CHAPTER I INTRODUCTION There are 3 topics related to the alimentary and hepatobiliary system and disorders block that

will be discussed in this paper; cleft lip and palate, leukoplakia, and intussusception. Each topic is further elaborated in its own chapter. Orofacial clefts, ie. cleft lip (CL), cleft lip and palate (CLP), are among the most common congenital anomalies. Approximately 1 case of orofacial cleft occurs in every 500-550 births. In the United States, 20 infants are born with an orofacial cleft on an average day, or 7500 every year.1 Children who have an orofacial cleft require several surgical procedures and complex medical treatments; the estimated lifetime medical cost for each child with an orofacial cleft is $100,000, amounting to $750 million for all children with orofacial cleft born each year in the United States. Also, these children and their families often experience serious psychological problems.2 The correct diagnosis of a cleft anomaly is fundamental for treatment, for further genetic and etiopathological studies, and for preventive measures correctly targeting the category of preventable orofacial clefts.3 The World Health Organization (WHO) first defined oral leukoplakia as a white patch or plaque that could not be characterized clinically or pathologically as any other disease; therefore, lichen planus, candidiasis, and white sponge nevus were excluded.4 No etiologic factor can be identified for most persistent oral white plaques (ie, idiopathic leukoplakia). The histopathologic features are highly variable, ranging from hyperkeratosis and hyperplasia to atrophy and severe dysplasia.4 Patients with idiopathic leukoplakia have the highest risk of developing cancer. In studies of these patients, 4-17% had malignant transformation of the lesions in less than 20 years. The risk of developing malignancies at lesion sites is 5 times greater in patients with leukoplakia than in patients without leukoplakia.4

Estimates of malignant transformation vary from 3-33% over a 10-year period. However, many innocuous leukoplakias are not always followed up in some centers, and the studies are often small. As many as 30% of leukoplakias can regress if habits are stopped.5 Patients must be aware that lesions may recur. They should be able to monitor the lesions and report any changes. They should maintain excellent oral hygiene. Patients should avoid any causal factor, such as use of tobacco and alcohol. Leukoplakias can regress under these circumstances. Any degree of dysplasia in a lesion at a high-risk site must be taken seriously and the lesion should be removed. Occasionally, patients are treated by photodynamic therapy or topical cytotoxic agents. Patients should be examined regularly, probably at 3- to 6-month intervals.5 Intussusception is a common cause of childhood intestinal obstruction, occurring more frequently in white children aged 6 months to 2 years and in more males than in females (3:1-2). When this condition occurs in neonates and in children older than 2 years, there is a high incidence of associated bowel abnormality that serves as an initiating lead point for intussusception (about 5% of patients are found to have a lead point). In addition, intussusception is known to occur with greater frequency in children who have undergone recent abdominal surgery, either intraperitoneal or retroperitoneal operations. It is thought that early adhesions or focal edema of the bowel wall create a lead point for the intussusception.6 Invagination of a bowel segment (usually, the small bowel) into the lumen of the more distal bowel (usually, the colon) occurs. The invaginated segment (intussusceptum) is carried distally by peristalsis. Mesentery and vessels become involved with the intraluminal loop and are squeezed within the engulfing segment (intussuscipiens). Almost all occurrences are acute, and bowel obstruction is often the presenting sign of intussusceptions.7

CHAPTER II CLEFT LIP AND PALATE 2.1 Risk Factor There are many risk factors associated with cleft lip and palate. Ethnicity, family history, maternal exposure to environmental factors, maternal diet that cause the formation of cleft lip as well as gender are predisposing factors.1 Family Histo ry Maternal Obesit y

Race

RISK FACTOR S
Environmental Factors Figure 1. Risk Factor of Cleft Lip and Palate1

Sex

2.2

Etiology and Epidemiology There are various causes of cleft lip and palate. In general, any factor that could prevent the processes from reaching each other by slowing down migration, multiplication, or both of neural crest cells by stopping tissue growth and development for a time or by killing some cells that are already in that location would cause a persistence of a cleft. Also, the epithelium that covers the mesenchyme may not undergo programmed cell death, so that fusion of processes cannot take place.1 However, among those that have been identified are genetic factors and environmental factors. It is believed that genetic factors give the baby a predisposition for the disease, but the exposure to environmental factors trigger the occurrence.2

