18.2.1 Bladder Exstrophy

Bladder exstrophy is very rare. Its incidence is 1:50 000 with a male to female ratio of 3:1 [4]. Antenatal diagnosis is difficult with characteristic non‐visualisation of the bladder, accompanied by a low‐set umbilical cord, a short phallus, and an irregular lower abdominal wall (Figures 18.1 and 18.2). Antenatal counselling of the parents is necessary so that they understand the nature and implications of bladder exstrophy, the surgical management, and long‐term outcome [2].

The clinical features of bladder exstrophy is related to its pathogenesis (Figure 18.1–18.4): [4]

1. The bladder is open to external environment along with the anterior abdominal wall, and so is the urethral plate with a visible verumontanum in males and a short open urethra running between the open bladder and the vagina in females. The ureters drain directly onto the open bladder plate; the ureteric orifices are laterally placed which can lead to vesicoureteric reflux (VUR). If neglected, the exposed urothelium undergoes intestinal metaplasia.
   
2. There is a low‐set umbilicus cranially with associated umbilical hernias, split (diversification) rectus abdominis muscles laterally, and an open pelvic ring caudal to the open bladder plate.
   
3. The symphysis pubis diastasis (widening) can vary, reaching a defect of up to 5 cm in newborns with severe forms of exstrophy. This is due to external rotation of the pelvic bones along the sacroiliac joints.
   
4. The corpora are separate and attached to the inferior border of the ipsilateral inferior pubic rami. This leads to a shortened, broad, and open penis with deficiency of dorsal foreskin in males, and separate, bifid clitoral bodies and the urethra barely present, short vaginal canals, and can lead to uterine prolapse in females.
   
5. The anus is anteriorly placed due to the abnormal development of the anterior abdominal muscles. There might be associated rectal prolapse, compounding faecal incontinence.
   
6. In the male, the urethra is represented by a strip of urothelium on the dorsum of a short, broad, up‐turned penis. The testicles are undescended. Inguinal hernias are a common association (80% in boys, 15% in girls).
   
7. Superior vesical fissure: Here the exstrophy is restricted to the apex of the bladder. The remainder of the bladder is correctly formed (Figure 18.5).

18.2.1.1 Management

The suspected defects can be seen on prenatal ultrasound, which can help with parental counselling and planning of delivery and further management.

After birth, the bladder plate is covered with cling‐film, the umbilical cord clamp is replaced with a suture tie to avoid trauma to the bladder plate, and the neonate is transferred to appropriate paediatric urology referral centre. Closure is advisable in the first few days of life; however, it can be delayed in cases of premature babies that need a long period of stabilisation and growth.

Preoperative work‐up should include a baseline renal ultrasound and routine blood tests. Other congenital abnormalities are not common with bladder exstrophy. Vitamin K should be administered to the neonate and antibiotic cover is not necessary. As neonates with this condition are usually healthy otherwise, intravenous access is not required preoperatively and the babies can breastfeed [4].

18.2.1.2 Surgery

18.2.1.2.1 Primary Closure of Bladder Plate and Reconstruction of the Lower Abdominal Wall

The primary closure of bladder exstrophy is performed under general anaesthesia and an epidural catheter is preferable because it provides excellent postoperative analgesia.

The primary bladder closure, lower abdominal wall reconstruction, and approximation of the pubic bones are generally achievable without osteotomies in early closure. For delayed closures (which is practiced in several centres across the world) or in cases with wide pubic diastasis, pelvic osteotomies with external fixators are needed. Inguinal hernias are repaired during this procedure when present. Complications after bladder closure include partial or complete wound dehiscence, a tight closure with outflow obstruction, and upper tract dilatation, which in combination with UTIs, may lead to renal damage [4, 5].

18.2.1.2.2 Continence Procedures

In females, the primary closure is rarely adequate to achieve continence, and in the majority of patients with bladder exstrophy, secondary procedures will be necessary for continence and genital reconstruction to achieve continence and cosmesis [6].

Three surgical approaches are currently followed in various part of the world:

1. Complete primary repair of bladder exstrophy ( CPRE) [7–16]. Mitchell suggested a complete anatomical reconstruction at the time of the primary closure. The bladder plate is fully mobilised and the bladder neck, urethra, and penis are reconstructed in one setting. This technique is thought to create a bladder outlet resistance early in life, allowing for bladder cycling and growth. The division of the intersymphyseal ligaments allows the appropriate anatomic placement of the bladder neck and posterior urethra deep into the pelvis in its orthotopic position.
   

