty.

The effects of soft cryotherapy on conjunctiva and cornea in isolated pig eyes and comparison with standard liquid nitrogen: A pilot ex vivo study.

To evaluate the immediate effects on cornea and conjunctiva of a cryosurgical method based on the application of a dimethyl ether, propane and isobutene solution (DMEPI, Histofreezer® ), and of Liquid Nitrogen (LN2 ; Cry-Ac Cryogun® ). A total of 52 isolated pig eyes were obtained at the slaughterhouse, preserved for less than one hour in Ringer Lactate and divided into four groups. The first group included eyes treated with two applications of DMEPI in the center of the cornea, the second group eyes treated with DMEPI on the third eyelid's conjunctiva, the third group eyes treated with LN2 on the third eyelid's conjunctiva and the fourth group included eyes treated with LN2 on the central cornea. Each cryogen application (0.8cm area) lasted 40seconds. Each group included one (untreated) control eye. The eyes were submitted for routine histopathological evaluation. Histological alterations were recorded and scored with a semiquantitative scoring system. No tissue alteration was detected on the conjunctiva, in any of the groups. Treated corneas showed mild to moderate cytoplasmic vacuolization of epithelial cells, shrinkage and hypereosinophilia of small groups of basal epithelial cells and stromal cleft formation. Soft cryosurgery caused no severe acute histologically detectable damage to cornea and conjunctiva in isolated pig eyes, and no significant difference was observed when LN2 and DMEPI treatments were compared. Further in vivo studies should be performed in order to verify possible delayed effects and the clinical efficacy of DMEPI cryosurgery in specific corneal and/or conjunctival diseases.

The double coil molder: A modified presurgical nasoalveolar molding appliance for bilateral cleft correction

A cleft formation in infants is quite disturbing for the parents as it extremely affects the esthetics of the infant. Other than esthetics, it also disturbs the normal functioning of the infant. The reduction of this deformity in bilateral cleft patients is done by bringing the deviated premaxilla medially using a technique called presurgical nasoalveolar molding (PNAM) technique. The deviated premaxilla is mainly due to the growth of the nasal septum and the effect of its growth on the vomero-premaxillary suture. We present a case of bilateral cleft lip and palate which is treated by a double coil molder which is a modified PNAM appliance, followed by surgery of the lip and the palate. A follow-up inspection is done to check the outcome of the therapy on the long term.

Epignathi Teratoma Co-Existing with Tongue Choristoma and Cleft Palate in a Neonate: Report of a Rare Case and Review of Literature

Background: Oral epignathus teratoma is an extremely rare neoplasm that occurs exclusively in neonates. The tumor can grow to a large size obstructing airways and it may prevent fusion of the nasal septum with the palatine processes, which may result in cleft palate formation. The rare tumor may also co-exist with other congenital malformations such as hamartoma and choristoma causing airway obstruction and death. Case report: We present a case of a one-day-old male neonate who presented with oral mass associated with difficulty in breathing and inability to suck breast milk. Computed Tomography (CT) scan revealed multiple masses involving the alveolar, palate, and tongue along with cleft palate. Emergency surgery was done to relieve the airway and histology confirmed epignathi teratoma with tongue choristoma. Conclusion: Epignathus teratoma is a rare condition that requires prenatal prompt diagnosis. However, in countries with underprivileged hospital facilities, early surgical intervention during the neonatal period is what is required to save the patient from airway obstruction. Association of the tumor with midline anomalies is mostly the norms, however, 5% of cases with malignant transformation have been reported and the tumor is commonly associated with endodermal sinus tumor. Therefore long term follow-up of patients with serum tumor markers is highly recommended.

Msx1 deficiency interacts with hypoxia and induces a morphogenetic regulation during mouse lip development.

Nonsyndromic clefts of the lip and palate are common birth defects resulting from gene-gene and gene-environment interactions. Mutations in human MSX1 have been linked to orofacial clefting and we show here that Msx1 deficiency causes a growth defect of the medial nasal process (Mnp) in mouse embryos. Although this defect alone does not disrupt lip formation, Msx1-deficient embryos develop a cleft lip when the mother is transiently exposed to reduced oxygen levels or to phenytoin, a drug known to cause embryonic hypoxia. In the absence of interacting environmental factors, the Mnp growth defect caused by Msx1 deficiency is modified by a Pax9-dependent 'morphogenetic regulation', which modulates Mnp shape, rescues lip formation and involves a localized abrogation of Bmp4-mediated repression of Pax9 Analyses of GWAS data revealed a genome-wide significant association of a Gene Ontology morphogenesis term (including assigned roles for MSX1, MSX2, PAX9, BMP4 and GREM1) specifically for nonsyndromic cleft lip with cleft palate. Our data indicate that MSX1 mutations could increase the risk for cleft lip formation by interacting with an impaired morphogenetic regulation that adjusts Mnp shape, or through interactions that inhibit Mnp growth.

