**Abstract**

Anaplastic carcinoma thyroid, also known as undifferentiated thyroid carcinoma, is a rare but highly aggressive malignant tumor, which accounts for 2–3% of all thyroid malignancies. It is mostly seen in elderly females in their 6th or 7th decade. It carries a very bad prognosis with an average median survival of 5 months. Patients often present with a rapidly growing, painful, woody hard lower anterior neck mass fixed to underlying structures. In addition to local invasion, patients also present with regional nodal spread and distant metastasis. Though the risk factors for anaplastic carcinoma thyroid are unknown, most of them develop in the setting of long-standing goiter, possibly in an undiagnosed, well-differentiated thyroid carcinoma. Management of anaplastic carcinoma thyroid demands a multidisciplinary approach with the involvement of surgeon, radiation oncologist, radiologist, and endocrinologist. The conventional treatment of anaplastic carcinoma thyroid includes surgery, radiation, and chemotherapy. Recently, multitarget tyrosine kinase inhibitors are also incorporated into the treatment. However, prognosis of the disease is very poor with 4 months of overall survival of 35% and overall disease-specific mortality of 98–99%. In this chapter, we discuss how to approach the condition and various treatment strategies to provide improved treatment outcomes for patients diagnosed with anaplastic carcinoma thyroid.

**Keywords:** anaplastic carcinoma thyroid, presentation, investigations, surgery, radiation, chemotherapy, targeted agents


**1. Introduction**

Endoscopy is the examination and inspection of the interior of body organs, joints or cavities through an endoscope. Endoscopic surgery uses scopes that go through small incisions or natural body openings to diagnose and treat disease. Another popular term is minimally invasive surgery (MIS), which emphasizes that diagnosis and treatment can be done with reduced body invasion. Endoscopes are revolutionary surgical tools that provide detailed video images, allowing visualization of internal structures through a skin incision the width of a thumb and an entry into the organ smaller than a pushpin. Small instruments that can cut, sample, or destroy abnormal tissue or tumors can also be passed through these tubes, allowing intricate surgery to be performed with little or no trauma. Endoscopy allows physicians to peer through the body's passageways.

**Construction** An endoscope uses two fiber optic lines. A "light fiber" carries light into the body cavity and an "image fiber" carries the image of the body cavity back to the physician's viewing lens. The portion of the endoscope inserted into the body may be rigid or flexible, depending upon the medical procedure. There is also a separate port to allow for administration of drugs, suction, and irrigation. This port may also be used to introduce small folding instruments such as scalpels, scissors, forceps, brushes, snares and baskets for tissue excision (removal), sampling, or other diagnostic and therapeutic work. They are inserted through different incisions and are used to perform the operation. Endoscopes may be used in conjunction with a camera or video recorder to document internal mages. New endoscopes have digital capabilities for manipulating and enhancing video images (Figures 1 and 2).

© 2015 The Author(s). Licensee InTech. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and eproduction in any medium, provided the original work is properly cited.

as scalpels, scissors, forceps, brushes, snares and baskets for tissue excision (removal), sampling,

or other diagnostic and therapeutic work. They are inserted through different incisions and are

used to perform the operation. Endoscopes may be used in conjunction with a camera or video

**Figure 1.** This figure shows an endoscope. The "image fiber" leads from the ocular (eye piece) to the inserted end of the scope. The "light fiber" is below and leads from the light source to the working end of the endoscope. **to the inserted end of the scope. The "light fiber" is below and leads from the light source to**

**Figure 1**: **This figure shows an endoscope. The "image fiber" leads from the ocular (eye piece)**

**Figure 2: Endoscopic surgery equipment and instruments Figure 2.** Endoscopic surgery equipment and instruments

#### **1.1. Endoscopic plastic surgery**

**the working end of the endoscope.**

2

Endoscopic plastic surgery is one of the newest plastic surgery techniques. It allows surgeons to operate with fewer conspicuous incisions, reducing obvious scars. Improvements in technology have enabled surgeons to use endoscopy for many cosmetic procedures, including facelifts, forehead lifts, etc. Endoscopy can also be used in some reconstructive procedures. In many cases, the use of endoscopy results in shorter recovery.

Candidates must be in good health, have no active diseases or serious pre-existing medical conditions, and must have realistic expectations of the outcome of the surgery.  Primary and secondary smoking decreases blood flow to the body's tissues. This can result in prolonged wound healing, skin loss, infection, increased scarring, and a number of other complications depending on the kind of procedure performed.

The endoscope is merely a new tool to better achieve just that objective. Outcome enhance‐ ments initially predominated in aesthetic applications, but widespread use also in reconstruc‐ tive endeavors has proved that today there is indeed a broad scope for minimally invasive surgery.

**Figure 1.** This figure shows an endoscope. The "image fiber" leads from the ocular (eye piece) to the inserted end of the

Endoscopic plastic surgery is one of the newest plastic surgery techniques. It allows surgeons to operate with fewer conspicuous incisions, reducing obvious scars. Improvements in

scope. The "light fiber" is below and leads from the light source to the working end of the endoscope.

**Figure 1**: **This figure shows an endoscope. The "image fiber" leads from the ocular (eye piece)**

**to the inserted end of the scope. The "light fiber" is below and leads from the light source to**

as scalpels, scissors, forceps, brushes, snares and baskets for tissue excision (removal), sampling,

or other diagnostic and therapeutic work. They are inserted through different incisions and are

used to perform the operation. Endoscopes may be used in conjunction with a camera or video

recorder to document internal mages. New endoscopes have digital capabilities for

manipulating and enhancing video images (**Figures 1 and 2**).

488 A Textbook of Advanced Oral and Maxillofacial Surgery Volume 2

**Figure 2: Endoscopic surgery equipment and instruments Figure 2.** Endoscopic surgery equipment and instruments

**1.1. Endoscopic plastic surgery**

**the working end of the endoscope.**

2

The goal of what today would be considered minimally invasive surgery may be to even surpass the outcomes possible with traditional open techniques, with diminished patient morbidity including accelerated recovery time and, at the same time, reducing overall healthcare costs. Initially conceived as a means to allow the direct examination of internal organs while avoiding large incisions, the origins of the clinical application of this concept can be traced back to Hippocrates in ~400 BC who used a rectal speculum to examine hemorrhoids. [1] The centuries to follow fostered slow, incremental improvements in instrumentation and light sources that would eventually allow the requisite access as well as proper illumination of the operative field. However, not until the 1950s did the advent of fiber-optic technology permit the transmission of light from an external light source along long, flexible glass or plastic threads so that a clear image could be obtained, yet now without risk of thermal injury.[1]

In 1990, ongoing research efforts at the University of Alabama at Birmingham culminated in reports of a broad clinical experience in endoscopy including endoscopic brow lift.[2] Nowhere were the early demands for minimally invasive surgery so prevalent than in cosmetic surgery.[3]

The interest in aesthetic endoscopic plastic surgery still predominates today, [4]-[11] and there is a concomitant explosion of novel applications in reconstructive surgery. An early thrust of the latter included relatively simple maneuvers such as the removal of benign lesions, decompressive fasciotomy for extremity compartment syndrome,[14] or retrieval of spare body parts such as tendon,[15] vein,[16] or nerve[17],[18] grafts. Congenital deformities such as torticollis[19] especially in the pediatric age group, [13] have been well suited to endoscopic correction, as the cosmetic result often is a major consideration. Acquired defects like facial fractures[20] may be directly or indirectly repaired. More complex indications for various tissue manipulations have included the safe placement of tissue expanders [21], [22] or harvest of local[23] or free adipofascial, muscle, and visceral flaps using endoscopic assistance. The realm in the future may be endoscopic robotic surgery for even greater precision, including not just the difficult and safe dissection of the vascular pedicles of all flaps but also the performance even of the microanastomoses themselves.[23], [24] The capability for all these tissue manipulations could someday then be routinely performed in any distant land or even on another planet, where the immediate availability and skills of a surgeon will no longer be a concern!

