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Guerreiro Cardoso",coverURL:"https://cdn.intechopen.com/books/images_new/998.jpg",editedByType:"Edited by",editors:[{id:"63142",title:"Prof.",name:"Paulo",surname:"Cardoso",slug:"paulo-cardoso",fullName:"Paulo Cardoso"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"1883",title:"Special Topics in Cardiac Surgery",subtitle:null,isOpenForSubmission:!1,hash:"8af20f3f7f0efabe6eadc5b3b9651c96",slug:"special-topics-in-cardiac-surgery",bookSignature:"Cuneyt Narin",coverURL:"https://cdn.intechopen.com/books/images_new/1883.jpg",editedByType:"Edited by",editors:[{id:"63113",title:"Prof.",name:"Cuneyt",surname:"Narin",slug:"cuneyt-narin",fullName:"Cuneyt Narin"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"2698",title:"Current Concepts in General Thoracic Surgery",subtitle:null,isOpenForSubmission:!1,hash:"dacb5220571f2caf1bd8f3e8adeaff55",slug:"current-concepts-in-general-thoracic-surgery",bookSignature:"Lucio Cagini",coverURL:"https://cdn.intechopen.com/books/images_new/2698.jpg",editedByType:"Edited by",editors:[{id:"141680",title:"Dr.",name:"Lucio",surname:"Cagini",slug:"lucio-cagini",fullName:"Lucio Cagini"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}}],publishedBooksByAuthor:[{type:"book",id:"998",title:"Topics in Thoracic Surgery",subtitle:null,isOpenForSubmission:!1,hash:"96a2e108171c3c4b3c35d81f83baf622",slug:"topics-in-thoracic-surgery",bookSignature:"Paulo F. Guerreiro Cardoso",coverURL:"https://cdn.intechopen.com/books/images_new/998.jpg",editedByType:"Edited by",editors:[{id:"63142",title:"Prof.",name:"Paulo",surname:"Cardoso",slug:"paulo-cardoso",fullName:"Paulo Cardoso"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}}]},onlineFirst:{chapter:{type:"chapter",id:"81688",title:"Prolapsing Hemorrhoids",doi:"10.5772/intechopen.104554",slug:"prolapsing-hemorrhoids",body:'Hemorrhoids are a disease of the anorectal area, that is often found in clinical practice, it is an enlargement and prolapsing (shift to the distal) of the anal cushion that gives clinical signs and symptoms [1]. Dilation and deformity of the blood vessels in the anal cushions, accompanied by destruction of the supporting tissues are the main pathological conditions of hemorrhoids. Inflammatory reactions and hyperplasia of blood vessels can also be found in hemorrhoids [2, 3].
Patients with complaints of bloody stools or anal discomfort are often caused by hemorrhoids, but the exact prevalence is unknown and will be lower than reality because many are under-reported and patients are self-medicating. The prevalence varies greatly from country to country, depending on the recording system. Data in the United States in 1990 showed that more than 10 million people suffered from hemorrhoids, or about 4.4% of the total population, while in the UK it was reported to be 13–36% of the general population [3]. The prevalence of men and women is comparable, and mostly occurs at the age of 45–65 years. White and high socioeconomic populations are more frequently affected than blacks and low socioeconomic populations [2].
Considering that hemorrhoids are the most common anal canal abnormalities and also the reason for patients’ visits to the doctor or physician, a deep understanding of the anatomy, physiology, pathogenesis, risk factors, diagnosis, and rational management is needed for doctors, to be able to treat hemorrhoids correctly and effectively, so that the patient is protected from irresponsible hemorrhoid management practices.
The anal canal is a continuation of the distal rectum. The surgical anal canal is formed by the hindgut in the proximal part and the anoderm in the distal part, and the border between both is dentate lines. The proximal part of the anus is covered by a mucous line. The superior rectal artery that flows through the anal canal will branch into two, to the left and right. The right branch of the superior rectal artery branches into anterior and posterior branches. This artery will form an arteriovenous plexus located in the right anterior, right posterior, and left lateral regions, which will be covered by mucosa that produces an anal cushion. For practical purposes, from a perineal view, we call it 11.00 o’clock the right anterior, 07.00 o’clock the right posterior, and 03.00 o’clock the left lateral anal cushion [4].