Maternal exposure to hypoxia during pregnancy, cigarette smoke, alcohol and illicit drugs are also common risk factors are known environmental risk factors. Pesticide exposure has also been pointed out. Maternal diet and vitamin intake; retinoid, anticonvulsant drugs, nitrate compounds, organic solvents, parental exposure to lead and illegal drugs also contribute to the occurrence of cleft lip and palate.2 Epidemiological data suggests that in general, all typical orofacial cleft types combined occur in white populations with a frequency of 1 per 500-550 live births. The prevalence rate of clefts in different racial groups is considerable. The lowest rate is for blacks. A high prevalence of cleft lip with or without cleft palate was found for the Japanese population, and the highest prevalence was found for the North American Indian populations. In contrast, no remarkable variation among races was found in cleft palate. In particular, its prevalence did not significantly vary between black and white infants or between infants of Japanese and European origin in Hawaii.1 The sex ratio in patients with clefts varies. In whites, cleft lip and cleft lip and palate occur significantly more often in males, and cleft palate occurs significantly more often in females. In cleft lip with or without cleft palate, the sex ratio correlates with the severity and laterality of the cleft. A large study of 8,952 orofacial clefts in whites found the male-to-female sex ratio to be 1.5-1.59:1 for cleft lip, 1.98-2.07:1 for cleft lip and palate, and 0.72-0.74:1 for cleft palate.1 2.3 Pathogenesis and Pathophysiology The embryological development of the upper lip and nose requires a sequence of complex, genetically programmed events. This involves fusion of the 5 major facial prominences occurring between the 3rd and 8th week of gestation, with lip development between the 3rd and 7th weeks, and palate development between the 5th and 12th week.1 The complexity of this cranio-facial developmental pathway and the numerous developmental points at which clefting could be induced is reflected in the heterogeneity of the phenotypic expression of the condition. 1

Cleft lip and/or palate: the maxillary, medial nasal and lateral nasal prominences converge through a complicated process of epithelial bridging, programmed cell death and sub-epithelial-mesenchymal penetration. Cleft lip and/or palate is likely to be secondary to a defect of epithelial fusion or mesenchymal growth, processes involving many possible genetic loci or intracellular signalling pathways. This results in interrupted fusion of the maxillary and median nasal prominences. In bilateral cleft lip with or without cleft palate, the arterial network and musculature of the lateral elements parallel that of the lateral segment of the uni-lateral deformity. The abnormal insertion of the cleft lip musculature follows the cleft margin up to the piriform aperture, and the prolabial segment receives its blood supply from the septal, columellar, and pre-maxillary vessels.

Isolated uni-lateral cleft lip: the orbicularis oris (OO) is a ring of concentric muscle that constricts and puckers the sphincter of the mouth. In isolated uni-lateral cleft lip, the OO fibres on the cleft side insert into the nasal base, and the central (non-cleft) OO fibres abnormally insert into the nasal spine and septum. This causes the base of the nose to splay laterally when the infant smiles.

Isolated cleft palate: the development of the palate involves fusion of the lateral palatal shelves and nasal septum in an anteroposterior direction from the incisive foramen to the uvula. A cleft palate is formed when normal palatal development is interrupted before the 12th week of gestation. The degree of clefting can range from a complete isolated cleft palate to a bifid uvula. Deformational cleft palate is seen in Pierre Robin sequence, where a small mandible (micrognathia) limits the space for the tongue, and the prominent tongue (glossoptosis) mechanically obstructs palatal fusion leading to the classic triad of micrognathia, glossoptosis and an isolated cleft palate.

Midline clefts of the nose and/or lip: these are likely to arise from an interruption in the fusion of the paired median nasal prominences during embryological development. Most median facial deformities represent

developmental field defects, and are sporadic with multiple aetiological factors. In facial morphogenesis, neural crest cells migrate into the facial region, where they form the skeletal and connective tissue and all dental tissues except the enamel. Vascular endothelium and muscle are of mesodermal origin. The upper lip is derived from medial nasal and maxillary processes. Failure of merging between the medial nasal and maxillary processes at 5 weeks' gestation, on one or both sides, results in cleft lip. Cleft lip usually occurs at the junction between the central and lateral parts of the upper lip on either side. The cleft may affect only the upper lip, or it may extend more deeply into the maxilla and the primary palate. (Cleft of the primary palate includes cleft lip and cleft of the alveolus.) If the fusion of palatal shelves is impaired also, the cleft lip is accompanied by cleft palate, forming the cleft lip and palate abnormality. 1 Cleft palate is a partial or total lack of fusion of palatal shelves. It can occur in numerous ways: 1

Defective growth of palatal shelves Failure of the shelves to attain a horizontal position Lack of contact between shelves Rupture after fusion of shelves