## **2. Endoscopic sinus surgery**

The sinuses are air-filled holes in the skull. They are connected to the nose and can get infected leading to discharge, pain, etc. This may be caused by allergies, polyps, abnormal shape or swelling inside the nose. Medical therapies, such as antibiotics, steroids, nasal sprays and decongestants will often cure bouts of sinusitis. Sinus surgery is advocated in those patients who fail to improve after medication. There are circumstances when immediate sinus surgery is warranted. Tumors of the sinuses, whether benign or malignant, often require surgical removal. Surgery may be the only option for some patients whose sinus condition aggravates other medical problems such as asthma. Cancer or immunocompromised patients may require drainage for culture or for treatment of a fungal infection. In the past, surgeries requiring an incision under the lip (Caldwell-Luc) or face (external ethmoidectomy) were used to drain sinus cavities. Most procedures are now performed using endoscopic technology (via small cameras through the nose), eliminating the need for external incisions. Endoscopic sinus surgery uses small rods of light with a camera (endoscope) to operate through the nostrils into the sinuses (Figure 3). performed using endoscopic technology (via small cameras through the nose), eliminating the need for external incisions. Endoscopic sinus surgery uses small rods of light with a camera (endoscope) to operate through the nostrils into the sinuses (**Figure 3**).

**Figure 3.** Entry to the sinus from the nostrils

the septum to improve nasal airflow.

**Functional Endoscopic Sinus Surgery**

5

**Figure 3: Entry to the sinus from the nostrils** This does not involve any incisions on the face, but may be combined with other external This does not involve any incisions on the face, but may be combined with other external approaches, which may involve cuts. This surgery is usually done under general anesthesia for patient comfort. A CT scan will serve as a road map for the surgeon. ESS has presented a new philosophy allowing the surgeon to target the ostiumeatal complex (OMC). Obstruction of the OMC can lead to subsequent infection of the maxillary, frontal and sphenoid sinuses.

approaches, which may involve cuts. This surgery is usually done under general anesthesia for

patient comfort. A CT scan will serve as a road map for the surgeon. ESS has presented a new

philosophy allowing the surgeon to target the ostiumeatal complex (OMC). Obstruction of the

OMC can lead to subsequent infection of the maxillary, frontal and sphenoid sinuses.

Accordingly, ESS removes thickened and diseased tissue blocking the OMC. Most of the healthy

tissue in the sinuses is undisturbed allowing for faster and better overall recovery. Endoscopic

surgery can also be utilized for removal of polyps, nasal masses and sometimes straightening

Functional endoscopic sinus surgery (FESS) is the mainstay in the surgical treatment of **sinusitis**

and **nasal polyps**, including bacterial, fungal, recurrent, acute and chronic sinus problems. FESS

is a relatively recent surgical procedure that uses nasal **endoscopes** (using **Hopkins rod lens**

**technology**) through the nostrils to avoid cutting the skin. FESS came into existence through the

pioneering work of Drs. Messerklinger (in 1960 to 1970's) and his assistant Stamberger who

Accordingly, ESS removes thickened and diseased tissue blocking the OMC. Most of the healthy tissue in the sinuses is undisturbed allowing for faster and better overall recovery. Endoscopic surgery can also be utilized for removal of polyps, nasal masses and sometimes straightening the septum to improve nasal airflow.

### **2.1. Functional endoscopic sinus surgery**

Functional endoscopic sinus surgery (FESS) is the mainstay in the surgical treatment of **sinusitis** and **nasal polyps**, including bacterial, fungal, recurrent, acute and chronic sinus problems. FESS is a relatively recent surgical procedure that uses nasal **endoscopes** (using **Hopkins rod lens technology**) through the nostrils to avoid cutting the skin. FESS came into existence through the pioneering work of Drs. Messerklinger (in 1960 to 1970's) and his assistant Stamberger who became chief of the ENT department in Graz, Austria. Other surgeons have made additional contributions (first published in the USA by Kennedy in 1985).[25]

By the early 1990's endoscopic sinus surgery become one of the most popular procedures. In their 1990 publication, Stamberger [26] mentioned operating 4500 patients, roughly 450 patients annually. Most procedures were very limited surgical procedures; diseased ethmoid compartments were operated on (usually the ethmoidal bulla), stenotic clefts were widened (uncinate process) and prechambers (agar nasi cells) to the frontal and maxillary sinuses were freed from disease.

#### **2.2. Indications**

tissue manipulations could someday then be routinely performed in any distant land or even on another planet, where the immediate availability and skills of a surgeon will no longer be

The sinuses are air-filled holes in the skull. They are connected to the nose and can get infected leading to discharge, pain, etc. This may be caused by allergies, polyps, abnormal shape or swelling inside the nose. Medical therapies, such as antibiotics, steroids, nasal sprays and decongestants will often cure bouts of sinusitis. Sinus surgery is advocated in those patients who fail to improve after medication. There are circumstances when immediate sinus surgery is warranted. Tumors of the sinuses, whether benign or malignant, often require surgical removal. Surgery may be the only option for some patients whose sinus condition aggravates other medical problems such as asthma. Cancer or immunocompromised patients may require drainage for culture or for treatment of a fungal infection. In the past, surgeries requiring an incision under the lip (Caldwell-Luc) or face (external ethmoidectomy) were used to drain sinus cavities. Most procedures are now performed using endoscopic technology (via small cameras through the nose), eliminating the need for external incisions. Endoscopic sinus surgery uses small rods of light with a camera (endoscope) to operate through the nostrils into

performed using endoscopic technology (via small cameras through the nose), eliminating

the need for external incisions. Endoscopic sinus surgery uses small rods of light with a

This does not involve any incisions on the face, but may be combined with other external

This does not involve any incisions on the face, but may be combined with other external approaches, which may involve cuts. This surgery is usually done under general anesthesia for patient comfort. A CT scan will serve as a road map for the surgeon. ESS has presented a new philosophy allowing the surgeon to target the ostiumeatal complex (OMC). Obstruction of the OMC can lead to subsequent infection of the maxillary, frontal and sphenoid sinuses.

approaches, which may involve cuts. This surgery is usually done under general anesthesia for

patient comfort. A CT scan will serve as a road map for the surgeon. ESS has presented a new

philosophy allowing the surgeon to target the ostiumeatal complex (OMC). Obstruction of the

OMC can lead to subsequent infection of the maxillary, frontal and sphenoid sinuses.

Accordingly, ESS removes thickened and diseased tissue blocking the OMC. Most of the healthy

tissue in the sinuses is undisturbed allowing for faster and better overall recovery. Endoscopic

surgery can also be utilized for removal of polyps, nasal masses and sometimes straightening

Functional endoscopic sinus surgery (FESS) is the mainstay in the surgical treatment of **sinusitis**

and **nasal polyps**, including bacterial, fungal, recurrent, acute and chronic sinus problems. FESS

is a relatively recent surgical procedure that uses nasal **endoscopes** (using **Hopkins rod lens**

**technology**) through the nostrils to avoid cutting the skin. FESS came into existence through the

pioneering work of Drs. Messerklinger (in 1960 to 1970's) and his assistant Stamberger who

camera (endoscope) to operate through the nostrils into the sinuses (**Figure 3**).

a concern!

**2. Endoscopic sinus surgery**

490 A Textbook of Advanced Oral and Maxillofacial Surgery Volume 2

the sinuses (Figure 3).

**Figure 3: Entry to the sinus from the nostrils**

**Figure 3.** Entry to the sinus from the nostrils

the septum to improve nasal airflow.