Safe and effective subcutaneous adipolysis in minipigs by a collagenase derivative.

Adipocytes attached to the extracellular matrix (ECM) mainly consist of collagen in adipose tissues, while the degradation of ECM by collagenase induces the apoptosis of adipocytes, leading to a decrease in local subcutaneous adipose. To achieve this goal, we are developing a mutant collagenase H (ColH) to remove local subcutaneous fat such as submental fat (SMF). Three vectors were constructed for expressing rColH(FM, mutant for fat melting, with 6xHis tag), rColH(WT, wild-type, with 6xHis tag), and rColH(E451D, E451D mutant, without 6xHis tag) in Escherichia coli. rColH(FM) & rColH(WT) were purified by Ni Sepharose on a laboratory scale, while rColH(E451D) was purified by five chromatography purification steps on a large scale. Then, the stability of rColH(FM) and rColH(WT) was tested by SDS-PAGE to investigate the influence of the E451D mutation on stability. Afterwards, the enzyme kinetics of ColH (mutant or wild-type, with or without His tag) were investigated and compared. Finally, the adipolysis of rColH(E451D) at various doses was tested in vitro and in vivo. The ultrasound results in minipigs suggested that effective adipolysis was induced by rColH(E451D) compared with the negative control, and the histological results suggest dose-dependent fibrosis, necrosis, inflammation and cholesterol cleft formation. These findings indicate the possibility of rColH(E451D) becoming a new injectable drug to safely remove subcutaneous adipose.

MiR-106a-5p modulates apoptosis and metabonomics changes by TGF-β/Smad signaling pathway in cleft palate

BackgroundThe molecular mechanisms of abnormal palatogenesis were investigated in this study. A key regulator, miR-106a-5p, and its target pathway were analyzed. ObjectivesThis research is trying to clarify the underlying mechanism of the modulation of miRNA transcription during the formation of cleft palate by 7T and 9.4T NMR metabolomic platforms. MethodDifferentially expressed miRNAs and mRNAs were analyzed by microarray analysis and verified by qRT-PCR. The protein expression in TGFβ signaling pathways were analyzed by Western Blotting. The relationship between miR-106a-5p and TGFβ were analyzed by luciferase reporter assay. Cell apoptosis were analyzed by flow cytometer. And finally, the metabonomics were analyzed by NMR and multivariate data analysis models (MVDA). ResultsThe expression of miR-106a-5p increased in cleft palatal tissue and negatively correlated with the protein level of Tgfbr2. The luciferase assay further proved that the tgfbr2 was a direct target of miR-106a-5p. In another aspect, miR-106a-5p increased apoptosis level in palatal mesenchymal cells, possibly because its inhibition of TGFβ signaling pathway. Moreover, low cholesterol and choline levels with high citric acid and lipid levels were observed by 7T and 9.4T NMR metabonomic analysis, which inferred the disorder of cell membrane synthesis in cleft palate formation. Furthermore, transformation from choline to phosphatidylcholine regulated by miR-106a-5p was also disrupted, resulting in phosphatidic choline synthesis disorder and reduced cell membrane synthesis. ConclusionsThe regulatory mechanism of cleft palate was studied at transcriptional and metabolomics levels, which may provide important information in understanding the primary cause of this abnormality.

Pancreatic Adenocarcinoma in a Young Woman

Despite significant improvement in the management strategy, pancreatic cancer continues to be a great challenge for surgeons and oncologists. Length of survival largely depends upon stage at diagnosis and a completeness of resection. Distal pancreatectomy with RO resection has been reported as a favorable method in selected pancreatic body and tail tumors. Additional organ resections are rarely required. A young woman was diagnosed with a tumor in the body and tail of the pancreas that required splenectomy in addition to dista1 pancreatectomy. Postoperative course was uneventful. Histopathology revealed the tumor as moderately differentiated adenocarcinoma with extensive areas of necrosis, haemorrhage and cholesterol cleft formation. Resected end of pancreas was free of tumor. She has completed a course of chemotherapy and is doing well after 8 months of surgery.
 Journal of Surgical Sciences (2014) Vol. 18 (2) : 78-82

Bone and soft tissue palatal morphology and potential anchorage sides in cleft palate patients