The secondary palate develops from the right and left palatal processes. Fusion of palatal shelves begins at 8 weeks' gestation and continues usually until 12 weeks' gestation. One hypothesis is that a threshold is noted beyond which delayed movement of palatal shelves does not allow closure to take place, and this results in a cleft palate. 1 2.4 Clinical Manifestation Cleft lip can occur as a unilateral (on the left or right side) or as a bilateral anomaly. The line of cleft always starts on the lateral part of the upper lip and continues through the philtrum to the alveolus between the lateral incisor and the canine tooth, following the line of sutura incisiva up to the foramen

incisivum. The clefting anterior to the incisive foramen (ie, lip and alveolus) is also defined as a cleft primary palate. Cleft lip may occur with a wide range of severity, from a notch located on the left or right side of the lip to the most severe form, bilateral cleft lip and alveolus that separates the philtrum of the upper lip and premaxilla from the rest of the maxillary arch. 1 When cleft lip continues from the foramen incisivum further through the sutura palatina in the middle of the palate, a cleft lip and palate (either unilateral or bilateral) is present.2 A wide range of severity may be observed. The cleft line may be interrupted by soft (skin or mucosa) bridges, hard (bone) bridges, or both, corresponding to a diagnosis of an incomplete cleft. This occurs in unilateral and bilateral cleft lip and palate.2 Several subtypes of cleft palate can be diagnosed based on severity. The uvula is the place where the minimal form of clefting of the palate is observed. However, a relatively high prevalence of this anomaly in the general population suggests that a certain proportion may represent the very far end of a normal variability. A more severe form is a cleft of the soft palate. A complete cleft palate constitutes a cleft of the hard palate, soft palate, and cleft uvula. The clefting posterior to the incisive foramen is defined as a cleft of secondary palate.3 2.5 Diagnosis and Management Traditionally, the diagnosis is made at the time of birth by physical examination. Recent advances in prenatal diagnosis have allowed obstetricians to diagnose facial clefts in utero. Medical tests may be done to rule out other possible health conditions.3 Cleft lip can be easily diagnosed by performing ultrasonography in the second trimester of pregnancy when the position of the fetal face is located correctly. 1 Cleft lip and palate is very treatable; however, the kind of treatment depends on the type and severity of the cleft.3

The cleft lip can be repaired by surgical therapy within the first 23 months after birth. While surgery to repair a cleft lip can be performed soon after birth, the often preferred age is at approximately 10 weeks of age, following the "rule of 10s" coined by surgeons Wilhelmmesen and Musgrave in 1969 (the child is at least 10 weeks of age; weighs at least 10 pounds, and has at least 10g hemoglobin). If the cleft is bilateral and extensive, two surgeries may be required to close the cleft, one side first, and the second side a few weeks later. The most common procedure to repair a cleft lip is the Millard procedure pioneered by Ralph Millard. 3 Often an incomplete cleft lip requires the same surgery as complete cleft. This is done for two reasons. Firstly the group of muscles required to purse the lips run through the upper lip. In order to restore the complete group a full incision must be made. Secondly, to create a less obvious scar the surgeon tries to line up the scar with the natural lines in the upper lip (such as the edges of the philtrum) and tuck away stitches as far up the nose as possible. Incomplete cleft gives the surgeon more tissue to work with, creating a more supple and natural-looking upper lip. 3 In some cases of a severe bi-lateral complete cleft, the premaxillary segment will be protruded far outside the mouth. 3 Nasoalveolar molding followed by surgery can improve long-term nasal symmetry among patients with complete unilateral cleft lip-cleft palate patients compared to surgery alone, according to a retrospective cohort study. Significant improvements in nasal symmetry were observed in the measurements of the projected length of the nasal ala, position of the superoinferior alar groove, position of the mediolateral nasal dome, and nasal bridge deviation. 3 Cleft palate can also be corrected by surgery, usually performed between 6 and 12 months. Approximately 20-25% only require one palatal surgery to achieve a competent velopharyngeal valve capable of producing normal, nonhypernasal speech. However, combinations of surgical methods and repeated surgeries are often necessary as the child grows. One of the new innovations

