Wednesday, March 16, 2016

Craniopharyngiomas Surgery

Background


Craniopharyngiomas are benign epithelial tumors of the sellar region but can have significant neurological and endocrinological consequences and may require treatment that will cause further morbidity. The first description of a craniopharyngioma is credited to Zenker, who made this observation in 1857. Following this, Mott and Barrett, in 1899, documented the occurrence of these tumors and postulated that they arose from the hypophyseal duct or Rathke pouch. This was subsequently partially confirmed in 1904, when Erdheim described the tumors histologically and suggested that they arose from remnants of the Rathke duct. Finally, in 1932, Cushing introduced the term “craniopharyngioma,” which has been widely used thereafter.
Coronal MRI shows a craniopharyngioma in the suprasellar space that causes compression of the optic nerves and chiasm. 
a Critical Images slideshow, to review cases including meningiomas, glioblastomas and craniopharyngiomas, and to determine the best treatment options based on the case history and images.

History of the Procedure

Evolution of surgical treatment for craniopharyngiomas is closely related to development of the surgical techniques of sella turcica. The first surgical techniques for craniopharyngioma originated in 1891 with the first trepanation done by Selke, then the first successful transcranial approach performed by Horsley in 1907.
The progress of the surgical techniques continued with the first successful resection of craniopharyngioma through a transsphenoidal approach by Eiselsberg in 1910, which was improved by Halstead as a sublabial transsphenoidal resection in the same year. Harvey Cushing created the foundations of craniopharyngioma patient treatment with hormone replacement therapy, but also, in 1919, he developed and performed the first successful resection through the trans-lamina terminalis approach of a retrochiasmatic craniopharyngioma. Later, in 1924, he performed a transcallosal resection of a craniopharyngioma.As technology in diagnostic imaging has improved so has the surgical treatment of craniopharyngioma.

Problem

Craniopharyngiomas are benign, extra-axial, slow-growing tumors that arise from the anterior margin of the sella turcica and predominantly involve the sella and suprasellar space.They rarely metastasize but are locally invasive (typically the hypothalamus), and treatment, particularly surgical attempts at total resection, can result in significant morbidity. As craniopharyngiomas grow, they can cause significant neurological complications, including visual loss, pituitary insufficiency, and hypothalamic damage, and recurrence, both local and meningeal, is often seen and adds to patient morbidity. Malignant transformation of craniopharyngiomas is rare but has been reported after multiple recurrences and after radiation.

Epidemiology

Frequency

The incidence of newly diagnosed craniopharyngiomas is 0.13-2 persons per 100,000 population per year. Even though in some regions such as Japan and parts of Africa, craniopharyngiomas appear with a higher incidence In the United States, approximately 350 new cases of craniopharyngioma are diagnosed every year. Distribution by age is bimodal, with the peak incidence in children at aged 5-14 years and in adults at age 50-75 years. Craniopharyngiomas account for 1-3%of all brain tumors, and half of these tumors occur in childhood. Craniopharyngiomas account for 5-10% of brain tumors in children., No sex predilection exists, and they equally occur in males and females. No genetic relationship is currently known; however, a few familial cases have been reported in the literature.

Etiology

Although the histologic description of craniopharyngiomas was first described over a century ago, considerable debate still exists. Currently, 3 theories are widely accepted, and from these, 3 histologic variants have been derived. They are as follows:
  • The embryogenetic theory suggests that the adamantinomatous type ("adamantinoma") arises from epithelial remnants of the Rathke pouch or the craniopharyngeal duct (the embryonal structure along which the eventual adenohypophysis and infundibulum migrate). Tumors can occur anywhere along the course of this duct, from the pharynx to the sella turcica and third ventricle, which partially explains the location of the tumor.
  • The metaplastic theory suggests that the squamous papillary type results because of metaplasia of squamous epithelial cell rests that arise from squamous cell nests normally found at the junction of the pituitary stalk and pars distalis.
  • Another theory postulates that this tumor is a midline congenital tumor not fundamentally different from an epidermoid cyst.