**Functional Endoscopic Sinus Surgery**

5

The most common indication for endoscopic sinus surgery is "chronic rhinosinusitis". Chronic rhinosinusitis is a term applied to various nasal processes which involve inflammation of the nose and sinuses that do not adequately improve with medical management. Less common indications include (but are not limited to): recurrent infections (rather than chronic inflam‐ mation), complications of sinus infections, nasal polyps, mucoceles, chronic sinus headaches, impaired sense of smell, tumors of the nasal and sinus cavities, cerebrospinal fluid leaks, nasolacrimal duct obstruction, choanal atresia, and the need to decompress the orbit. Addi‐ tionally, recent advances in endoscopic techniques allow the operator to provide access to areas of the brain and pituitary gland for neurosurgeons or to the orbits (eye sockets) for certain ophthalmology procedures.

#### **2.3. Technique**

The frontal, maxillary, and anterior ethmoid sinuses drain into the middle meatus. Posterior ethmoids drain into the superior meatus. Sphenoid sinuses drain into the sphenoethmoid recess. Telescopes with diameters of 4mm (adults) and 2.7mm (pediatrics) and with a variety of viewing angles (0 to 30, 45, 70, 90, and 120 degrees) provide good illumination of the inside of the nasal cavity and sinuses. High-definition cameras, monitors and a host of tiny articu‐ lating instruments aid in identifying and restoring the proper drainage and ventilation relationships between the nose and sinus cavities. Cultures and biopsies can be easily obtained to yield valuable diagnostic information to guide postoperative therapy for optimal long term results.

All the sinuses can be accessed at least to some degree by means of this device: The frontal sinuses located in the forehead, the maxillary sinuses in the cheek bones, the ethmoid sinuses between the orbits, and the sphenoid sinuses are located in the back of the nasal cavity at the base of the skull.

## **2.4. Extended approaches**

Endoscopic access to pituitary tumors has been successfully accomplished for many years. More recently, further advanced techniques have allowed the paranasal sinuses to be a relatively low-morbidity approach to selected tumors even inside the skull or brain.

### **2.5. Benefits of ESS**

The overall goal of sinus surgery is to improve the drainage pathway of the sinuses. By opening the natural drainage pathway of the diseased sinus, the frequency, duration and severity of infections should be reduced. Sinus surgery is not without risk, but it does have major benefits. Sinus issues left uncorrected may lead to abscess formation, permanent loss of sense of smell vision, or even death. Benefits of sinus surgery include asthma relief, polyps and fungus removal and less recurrence of sinus infections.

Although there are patients who have mechanical obstruction due to their particular anatomy, many patients have an intrinsic problem with the lining (mucous membrane) of their nose and sinuses. While the patients with mechanical obstruction, will receive the maximal benefit from surgery, the benefit for patients with mucous membrane disease is also tangible because the larger opening created during surgery will allow better drainage and more medication and rinses to get into the sinuses and help treat the diseased lining.

One of the most important benefits of surgery is the ability to deliver medications (e.g. sprays, rinses, nebulized drugs) to the lining of your sinuses after they have been accessed. Therefore, surgery is an adjunct to, not a replacement for, proper medical management. It is important to note, however, that if you are one of the patients who have diseased mucous membranes or form nasal polyps, no amount of surgery can change this fact. So although surgery plays a role in managing the disease, it may not cure sinus disease with polyps or other types of chronic inflammation. Therefore, it should be emphasized that surgery is one of the multiple steps in managing the disease.

#### **2.6. Possible risks and complications related to functional endoscopic sinus surgery**

Extreme care is required with this surgery due to the proximity of the sinuses to the eyes, optic nerves, brain and internal carotid arteries. However, these serious risks are rare occurrences and there are many potential benefits from a well-performed endoscopic sinus surgery with appropriate indications. All surgical procedures have risks and complications namely:

**1.** Bleeding from the nose in the days following the operation

**2.** Infection

to yield valuable diagnostic information to guide postoperative therapy for optimal long term

All the sinuses can be accessed at least to some degree by means of this device: The frontal sinuses located in the forehead, the maxillary sinuses in the cheek bones, the ethmoid sinuses between the orbits, and the sphenoid sinuses are located in the back of the nasal cavity at the

Endoscopic access to pituitary tumors has been successfully accomplished for many years. More recently, further advanced techniques have allowed the paranasal sinuses to be a

The overall goal of sinus surgery is to improve the drainage pathway of the sinuses. By opening the natural drainage pathway of the diseased sinus, the frequency, duration and severity of infections should be reduced. Sinus surgery is not without risk, but it does have major benefits. Sinus issues left uncorrected may lead to abscess formation, permanent loss of sense of smell vision, or even death. Benefits of sinus surgery include asthma relief, polyps and fungus

Although there are patients who have mechanical obstruction due to their particular anatomy, many patients have an intrinsic problem with the lining (mucous membrane) of their nose and sinuses. While the patients with mechanical obstruction, will receive the maximal benefit from surgery, the benefit for patients with mucous membrane disease is also tangible because the larger opening created during surgery will allow better drainage and more medication and

One of the most important benefits of surgery is the ability to deliver medications (e.g. sprays, rinses, nebulized drugs) to the lining of your sinuses after they have been accessed. Therefore, surgery is an adjunct to, not a replacement for, proper medical management. It is important to note, however, that if you are one of the patients who have diseased mucous membranes or form nasal polyps, no amount of surgery can change this fact. So although surgery plays a role in managing the disease, it may not cure sinus disease with polyps or other types of chronic inflammation. Therefore, it should be emphasized that surgery is one of the multiple steps in

**2.6. Possible risks and complications related to functional endoscopic sinus surgery**

Extreme care is required with this surgery due to the proximity of the sinuses to the eyes, optic nerves, brain and internal carotid arteries. However, these serious risks are rare occurrences and there are many potential benefits from a well-performed endoscopic sinus surgery with appropriate indications. All surgical procedures have risks and complications namely:

relatively low-morbidity approach to selected tumors even inside the skull or brain.

results.

base of the skull.

**2.5. Benefits of ESS**

managing the disease.

removal and less recurrence of sinus infections.

492 A Textbook of Advanced Oral and Maxillofacial Surgery Volume 2

rinses to get into the sinuses and help treat the diseased lining.

**1.** Bleeding from the nose in the days following the operation

**2.4. Extended approaches**

#### **2.7. CT navigation**

**Computed tomography** (CT) navigation is a tool that may be used by surgeons to better correlate surgical anatomy with pre-operative CT imaging. A computer is used to identify the 3-dimensional location of a probe tip placed within the patient's nose or sinuses.

Definitive proof that CT navigation improves outcomes and decreases complications is lacking. A Swedish study of 212 patients undergoing sphenoethmoidectomy published in 2008 concluded that the clinical success of the procedure was similar with or without the use of CT navigation, and that the rate of complications might be slightly reduced.[27]


*3.1.3 Limitations and possible complications of phakic intraocular lenses*

The complications relating to pIOLs can, at times, be more disabling than those from keratorefractive surgery. Night vision problems, corneal decompensation, glaucoma, cataract formation, dyscoria, uveitis, and endophthalmitis are potential complications after pIOL implantation. Night vision problems such as glare, halos, and diplopia are related to decentration of the pIOL and/or an optic diameter that is too small relative to the pupil size [61].

Surgically induced astigmatism is an issue primarily correlated with rigid Verisyse lenses and incision diameter. However, some investigators reported that the resulting surgically induced astigmatism (SIA) was less than expected [62, 63]. However, when compared with the Veriflex pIOL and ICL, the SIA was significantly higher [64].

Implantation of a pIOL, whether iris fixated or positioned in the posterior chamber, is associated with an accelerated decrease in endothelial cell density (ECD) [60]. Damage to the corneal endothelium may be due to the direct contact between pIOL and the inner surface of the cornea during implantation, from postoperative changes in pIOL position, or from subclinical inflammation, and direct toxicity to the endothelium. The magnitude of ECD loss after phakic intraocular lens implantation surpasses the expected natural annual decrease of 0.6% as reported in a 1997 benchmark study based on 42 adults [65]. Following implantation of an iris-claw phakic intraocular lens, the loss of ECD is highest during the first year varying between 0.75 and 7.2% [66]. Thereafter, the ECD loss continues without following an obvious pattern, to about 8.9% after 10 years. However, with an ICL the impact on the endothelium is claimed to be lower because the implant is placed in the posterior chamber further away from the endothelium itself. For the ICL the ECD loss is about 1.7% after 2 years [60] increasing to 6.2% after 8 years [54] and up to 19.75% after 12 years [67].