There are two anal canal sphincters, the internal anal canal sphincter (IAS) as a continuation and thickening of the circular layer of rectal muscle and the external anal sphincter (EAS). The IAS is made of smooth muscle. It is an involutory muscle, while the external sphincter muscle is a voluntary muscle consisting of three layers—deep, superficial, and subcutaneous [1]. Anal incontinence during rest is caused by the contraction of the IAS and anal cushion, which participate 70–80% and 20–30%, respectively. During defecation, the anal cushion will prolapse downward to protect the anal crypt, estuary of the anal gland, and anal canal skin, and return after defecation. The ability of the anal cushion to return is due to the function of the muscle of Treitz, the continuation of muscle fiber from the longitudinal muscle fiber of the rectum. The Treitz muscle consists of two parts—the submucous muscle and the Park ligament, where the last part of it is located at the bottom of the anal cushion [4].
According to Aigner, et al., (2009), there are sphincter-like structures in the vascular plexus, formed by thickened tunica media that contain 5–15 layers of smooth muscle cells located between the vascular plexus and the subepithelial space of the anal cushions in normal anorectal specimens. The role of these sphincter-like structures is to coordinate the filling and drainage of the anorectal vascular plexus. This vascular plexus is without tunica media and larger than usual, like a lacuna [5].
The pathogenesis of hemorrhoids is still largely unknown. Hemorrhoids occur based on the theory of varicose veins, as in the case of leg varicose veins, but in the case of hemorrhoids, they occur in the anus. This theory has been abandoned because various studies have shown that varicose veins and hemorrhoids are different entities. There was no increase in the incidence of hemorrhoids in patients with portal hypertension. The theories of vascular hyperplasia and hypertrophy of the anal sphincter are not supported by the evidence. Today, the theory of the sliding of the anal cushions is widely accepted [2, 4].
As it has been stated in the physiology of the anus and rectum, the anal cushion plays a role in protecting the anal canal during defecation. After the stool comes out, the anus cushions will return to their place due to the work of the Treitz muscles. In constipation, there will be difficulty in defecating. The patient will push a lot so that the anal cushions are often forced to shift distally. Over time, it will be followed by damage to the supporting tissue, so that the anal cushions cannot return to their own position. Prolapsing anal cushions will be followed by venous dilatation, vascular thrombosis, degeneration of fibroelastic tissue, and damage to the Treitz muscles. Inflammatory reactions are also seen in the vascular wall and the surrounding supporting tissues, ulceration, ischemia, and thrombosis [4].
Several enzymes play a role in the degradation of the supporting tissues of the anal pads. Matrix metalloproteinase (MMP), a zinc-dependent proteinase, is the most potent enzyme and is capable of degrading elastin, fibronectin, and collagen. MMP-9 is overexpressed in hemorrhoids and degrades elastin fibers. Activation of MMP-2 and MMP-9 by thrombin, plasmin or other proteinases results in damage to the capillary bed and stimulates the vascular proliferative activity of TGF (transforming growth factor). This also explains the thinning of the tunica media in the sphincter-like structures that control blood flow from the arteries to the venous plexus. Hemorrhoids have an overexpressed endoglin attachment site with TGF. Microvascular density also increases, influenced by Vascular Endothelial Growth Factors (VEGF), which increases, especially when there is thrombosis [4].
Morphological and hemodynamic studies showed that in hemorrhoids there was an increase in the diameter of the branches of the superior rectal artery, the amount of blood flowing and its flow rate increased significantly. There is a correlation between the diameter of the arterial branches and the degree of hemorrhoids [6]. Physiological changes in the anal canal in hemorrhoids have also been reported. Anal canal pressure at rest in patients with prolapsed and unprolapsed hemorrhoids was higher than in normal people, without internal anal sphincter hypertrophy. This pressure will decrease after hemorrhoidectomy is performed, so it can be said that this increase in pressure is due to the effect of hemorrhoids, not the cause [7].
Constipation is widely believed to be a risk factor for the occurrence of hemorrhoids, through the sliding mechanism of the anal cushion, as previously stated, but diarrhea has also been reported to increase the risk of hemorrhoids, through an unclear mechanism. Pregnancy is also a predisposing factor for hemorrhoids due to increased intra-abdominal pressure causing congestion of the anal cushion, and the patient can recover after delivery. Many other risk factors have been reported for the occurrence of hemorrhoids, such as a low-fiber diet, spicy foods, and drinking alcohol [2, 4, 7].