Pathophysiology

In the World Health Organization (WHO) classification, craniopharyngiomas are divided into 2 groups, adamantinomatous and papillary. There does not appear to be a difference in terms of prognosis, surgical resection, radiosensitivity, and life-expectancy between these groups.

Presentation

The onset of symptoms is generally insidious, with a delay of approximately 1-2 years between initial symptoms and diagnosis. The clinical presentation can include a wide range of symptoms, which depend on the location of the tumor and involvement of adjacent structures. Headache is the most common presenting symptom, followed by endocrine deficiencies and visual disturbances. Headache is usually due to either the tumor’s mass effect or hydrocephalus (from obstruction of the foramen of Monro, third ventricle, or aqueduct of Sylvius), which occurs in 15-30% of patients. This obstructive hydrocephalus may, on rare occasion, require emergent neurosurgical management.
Endocrine disturbances are related to direct compression from the tumor. Endocrine deficiency is most commonly in growth hormone (75%), followed by gonadotropin deficiency (40%), thyroid-stimulating hormone (25%), and corticotropin (25%).Growth failure can be seen in up to 93% of children with craniopharyngioma and is related to either growth hormone deficiency, hypothyroidism, or both. Adults have more varied presentation and may develop sexual or menstrual dysfunction. Eighty-eight percent of men experience decreased sex drive, while 82% of women have amenorrhea. Other endocrine dysfunction may lead to precocious puberty and obesity.
Large tumors in adults can cause psychiatric symptoms, memory loss, apathy, incontinence, depression, and hypersomnia. Long-standing cognitive deficits and profound memory loss have been reported and suggest a worse prognosis. Visual deficits are caused by compression of the optic chiasm from suprasellar tumor growth. Classically, the tumor presents as a bitemporal hemianopsia, but it may also manifest as homonymous hemianopsia, scotoma, or optic atrophy with papilledema.
Other presenting symptoms can include chemical meningitis from rupture of cyst contents into the subarachnoid space and resulting in headaches, stiff neck, and seizures.

Indications

Surgical treatment is indicated in most cases of craniopharyngioma, but surgeons have often approached this tumor with either an aggressive attempt at gross total resection of the tumor or a more conservative approach with a planned subtotal removal of the tumor followed by radiation therapy. Contemporary radiation techniques deliver radiation more accurately, thus preserving the important anatomic structures around or near the tumor.
The decision for either approach should take into consideration the anatomic localization of the tumor, size, invasion of the nearby structures, and the nature of the tumor. The most common indication for surgery is neurologic compromise from tumor mass effect. In children, hypothalamic and endocrine dysfunction may develop before visual defects are noticed. Obesity and lethargy are common in children with craniopharyngiomas. In general, any mass lesion in the pituitary sella and suprasellar area should undergo a biopsy or resection, if feasible. Radiotherapy is indicated in recurrence or in the treatment of residual tumor.

Relevant Anatomy

Craniopharyngiomas have been surgically divided into 3 groups: sellar, prechiasmatic, and retrochiasmatic. Sellar-located tumors may be suprasellar (75%), infrasellar (21%), or intrasellar (4%). These tumors occasionally grow into the third ventricle, causing hydrocephalus. The arterial supply is usually from the anterior cerebral and anterior communicating arteries or from the internal carotid and posterior communicating arteries.
Craniopharyngiomas are usually avascular on angiography but may encase or displace vessels that form the circle of Willis. Usually, the internal carotid artery (ICA) is displaced laterally, the anterior cerebral artery (ACA) is displaced anteriorly, and the basilar artery is displaced posteriorly.
A craniopharyngioma does not receive blood supply from the posterior circulation, unless it is parasitized from the floor of the third ventricle. As these tumors enlarge, they may elevate and infiltrate the optic chiasm as well as the hypothalamic region. Occasionally, they extend into the pituitary fossa or posteriorly to the ventral pons, and rarely, they invade the basal ganglia or the brain parenchyma.
When predominantly in the sella, these tumors erode the bony floor and enlarge the sella.