In our experience after ICL implantation, there is a linear decrease in ECD over a 3-year period, without any signs of exponential EC loss or reaching a plateau or stable ECD during this time (**Figure 5**).

With modern pIOL designs, increased intraocular pressure (IOP) seems to be relatively uncommon after 3 months postoperatively and is typically thought to be related to corticosteroid response [68]. Posterior chamber pIOLs cause narrowing of anterior chamber angle due to its position in ciliary sulcus, and its sizing (too long lenses which cause excessive vaulting >750 μm) is closely correlated with possible angle-closure glaucoma, pupillary block glaucoma, or pigmentary dispersion glaucoma [69, 70]. Given the risk of pupillary block, peripheral iridectomy or iridotomy is carried out as a preventative measure in anterior pIOL procedures, while in newer models of ICL with aquaport, technology is not needed.

Pupil ovalization/iris retraction is mainly correlated with iris-fixated pIOL and can occur if fixation of the pIOL haptics is performed asymmetrically [61, 68, 71]. No progressive pupil ovalization has been reported.

Formation of cataract due to the iris-claw pIOL is unlikely because the pIOL is inserted over a miotic pupil without contact with the crystalline lens [61]. The incidence of cataract formation was 1.1% for the iris-fixated pIOL. The overall incidence of cataract formation for posterior chamber pIOLs was 9.60%, which is significantly higher in comparison to iris-fixated pIOLs [72]. With various generations of the ICL, appearance of cataract formation is different. The less vaulted

**Figure 5.**

*Mean endothelial cell density during the 3-year follow-up (28 eyes); ± SD error bars are included indicating the variance in the data.*

model V3 caused a higher incidence of cataract formation than the newer V4 and V5 models [73]. With the V4 model, the recently published FDA study showed an incidence of 2.1% anterior subcapsular opacities, which is the most common type of cataract after pIOL [59]. Possible reasons are operative trauma, continuous or intermittent contact of the posterior chamber pIOL with the crystalline lens, insufficient nutrition through anterior chamber flow between the posterior chamber pIOL and the crystalline lens, and chronic subclinical inflammation with disruption of the blood-aqueous barrier due to friction between the pIOL and posterior iris or the haptic on the ciliary sulcus [74–76].

The risk of uveitis is a concern given the proximity of pIOLs to the iris, but it does not seem to be a significant long-term complication with modern designs. With iris-fixated pIOLs, a difficulty with enclavation of the iris can lead to iris atrophy and decentration of the implant [52]. Retinal detachment seems to be uncommon and lower than in clear lens extraction cases [68, 77]. A few cases of endophthalmitis have been reported after pIOL implantation, but it seems less common after pIOL implantation and then after cataract surgery [78, 79].

#### **3.2 Refractive lens exchange**

Refractive lens exchange (RLE) is by definition used to indicate the replacement of the cataractous/clear crystalline lens with an intraocular lens (IOL) to achieve emmetropia/near emmetropia. The improved efficacy, predictability, and safety of modernday phacoemulsification have resulted in a resurgence of lens extraction as a modality for correction of high myopia. Increased numbers of RLE are being performed worldwide, especially in patients not suitable for LASIK or pIOL or with early lens changes in the presbyopia age group [80, 81]. Optics of the IOL confer better quality of vision as compared with LASIK, and this optical quality does not degrade with time except in the presence of a posterior capsular opacification. The refractive results are predictable and stable with a larger range of refractive correction possible than with either LASIK or pIOL. RLE addresses refractive error and cataract and with the use of modern multifocal IOLs results in a significant degree of spectacle independence for the patient. Visual recovery is faster, and it is more cost-effective, as the higher cost of pIOLs and future cataract surgery is eliminated. The principles of surgery are in the domain of most cataract/anterior segment surgeons [82].

Overall, patient satisfaction scores after implantation of multifocal IOLs are high. For example, using a 0–10 self-recording analogue scale, you can expect

**111**

*Surgical Correction of Myopia*

*DOI: http://dx.doi.org/10.5772/intechopen.85644*

acuity as demonstrated in **Figure 6**.

**Figure 6.**

*multifocal IOLs.*

visual performance and jeopardize the result [85].

typical average satisfaction scores of 8.8 (Zeiss bifocal IOL, n = 48, range 2–10) and 9.00 (Zeiss trifocal IOL, n = 52, range 4–10). On closer examination satisfaction scores are closely linked to post-op uncorrected distance and intermediate, visual

*Postoperative uncorrected distance visual acuity and patient satisfaction after RLE with implantation of*

Advanced technology multifocal IOLs tend to be less forgiving with respect to the surgical technique, multifocal IOL power selection, ocular comorbidities, and patient selection. Comorbidities such as dry eye, vitreomacular pathology, or implant decentration may be tolerated in patients after a monofocal IOL implantation. However, these are much less tolerated by the multifocal IOL patients [83, 84]. Presbyopia-correcting intraocular lenses should provide post-op emmetropia for the best visual outcome, as small amounts of residual refractive errors can limit

In evaluating the highly myopic patient, several aspects apart from the routine cataract/refractive surgery assessment should be noted. A detailed past ocular history is important, as previous refractive surgery or phakic intraocular lens implants or retinal problems (e.g., vitrectomy for previous retinal detachment) will affect lens formula choices and their final prognosis. Preoperative assessment should also include a detailed clinical examination of their lens status (e.g., cataract density and any zonular weakness) and refraction status of both eyes, as well as a dilated examination of the fovea and periphery for any retina disorder (e.g., myopic choroidal neovascular membrane, macular schisis, retinal tears, or detachment). Other issues for discussion include the potential use of toric or multifocal IOLs. Ideally, a larger haptic platform toric lens should be used in high myopes to reduce the risk of postoperative lens rotation, as the capsular bag is often large and floppy. In some cases, the use of a capsular tension ring to stretch the capsular bag may be required to prevent rotations.

*3.2.1 Preoperative examination and indications for refractive lens exchange*

Multifocal IOLs should only be used in an eye with no retinal disorder [86].

pathology, absence of uveitis, or any kind of ocular inflammation.

Inclusion criteria are more than 40 years of age with myopia not amenable to conventional laser refractive surgery (e.g., high refractive error, corneal irregularities, thin cornea) or phakic IOLS (e.g., shallow anterior chamber, poor endothelial cell count, early cataract changes), presbyopic myopic patients who want reasonable independence from glasses for both distance, and near-vision, myopic patients with early lens changes who desire refractive correction [80, 86]. For multifocal IOL it is important to rule out any irregularities of iris or pupil function, evolving retinal

**Figure 6.**

*Intraocular Lens*

**Figure 5.**

*variance in the data.*

model V3 caused a higher incidence of cataract formation than the newer V4 and V5 models [73]. With the V4 model, the recently published FDA study showed an incidence of 2.1% anterior subcapsular opacities, which is the most common type of cataract after pIOL [59]. Possible reasons are operative trauma, continuous or intermittent contact of the posterior chamber pIOL with the crystalline lens, insufficient nutrition through anterior chamber flow between the posterior chamber pIOL and the crystalline lens, and chronic subclinical inflammation with disruption of the blood-aqueous barrier due to friction between the pIOL and posterior iris or

*Mean endothelial cell density during the 3-year follow-up (28 eyes); ± SD error bars are included indicating the*