of cleft lip and cleft palate repair is the Latham appliance. The Latham is surgically inserted by use of pins during the child's 4th or 5th month. After it is in place, the doctor or parents turns a screw daily to bring the cleft together to assist with future lip and/or palate repair. 3 If the cleft extends into the maxillary alveolar ridge, the gap is usually corrected by filling the gap with bone tissue. The bone tissue can be acquired from the patients own chin, rib or hip. 3 After closing the cleft through surgical procedure, things to be considered are the speech and hearing ability of the patients. A tympanostomy tube is often inserted into the eardrum to aerate the middle ear. This is often beneficial for the hearing ability of the child. 3 Speech problems are usually treated by a speech-language pathologist. In some cases pharyngeal flap surgery or augmentation pharyngoplasty is performed to reduce the escape of nasal airflow in speech sounds requiring oral air pressure, to improve the pronunciation of those sounds, and reduce nasality in those parts of speech that are not normally nasalized. The speechlanguage pathologist may also be called on to correct incorrect speaking habits that the child developed before the cleft was corrected surgically. 3 2.6 Prognosis Although treatment may continue for several years and require several surgeries, most children with a cleft lip and palate can achieve normal appearance, speech, and eating. However, some people may have continued speech problems. 3

CHAPTER III LEUKOPLAKIA 3.1 Risk Factor Leukoplakia is a white lesion that, unlike oral candidiasis, cannot be removed by rubbing the mucosal surface. The areas of leukoplakia are usually small but may be several centimeters in diameter. Histologically, they are often hyperkeratoses occurring in response to chronic irritation (e.g., from tobacco and dentures); about 2-6%, however, represent either dysplasia or early invasive squamous cell carcinoma.4 There are some risk factors that contribute to the occurrence of leukoplakia: a. Age Those with age older than 65 have increased risk of having leukoplakia. b. Sex More men than women get leukoplakia. In women, the condition more often develops into cancer. c. Lifestyle Tobacco (especially smokeless tobacco) and long-time alcohol use increase the vulnerability of getting leukoplakia. d. Conditions Incidence of leukoplakia increase in those with diminished immune system, such as in HIV-positive patients. 3.2 Etiology and Epidemiology No etiologic factor can be identified for most persistent oral leukoplakias (idiopathic leukoplakia). Known causes of leukoplakia include the following:5

Trauma (eg, chronic trauma from a sharp or broken tooth or from mastication may cause keratosis) Tobacco use: Chewing tobacco is probably worse than smoking. Alcohol

Infections (eg, candidosis, syphilis, Epstein-Barr virus infection): EpsteinBarr virus infection causes a separate and distinct nonpremalignant lesion termed hairy leukoplakia.

Chemicals (eg, sanguinaria) Immune defects: Leukoplakias appear to be more common in transplant patients. Epidemiological study shows that leukoplakia is uncommoon, possibly occurring in less than 1% of adults. An increased prevalence is observed in communities and races with hibh tobacco use, such as Southeast Asia. Males have the highest incidence of leukoplakias. Leukoplakias are usually seen in adults older than 40.5

3.3

Pathogenesis and Pathophysiology No etiologic factor can be identified for most persistent oral white plaques (ie, idiopathic leukoplakia). The histopathologic features are highly variable, ranging from hyperkeratosis and hyperplasia to atrophy and severe dysplasia. Patients with idiopathic leukoplakia have the highest risk of developing cancer. In studies of these patients, 4-17% had malignant transformation of the lesions in less than 20 years. The risk of developing malignancies at lesion sites is 5 times greater in patients with leukoplakia than in patients without leukoplakia.5 Dysplastic lesions do not have any specific clinical appearance; however, where erythroplakia is present, dysplasia is likely. Dysplasia is evident in 1725% of biopsy samples of leukoplakias. Erythroleukoplakias, verrucous leukoplakias, and nodular leukoplakias show an increasing frequency of dysplastic histologic changes or aneuploidy. 5 Leukoplakias that are speckled, or erythroleukoplakic, are usually dysplastic or frank carcinomas. Nodular or verrucous lesions are also sinister, but homogenous leukoplakias are far less likely to be potentially malignant. 5 Most idiopathic leukoplakias are homogenous leukoplakias and show little evidence of dysplastic histologic changes or aneuploidy. However, studies