Contraindications

Surgery is contraindicated in patients with cardiac or respiratory abnormalities that make the risk of general anesthesia unacceptably high. Moreover, patients who take chronic anticoagulation medication must cease medication and demonstrate normal coagulation studies prior to surgery. Asymptomatic patients or those with a small tumor may be monitored with serial MRI scans. A small tumor in the pituitary region without mass effect or endocrine dysfunction may also be monitored with serial MRIs.

Laboratory Studies

Endocrine assessment

A full pituitary endocrine workup is usually mandatory. This includes evaluating the following:
  • Adrenocorticotropic hormone (ACTH or corticotropin)
  • Growth hormone (GH) and insulin growth factor (IGF-1)
  • Cortisol
  • Prolactin
  • Luteinizing hormone (LH)
  • Follicle-stimulating hormone (FSH)
  • Thyrotropin (ie, thyroid-stimulating hormone [TSH])
  • Triiodothyronine (T 3)
  • Thyroxine (T 4).
Any abnormalities should be corrected preoperatively but, at the very least, low cortisol levels and diabetes insipidus should be treated prior to any surgical procedure.

Imaging Studies

CT and MRI are the complementary examinations of choice. Today, the best imaging tool is MRI without and with contrast enhancement.

CT scan

Craniopharyngiomas can vary greatly in size, from a few millimeters to greater than 5 cm. On CT scan, 90% are at least partially cystic, 90% have calcifications, and 90% have nodular or rim enhancement. These tumors are heterogeneous, with the cystic component being hypodense on CT scan and the solid component being isodense or slightly hyperdense with variable enhancement with contrast.

MRI

An MRI with and without contrast is the preferred sequence of choice. On T1-weighted images, the cystic component is often hyperintense and the solid component is isointense, with enhancement of the rim or tumor nodule. On T2-weighted images, the cystic component is hyperintense, as is the solid component.
In the immediate postoperative period (within the first 48 hr), a contrast-enhanced MRI is usually performed to determine whether residual tumor is present, as well as to establish a baseline for future follow-up.

Other Tests

Ophthalmology assessment

Visual acuity and visual field assessment is required to delineate any deficit, including papilledema.

Histologic Findings

Craniopharyngiomas are usually composed of both solid and cystic components. Cyst walls may vary from thin membranes to thick, tough structures that may be hard and rigid because of calcifications. The interior is lined with stratified squamous epithelium with pearly keratin formations. The outside layer is columnar epithelium on a collagenous basement membrane. Calcifications are common; 90% of tumors in children have calcifications, as do 40% of these tumors in adults. Inside the tumor, fibrous tissue, necrotic debris, cholesterol clefts, and keratin pearls are commonly found.
The following 3 histologic phenotypes are seen in craniopharyngioma:
  • Adamantinomatous tumors (seen predominantly in children) resemble enamel-forming oropharyngeal neoplasms. The classic appearance is that of a cystic tumor, usually with a solid component. The cyst may contain fluid that can vary in color, but it usually has a tan appearance that is classically described as resembling “motor oil.” Extensive fibrosis and inflammation have also been observed, which result in dense adhesions between the mass and vasculature, a phenomenon that further contributes to the difficulty in resecting craniopharyngiomas.
  • Squamous papillary tumors (seen predominantly in adults) generally involve only a solid component, which is typically seen without calcifications. It is frequently located in the third ventricle and is usually more encapsulated than the other types and, thus, more easily resectable.
  • Mixed tumors are a combination of the adamantinomatous and papillary forms.
Craniopharyngiomas are known to not undergo malignant degeneration and are usually well defined.However, at the tumor margins, the epithelial fronds tend to penetrate deep into the brain tissue. This may cause a glial reaction in the surrounding brain, making complete resection difficult and possibly predisposing this tissue to traction injuries, particularly in the hypothalamus. The characteristic location of these tumors in the sellar and parasellar region, together with the different histologic subtypes, allows for the above theories that may explain the origin of these tumors.

Medical Therapy

No primary medical therapy exists for this tumor. Hormonal replacements are administered as needed if endocrine abnormalities exist.