The risk of uveitis is a concern given the proximity of pIOLs to the iris, but it does not seem to be a significant long-term complication with modern designs. With iris-fixated pIOLs, a difficulty with enclavation of the iris can lead to iris atrophy and decentration of the implant [52]. Retinal detachment seems to be uncommon and lower than in clear lens extraction cases [68, 77]. A few cases of endophthalmitis have been reported after pIOL implantation, but it seems less common after

Refractive lens exchange (RLE) is by definition used to indicate the replacement of the cataractous/clear crystalline lens with an intraocular lens (IOL) to achieve emmetropia/near emmetropia. The improved efficacy, predictability, and safety of modernday phacoemulsification have resulted in a resurgence of lens extraction as a modality for correction of high myopia. Increased numbers of RLE are being performed worldwide, especially in patients not suitable for LASIK or pIOL or with early lens changes in the presbyopia age group [80, 81]. Optics of the IOL confer better quality of vision as compared with LASIK, and this optical quality does not degrade with time except in the presence of a posterior capsular opacification. The refractive results are predictable and stable with a larger range of refractive correction possible than with either LASIK or pIOL. RLE addresses refractive error and cataract and with the use of modern multifocal IOLs results in a significant degree of spectacle independence for the patient. Visual recovery is faster, and it is more cost-effective, as the higher cost of pIOLs and future cataract surgery is eliminated. The principles of surgery are in the

Overall, patient satisfaction scores after implantation of multifocal IOLs are high. For example, using a 0–10 self-recording analogue scale, you can expect

the haptic on the ciliary sulcus [74–76].

**3.2 Refractive lens exchange**

pIOL implantation and then after cataract surgery [78, 79].

domain of most cataract/anterior segment surgeons [82].

**110**

*Postoperative uncorrected distance visual acuity and patient satisfaction after RLE with implantation of multifocal IOLs.*

typical average satisfaction scores of 8.8 (Zeiss bifocal IOL, n = 48, range 2–10) and 9.00 (Zeiss trifocal IOL, n = 52, range 4–10). On closer examination satisfaction scores are closely linked to post-op uncorrected distance and intermediate, visual acuity as demonstrated in **Figure 6**.

Advanced technology multifocal IOLs tend to be less forgiving with respect to the surgical technique, multifocal IOL power selection, ocular comorbidities, and patient selection. Comorbidities such as dry eye, vitreomacular pathology, or implant decentration may be tolerated in patients after a monofocal IOL implantation. However, these are much less tolerated by the multifocal IOL patients [83, 84].

Presbyopia-correcting intraocular lenses should provide post-op emmetropia for the best visual outcome, as small amounts of residual refractive errors can limit visual performance and jeopardize the result [85].

#### *3.2.1 Preoperative examination and indications for refractive lens exchange*

In evaluating the highly myopic patient, several aspects apart from the routine cataract/refractive surgery assessment should be noted. A detailed past ocular history is important, as previous refractive surgery or phakic intraocular lens implants or retinal problems (e.g., vitrectomy for previous retinal detachment) will affect lens formula choices and their final prognosis. Preoperative assessment should also include a detailed clinical examination of their lens status (e.g., cataract density and any zonular weakness) and refraction status of both eyes, as well as a dilated examination of the fovea and periphery for any retina disorder (e.g., myopic choroidal neovascular membrane, macular schisis, retinal tears, or detachment). Other issues for discussion include the potential use of toric or multifocal IOLs. Ideally, a larger haptic platform toric lens should be used in high myopes to reduce the risk of postoperative lens rotation, as the capsular bag is often large and floppy. In some cases, the use of a capsular tension ring to stretch the capsular bag may be required to prevent rotations. Multifocal IOLs should only be used in an eye with no retinal disorder [86].

Inclusion criteria are more than 40 years of age with myopia not amenable to conventional laser refractive surgery (e.g., high refractive error, corneal irregularities, thin cornea) or phakic IOLS (e.g., shallow anterior chamber, poor endothelial cell count, early cataract changes), presbyopic myopic patients who want reasonable independence from glasses for both distance, and near-vision, myopic patients with early lens changes who desire refractive correction [80, 86]. For multifocal IOL it is important to rule out any irregularities of iris or pupil function, evolving retinal pathology, absence of uveitis, or any kind of ocular inflammation.

#### *3.2.2 Limitations and possible complications of refractive lens exchange*

The commonest disadvantage is the loss of accommodation with the need for near-vision glasses in the cases of monofocal IOL and the inherent risk associated with intraocular surgery, especially in high myopes [80]. The risk for endophthalmitis in general cataract surgery with implantation of a posterior chamber IOL is 0.1–0.7% with an optimal antiseptic perioperative treatment regimen [87]. Lens surgery is significantly more challenging in a highly myopic eye for several reasons. The issues that we take for granted in an eye of normal length (22–25 mm) such as the accuracy of axial length measurements and the choice of lens formula become a significant issue in the highly myopic eye as the predicted refractive outcomes are not achieved consistently. Axial length measurement error has been largely overcome by the use of optical interferometry. Despite this, consistent hyperopic errors are still reported. Improved predictive results are obtained with the Barrett Universal II (software constants), Haigis (ULIB), SRK/T, Holladay 2 (software constants), and Olsen (software constants) formulas in eyes with axial lengths greater than 26.0 mm and IOL powers greater than 6.0 D. In the eyes with axial lengths greater than 26.0 mm and IOL less than 6.00 D, the Barrett Universal II formula (software constants) and the Haigis (axial length adjusted) and Holladay 1 formulas (axial length adjusted) should be used [88, 89].

Intraoperatively, a highly myopic eye is surgically more challenging as the anterior chamber is deeper, with a floppy and large capsular bag and occasionally zonular weakness [90]. The anterior chamber is often unstable, and it is even less stable in a previously vitrectomized high myopic patient. There is also a concern that with elongated axial lengths, there is a higher risk of bag instability that can cause impaired vision, and the more complicated the IOL design is, the more sensitive the IOL is to final centration. A study by Soda et al. found that in uncomplicated cataract surgery with an IOL in the bag, the maximum decentration can be 0.3 mm for a satisfying result [91]. In addition, it is reported that myopic patients may exhibit worse results with more reported subjective symptoms and measurable aberrations like coma and glare in mesopic and scotopic lighting conditions compared to non-myopic controls, after multifocal IOL implantation with approximately the same amount of decentration [91]. RLE may increase the risk for retinal detachment and is generally not considered in myopic pre-presbyopic patients who can still accommodate.

The incidence of retinal detachment is especially high among younger age groups (<50 years) and in the eyes with long axial length > 26 mm. The reported incidence of retinal detachment after RLE ranges from 2 to 8%. Meticulous surgery with minimal intraoperative vitreous disturbance and a regular follow-up postoperatively until the occurrence of posterior vitreous detachment can reduce the risk of retinal detachment further. With the higher risk of retinal detachment in younger patients, it is prudent to defer RLE in patients younger than 40 years if possible [92].

Other possible causes of unfavorable visual outcome after uncomplicated phacoemulsification are cystoid macular edema (CME) and choroidal neovascular membrane (CNVM). Overall incidence of subclinical CME diagnosed with optical coherence tomography (OCT) is 5%, and incidence of clinical CME is 3%; however, high myopia does not increase the risk of CME [93]. Reported incidence of CNVM after RLE for myopia is 12.5% [94]; however, whether this was related to the higher degree of myopia with preexisting lacquer crack that was missed or due to some inflammatory mediators and free radicals released after surgery cannot be conclusively proved. Because the reported incidence of CNVM after uncomplicated phacoemulsification is not high, we assume that it is secondary to the degree of myopia,

**113**

**Author details**

provided the original work is properly cited.

1 Specialty Eye Hospital Svjetlost, Zagreb, Croatia

2 School of Medicine, University of Rijeka, Croatia

\*Address all correspondence to<EMAIL_ADDRESS>
*Surgical Correction of Myopia*

**4. Conclusions**

*DOI: http://dx.doi.org/10.5772/intechopen.85644*

and it is prudent to perform OCT preoperatively in all RLE patients, especially those with more than 10 D of myopia. The presence of a myopic CNVM in the fellow eye is also considered as a risk factor for developing CNVM in the operated eye [80, 94].