   Patients whose bladder does develop will likely undergo fewer procedures than in a staged fashion. Continence has been reported after CPRE to be 76%, defined as dry intervals longer than two hours and spontaneous voiding without catheterizations. However, a significant percentage of patients will likely still require a formal bladder neck procedure to achieve continence. There are concerns with this technique related to a high‐pressure lower urinary system and VUR, urinary tract infections (UTIs), and renal scarring and damage. There is also rare risk of penile injury with loss of glans or penile skin or tissue with penile reconstruction at such a young age, and requirement for multiple procedures despite the name ‘complete repair’. Approximately 36–68% of patients will be left with a hypospadias after CPRE that will require further penile surgery.

   
   
2. Modern Staged Reconstruction of Exstrophy ( MSRE) [16–24]. Jeffs and Gearhart advocated MSRE, which has been the standard approach for many centres for many years. It includes an initial primary closure followed by a modified Cantwell‐Ransley epispadias repair in the first 6–12 months of life. The bladder is mobilised (Figure 18.6). The edges of the mobilised bladder and urethra are rolled in to make a new bladder and urethra. The tissues on either side of the bladder neck are mobilised and sewn together. To help closure, an osteotomy is performed through the iliac bone just lateral to the sacroiliac joint. A second operation may be necessary a few years later to achieve continence (Figure 18.7).
   

   The ongoing incontinence is considered to preserve renal function and at the same time, the bladder may develop with the presence of some outlet resistance. The bladder neck repair (i.e. Young‐Dees‐Leadbetter) for continence is performed between five and nine years of age, when an adequate bladder capacity is achieved, and the patient and family desire continence. Ureteric reimplantation is carried out at this stage through long submucosal tunnels to prevent reflux.

   
   

   If the bladder capacity is not good, the patient is left incontinent until the bladder grows and maturity improves or diversion with an augmentation with a catheterisable channel and bladder neck closure when necessary, which is also the procedure of choice in the case of failed bladder neck reconstruction, is used.

   
   

   Day and night‐time continence of can reach about 75%, with the patients voiding per urethra without augmentation or intermittent catheterization. Social continence, defined as dry for more than three hours during the day but damp at night, was found in a further 10%. Patients with a mean capacity greater than 100 ml at the time of the bladder neck reconstruction had better outcomes. In males after closure, epispadias, and bladder neck reconstruction, the total complication rate was 41.7%, and in females after bladder closure and bladder neck reconstruction, the total complication rate was 19.5%. In a series of successful bladder growth 19.4% of males and 17% of females had failed bladder neck reconstruction and have undergone or will require an augmentation with a catheterisable stoma and bladder neck closure as indicated. Major complications are reported at 11% (e.g. bladder dehiscence or prolapse, orthopaedic or neurological complications) and minor complications again at 11% (i.e. bladder outflow obstruction [BOO], urethrocutaneous fistula, surgical site infection, UTIs, etc.).

   
   
3. The Kelly procedure (radical soft‐tissue mobilisation) [4, 5, 25, 26]. This surgical technique for continence that was first advocated by J. H. Kelly in the 1980s. Its concept is that continence in bladder exstrophy can be achieved by repairing the disorganised pelvic floor musculature involved in normal continence. An examination under anaesthesia and cystoscopy is carried out at three months after bladder closure to assess the anatomy, capacity, and outlet. The Kelly operation is carried out after the age of nine months. It is performed irrespective of bladder capacity. The bladder is opened in the midline and bilateral ureteric reimplantation (Cohen) is performed. The pelvic floor, penile corpora bodies, and urethra are radically mobilised. The penile corpora along with the periostium are mobilised off from the lower border of the inferior pubic rami with great care to the pudendal nerves and vessels that must be preserved as they run through Alcock canal. Then the penile corpora can be completely mobilised towards the midline, thus increasing their length and protrusion. The urethral plate is dissected from the corpora and glans. A bladder neck repair is performed with excision of two small mucosal triangles lateral to the verumontanum. The tubularisation continues distally, and if the penile length is not compromised, a complete reconstruction of the penis and urethra could be carried out. However, the urethra is usually deemed short, and therefore, brought to a perineal position in males. The perineal muscle is wrapped around the proximal urethra, in an attempt to recreate the sphincter. The corpora are externally rotated to correct the dorsal chordee and joined in the midline. The glans is reconstructed and the shaft skin cover provided. The abdominal wall is closed.
   