have revealed carcinoma or severe dysplasia in the excision specimens of approximately 5% of leukoplakias excised when the diagnostic biopsy specimens had revealed no dysplasia. 5 Carcinoma in situ is a controversial term used for severe dysplasia in which the abnormalities extend throughout the thickness of the epithelium. All the cellular abnormalities characteristic of malignancy may be present; only invasion of the underlying connective tissue is absent. Top-to-bottom epithelial dysplasia, like other dysplastic lesions, has no characteristic clinical appearance, although erythroplasia often proves to be carcinoma in situ or early invasive carcinoma. 5 3.4 Clinical Manifestation Leukoplakia has a varied clinical appearance and its appearance frequently changes over time. Change or progression over time accounts for yet another unique aspect of leukoplakia, it is one of the few diseases in which long duration is not evidence of harmless future behavior. Lesions of long duration have a greater risk of malignant transformation than those of short duration, and the older a leukoplakia the worse is its prognosis.4 Leukoplakias are white lesions that cannot be removed with a gauze swab. Most leukoplakias are smooth, white plaques (homogeneous leukoplakias), occur on the lip, the buccal mucosae, or the gingivae. Some leukoplakias are white and warty (verrucous leukoplakia), some are mixed white and red lesions (erythroleukoplakias or speckled leukoplakias). Dysplastic lesions do not have any specific clinical appearance; however, where erythroplasia is present, dysplasia, carcinoma in situ, and frank carcinomas are more likely to be seen. The site of the lesion is relevant; leukoplakias on the floor of the mouth or on the ventrum of the tongue and the lip are sinister. The size of the lesion appears to be irrelevant. Even small dysplastic lesions may lead to multiple carcinomas and a fatal outcome.5

3.5

Diagnosis and Management The first diagnostic method should be performed is physical examination. A systematic intraoral examination including the lateral tongue, floor of the mouth, gingiva, buccal area, palate, and tonsillar fossae and palpation of the neck for enlarged lymph nodes should be part of any general physical examination, especially in patients over the age of 45 who smoke tobacco or drink immoderately.4 Oral biopsy is performed to detect the dysplastic cells. Intraoral staining with 1% toluidine blue may aid in selection of the most suspicious biopsy site.4 The recently introduced, computer-assisted, oral brush biopsy is a detection tool providing evidence of cellular abnormalities in precancerous and cancerous lesions. With the aid of a highly specialized, neural, networkbased, image-processing system specifically designed to detect oral epithelial precancerous and cancerous cells, the pathologist can detect as few as 1 or 2 abnormal individual cells in several hundred thousand cells. The detection of 1 or 2 such abnormal cells is sufficient to warrant a histologic specimen obtained by scalpel biopsy.5 The histopathologic features are highly variable, ranging from hyperkeratosis and hyperplasia to atrophy and severe dysplasia. The histologic assessment of oral epithelial dysplasia is notoriously unreliable. Many studies show interpathologist and intrapathologist variation in diagnosing dysplasia. Besides the fact that the criteria for diagnosing dysplasia are ill defined, another serious problem exists. A tissue specimen from a biopsy may not be representative of the whole lesion. Latent carcinomas may be missed.5 Molecular and genetic analysis of premalignant and malignant tissue has produced increasing evidence of genetic instability (including microsatellite instability, cell cycle-regulatory gene P16 and P14 deletions and hypermethylation, and mutations in P53); and clonal alterations, such as loss of retinoic acid -receptor expression, occur during the early stage of aerodigestive tract carcinogenesis. These molecular and epidemiologic studies provide the foundation on which clinical trials have been designed to evaluate the role of retinoids and other compounds in the reversal of

premalignancy and the possible reduction in the 4-5% annual rate of second primary tumors.4 Once the diagnosis is established, thorough management should be done. The objective of care is to detect and to prevent malignant change. Several management regimens have been suggested; however, no large trials have shown a definitive, reliable treatment. Yet, possible courses of action include medical therapies (eg, anti-inflammatory agents, vitamins, cytotoxic agents) and surgical removal (eg, scalpel, laser, cryoprobe, electrosurgery, photodynamic therapy).5 Patients should avoid any causal factor, such as use of tobacco and alcohol. Leukoplakias can regress under these circumstances. Any degree of dysplasia in a lesion at a high-risk site must be taken seriously and the lesion should be removed. Occasionally, patients are treated by photodynamic therapy or topical cytotoxic agents. Patients should be examined regularly, probably at 3- to 6-month intervals. A diet rich in fresh fruits and vegetables may help prevent cancer.5 A number of clinical trials have suggested a role for beta-carotene, vitamin E, and retinoids in producing regression of leukoplakia and reducing the incidence of recurrent SCCs. Retinoids suppress head and neck and lung carcinogenesis in animal models and inhibit carcinogenesis in individuals with premalignant lesions. They also seem to reduce the incidence of second primary cancers in head and neck and lung cancer patients previously treated for a primary.4 Retinoids appear to be very effective but can have severe adverse effects on liver function and may cause teratogenicity.5 3.6 Prognosis Some leukoplakias are potentially malignant. Dysplasia currently appears to be the best predictor of malignant potential. As many as 25% of leukoplakias are dysplastic at the first visit. Malignant change appears to be more frequent among nonsmokers than among smokers.5