Hemorrhoids due to prolapse of the anal cushions are called internal hemorrhoids. The lump is covered with mucosa and is often accompanied by the skin of the anal canal, thus forming mixed hemorrhoids, but the predominance is internal hemorrhoids. If only the external hemorrhoidal plexus is dilated, it is called external hemorrhoids. On histological examination of the surgical specimen for internal hemorrhoids, a very marked widening of the vascular plexus and fragmentation of the Treitz muscles will be found. When examined deeply, an increase in leukocytes both inside and outside the blood vessels (inflammatory component) and, with special staining, thinning of the blood vessel walls due to thinning of the tunica media (sphincter-forming muscles) will be seen. External hemorrhoids are mainly dilated subcutaneous veins accompanied by an inflammatory reaction, but patients often present with pain due to a thrombus [2, 3, 4].
Stages of internal hemorrhoids need to be determined before starting therapy because the stage will greatly determine the choice of therapy.
Internal Hemorrhoid grade. Grade I: no prolapse seen from outside, but can be seen by
Grade I: anal cushion bleeding but no prolapse. Grade II: anal cushions prolapse out of the anus during defecation, but can spontaneously return. Grade III: prolapsed anal cushions that protrude from the anus during defecation but require manual assistance to return to their original position. Grade IV: prolapsed anal cushions out the anus and cannot be reposed manually.
The American Society of Colorectal Surgery (ASCS) made a modification to Goligher grading because in Goligher the classification is based on what the patient says, but in ASCS it is based more on examination. In grades II and III, a Valsalva test should be performed, while in grade IV, this includes being able to manually reposition the prolapsed anal cushions, which will soon come back out. In grade IV, due to obstruction of venous return by the anal sphincter, often accompanied by incarceration and thrombosis under the anal mucosa or skin (Figure 2).
Grade IV mixed hemorrhoids with thrombus in external (orange arrow) and internal (yellow arrow) components.
Because patients often present with fresh bloody stools and lumps in the anus, the following diseases should be considered: Anorectal malignancy (adenocarcinoma, squamous cell carcinoma, and malignant melanoma), rectal prolapse, prolapsed rectal polyp, anal fistula, anal fissure, Crohn’s disease, and condyloma acuminata [2]. Each has different signs and symptoms, so recognizing the signs and symptoms of each will lead to a good diagnosis.
Bleeding in hemorrhoids is often fresh red blood without pain. This is different from an acute anal fissure, which causes fresh bloody stools accompanied by intense pain because there is an injury in the anal canal skin, which is rich in pain receptor nerves (somatic nerves). The color of the blood in hemorrhoidal bleeding is fresh because the source of the blood is the arteriovenous shunt. Rectal bleeding in rectal carcinoma is often reddish, along with the mucus. Left colon carcinoma is often accompanied by small stools with blood on their surface, while bleeding in the right colon carcinoma is often brown in color with diarrhea. A positive occult blood test should be considered more proximal to the source of bleeding, so a colonoscopy is recommended to detect the source of bleeding [1]. The prolapsed mucosa will secrete mucus which can irritate the anal skin, causing itching. In large hemorrhoids, the patient may feel incomplete defecation or feeling of fullness in the rectum. Pain in hemorrhoids only occurs when a thrombus occurs, especially in the blood vessels under the skin or at grade IV, which is constricted by a strong anal sphincter, causing strangulation [3].
With the patient in the lithotomy or Sim\'s position, laying on the left side with maximum flexion in the hip and knee joints, inspections are carried out in the perineal and anal areas to detect possible skin tags, external hemorrhoids, skin inflammation due to irritation by mucus and feces, the presence of fissures or anal fistula. (Figure 3). When the prolapsed anal cushion is visible, it is necessary to identify the position and number of the main lumps, the presence or absence of the prolapsed anal canal skin, and the presence of thrombus or ulceration [3].
In Sim’s position, spreading the anus by the left and right finger and asking the patient to strain, two nodules can be seen at 03.00, and 07.00 o’clock, in this case, anal fissure can also be seen at 06.00 o;clock (black arrow). (Personal collection).