Surgical Therapy

The initial surgical decision concerns the approach. If the predominant portion of the tumor is intrasellar, the approach is usually transsphenoidal. Often, the suprasellar component can be delivered into the sella and evacuated. Further, the transsphenoidal approach is well tolerated by patients and is preferable to a craniotomy, when feasible.
If the pituitary sella is not enlarged, the transsphenoidal approach is generally not preferred. A craniotomy is usually necessary when the predominant component is suprasellar, although certain suprasellar masses may be located through an extended transsphenoidal approach. New technology in optics and instrumentation has now permitted many transsphenoidal procedures to be done exclusively through the endoscope. Specialized training is needed in these techniques, but in some instances, even large tumors in the suprasellar space can be safely removed or debulked.
The pterional craniotomy is the standard craniotomy approach to suprasellar lesions because it allows good visualization of the optic nerves, chiasm, and surrounding structures. Variations of the pterional craniotomy have been proposed to include resection of the orbital rim and zygoma so as to provide a more defined view of the skull base and thereby allow better access to the superior aspects of this tumor. These approaches lend themselves to less frontal lobe retraction in order to visualize the operative site.
A subfrontal approach is appropriate for lesions that lie anterior to the optic chiasm, but this may be difficult to determine preoperatively. Under rare circumstances, a transcallosal approach is necessary when the tumor is entirely within the third ventricle. The drawback to this approach is the inability to identify the optic chiasm and pituitary stalk early in the dissection.
Cystic tumors are amenable to either a transsphenoidal approach or a pterional craniotomy. The solid components often adhere to the optic chiasm or hypothalamus and, therefore, may be difficult to remove in their entirety.
Cyst aspiration combined with intracavitary phosphorus-32 (32 P) instillation is an alternative to traditional surgical resection (see video below). Good long-term control of tumor growth has been demonstrated; however, a tumor with significant solid components is not likely to respond to(32P) .Intracystic chemotherapy with bleomycin has also been tried, with some success in short-term reduction of cyst size.Intracavitary therapy requires that an Ommaya reservoir be placed into the cyst. Care needs to be taken that the catheter tip openings are in the cyst itself and that there is no spillage of cyst contents or injected material outside the cyst wall.

Dissection of craniopharyngioma cyst with aspiration.

Grading

In an attempt to balance the advantages of an aggressive surgical resection against the risk of significant morbidity, a preoperative grading system (for children) has been proposed. This system considers the extent of invasion of the hypothalamus by the tumor and is as follows:
  • Type 0: The tumor represents no hypothalamic involvement.
  • Type 1: The tumor distorts or elevates the hypothalamus, but the latter is still visible.
  • Type 2: The hypothalamus is no longer visible.
Consequently, some proposed that a gross total resection be attempted in type 0 and type 1 tumors and that a subtotal resection be attempted in a type 2 tumor, leaving only the hypothalamic component. Although this grading system was developed in a pediatric population, applying it to an adult population is certainly feasible. Some evidence exists, however, that the craniopharyngiomas that arise in adults are less likely to invade the hypothalamus.
A newer classification system proposed by Kassam et al uses a scheme that divides tumors according to their suprasellar extension, based upon the endoscopic expanded endonasal approach (EEA), and is as follows:
  • Type I - Preinfundibular
  • Type II - Transinfundibular (extending into the stalk)
  • Type III - Retroinfundibular, extending behind the gland and stalk, and has 2 subdivisions (IIIa, extending into the third ventricle; and IIIb, extending into the interpeduncular cistern)
  • Type IV - Isolated to the third ventricle and/or optic recess and is not accessible via an endonasal approach