Surgical treatment of myopia is a viable, safe, efficient, and predictable method for treating patients with myopia. There are several options of surgical treatment; we as doctors must always use our best judgment and available data to make sure we recommend the best method for each patient and their respective needs while taking into account any possible risk and contraindications. Among elective procedures in medicine, myopia treatment is one of the most commonly performed surgeries

because of the positive effect it brings the patients' quality of life.

© 2019 The Author(s). Licensee IntechOpen. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/ by/3.0), which permits unrestricted use, distribution, and reproduction in any medium,

Maja Bohac1,2\*, Maja Pauk Gulic1,2, Alma Biscevic1,2 and Ivan Gabric1,2

and it is prudent to perform OCT preoperatively in all RLE patients, especially those with more than 10 D of myopia. The presence of a myopic CNVM in the fellow eye is also considered as a risk factor for developing CNVM in the operated eye [80, 94].


**6.2 Transport**

When contraction traverses at 50% occlusion, there is a higher tendency for the particles to undergo circulation; favoring mixing [56]. However, at 80% occlusion, the particles tend to under more of axial displacement and less of a radial displacement with no circulation; favoring transport. Particles positioned near the center were found to travel a longer distance in comparison to those near the wall. Such behavior reminds us the parabolic velocity profile in case of pressure driven flows in pipe. Previous studies corroborates with the understanding that the flows in occlusion regions tend to show a parabolic profile [44]. Rheological effects of the particle displacement suggest that the eccentricity of the particle trajectory for Newtonian fluid is more and undergoes a near complete circulation. Particle trajectory for dilatants showed formation of a complete circulation. For fluid having flow behavior index less than 1.0, following observations were made (1) particles tend to travel with higher velocity over longer distance and (2) particles showed more of a radial predominance. There were no significant changes in the flow developed by introducing the LLS; however, due to additional momentum along the axial direction they tend to suppress the radial displacement of the tracer leading to a more translocation. The transport has been linked to malabsorption of the nutrients and electrolyte concentration. Alternations in the intestinal transit can disturb the equilibrium of osmolality and intestinal absorption leading to diarrhea or constipation [57]. Knowledge of the intestinal transit of bolus is essential when design the drug. Orally administered drugs have to be tuned to the environmental conditions of the small intestine so that drug bioavailability can be maximized. Since the physical properties of the meal, such as viscosity can greatly influence the transport behavior, clinical preparation of the food can be administered to help manage the patient suffering from motility disorders.

#### **6.3 Frictional advantage**

Frictional effects of the intestinal wall have been attributed to a disadvantage when considering transport. By estimating the flow resistance, the author was able to assess the importance of the slowing down of the fluid flow and increase in the retention time of the fluid near the mucosa; providing more time to undergo chemical digestion and absorption [56]. The extent of friction offered by the intestine to fluid of different flow behavior index (n = 0.6, 1.0, and 1.4) suggests that the friction is highest for pseudo-plastics and decreases with increase in flow behavior index [56]. In addition to this, friction is found to be dependent on pressure gradient; showing increasing trend with increase in pressure. They are linearly related to the Reynolds number; higher the *Re* higher is the resistance. Since the friction is analyzed for a channel with smooth inner surface, we presume that the contribution resulting from plicae circulares would be much higher.

Friction is more at the occlusion center and drops significantly as one recedes away from occlusion center to the wave end. The friction due to mucosal layer of the intestine is a subject matter of interest to intestinal digestion. We may consider the problem similar to the flooding of the terrain occupied by numerous trees. At the flood end, where the fluid velocity is very high, the fluid particles tend to slow down upon interacting with the tree. Since the surface area of the tree is more, the effectiveness to slow the fluid particle is much higher. In physiology, such resistance to flow is provided by the intestinal folds of mucosa known as the plicae circulares or the valves of kerckring. The author speculates that these structures help in reducing the luminal transport and increase the time of retention of the fluid near the mucosa so as to allow for increased absorption of the nutrients. Depending on the flow regime, the flow may be highly agitated to flush the contents and allow for replenishment of the nutrient-rich contents. Such a behavior prevents the formation of trapped fluids and cause continuous flushing of the mucosa without stagnation. Such understanding is necessary to know the dynamics of nutrient transport near the intestinal mucosa and equilibration. While, stagnation of the acidic contents near the duodenum can have drastic impact on the mucosal layer leading to duodena ulceration.

#### **6.4 Power demands of peristalsis**

Contraction leading to flow is majorly determined by the muscular contractions of the circular and longitudinal muscle layers of the intestine. Although extramural pressure forces may contribute in the modulating the flow patterns, much of the mechanics is initiated and driven by the muscles. Efficiency to pump is defined as the ratio of energy due to pressure force to the energy spent by intestine through muscular contraction. The circular contractions are majorly known to cause the positive displacement of the fluid, and hence primarily responsible to transport. However, the LLS results in the developed for axial forces that are small in comparison to circular contraction and have minor contribution to efficiency at lower occlusions. LLS is advantageous at higher occlusion, where they primarily help to forcefully shrink the intestinal wall along the axial direction to concentrate more circular fibers. The energy spent on contraction can be reduce dramatically from 26.5 (CC along) to 22.5 units (CC with 0.65% LLS) approximately; a 15% reduction in energy spent by the intestinal motility to drive shear thickening fluid. However, in contrast to the above, we also identify that power advantage of LLS negatively correlates for shear-thinning fluid driven by CC with 0.65% LLS. Suggesting that rheology of the luminal contents shares some relation with the nature of LLS. This emphasizes an important observation as to whether such a correlation exists, and

**63**

*Biomechanics of the Small Intestinal Contractions DOI: http://dx.doi.org/10.5772/intechopen.86539*

energy it spends to perform the peristalsis.

**6.5 What is the optimal parameter space for contractility?**

if so, how does the intestine senses the fluid rheology? Although there are no direct sensors to detect the rheology or viscosity of the contents, we speculate that the gut may use an indirect mechanism to serve the purpose of assessing the rheology through stretch sensors. Since this sensor respond to distension, we also speculate that the difficulty to pump highly viscous fluid are reflected in the form of stretch. The concept of mechanical sensing of the stretch in the intestinal wall was observed by infusing a larger bolus of isotonic saline directly into the intestinal lumen [58]. The study reported that a controlled distension of the intestine activates a subset of vagal sensory neurons. Perhaps, the sensors data are relayed to the higher centers of the brain or through the local reflex to trigger certain feedback controls. Somehow, the intestine is aware of the trade-offs between the power demands of peristalsis at a certain occlusion against the percentage LLS. It may not prefer to contract at higher LLS for circular contraction of lower occlusion; since it would be non-economical. However, on the contrary, it is economical to contract at higher LLS for circular contraction of higher occlusion; an optimal strategy in conserving the amount of

The intestine has its own ability to perform muscular contraction to an extent that can be mapped onto a phase space (multidimensional space in which each state variable represented by an axis is constructed to specify the state of a physical system at a given point of time). To derive such plots for intestine, we resorted to literature reports related to the clinical observations of the intestinal motility during fed and fasted state, and, normal and pathology condition [22]. The parameters of interest are: incidence of propagatory versus stationary contractions per min, percentage incidence of antegrade and retrograde propagating waves, frequency of the wave, wave velocity in mm/s, and duration of MMC (interdigestive contractions) cycle. The ability of the intestine to perform digestion optimally depends on how well it coordinates with neurohormonal system. Eliciting segmental contraction on duodenal infusion of fat or hydrochloric acid requires that the contents are mixed well with the biliopancreatic secretions to cause buffering and emulsification. Such motility patterns are known to transform the fat into droplets which help providing more surface area for lipase binding to take place and perform the digestion [59]. Previous study by the author shows intestinal preference to digestion especially extent of mixing, and volume of mixing, and to-and-fro motion of contents [44]. Since the peristalsis provides sufficient shearing forces to help cause the droplet formation, we learn that some correlation exist between the motility and emulsification. Similarly, transport of the contents requires forceful expulsion of the contents by through muscular contraction of the intestinal wall; which demands generation of sufficient forces or right motility patterns. Studies indicate that the intestine utilizes the LLS at its advantage to perform forceful contractions; with peak LLS not exceeding 65% [18, 52]. The optimal choice of wavelength at which the shearing attains its maximum value is equal to the intestinal diameter (1 unit); higher wavelength (1.5 units) is inefficient [56]. Similarly occlusive contractions show two functions—mixing at lower occlusion and transport at higher occlusion. The choice of occlusion is dependent on whether the meal needs further processing or not.