AimThe aim of this study was to evaluate palatal vertical bone thickness and density in relation to soft tissue on the hard palate for better selection of adequate bone regions for the insertion of orthodontic mini-implants (MIs) in cleft palate patients. Materials and methodsCone beam computed tomography scans (CBCT) were obtained from 60 patients (mean age range 9–12). The study population included patients with isolate right side cleft palate formation (n = 20; 6 females; 14 males), left side cleft palate formation (n = 20; 9 females; 11 males) and without cleft formation as control group (n = 20; 15 females; 5 males). Bone and soft tissue measurements were performed vertical at a 90° angle to the bone surface, on previously defined measurement points (n = 88) on the hard palate. Bone density was measured on ten vertical layers in caudo-cranial direction. ResultsIn non-cleft patient the highest bone thickness was in the anterior palate and decreased significantly in posterior direction. In patients with right and left cleft palate, the highest vertical bone level could be observed at the palatal premaxillary border opposite to the cleft side. Patients in the control group showed a significantly lower vertical soft tissue thickness than patients with palatal cleft formation. The evaluation of bone density showed no significant differences in all three groups. ConclusionThe results suggest that the favorable region for orthodontic MI placement is in the similar anatomical region compared to non-cleft patients, but differs from one side in each group. In unilateral cleft palate patients, the highest bone level was found on the anterior palate side opposite to the cleft side, indicating the most effective region for MIs placement.

The Pathogenesis of Osteochondrosis in Humans and Animals

Osteochondrosis is a disease involving failure of endochondral ossification that occurs in growing animals and children in highly specific predilection sites, resulting in the formation of a cartilaginous or osseocartilaginous flap that causes pain and locking of the joint. In veterinary medicine, the term “osteochondrosis” (OC) is used for all stages of the disease and all affected sites. In human medicine, “osteochondritis dissecans” (OCD), is the preferred term for clinical disease involving the distal femur/knee joint. In other affected sites in humans, the disease is named after the physician(s) who first recognized it at that site; the disease in humans is further subdivided into adult and juvenile forms. Until very recently, subclinical disease was not recognized in humans as the only available tissue for study was the flap removed surgically from the affected joint, which often had been present for months to years. Subclinical disease, however, is well recognized in animals due to study of predilection sites at ages prior to the age of onset of clinical disease, work that are not possible in humans. Because the appearances of the subclinical and clinical disease are completely different, and because only end‐state tissue has been available for study of the disease in humans, the pathogenesis of the disease has been poorly understood in human medicine. In pigs and horses, it has been well demonstrated that subclinical lesions of osteochondrosis involving the articular‐epiphyseal cartilage complex are composed of areas of necrotic epiphyseal cartilage that often surround necrotic cartilage canal blood vessels. The overlying articular cartilage and subjacent subchondral bone are not initially affected; however, as endochondral ossification proceeds these areas of necrotic cartilage cause a delay in the ossification front that is visible in imaging studies. Study of both naturally‐occurring and surgically‐induced disease in animals have unequivocally demonstrated that failure of cartilage canal blood supply is the cause of these lesions. Traumatic forces to the surface of the articular cartilage, even when minimal in severity, may result in collapse of the necrotic epiphyseal cartilage and cleft formation through the overlying articular cartilage, resulting in the well‐recognized clinical disease. Recent development of magnetic resonance imaging methods to identify cartilage canal vessels and areas of cartilage necrosis, as well as access to human cadaveric knee specimens, have provided strong evidence that the pathogenesis of OC/OCD in animals and humans is identical and that subclinical disease in humans occurs years before clinical disease is evident. This work provides the potential for the development of new methods of early detection of disease in humans and methods for monitoring its response to treatment.Support or Funding InformationNIH/NIAMS R01AR070020; NIH/OD K01OD021293; WM Keck FoundationThis abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Two novel genes TOX3 and COL21A1 in large extended Malay families with nonsyndromic cleft lip and/or palate.

BackgroundNonsyndromic cleft lip and/or palate is one of the most common human birth defects worldwide that affects the lip and/or palate. The incidence of clefts varies among populations through ethnic, race, or geographical differences. The focus on Malay nonsyndromic cleft lip and/or palate (NSCL/P) is because of a scarce report on genetic study in relation to this deformity in Malaysia. We are interested to discuss about the genes that are susceptible to cause orofacial cleft formation in the family.MethodsGenome‐wide linkage analysis was carried out on eight large extended families of NSCL/P with the total of 91 individuals among Malay population using microarray platform. Based on linkage analyses findings, copy number variation (CNV) of LPHN2, SATB2, PVRL3, COL21A1, and TOX3 were identified in four large extended families that showed linkage evidence using quantitative polymerase chain reaction (qPCR) as for a validation purpose. Copy number calculated (CNC) for each genes were determined with Applied Biosystems CopyCallerTM Software v2.0. Normal CNC of the target sequence expected was set at two.ResultsGenome‐wide linkage analysis had discovered several genes including TOX3 and COL21A1 in four different loci 4p15.2‐p16.1, 6p11.2‐p12.3, 14q13‐q21, and 16q12.1. There was significant decreased, p < 0.05 of SATB2, COL21A1, and TOX3 copy number in extended families compared to the normal controls.ConclusionNovel linkage evidence and significant low copy number of COL21A1 and TOX3 in NSCLP family was confirmed. These genes increased the risks toward NSCLP formation in that family traits.