Estimates of malignant transformation vary from 3-33% over a 10-year period. However, many innocuous leukoplakias are not always followed up in some centers, and the studies are often small. As many as 30% of leukoplakias can regress if habits are stopped. A poorer prognosis is noted in females, nonsmokers, moderate or severe epithelial dysplasia, and lesions in high-risk sites, such as the floor of the mouth.5

CHAPTER IV INTUSSUSCEPTION 3.1 Risk Factor Intussusception is a process in which a segment of intestine invaginates into the adjoining intestinal lumen, causing bowel obstruction.6 There are some conditions that can increase the risk of intussusception, including:6 a.Age Children are much more likely to develop intussusception than adults are. It is the most common cause of bowel obstruction in children between the ages of 3 months and 6 years, with the majority of cases occurring in children younger than 1 year. b.Sex Intussusception affects boys more often than girls. c.Abnormal Intestinal Formation at Birth Malrotation, a condition present at birth (congenital) in which the intestine doesnt develop correctly, also is a risk factor for intussusception. d.Prior History of Intussusception The risk of developing intussusception increases in those who have prior history of this disease. 3.2 Etiology and Epidemiology The cause of most intussusception is unknown. It is postulated that gastrointestinal infection or the introduction of new food proteins results in swollen Peyer patches in the terminal ileum. The prominent mounds of tissue lead to mucosal prolapse of the ileum into the colon, thus causing an intussusception. In 2-8% of patients, recognizable lead points for the intussusception are found, such as a Meckel diverticulum, intestinal polyp, neurofibroma, intestinal duplication, hemangioma, or malignant conditions such as lymphoma. Lead points are more common in children older than 2

year of age. Intrauterine intussusception is associated with the development of intestinal atresia.7 The true prevalence of intussusception is difficult to be obtained because of a wide geographic variation in incidence of intussusception among countries and cities within a country. There is no significant difference in the incidence of intussusception is reported between races. Most series report a slight preponderance of males, with a male-to-female ratio of approximately 3:2.6 Two thirds of children with intussusception are younger than 1 year; most commonly, intussusception occurs in infants aged 5-10 months. Although extremely rare, intussusception has been reported in the neonatal period. Intussusception can account for as many as 25% of abdominal surgical emergencies in children younger than 5 years, exceeding the incidence of appendicitis. Intussusception is the most common cause of intestinal obstruction in patients aged 5 months to 3 years.6 3.3 Pathogenesis and Pathophysiology The pathogenesis of intussusception is believed to be secondary to an imbalance in the longitudinal forces along the intestinal wall. This imbalance can be caused by a mass acting as a lead point or by a disorganized pattern of peristalsis (eg, an ileus in the postoperative period). Electrolyte derangements associated with various medical problems can produce aberrant intestinal motility, leading to its invagination. Recent experimental studies in animals showed that abnormal intestinal release of nitric oxide, an inhibitory neurotransmitter, caused relaxation of the ileocecal valve predisposing to ileocecal intussusception. Other studies have demonstrated that the use of certain antibiotics leads to ileal lymphoid hyperplasia and intestinal dysmotility with resultant intussusception.6 As a result of the imbalance, an area of the intestinal wall invaginates into the lumen, with the rest of the intestine following. The invaginating portion of the intestine (ie, intussusceptum) completely invaginates into the receiving portion of the intestine (ie, intussuscipiens). This process continues and more

proximal areas follow, allowing the intussusceptum to proceed along the lumen of the intussuscipiens. 6 If the mesentery of the intussusceptum is lax and the progression is rapid, the intussusceptum can proceed to the distal colon or sigmoid and even prolapse out the anus. The mesentery of the intussusceptum is invaginated with the intestine, leading to the classic pathophysiologic process of any bowel obstruction. 6 Early in this process, lymphatic return is impeded; then, with the rise in the pressure within the wall of the intussusceptum, venous drainage is impaired. Finally, the pressure reaches a point at which arterial inflow is inhibited, and infarction ensues. The mucosa is most sensitive to ischemia because it is farthest away from the arterial supply. Ischemic mucosa sloughs off, which initially leads to the heme-positive stools and then the classic "currant jelly stool" (a mixture of sloughed mucosa, blood, and mucus). If untreated, the process progresses to transmural gangrene and perforation of the leading edge of the intussusceptum. 6 3.4 Clinical Manifestation In typical cases there is sudden onset, in a previously well child, of severe paroxysmal colicky pain that recurs at frequent intervals and is accompanied by straining efforts with legs and knees flexed and loud cries. The infant may initially be comfortable and play normally between the paroxysms of pain; but if the intussusception is not reduced, the infant becomes progressively weaker and lethargic. At times, the lethargy is out of proportion to the abdominal signs. Eventually a shocklike state may develop with fever. The pulse becomes weak and thready, the respirations become shallow and grunting, and the pain may be manifested only by moaning sounds. Vomiting occurs in most cases and is usually more frequent early. In the later phase, the vomitus becomes bile stained. Stools of normal appearance may be evacuated during the first few hours of symptoms. After this time, fecal excretions are small or more often do not occur and little or no flatus is passed. Blood generally is passed in the first 12hr but at times not for 12 days and