**7. From wall shear and strain to influencing cell biology of the intestine**

As a result of the mechanical forces arising from muscular contraction (CC, LLS, due to muscularis mucosa) or due to luminal contents (distension during

*Biomechanics of the Small Intestinal Contractions DOI: http://dx.doi.org/10.5772/intechopen.86539*

*Digestive System - Recent Advances*

Frictional effects of the intestinal wall have been attributed to a disadvantage when considering transport. By estimating the flow resistance, the author was able to assess the importance of the slowing down of the fluid flow and increase in the retention time of the fluid near the mucosa; providing more time to undergo chemical digestion and absorption [56]. The extent of friction offered by the intestine to fluid of different flow behavior index (n = 0.6, 1.0, and 1.4) suggests that the friction is highest for pseudo-plastics and decreases with increase in flow behavior index [56]. In addition to this, friction is found to be dependent on pressure gradient; showing increasing trend with increase in pressure. They are linearly related to the Reynolds number; higher the *Re* higher is the resistance. Since the friction is analyzed for a channel with smooth inner surface, we presume that the contribution

Friction is more at the occlusion center and drops significantly as one recedes away from occlusion center to the wave end. The friction due to mucosal layer of the intestine is a subject matter of interest to intestinal digestion. We may consider the problem similar to the flooding of the terrain occupied by numerous trees. At the flood end, where the fluid velocity is very high, the fluid particles tend to slow down upon interacting with the tree. Since the surface area of the tree is more, the effectiveness to slow the fluid particle is much higher. In physiology, such resistance to flow is provided by the intestinal folds of mucosa known as the plicae circulares or the valves of kerckring. The author speculates that these structures help in reducing the luminal transport and increase the time of retention of the fluid near the mucosa so as to allow for increased absorption of the nutrients. Depending on the flow regime, the flow may be highly agitated to flush the contents and allow for replenishment of the nutrient-rich contents. Such a behavior prevents the formation of trapped fluids and cause continuous flushing of the mucosa without stagnation. Such understanding is necessary to know the dynamics of nutrient transport near the intestinal mucosa and equilibration. While, stagnation of the acidic contents near the duodenum can have drastic

Contraction leading to flow is majorly determined by the muscular contractions of the circular and longitudinal muscle layers of the intestine. Although extramural pressure forces may contribute in the modulating the flow patterns, much of the mechanics is initiated and driven by the muscles. Efficiency to pump is defined as the ratio of energy due to pressure force to the energy spent by intestine through muscular contraction. The circular contractions are majorly known to cause the positive displacement of the fluid, and hence primarily responsible to transport. However, the LLS results in the developed for axial forces that are small in comparison to circular contraction and have minor contribution to efficiency at lower occlusions. LLS is advantageous at higher occlusion, where they primarily help to forcefully shrink the intestinal wall along the axial direction to concentrate more circular fibers. The energy spent on contraction can be reduce dramatically from 26.5 (CC along) to 22.5 units (CC with 0.65% LLS) approximately; a 15% reduction in energy spent by the intestinal motility to drive shear thickening fluid. However, in contrast to the above, we also identify that power advantage of LLS negatively correlates for shear-thinning fluid driven by CC with 0.65% LLS. Suggesting that rheology of the luminal contents shares some relation with the nature of LLS. This emphasizes an important observation as to whether such a correlation exists, and

resulting from plicae circulares would be much higher.

impact on the mucosal layer leading to duodena ulceration.

**6.4 Power demands of peristalsis**

**6.3 Frictional advantage**

**62**

if so, how does the intestine senses the fluid rheology? Although there are no direct sensors to detect the rheology or viscosity of the contents, we speculate that the gut may use an indirect mechanism to serve the purpose of assessing the rheology through stretch sensors. Since this sensor respond to distension, we also speculate that the difficulty to pump highly viscous fluid are reflected in the form of stretch. The concept of mechanical sensing of the stretch in the intestinal wall was observed by infusing a larger bolus of isotonic saline directly into the intestinal lumen [58]. The study reported that a controlled distension of the intestine activates a subset of vagal sensory neurons. Perhaps, the sensors data are relayed to the higher centers of the brain or through the local reflex to trigger certain feedback controls. Somehow, the intestine is aware of the trade-offs between the power demands of peristalsis at a certain occlusion against the percentage LLS. It may not prefer to contract at higher LLS for circular contraction of lower occlusion; since it would be non-economical. However, on the contrary, it is economical to contract at higher LLS for circular contraction of higher occlusion; an optimal strategy in conserving the amount of energy it spends to perform the peristalsis.

#### **6.5 What is the optimal parameter space for contractility?**

The intestine has its own ability to perform muscular contraction to an extent that can be mapped onto a phase space (multidimensional space in which each state variable represented by an axis is constructed to specify the state of a physical system at a given point of time). To derive such plots for intestine, we resorted to literature reports related to the clinical observations of the intestinal motility during fed and fasted state, and, normal and pathology condition [22]. The parameters of interest are: incidence of propagatory versus stationary contractions per min, percentage incidence of antegrade and retrograde propagating waves, frequency of the wave, wave velocity in mm/s, and duration of MMC (interdigestive contractions) cycle. The ability of the intestine to perform digestion optimally depends on how well it coordinates with neurohormonal system. Eliciting segmental contraction on duodenal infusion of fat or hydrochloric acid requires that the contents are mixed well with the biliopancreatic secretions to cause buffering and emulsification. Such motility patterns are known to transform the fat into droplets which help providing more surface area for lipase binding to take place and perform the digestion [59]. Previous study by the author shows intestinal preference to digestion especially extent of mixing, and volume of mixing, and to-and-fro motion of contents [44]. Since the peristalsis provides sufficient shearing forces to help cause the droplet formation, we learn that some correlation exist between the motility and emulsification. Similarly, transport of the contents requires forceful expulsion of the contents by through muscular contraction of the intestinal wall; which demands generation of sufficient forces or right motility patterns. Studies indicate that the intestine utilizes the LLS at its advantage to perform forceful contractions; with peak LLS not exceeding 65% [18, 52]. The optimal choice of wavelength at which the shearing attains its maximum value is equal to the intestinal diameter (1 unit); higher wavelength (1.5 units) is inefficient [56]. Similarly occlusive contractions show two functions—mixing at lower occlusion and transport at higher occlusion. The choice of occlusion is dependent on whether the meal needs further processing or not.