Genome-Wide mRNA-Seq Profiling Reveals that LEF1 and SMAD3 Regulate Epithelial-Mesenchymal Transition Through the Hippo Signaling Pathway During Palatal Fusion.

Epithelial-mesenchymal transition (EMT) of the medial edge epithelium (MEE) occurs through fusion of the palatal shelves and is a crucial step in palatogenesis. The key genes, however, and the related signaling pathway of EMT are not yet fully understood. Therefore, the aim of this study was to reveal the key genes and the related signaling pathway of EMT during palatal fusion. C57BL/6J mice at embryonic gestation day 14.5 (E14.5; n = 6) were used to establish the cleft palate model for mRNA-Seq (HiSeq X Ten). The Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed for functional annotations of the differentially expressed genes. Quantitative polymerase chain reaction (qPCR) assays were used to validate the RNAseq data. A total of 936 differentially expressed genes, including 558 upregulated and 378 downregulated genes were identified in cases versus controls, respectively. Among these genes, the GO analysis showed that Lymphoid Enhancer-Binding Factor 1 (LEF1) and SMAD Family Member 3 (SMAD3) significantly enriched biological processes, which were EMT related. The KEGG analysis showed that these genes regulated EMT through the Hippo signaling pathway. LEF1 and SMAD3 were downregulated, and the qPCR results corroborated the RNA-seq data. These results demonstrate that LEF1 and SMAD3 inhibits EMT at the MEE through the Hippo signaling pathway; and that this could contribute to cleft palate formation in embryonic palatal fusion at E 14.5.

Histologic diagnosis and grading of esophageal acute graft-versus-host disease.

Acute intestinal graft-versus-host disease (GvHD) is a serious threat after allogeneic hematopoietic stem cell transplantation (alloHSCT). Although criteria for the histological diagnosis and grading of GvHD are well established for most parts of the gastrointestinal tract, evidence-based criteria have not yet been defined for the esophagus. Here, we evaluated esophageal biopsies obtained from 51 patients who underwent alloHSCT and compared the findings with those within the stomach and duodenum. In 32 of 51 biopsy samples of the esophagus, we identified a continuum of histological features of acute GvHD, ranging from vacuolar degeneration and single-cell apoptosis to the formation of clefts and mucosa denudation in advanced cases. These findings correlated with GvHD involving the stomach and duodenum and the clinical manifestations of GvHD in other organs. We therefore conclude that acute GvHD and esophageal GvHD can be diagnosed and graded histologically. Our findings may help to establish the histological diagnosis of acute GvHD using endoscopic biopsies from the esophagus and to explain the alterations observed in the esophageal mucosa in patients after alloHSCT.

Prevalence of Hypodontia in Unilateral and Bilateral Cleft Lip and Palate Patients Inside and Outside Cleft Area: A Case-Control Study.

The aim of this study is to evaluate the prevalence and distribution of hypodontia, inside and outside the cleft area, in an Italian population with a non-syndromic unilateral (UCLP) and bilateral (BCLP) cleft lip and palate on panoramic radiographs and comparing it with a control sample. Case group was ethnically uniform and consisted in 233 patients. The control group was composed of 1000 subjects. Patients included were between seven and fifteen years old. Descriptive analysis, using absolute and relative frequencies, was performed to check out the prevalence of gender distribution, hypodontia and cleft formation. Statistical analysis was conducted with Chi-squared test, Yate's correction and the Fisher's exact test. The power was set higher than 0.8 for each test. 160 cleft patients (68.68%) presented at least one missing tooth, while 88 patients in the control groups presented agenesis (8.80%). A statistically significant difference was found in case and control groups for upper lateral incisors (37.34% and 48.07% in the case group against 2.50% and 2.60% in the control group), upper and lower second premolars (8.58%, 6.44%, 5.58% and 6.01% in the cleft group and 0.60%, 0.60%, 2.50% and 2.70% in the control group). Higher prevalence of dental agenesis in the maxillary dental arch is explained by the cleft defect. Higher prevalence of mandibular second premolars agenesis cannot be explained by the anatomical defect and suggests a multifactorial aetiology, including environmental and genetic factors, of the cleft condition.