Keep in mind that, other than hemorrhoids, other prolapses are rectal prolapse and rectal polyps. In a prolapsed rectal polyp, it will appear as a round lump covered with mucosa and have a stalk (Figure 4a and b). The rectal prolapse is concentric or circular in shape (not lumpy or no radial indentation), not followed by prolapse of the anal skin, and the finger can enter between the prolapse and the anal canal wall [9]. If during the initial examination there is no prolapsed lump, the patient is asked to strain so that prolapse can occur, or more effectively, the patient is asked to squat and be asked to push into the toilet. In addition to the prolapse examination as mentioned above, wait a while to observe the ability of the prolapsing anal cushion to spontaneously disappear, due to self repositioning, or must be pushed with your fingers [8].
a. Prolapse of rectal polyps, b. the polyps stalk can be seen after retracted outside. (Personal collection).
Anal melanoma can affect the anal canal and distal rectum, and the majority of tumors are located within 6 cm proximal to the anal verge. There are two types, melanotic, which consists 70% of cases and amelanotic 30%. Amelanotic melanoma is mostly located in the mucosa. Anal melanoma is a rare anal neoplasm. It accounts for approximately 1–4% of anal neoplasms and is female predominant. The signs are an anal lump, pain, and bleeding [10].
Melanotic anal melanoma can be confused with hemorrhoids with thrombosis, as both cause black discoloration. Hemorrhoid thrombus is usually more painful, and the pain will subside after day 3 due to the shrinkage of the lump. This phenomenon is not found in melanotic anal melanoma. The presence of a satellite nodule is also specific to melanoma (Figure 5a). The diagnosis is based on the histological picture of the biopsy specimen. A CT scan is needed to confirm the degree of infiltration, lymph node involvement, and distant metastasis. In Figure 5b, the tumor has already infiltrated the anal sphincter. The abdominal perineal ano-recto-sigmoidectomy (Mile’s procedure) with permanent sigmoidostomy is the surgery of choice [1, 10].
Anal melanoma, melanotic type. a. with satellite nodule (arrow), b. infiltration to anal sphincter on CT scan (Personal collection).
The patient should also have a digital rectal examination (DRE). Uncomplicated internal hemorrhoids are often vaguely palpable as a soft anorectal mass that is absent in normal people, but when a thrombus or scar tissue has occurred, something harder or a narrowing due to a stricture may be felt. During DRE, anal sphincter tone, prostate enlargement, and the presence of other abnormalities in the rectum, as well as outside the rectum in women, such as the uterus and adnexa, should also be evaluated. To palpate rectal cancer that cannot be reached by fingers, it can be done bimanually (one hand on the lower abdomen and pressing down) or the patient is asked to push (Valsalva test). When there is a rectal tumor in a high position and mobile, it is often palpable with the maximal position of the finger during a digital rectal examination. Patients with complaints of pain in the rectal area have the possibility of fissures, but there is also the possibility of arthritis of the sacro-coccigeal joint. For this reason, during a digital rectal examination, it should not be forgotten to move the coccyx from the sacrum bone. The presence of arthritis will cause pain with movement [1, 3].
During anuscopy, the size of the hemorrhoidal nodule, position, level of inflammation, and the possibility of bleeding should be assessed. When a colonoscopy is performed, the retroflexed position of the scope can see hemorrhoids in the rectum. Likewise, a transparent anoscope can clearly see the anal canal and hemorrhoids. Photo documentation can be made during endoscopy [1, 2, 3].
As rectal bleeding is the main complaint of internal hemorrhoid, should a routine complete colon examination be done to rule out other causes of bleeding? American Society of Colon and Rectal Surgeons (ASRC) recommends patients with—a) rectal bleeding, b) positive fecal immunochemical testing (FTT), c) positive FTT-fecal DNA test, d) patients with high risk for colorectal malignancy such as d.1) age 50 years or more if no complete examination within 10 years, d.2) age 40 years or more or 10 years younger with history of first degree relative of colorectal cancer or advanced adenoma diagnosed at age less than 60 years, and d.3) age 40 years or more or 10 years younger with history positive for two first degree relatives with advance adenomas or colorectal carcinomas [8].