Radiation therapy

Radiation is indicated in patients who had a subtotal resection of craniopharyngioma or with recurrence of the disease. Types of radiation therapy include stereotactic radiosurgery (SRS) and fractionated external beam radiation therapy.
Stereotactic techniques (SRS) are based on localization of the target through stereotactic frame coordinates (attached to the head as in Gamma Knife) or non–frame-based techniques (CyberKnife). Small tumors can be treated with a single fraction of radiation that delivers a high dose of radiation with rapid falloff to minimize the dose to surrounding structures. A larger target volume or proximity to the optic nerve and chiasm may require use of fractionated SRS techniques designed to minimize damage to healthy structures. The dose delivered is usually limited by the optic chiasm, which ideally should receive less than 10 Gy.
External beam radiation therapy uses 3-dimensional planning to deliver radiation with a margin around the tumor. Up to 30 fractions may be used to deliver an effective total dose while keeping daily doses low. Recurrence of tumor is higher when total dose is less than 54 Gy, while complications increase with doses greater than 62 Gy.
Recent data support the concept of subtotal resection followed by radiation therapy as an effective therapy equal in outcome to gross total resection but with fewer complications.

Sagittal MRI shows a cystic craniopharyngioma in the suprasellar space with extension into the third ventricle.

Preoperative Details

Preoperative workup includes an endocrinologic evaluation, particularly to exclude hypoadrenalism and hypothyroidism, both of which increase surgical mortality rates. Dexamethasone may be started prior to surgery to decrease edema.

Intraoperative Details

Successful transsphenoidal resection of a craniopharyngioma requires a generous removal of the contents of the sella turcica. Adequate suprasellar decompression occurs when the arachnoid membrane that surrounds the tumor descends into the operative field. Cerebrospinal fluid (CSF) leakage occurs if the arachnoid is disrupted.
The goal of a craniotomy is gross total removal of the tumor with preservation of the optic apparatus and pituitary stalk. Understanding the anatomy in this region is key to accomplishing this goal. The optic chiasm is nearly always elevated, and the pituitary stalk is usually displaced posteriorly. The stalk may be identified by the striate pattern of portal vessels along its surface. The lamina terminalis may need to be opened for access into the third ventricle. The goal of tumor removal must not outweigh the need for preservation of neural structures; therefore, leaving undisturbed a tumor that is densely adherent to the optic apparatus, anterior cerebral artery, or hypothalamus is advisable.
In general, because long-term tumor control is excellent with radiation therapy following subtotal tumor removal, a conservative approach to tumor resection is usually advised.In some patients, however, a good cleavage plane exists between tumor and brain, and a true complete resection can be accomplished. Surgical judgment is crucial in the assessment of this possibility.

Follow-up

Performing a full postoperative endocrine evaluation as well as repeated imaging studies is advisable. MRI scans are typically obtained immediately postoperatively (within 48 h), at approximately 3 months, and annually thereafter. Long-term follow-up also includes visual-field and pituitary hormone testing.

Complications

The most common complications are related to injury of the adjacent neural structures. Vision may worsen because of unavoidable optic apparatus manipulation.
Postoperatively, many patients demonstrate hypopituitarism. In order to offset this, they are usually given physiologic doses of hydrocortisone as well as a dexamethasone taper to decrease the edema associated with the surgical approach.
Diabetes insipidus may develop and may require treatment with fluid replacement and, occasionally, vasopressin or its synthetic analogue, desmopressin. Some patients have diabetes insipidus as well as disruption of their thirst sensation. These patients pose a difficult management problem and are at high risk for developing hypernatremia. Injuries to the hypothalamus can cause other behavioral changes, including caloric balance disturbance, memory disturbance, and changes in affective behavior.
In rare cases, development of radiation-induced gliomas may occur. This long-term complication has a latency period of greater than 10 years, frequently involves the temporal lobe, and has been predominantly reported in patients who underwent conventional fractionated radiotherapy in their childhood.

Axial MRI shows a craniopharyngioma cyst that contains proteinaceous fluid in the third ventricle. The cyst fluid appears hyperintense.