   In girls, the clitoral corpora are similarly mobilised, with the labia minora attached. The pelvic floor is mobilised and the pudendal nerves are again identified and preserved. After the bladder neck repair, the pelvic muscle is wrapped around the urethra and vagina. The clitoral bodies are brought together in the midline.

   
   

   The hypospadiac meatus in boys can be repaired in two stages with the use of buccal, labial, or posterior auricular grafts in the future. In girls, no further genital reconstruction is required.

   
   

   Although published follow‐up data are limited, good continence outcomes in patients with spontaneous voiding are reported with the Kelly procedure. Continence (complete or partial) is reported in 63.5–70%. In a not as yet published series that was presented at the European Society for Paediatric Urology (ESPU) conference 2015, the Paediatric Urology team of Great Ormond Street Hospital reported 64% spontaneous voiding continence in boys and 79% in girls five years after the Kelly operation in patients who also underwent the primary closure of bladder exstrophy at the same institution. Pelvic floor exercises and biofeedback is applied to the patients when they are old enough to cooperate to enhance the function of the pelvic floor muscles. Complications after this procedure include fistula formation (10%), vulval scarring and dehiscence (5%), recurrent UTIs (59%), urethral stricture (7%), wound dehiscence (11%), and infective bladder calculi (7%). Renal scarring on nuclear medicine scans was 10%, urethral clean intermittent catheterization (CIC) was performed in 3.5%, and bladder augmentation was carried out in 10% of patients in the Great Ormond Street Hospital series. Penile injury and glans loss is extremely rare and erectile dysfunction has not been reported [25–29].

   
   

   The complexity of bladder exstrophy and its surgery mandates that the management of patients with this condition should be done at exstrophy centres of excellence and by multidisciplinary teams with standardised assessments and management regimens

18.2.2 Epispadias

When the cloacal membrane is less extensive (Figure 18.8), its dissolution leaves a defect in the urethra that may be restricted to the glans or may form a strip along the short curved penis. The urethral meatus opens onto the dorsal penis, either in the glans, penile shaft, or in the penopubic region (Figure 18.9).

In males, epispadias is associated with dorsal chordee with incomplete foreskins, dorsally. The leads to an upward curvature and a hooded glans. In females, there is a bifid clitoris and poorly developed labia. There is associated urethral sphincter disruption leading to incontinence. Incidence in males is 1:120 000 and in females 1:400 000.

18.2.3 Cloacal Exstrophy

Cloacal exstrophy is the most severe abnormality in the exstrophy spectrum that is compatible with viability. It is extremely rare, occurring in 1 in 200 000–400 000 live births. The male to female ratio has been reported in a large contemporary study to be equal between the sexes, 1:1 [4, 45].

Prenatal diagnosis is possible and based on major criteria (i.e. non‐visualisation of the bladder, a large midline infra‐umbilical anterior wall defect or a cystic anterior wall structure, an omphalocoele and a myelomeningocoele) and minor criteria (i.e. lower extremity anomalies, renal anomalies, ascites, widened pubic arches, narrow thorax, hydrocephalus, and a single umbilical artery) [46].

When a prenatal diagnosis is made, parents should be counselled by an experienced exstrophy surgeon and referred to an exstrophy centre of excellence for delivery whenever possible [47].

Cloacal exstrophy includes findings of exstrophy of the hindgut and bladder complex (Figure 18.10), bifid phallus, wide pubic diastasis, prolapsing terminal ileum and proximal colon, imperforate anus, and an omphalcele (Figure 18.11). When seen coexisting with omphalocele, imperforate anus, and spinal defects it is considered part of the OEIS complex [48]. The lower urinary tract is typically composed of two hemi‐bladders exstrophy on either side of the midline each with its ureteric orifice and rudimentary phallus. Between them, a length of intestine with two openings represents the ileocaecal region a characteristic elephant trunk appearance. The upper opening leads into the ileum and discharges small bowel content; the lower one leads into a loop of large bowel, which ends blindly in front of the sacrum. There maybe one or two appendices. The anus is imperfect, and there is usually spina bifida. Variations, however, are frequent.