The most common complication for hemorrhoid patients is bleeding. Bleeding varies, from just spots that drip after defecation to heavy bleeding chronic. Slight bleeding may result in microcytic hypochromic anemia, while if the bleeding is profuse, patients may come down with hypovolemic shock. The profuse bleeding is an emergency, so it must be managed immediately [1, 2, 3]. Another complication is thrombosis of the veins, which can be located under the mucosa or the skin. Thrombosis of the skin or mucosa near the skin will be very painful, prompting the patient to seek treatment immediately. Prolapsed hemorrhoids accompanied by a strong anal sphincter can result in compression of the blood flow, resulting in strangulation and even necrosis [1].
Management of hemorrhoids depends on the stage. Management includes dietetic management and lifestyle changes (controlling risk factors), administration of drugs, and nonsurgical and surgical interventions. In grade I, II, and small III hemorrhoids, management starts with dietetic management, changing lifestyle, and administration of drugs, if those fail then nonsurgical intervention is considered. In major stages III and IV, the main choice is surgery plus dietetic management and lifestyle changes. In cases of acute thrombosis or strangulation, emergency surgery is required [8].
Patients with hemorrhoids are very prone to bleeding, and the lumps may become more swollen when the stool is hard because the defecation must be strained hard. To avoid this, the stool must be soft so that it does not cause trauma. This could be achieved by increasing a high-fiber diet or adding a bulking laxative to the diet, such as bran or methylcellulose, to facilitate defecation. A meta-analysis study showed that a high-fiber diet reduced the risk of complaints and bleeding in up to 50% of cases, although it did not improve complaints of prolapse, pain, and itching [11]. A high-fiber diet is very effective for hemorrhoids that do not prolapse [1, 3].
Controlling the manageable risk factors by modification of lifestyle plays a role in the healing process of hemorrhoids [3]. Patients who initially do not like fiber foods should be advised to consume high fiber, drink enough water, and do regular physical activity to facilitate defecation. The recommended amount of fiber per day is 35 gr [1]. Foods that contain high fat should be avoided because they do not support the formation of large and loose stools, as well as drugs that cause constipation or even diarrhea, should also be avoided. The wrong way of defecating must be corrected. Avoid defecating by pushing too hard and sitting on the toilet for too long (smoking, reading newspapers, playing with cell phones, etc.) [2]. By squatting, it is easier to pass stool, because the puborectal muscle is more relaxed. One study shows that defecating in a squatting position only takes 1 minute, as opposed to a sitting position that needs 4–15 minutes [12]. When you are used to defecating by sitting on the toilet, by propping your feet higher, the position would be more like squatting. After defecation, the anoperineal must be clean. Remaining feces in the anal canal, for example in the anal crypts, can stimulate inflammation.
Flavonoids are herbal medicines that are given orally. This drug was originally indicated as a blood vessel strengthening agent (venotonic) and an anti-edema agent in the treatment of varicose veins in the legs. These flavonoids have been studied in varicose veins. They have the ability to increase vascular tone, decrease venous capacity, decrease capillary permeability, increase lymphatic drainage, and have anti-inflammatory effects. Although the mechanism of healing in hemorrhoids is not clear, this drug has been widely used in Europe and Asia. The micronized purified flavonoid fraction (MPFF) consisting of 90% diosmin and 10% hesperidin is the most commonly used flavonoid in clinical practice. This fine shape (less than 2 microns in size), allows absorption to be easier so that it works faster [13].
A recent meta-analysis showed that MPFF treatment provided significant benefits for bleeding (odds ratio [OR] 0.082, p < 0.001), discharge/leakage (OR 0.12, p < 0.001), and overall improvement according to patients (OR 5.25, p < 0.001) and investigators (OR 5.51, p < 0.001). MPFF also reduces pain (OR 0.11, P = 0.06) [14]. The recommended dose in the acute phase is 3x1 gr in the first 3–4 days and then decreases to 2x1 gr. The medication can be stopped gradually, according to the patient\'s response. Long-term use of this medication is reported to be safe. The medication is also reported to be safe to be used in pregnant women [13].
Purple leaf (Grapthopylum pictum extract/GPE), which also contains flavonoids, has been shown to be useful in improving the complaints of hemorrhoids in developing countries. In a study for patients with hemorrhoids, with a pre and post-test-only group design, it was reported that GPE reduces the signs and symptoms [15]. In animal studies, inducing anal Wistar rats with croton oil, showed that GPE, reduces inflammatory markers [16], accelerates ulcer healing [17], and reduces edema [18]. Currently, in Indonesia, GPE can be considered a standardized herb. To be recognized as a phytopharmaca, it needs to be continued with better clinical trials.