infrequently not at all; 60% of infants pass a stool containing red blood and mucus, the currant jelly stool. Some patients have only irritability and alternating or progressive lethargy.7 Palpation of the abdomen usually reveals a slightly tender sausage-shaped mass, sometimes ill defined, which may increase in size and firmness during a paroxysm of pain and is most often in the right upper abdomen, with its long axis cephalocaudal. If it is felt in the epigastrium, the long axis is transverse. About 30% of patients do not have a palpable mass. The presence of bloody mucus on the finger as it is withdrawn after rectal examination supports the diagnosis of intussusception. Abdominal distention and tenderness develop as intestinal obstruction becomes more acute. On rare occasions, the advancing intestine prolapses through the anus. This prolapse can be distinguished from prolapse of the rectum by the separation between the protruding intestine and the rectal wall, which does not exist in prolapse of the rectum. 7 Ileoileal intussusception may have a less typical clinical picture, the symptoms and signs being chiefly those of small intestinal obstruction. Recurrent intussusception is noted in 58% and is more common after hydrostatic than surgical reduction. Chronic intussusception, in which the symptoms exist in milder form at recurrent intervals, is more likely to occur with or after acute enteritis and may arise in older children as well as in infants. 7 3.5 Diagnosis and Management The clinical history and physical findings are usually sufficiently typical for diagnosis. Plain abdominal radiographs may show a density in the area of the intussusception. A barium enema shows a filling defect or cupping in the head of barium where its advance is obstructed by the intussusceptum. A central linear column of barium may be visible in the compressed lumen of the intussusceptum, and a thin rim of barium may be seen trapped around the invagination intestin in the folds of mucosa within the intussuscipiens (coiled-spring sign), especially after evacuation. Retrogression of the

intussusceptum under the pressure of the enema and gaseous distention of the small intestine from obstruction are also useful radiographic signs. Ileoileal intussusception is usually not demonstrable by barium enema but is suspected because of gaseous distention of the intestine above the lesion. The use of air enemas in the diagnosis and treatment of intussusception has supplanted hydrostatic reduction. Reflux of air into the terminal ileum and the disappearance of the mass at the ilocecal valve document successful reduction. Air reduction is associated with fewer complications and lower radiation exposure than traditional hydrostatic techniques.7 Laboratory investigation is usually not helpful in the evaluation of patients with intussusception. Leukocytosis can be an indication of gangrene if the process is advanced. Dehydration is depicted by electrolyte imbalances.6 Ultrasonography is a noninvasive modality that can aid in making the diagnosis of intussusception. Its accuracy reaches 100%. Hallmarks of ultrasonography include depiction of the intussusceptum and its mesentery within the intussuscipiens. Ultrasonography is highly operator dependent; therefore, interpret result with caution.(medscape) The diagnostic findings of intussusception include a tubular mass in longitudinal views and a doughnut or target appearance in transverse images. Ultrasonography is also useful in demonstrating reduction of the intussusception by hydrostatic or air techniques.7 In histologic examination, typical findings in a segment of intestine which is resected at the time of operative reduction are intestinal obstruction with edema, congestion, lymphocytic infiltration, and transmural infarction.6 The differential diagnoses of intussusception can be appendicitis, colic, cyclic vomiting syndrome, gastroenteritis, and volvulus.6 Reduction of an acute intussusception is an emergency procedure and performed imediately after diagnosis in preparation for possible surgery. In patients with prolonged intussusception with signs of shock, peritoneal irritation, intestinal perforation, or pneumatosis intestinalis, reduction should not be attempted.7