Abnormalities from other systems are common and involve the nervous system (spina bifida), skeletal anomalies, gastrointestinal anomalies (e.g. omphalocele, malrotation, bowel duplication, duodenal atresia, duodenal web, Meckel’s diverticulum, and short gut syndrome), upper urinary tract anomalies (e.g. pelvic kidneys, renal agenesis, hydronephrosis, hydroureter, multicystic dysplastic kidney (MCDK), fusion anomalies, ectopic ureter, ureteric duplication, congenital stricture, and megaureter), genital tract anomalies (e.g. uterine duplication, bicornuate uterus, vaginal duplication, vaginal agenesis, and undescended testes) and cardiovascular and pulmonary anomalies (e.g. cyanotic heart disease, aortic duplication, vena caval duplication, bilobed lung and an atretic upper lobe bronchus) [4, 45, 49–51].

Management of these complex patients should be carried out in a specialised exstrophy centre. The bowel and bladder plates should be kept covered with a clear cling film wrap as for bladder exstrophy. Often the severity of cloacal exstrophy is enhanced by the nature and severity of the associated anomalies and these in turn may delay the surgical management for several months. Immediate management is intended to medically stabilise the newborns that are usually premature.

A renal and spinal ultrasound (and if needed a spinal magnetic resonance image [MRI]) should be carried out early along with full blood tests and assessment for cardiac anomalies [52]. Optimal feeding to establish growth is necessary. Evaluation should involve a multidisciplinary team to perform an assessment of all the comorbidities and plan the short‐ and long‐term reconstruction. Decisions should only be made after appropriate parental counselling and education. This often will require a chromosomal analysis. As surgical techniques for phallic reconstruction have evolved, a functional and cosmetically acceptable phallus can now almost always be constructed, and it is the general consensus amongst experts that it is important to assign gender that is consistent with karyotype [51].

In patients with spinal conditions, a neurosurgical evaluation and closure should be undertaken as soon as the infant is medically stable. Long‐term follow‐up is important because up to 33% of children can have symptomatic spinal cord tethering [53].

One of the important decisions to make during the initial operative planning is whether to perform a one‐ or two‐stage closure [54–56]. A one‐stage repair is preferred, if possible, to minimise the number of neonatal procedures necessary and also allow the bladder to be closed, reducing the risk of trauma and polyp formation, and potentially improve its chances at normal development. During either a one‐ or two‐stage procedure, an omphalocele if present, is excised; the exstrophy plate is dissected from the skin and rectus abdominis muscles laterally; and the bowel is carefully separated from the hemi‐bladders. The hindgut is tubularised and brought out as an end colostomy usually onto the left iliac fossa. The location of the stoma should be such to allow for an effective placement of an appliance. Ileostomies have been widely used in previous years, but they have been associated with malabsortion and nutritional problems. The hemi‐bladders are approximated in the midline to create a single bladder plate, which may then be closed as in primary bladder exstrophy closure. Bilateral osteotomies are performed because usually the closure is delayed and the pubic diastasis is wide. These should allow for a tension‐free closure, but if this is not possible, then the use of a silo to cover the residual abdominal wall defect is advisable. In cases where a two‐staged approach is decided (i.e. in the presence of a large omphalocele defect and respiratory or haemodynamic instability etc.), bladder closure and osteotomy may be delayed until respiratory and gastrointestinal stability are achieved [57, 58].

Preserving as much bowel tissue possible is essential to enhance absorption and avoid complications of short bowel, thus helping the survival rate of these patients [59]. Parenteral nutrition is necessary until enteric feeds are established. Also, any possible distal bowel and appendices should be preserved because they may be used for future reconstruction and stoma formation. When the child is older and if an adequate hindgut exists and there are no neurologic deficits, then a pull through procedure could be performed via the posterior sagittal approach. The majority of these patients however have been reported incontinent of faeces [4, 45].

Patients with cloacal exstrophy are incontinent for urine. Intermittent catheterization is likely to be needed for emptying especially in the presence of spinal defects. Surgery to produce a continent reservoir should be delayed until the child is old enough to participate in self‐care. The choice between a catheterisable urethra and catheterisable stoma should be made according to the adequacy of the urethra and bladder neck, bladder capacity, gender, and orthopaedic status [60, 61].