It is an oral drug that has a venotonic effect (strengthens veins), reduces capillary permeability, inhibits thrombotic aggregation, and increases blood viscosity, which results in reducing edema. Calcium dobesilates are often used for leg varicose veins and diabetic retinopathy. Research on hemorrhoids using calcium dobesilate combined with fiber supplementation has also shown good clinical effects, namely reducing bleeding and inflammation [2].
Forms of topical treatment of hemorrhoids are zalf, cream, or rectal suppositories. The purpose of topical treatment is to reduce the symptoms, so most of the ingredients are local anesthetics, corticosteroids, antibiotics, and anti-inflammatory drugs. There is not yet sufficient scientific evidence to support the use of topical treatment [8]. This drug can be purchased without a prescription. It is important to remember that topical treatments are only used in the acute stage. Long-term use of topical treatment can result in thinning the mucosa so that it bleeds easily or the possibility of fungal growth. It is highly recommended that after the acute stage has passed, the drug should be stopped and other drugs given orally, such as the flavonoids described above, should be continued zalf containing 0.2% glyceryl trinitrate or nifedipine, a calcium channel blocker, has been reported to reduce pain due to relaxation of the internal anal sphincter. There is also a topical vasoconstrictor, namely zalf, which contains 0.25% phenylephrine and is reported to reduce the complaints of hemorrhoid patients [19].
In the early stages of hemorrhoids, instrumentation can be performed in the private practice room, so it is called an “office-based procedure.” External hemorrhoids with thrombus—the thrombus can be removed under local anesthesia, while internal hemorrhoids can be performed with instrumentation. There are various types of instrumentation therapy, but the principle of action is the same. By performing fibrotization at the base of hemorrhoid, it is expected that the blood flow to the anal cushion will decrease and the prolapsed anal cushion will be shrunk and attracted cranially [2, 3].
Thrombectomy is the procedure of removing a thrombus (blood clot) from external hemorrhoid with a thrombus, performed under local anesthesia (Figure 6a). The pain of external hemorrhoids with thrombus occurs on the first day, and after the third day, the pain will decrease. Removing the thrombus will quickly relieve the pain. After the 3rd day, because the pain has subsided, there is no indication of thrombectomy. External hemorrhoid will heal through fibrotization of the thrombus into a skin tag [20].
Office-based procedure a. External hemorrhoid with thrombus, before and after excision b. Sclerotherapy c. Rubber Band Ligation. (illustrated by Kanaya).
Submucosal injection at the base of hemorrhoid (Figure 6b) with sclerosing agents, such as 5% phenol in oil, vegetable oil, quinine, urea hydrochloride, and hypertonic saline, will result in fibrotization at the base of hemorrhoid so that the anal cushion will be retracted cranially. Injections are often needed several times until the anal cushion is in a normal position. Sclerotherapy is indicated in grade I, and II hemorrhoids [3]. The correct injection should be perivasal. Injection errors may cause problems. Too superficially, they may cause ulceration. Too deep into the muscle causes pain and possibly strictures. Injections into the plexus venosus can cause upper abdominal or precordial pain. Too deep into the prostate can result in an abscess and damage the periprostatic nerves, which can cause erectile dysfunction. Or it can be as serious as retroperitoneal sepsis, as reported by Barwell et al. (1999) [21]. Prophylactic antibiotics are not needed for sclerotherapy, except for cases with immunodeficiency [1, 2, 3].
Binding of hemorrhoids with rubber rings (Figure 6c) will result in ischemia, necrosis, and healing by the formation of scar tissue that will fix the remaining connective tissue to the rectal wall. RBL is indicated for grade I, II, or small grade III hemorrhoids that do not improve with non-interventional treatment. It is important to keep in mind not to do the ligation too close to the dentate line because it will cause severe pain. Research shows ligation at 2 or 3 places at once or sequentially gives the same results, but post-procedural pain is higher in multiple banding [3]. Discomfort or pain in the rectum can be reduced by taking warm baths and avoiding hard stools by consuming high-fiber foods and drinking enough water, or, if necessary, laxatives. Other than pain, complications after RBL include the possibility of bleeding, mucosal ulceration, thrombosis of external hemorrhoids, and, very rarely, pelvic abscess [1, 2].