The success rate of radiologic reduction under fluoroscopic or ultrasonic guidance is approximately 50% if symptoms are present longer than 48 hr and 70-90% if reduction is done within the first 48 hr. bowel perforatons occur in 0,5-2,5% of attempted barium and hydrostatic (saline) reductions. The perforation rate with air reduction ranges from 0,1-0,2%.7 An ileoileal intussusception is best demonstrated by abdominal

ultrasonography. Reduction by instillation of barium, saline, or air may not be possible. Such intussusceptions may develop insidiously after bowel surgery and require reoperation if they do not spontaneously reduce. If manual operative reduction is impossible or the bowel is not viable, resection of the intussusception is necessary, with end-to-end anastomosis. 7 3.6 Prognosis Untreated intussusception in infants is almost always fatal; the chances of recovery are directly related to the duration of intussusception before reduction. Most infants recover if the intussusception is reduced within the first 24 hr, but the mortality rate rises rapidly after this time, especially after the second day. Spontaneous reduction during preparation for operation is not uncommon. 7 Recurrence rate of intussusception after nonoperative reduction is usually less than 10% but has been reported to be as high as 21%. Most intussusceptions recur within 72 hours of the initial event; however, recurrences have been reported as long as 36 months later. More than one recurrence suggests the presence of a lead point. A recurrence is usually heralded by the onset of the same symptoms as appeared during the initial event. Provide similar treatment for a recurrence unless the suggestion of a lead point is very strong; in which case, contemplate surgical exploration. The recurrence rates after air enema and barium enema are 4% and 10% respectively. Recurrences respond to nonoperative reduction in almost 95% of cases. 6

CHAPTER V SUMMARY Cleft lip and palate is common among congenital anomalies. Several risk factors of this disorder are ethnicity, family history, maternal exposure to environmental factors, maternal diet that cause the formation of cleft lip as well as gender. The genetic factor gives predisposition to this disease, but exposure to environmental factors trigger the occurrence. Epidemiological data suggests that in general, all typical orofacial cleft types combined occur in white populations with a frequency of 1 per 500-550 live births. Failure of merging between the medial nasal and maxillary processes at 5 weeks' gestation, on one or both sides, results in cleft lip.If the fusion of palatal shelves is impaired also, the cleft lip is accompanied by cleft palate, forming the cleft lip and palate abnormality. Traditionally, the diagnosis is made at the time of birth by physical examination.Cleft lip and palate is very treatable; however, the kind of treatment depends on the type and severity of the cleft. Speech problems are usually treated by a speech-language pathologist. After surgical intervention, most children with a cleft lip and palate can achieve normal appearance, speech, and eating. Leukoplakia is a white lesion that, unlike oral candidiasis, cannot be removed by rubbing the mucosal surface. Several predisposing factor to this disorders are age older than 65, male, tobacco use and alcohol consumption, and state of diminished immune system. No etiologic factor can be identified for most persistent oral leukoplakias (idiopathic leukoplakia), but several causes have been identified, which are related to the predisposing factors. Patients with idiopathic leukoplakia have the highest risk of developing cancer. In studies of these patients, 4-17% had malignant transformation of the lesions in less than 20 years. Leukoplakia has a varied clinical appearance and its appearance frequently changes over time. Most leukoplakias are smooth, white plaques (homogeneous leukoplakias), occur on the lip, the buccal mucosae, or the gingivae. Diagnostic method includes physical examination and oral biopsy. Some leukoplakias are potentially malignant. A poorer prognosis is noted in females, nonsmokers, moderate or severe epithelial dysplasia, and lesions in highrisk sites, such as the floor of the mouth.

Intussusception is a process in which a segment of intestine invaginates into the adjoining intestinal lumen, causing bowel obstruction. Several risk factors contribute to occurrence of this disease,ie. children younger than 1 year, boys, abnormal intestinal formation at birth, and prior history of intussusception. The cause of most intussusception is unknown. It is postulated that gastrointestinal infection or the introduction of new food proteins results in swollen Peyer patches in the terminal ileum. Two thirds of children with intussusception are younger than 1 year; most commonly, intussusception occurs in infants aged 5-10 months. There is no significant difference in the incidence of intussusception is reported between races. Most series report a slight preponderance of males, with a male-to-female ratio. The pathogenesis of intussusception is believed to be secondary to an imbalance in the longitudinal forces along the intestinal wall. In typical cases there is sudden onset, in a previously well child, of severe paroxysmal colicky pain that recurs at frequent intervals and is accompanied by straining efforts with legs and knees flexed and loud cries. The clinical history and physical findings are usually sufficiently typical for diagnosis. Another tests are plain abdominal radiography (or with contrast) and ultrasonography. Reduction of an acute intussusception is an emergency procedure and performed imediately after diagnosis in preparation for possible surgery.

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