In males with cloacal exstrophy, reconstruction of the penis is challenging. However, when adequate corporal tissue is present, epispadias repair can be performed at the same time of initial closure or later [62]. Also, when performed by experts, the Kelly procedure offers a great perspective in the cosmetic appearance of the external genitalia of boys [4]. Genital reconstruction in girls is usually done at the time of bladder closure and osteotomy. It is acceptable to leave the vaginas in situ, but further surgery will be needed to bring one of these to the perineum.

18.3.1 Patent Urachus

There causes continuous or intermittent drainage of sero‐sanguineous or purulent fluid from the umbilicus. If the umbilicus becomes infected, then there is periumbilical swelling, tenderness, and drainage. It is correlated to a BOO in 14% of cases, and in these cases, it acts as a ‘pop‐off’ mechanism. The diagnosis of a patent urachus can be done with ultrasonography and Micturating cystogram, which is also necessary to exclude BOO (Figure 18.13). A patent urachus needs to be excised. The excision is done through an extraperitoneal approach and the urachus needs to be excised completely, including a part of the bladder dome.

18.3.2 Urachal Sinus

This represents incomplete closure of the urachus with an ‘opening’ distally towards the umbilicus. Episodic infections of the sinus can lead to purulent drainage from the umbilicus and periumbilical tenderness. Usually it presents as a ‘wet’ umbilicus or a persistent granuloma after multiple cauterisation with silver nitrate. It can be diagnosed with ultrasonography or sinography is possible. In difficult diagnostic cases, a computed tomography (CT) or MRI maybe required. Treatment is again complete excision if the sinus persists for more than two months [65, 66].

18.3.3 Urachal Cyst

This presents as a fluid‐filled structure between the two obliterated ends of the urachus and is usually located in the distal third of the urachus. It is usually an incidental finding, or it can present as a suprapubic mass with fever, pain, and dysuria. In delayed diagnosis, the cyst may rupture towards the peritoneum, causing acute abdomen and peritonitis. The most common organism isolated is Staphylococcus aureus (in >50% of cases) [67]. The diagnosis is again set with ultrasonography, CT, or MRI, and the treatment is surgical excision. For very inflamed cysts, initial incision and drainage (two‐stage approach) is preferable [67, 68].

The surgical excision of urachal anomalies can be done through an open or laparoscopic approach [68–70]. Lately robotic‐assisted surgery has also been used [71]. The decision relates to the surgeon’s experience and the degree of inflammation [72–75]. The treatment of asymptomatic remnants remains controversial, but it is suggested that the presence of microcalcifications seen in imaging is in favour of excision [67, 75]. These calcifications seem to be related to chronic inflammation, which maybe in turn a predisposing factor for carcinogenesis. Urachal cancer is very rare (0.35–0.7% of bladder cancer) and extremely rare in childhood. Carcinoma of the urachus in the adult presents with haematuria. Cystoscopy shows a cherry‐sized lump at the air bubble, and a much larger mass outside it; biopsy reveals adenocarcinoma. Primary urachal rhabdomyosarcoma has been reported and carries a poor prognosis. It is more common in childhood and especially older than the age of 40 [76–79]. Therefore, many surgeons favour preventive removal of urachal remnants when diagnosed.

18.4.1 Bladder ‘Ears’

Innocent protrusions of the bladder are normal in male infants and common in women. In the adult male, they commonly accompany an inguinal hernia into the inguinal canal.

18.4.2 Megacystis

This is a very rare abnormality that can present antenatally, postnatally on ultrasound, or with UTIs. It is associated with high‐grade VUR. It can also be related to other conditions such as posterior urethral valves, Ehlers‐Danlos syndrome, and urethral diverticula. It can also be a manifestation of megacystis‐microcolon‐intestinal hypoperistalsis syndrome (MMIHS), which is characterised by neonatal abdominal distension due to bowel dilatation, severely dilated bladder, and severely dilated ureters. The causes of this rare syndrome are not known. Myogenic, neurogenic, or hormonal factors may be involved. It presents more commonly with functional neonatal intestinal obstruction and urinary retention [84]. There is clear preponderance of females, 70.6 vs. 29.4% in 227 MMIHS cases [85]. The survival rate is about 20% with the oldest survivor being 24 years old. Outcomes seem to be improving with the introduction of long‐term total parenteral nutrition (TPN) and multi‐organ transplantations.