An infrared light probe affixed to the base of hemorrhoid through the anoscope for 1.0–1.5 seconds will have an impact on tissue coagulation and evaporation of fluid in the cells so that hemorrhoid will shrink. The necrotic tissue will appear as white spots, which will heal as fibrotic tissue. This technique is safer than sclerotherapy [1].
This technique is relatively new, with an RFA spherical electrode anoscope connected to a radiofrequency generator, attached to the hemorrhoid tissue, which causes evaporation and coagulation of the tissue. In this way, the vascular component will be reduced and fixed to the underlying tissue through fibrotic tissue. Complications that have been reported are thrombosis, wound infection, and urinary retention. From the evaluation of this method, the risk of rebleeding and prolapse is still quite high [2].
Freezing hemorrhoid tissue with a cryotherapy probe is claimed to provide low pain because it is carried out at a low temperature, but in fact, several clinical trials have shown prolonged pain, prolapse, and foul-smelling discharge, so this method is now rarely used [2].
Laser energy can coagulate the venous plexus tissue. The patient is set in the lithotomy position. Local anesthetic infiltration is performed with xylocaine 20 mL 1% around the anal and perianal skin. A C-shape anoscope is used. A small cut is made in the skin of the anal canal close to hemorrhoid to be targeted for the laser shot. Then a small tube is inserted through which the laser probe will pass, followed by laser shots in several places, generally 5-6 shots, but it can be more, depending on the size of hemorrhoid. The direction of the probe and laser beam can be seen in Figure 7. After finishing one point, you can move to another point. The results and the complications were not significantly different from Milligan-Morgan hemorrhoidectomy, or stapler, but less painful [22].
Laser hemorrhoidoplasty. a. Dentate line, b. Schematic direction of laser shot. (Illustrated by Kanaya).
Are there any different indications between sclerotherapy and RBL? There is no difference in terms of indication, but RBL can be done for small IIIrd-degree internal hemorrhoids. If there are no different indications, which one is the best? Research comparing sclerotherapy and RBL concluded that RBL is superior in the resolution of anal protrusion but with higher pain [23]. A survey in the Netherlands reported that most surgeons who treat hemorrhoids choose RBL for the first treatment of Grade II or III internal hemorrhoids [24]. A combination of sclerotherapy and RBL can be done and may improve the result. Research by Kanellos et al. (2003) reported that for the treatment of IInd degree hemorrhoids, the combination of sclerotherapy and RBL is significantly more efficient than sclerotherapy or RBL alone, and RBL is better than sclerotherapy [25]. The results of laser hemorrhoidoplasty are promising [22]. But we are still waiting for long-term results in many cases, and the other problem is that the cost is very expensive.
Surgical treatment is indicated when nonsurgical treatment is unsuccessful or in hemorrhoids with complications. The presence of strangulation, bleeding that does not stop nonsurgically, and thrombosis indicates emergency surgery. If the presence of other anal canal diseases associated with hemorrhoids, such as fissures and fistulas that require surgery, can be considered for hemorrhoid surgery at once if hemorrhoids are also a complaint [3]. However, surgery is indicated for hemorrhoids in grades III and IV. In general, there are two kinds of surgery—the first is excision of the enlarged and prolapsed anal cushion, and the second is surgery to spare and fix the anal cushion (“anal cushion preserving surgery”).
Based on the understanding of the pathogenesis of hemorrhoids as varicose veins, an excision is an option, but based on the theory of sliding or prolapsing of the anal cushion, surgery by fixing the anal cushion toward the cranially is the superior choice. The discovery of increasing caliber and flow of the rectal artery in hemorrhoids and the presence of a sphincter-like structure, in the form of thickening of the tunica media, at the arteriovenous connection, that is thinning or missing in hemorrhoids, [5, 6] superior rectal artery ligation is more rational.
EH is a hemorrhoid surgery by removing the hemorrhoids, where nowadays the gold standard is radially removing the three largest lumps (11, 3, and 7 o’clock). Tissues are removed, including the mucosa and the venous plexus below it, without damaging the internal anal sphincter, and maintaining a normal mucosal bridge in between them. After excision, the lump can be left unstitched (Morgan Milligan technique Figure 8a) or sutured (Fergusson technique, Figure 8b) [1].
a. After removing three piles and leaving no suture (Milligan-Morgan) (Personal collection). b. After removing 3 piles and suturing is performed (Ferguson technique) (Illustrated by Kanaya).