Outcome and Prognosis

Total resection is the best chance for cure, although some series have reported good results with subtotal resection and fractionated radiation therapy. Small residual tumor, confirmed on postoperative MRI, is generally treated with external beam radiotherapy; however, stereotactic radiosurgery has been used. The use of proton beam radiotherapy for residual disease is currently being investigated. Although the amount of radiation is limited by the proximity to the optic chiasm, good long-term results are now being reported after radiosurgery.
Adverse effects of radiation therapy include endocrine dysfunction, optic neuritis, dementia, and radiation necrosis. In addition, radiation can induce tumors such as meningiomas, sarcomas, and gliomas. In pediatric cases, radiation is postponed to minimize its effects on intelligence quotient and growth. Survival rates for patients with surgery and radiation are better than with surgery alone because radiation helps deter regrowth when residual tumor is present.
Brachytherapy has also been used to treat cystic craniopharyngiomas. Radioisotopes are placed into the cystic portions of the craniopharyngioma. Phosphorus-32 (32 P), colloidal gold-198, colloidal yttrium-91, and bleomycin have all been used. Bleomycin causes shrinkage of the cyst but is highly toxic to neural structures.
In a review of brachytherapy for craniopharyngiomas, Van den Berge followed 31 patients for an average of 41 months.Twenty-nine percent showed improvement of visual acuity, while 13% had stable visual acuity, and 58% deteriorated. Similarly, 28% showed improvement of their visual fields, with 20% showing no change, and 52% deteriorating.

Mortality and morbidity

Overall, the surgical mortality rate is less than 5%, mostly from hypothalamic injury. Bilateral hypothalamic injuries lead to hyperthermia and somnolence. The 10-year survival rate, excluding non–tumor-related deaths, is 90%.
The recurrence of craniopharyngiomas is reported to be up to 24% with approximately a 7-year follow-up. The main risk factor for recurrence is the presence of the residual tumor. Tumor recurrence is higher in the first 3 years after surgery.
In patients with gross total removal of a craniopharyngioma, the 5-year recurrence-free rate is 84.9%, compared to 48.3% in patients with subtotal removal.Morbidity and mortality rates are higher with recurrence and mainly present as visual deficits, endocrine abnormalities, hypothalamic injury, and neurocognitive and neurobehavioral deficits.The visual impairment can be caused by direct damage during surgery or from a daily dose of radiation greater than 2 Gy. The cumulative probability for visual deficits after surgery/radiation is reported to be 36-48% with a 10-year follow-up.
Endocrine abnormalities are commonly seen in postoperative patients with craniopharyngioma. It presents as hypopituitarism and is reported with deficiencies of at least 3 pituitary hormones in 54-100%.Preoperative endocrine deficits do not improve after the surgery, although patients with diabetes insipidus may improve.Hypothalamic dysfunction after the surgery may present as obesity because of hyperphagia, water balance impairment, loss of temperature control, sleep disorders, and neurocognitive disorders. Hypothalamic damage may result from tumor invasion, direct surgical damage from the resection of adherent tumor, tumor recurrence, and radiation.
Hoffman followed 50 children with craniopharyngiomas.In his 1992 report, 90% had total excision, and tumor recurred in 34%. Of all 50 children, 56% were leading normal or nearly normal lives, often requiring endocrine replacement. Twenty-four percent were able to function reasonably well and to attend school despite intellectual, visual, or weight problems; 8% were significantly handicapped; and 6% died. Effenterre et al reported that failure to achieve an independent living function with poor integration and performance at work or school is seen in 16% of adults and 26% of children.The data from literature show the importance of preoperative planning with a reasonable decision in terms of maximal safe tumor resection and the avoidance of complications.

Future and Controversies

The largest divide in the treatment of craniopharyngiomas regards whether to perform a gross total excision or perform a subtotal resection followed by radiation therapy. Retrospective series support both philosophies. Surgical judgment must temper the enthusiasm for gross total removal at all costs. The use of 3-dimensional conformal radiation treatment (3D CRT), stereotactic radiosurgery (SRS), stereotactic radiotherapy (SRT), and intensity-modulated radiation therapy (IMRT) will further allow treatment of small tumor residua with little risk of neurologic deficit. The development of endoscopic techniques has placed greater emphasis on minimally invasive approaches, but this should not detract from surgical techniques that the surgeon feels most comfortable using.

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