Bladder duplication is extremely rare. It can be partial or complete, with the duplication being in the sagittal or coronal plane. In complete duplication, there are two hemi‐bladders usually in a sagittal plane, with the corresponding ipsilateral ureter draining within each hemi‐bladder and in continuation with a duplicated urethra. Associated anomalies include a duplicated penis, duplicated vagina and uterus, vertebral anomalies (usually lumbar), and hindgut anomalies. Often rectovesical, vesicovaginal, or vesicourethral fistulae are present. Diagnosis can be made with ultrasound, micturating cystourethrogram (MCUG), and cystoscopy, and treatment is necessary if there are symptoms such as urinary incontinence, UTIs, or upper tract obstruction [80, 86, 87].

Bladder septations are fibromuscular or mucosal septations that divide the bladder into equal or unequal compartments. They are diagnosed when they are symptomatic because of complications such as upper tract drainage impairment. They are diagnosed with MCUG and ultrasound.

Bladder agenesis is extremely rare and incompatible with life. Twenty‐three cases have been reported in live births, and all were female infants. In the absence of the bladder, the ureters are seen draining into the urethra, vagina, Gartner’s duct in girls, or the rectum. The urachus may stay patent. They are associated with hydroureteronephrosis, renal dysplasia or agenesis, agenesis of the prostate, seminal vessels, epididymis, penis, or vagina, and spinal, orthopaedic or hindgut anomalies. Diagnosis is made with ultrasound, MCUG, and MRI. In infants that survive, diversion is essential as initial management, and later in life, a neo‐bladder can be constructed [88–90].

18.5.1 Sacral Agenesis

These are exceedingly rare and represent a variation on the theme of failure of development of the neural canal. The child is born with an absence of most of the sacrum, and a lesion of the cauda equina leading to a neuropathic bladder. The diagnosis is obvious from a plain radiograph of the pelvis, but it is all too easy to miss the absence of the sacrum.

18.5.2 Presacral Dermoid

A congenital neural canal defect leads to the formation of a dermoid cyst between the sacrum and the rectum. Clinically, they may present with bizarre symptoms, few of which are serious unless the cyst becomes infected. On rectal examination, a large mass is found. Surgical intervention is only required if the cyst is causing obstruction or is associated with a cauda equina lesion and carries a high risk of producing a neuropathic bladder even if not already present.

18.6.1 Classification

UTIs can be divided based on site:

• Lower urinary tract (LUT) or cystitis: dysuria, frequency, urgency, malodorous urine, enuresis, haematuria, or lower abdomen or suprapubic pain.
  
• Upper urinary tract (UUT) or pyelonephritis: fever, chills, or flank, back, or lower chest pains. Symptoms of LUT may also be present.

Classified according to severity:

Typical UTI: could be asymptomatic or symptomatic;

• Simple UTI: low‐grade pyrexia with mild dehydration; generally, well.
  
• Severe UTI: high‐grade pyrexia (>39 °C), vomiting, moderate to severe dehydration; unwell.

Atypical UTI: seriously ill, non‐E. coli infection, poor urinary flow, deranged renal function, abdominal or bladder mass, septicaemia, and failure to respond to treatment within 48 hours.

Classification according to episode:

A single infection is treated successfully and does not recur. However, it can be a sign an underlying condition.

Recurrent UTIs could be due to bacterial persistence, unresolved infection (due to noncompliance with treatment, subtherapeutic antimicrobial level, malabsorption, or resistant organism), or reinfections and must be one of the following:

• one episode of cystitis with one episode of pyelonephritis.
  
• ≥2 episodes of pyelonephritis.
  
• ≥3 episodes of cystitis.

The clinical presentation of the UTI in children varies and is summarised in Table 18.1 [91].

18.6.2 History and Examination

The history is focused on enquiring about symptoms to distinguish between primary or recurrent infection. Also looking for risk factors for UTIs. The child should be examined from head to toe, looking for palpable masses, lymph nodes, tenderness, phimosis, labial adhesions, and stigmata of spina bifida or sacral agenesis.

18.6.3 Investigations

Infants and children presenting with unexplained fever of 38 °C or higher with or without the symptoms and signs suggestive of UTI should have a urine sample send for culture irrespective of the urine dip and microscopy result.