### **7. From wall shear and strain to influencing cell biology of the intestine**

As a result of the mechanical forces arising from muscular contraction (CC, LLS, due to muscularis mucosa) or due to luminal contents (distension during

gasification), the intestinal tissues are remodeled in accordance to the nature of forces. The epithelial and non-epithelial cells undergo various types of mechanical forces during the physiology function. Contractions of the circular muscle leads to generation of a tangential force along the periphery (shear) and contraction of longitudinal muscle layer leads to axial force (shear). In reality, such contractions are highly irregular and occur in conjunction that varies in wave geometry and kinetics (velocity). Shear forces at the mucosal layer affect the villi structure which modulates the adsorptive function of the organ and strain in the intramural structure affect the tissue (intestinal wall) and its compliance. The responsive nature of the intestine comes from the fact that the intestinal walls have several mechanosensitive cell types that respond to various types of mechanical stimuli such as—epithelial enterochromaffin cells (ECL), enteric neuronal cells (intrinsic and extrinsic), smooth muscle cells, and interstitial cells of Cajal (ICC). These cells contain ion channels (stretch-activated ion channel) that respond to mechanical forces and in response to stimuli they generate ionic currents in the channel thereby affecting mechanotransduction process. In mechanotransduction, the mechanical forces such as shear, stretch, and pressure trigger a biochemical pathway (through conformation change) initiating the chain reaction (involving second messengers) to affect the gene expression, and protein synthesis. *In vitro* experiment involving the seeding of scaffolds with human umbilical vein endothelial cells (HUVECs) demonstrated that the mechanical stimuli provided in the form of a pulsatile shear stress (12 ± 4 dyne cm−2 ) leads to changes in the expression of the mechanosensitive genes (Pecam1, Enos) [60].

#### **8. Conclusion**

The digestive process of the intestine is complex and depends on multiple parameters such as rheology of food, chemical composition, motility pattern, and neurohormonal signaling. In this chapter, we have addressed the question as to how the mechanics play a key role in performing the disintegration of the partially digested food through shearing action of the peristalsis. Both circular and longitudinal contraction participate in the process in a way to optimally perform the digestion at ease; which otherwise would be uneconomical. LLS is advantageous when driving contents having shear thickening behavior, where the longitudinal shortening brings the circular muscles closer to reduce the tension in the individual fibers during peristalsis. LLS have no significant contribution in the development of the flows. In conclusion, biomechanical studies indicate that the flow is highly sensitive to the motility patterns (geometry and wave parameters), and in order to perform the digestion, the intestine elicits the right kinds of contraction to perform the physiological functions (such as preventing duodenal ulceration through segmental contraction, buffering of chyme in the duodenum, preventing duodenogastric reflux, and digestion of meal).

#### **9. Future scope**

Previous study involving the 3D computer simulations of the flow provided details of relevance to physiology. Contraction types analyzed so far include: (1) stationary contractions (contractions that close and open at a given location) (a) closure type, (b) Opening type\*, (c) multiple contractions, (d) cluster/repetitive contractions; (2) propulsive contractions (contractions moving in either direction) (a) antegrade type, (b) retrograde type, (c) multiple contractions, (d) short distance traveling contractions\*, (e) long distance traveling contractions\*; and (3)

**65**

**Conflict of interest**

**Author details**

Ravi Kant Avvari

India

*bulb, and (4) distal duodenum.*

**Figure 8.**

There are no conflicts of interest.

provided the original work is properly cited.

*Biomechanics of the Small Intestinal Contractions DOI: http://dx.doi.org/10.5772/intechopen.86539*

mixed (mixture of both stationary and propulsive contractions)\*. The contractions marked with \* could not be analyzed due to computational limitations. This gives us a huge opportunity to the biomechanical engineers to explore the mechanism as to how the motility leads to digestion. Literature suggests a compartmental model to describe the physiological relevance of antrum, pylorus and the duodenum (**Figure 8**). The jejunal and ileal segments still remain a mystery as to how they

Sasi Institute of Technology and Engineering, Tadepalligudem, Andhra Pradesh,

© 2019 The Author(s). Licensee IntechOpen. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/ by/3.0), which permits unrestricted use, distribution, and reproduction in any medium,

*Compartment model of the APD segment showing various segments (1) stomach, (2) pylorus, (3) duodenal*

coordinate with each other and how they contribute to digestion.

\*Address all correspondence to<EMAIL_ADDRESS>
*Biomechanics of the Small Intestinal Contractions DOI: http://dx.doi.org/10.5772/intechopen.86539*

#### **Figure 8.**

*Digestive System - Recent Advances*

stress (12 ± 4 dyne cm−2

**8. Conclusion**

**9. Future scope**

genes (Pecam1, Enos) [60].

gasification), the intestinal tissues are remodeled in accordance to the nature of forces. The epithelial and non-epithelial cells undergo various types of mechanical forces during the physiology function. Contractions of the circular muscle leads to generation of a tangential force along the periphery (shear) and contraction of longitudinal muscle layer leads to axial force (shear). In reality, such contractions are highly irregular and occur in conjunction that varies in wave geometry and kinetics (velocity). Shear forces at the mucosal layer affect the villi structure which modulates the adsorptive function of the organ and strain in the intramural structure affect the tissue (intestinal wall) and its compliance. The responsive nature of the intestine comes from the fact that the intestinal walls have several mechanosensitive cell types that respond to various types of mechanical stimuli such as—epithelial enterochromaffin cells (ECL), enteric neuronal cells (intrinsic and extrinsic), smooth muscle cells, and interstitial cells of Cajal (ICC). These cells contain ion channels (stretch-activated ion channel) that respond to mechanical forces and in response to stimuli they generate ionic currents in the channel thereby affecting mechanotransduction process. In mechanotransduction, the mechanical forces such as shear, stretch, and pressure trigger a biochemical pathway (through conformation change) initiating the chain reaction (involving second messengers) to affect the gene expression, and protein synthesis. *In vitro* experiment involving the seeding of scaffolds with human umbilical vein endothelial cells (HUVECs) demonstrated that the mechanical stimuli provided in the form of a pulsatile shear

) leads to changes in the expression of the mechanosensitive

The digestive process of the intestine is complex and depends on multiple parameters such as rheology of food, chemical composition, motility pattern, and neurohormonal signaling. In this chapter, we have addressed the question as to how the mechanics play a key role in performing the disintegration of the partially digested food through shearing action of the peristalsis. Both circular and longitudinal contraction participate in the process in a way to optimally perform the digestion at ease; which otherwise would be uneconomical. LLS is advantageous when driving contents having shear thickening behavior, where the longitudinal shortening brings the circular muscles closer to reduce the tension in the individual fibers during peristalsis. LLS have no significant contribution in the development of the flows. In conclusion, biomechanical studies indicate that the flow is highly sensitive to the motility patterns (geometry and wave parameters), and in order to perform the digestion, the intestine elicits the right kinds of contraction to perform the physiological functions (such as preventing duodenal ulceration through segmental contraction, buffering of chyme in the duodenum, preventing duodenogastric reflux, and digestion of meal).

Previous study involving the 3D computer simulations of the flow provided details of relevance to physiology. Contraction types analyzed so far include: (1) stationary contractions (contractions that close and open at a given location) (a) closure type, (b) Opening type\*, (c) multiple contractions, (d) cluster/repetitive contractions; (2) propulsive contractions (contractions moving in either direction) (a) antegrade type, (b) retrograde type, (c) multiple contractions, (d) short distance traveling contractions\*, (e) long distance traveling contractions\*; and (3)

**64**

*Compartment model of the APD segment showing various segments (1) stomach, (2) pylorus, (3) duodenal bulb, and (4) distal duodenum.*

mixed (mixture of both stationary and propulsive contractions)\*. The contractions marked with \* could not be analyzed due to computational limitations. This gives us a huge opportunity to the biomechanical engineers to explore the mechanism as to how the motility leads to digestion. Literature suggests a compartmental model to describe the physiological relevance of antrum, pylorus and the duodenum (**Figure 8**). The jejunal and ileal segments still remain a mystery as to how they coordinate with each other and how they contribute to digestion.

### **Conflict of interest**

There are no conflicts of interest.

#### **Author details**

Ravi Kant Avvari Sasi Institute of Technology and Engineering, Tadepalligudem, Andhra Pradesh, India

\*Address all correspondence to<EMAIL_ADDRESS>
© 2019 The Author(s). Licensee IntechOpen. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/ by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.