It is still debatable which one is better, left open or sewn, because, from various studies, the results are inconsistent. Rationally, in sutured cases, it is very often that the wound will also open in the next couple of days, either because the thread is broken or the tissue is cut. For those reasons, many surgeons choose the open technique. However, a meta-analysis done by Batti et al. (2016) showed the superiority of closed hemorrhoidectomy (Ferguson) over open hemorrhoidectomy (Morgan Milligan) in reducing postoperative pain, risk of postoperative bleeding, and faster wound healing. The only advantage of Morgan Milligan is shorter operative time, while the other aspects, such as length of hospital stay, postoperative complications, recurrence, and risk of surgical site infection, were similar in both groups [26].
There is a circular hemorrhoid excision technique that involves removing the entire lump, including the skin, mucosa, and the underlying venous plexus while maintaining the internal anal sphincter, followed by circular suturing of the skin with the mucosa as well. This technique, known as the Whitehead technique, has been abandoned because of the severe postoperative pain and complications that often arise, namely the risk of injury to the internal anal sphincter, which will cause incontinence, strictures that will cause difficulty passing stools, and exposing the mucosa, which will cause frequent anal canals to be wet (wet anal syndrome/whipping anus) [27]. Because the anal mucosa is rich in nerves and is able to feel and distinguish the desire to defecate solid, liquid, or fart, there are two cases, which I noticed from my personal cases, of patients complaining of the urge to fart but passing stool after Whitehead hemorrhoid surgery. The other method of hemorrhoidectomy technique is submucosal hemorrhoidectomy, which involves removing the venous plexus only (Park’s technique). It is currently being discontinued because the technique is more difficult and the risk of bleeding is high [2].
As excisional hemorrhoidectomy is done by removing the anal cushion, the possibility of reducing anal resting pressure after surgery is possible. According to the findings of a study conducted by Li et al. (2012), patients with preoperative compromised continence may have further deterioration of their continence, and thus Milligan-Morgan hemorrhoidectomy should be avoided in such patients [28].
Although the long-term recurrence rate is significantly lower than other methods, the main problem with excisional hemorrhoidectomy is the excruciating postoperative pain. The pain is thought to be caused by a side-burning wound caused by the use of electrocautery. Research shows that the use of lower-temperature cutting energies, such as ligasures or ultrasonic blades (Harmonic scalpel) provides significantly less pain than electrocautery [29].
The pathology of grade III and IV internal hemorrhoids shows damage to the structure of the supporting tissue of the anal cushions, namely the Treitz muscle and the muscularis mucosae so that if it prolapses, it cannot be repositioned spontaneously but must be repositioned with fingers or cannot be reposed manually. In the beginning, the first effort to treat prolapse is made by performing sutures to fix anal cushions to the base of the hemorrhoids. However, this method still causes problems, namely bleeding and annoying pain, so this method is less attractive [2].
SH, which was introduced in 1988, is the most widely used method of repositioning the anal cushion [1]. A circular stapler is used to perform a circular excision of the mucosa of the distal rectum and reattach the cut with the stapler, repositioning the prolapsed anal cushions (Figure 9).
Stapler hemorrhoidopexy. a. purse-string suture on Morgani column in upper margin of internal hemorrhoids, b. thread knotted between anvil and stapler head, approximate both until save the position and then fire. c.After removing the stapler, the rest of the anal cushion retracted upside, (Illustrated by Kanaya) d. Accurate stapling if we have complete circular rectal tissue like donuts. (personal collection).
With circular rectal excision, it is expected that the branch of the superior rectal artery could be cut, and this would result in decreased anal cushion bleeding and the lump would shrink. However, the cutting of the rectal artery cannot be fully realized, because it will depend on the depth of the suture and the location of the artery at the suture level. The research showed that the superior rectal artery was located in the submucosa at 100% at 1 cm above the anorectal ring and 96.6% at 2 cm and 67.1% at 3 cm above the anorectal ring [30]. A study is needed to confirm rectal branch artery cutting in the rectal specimen of stapler hemorrhoidopexy.
A meta-analysis of a randomized controlled trial showed that compared to excisional hemorrhoidectomy, SH provides less pain, a shorter length of stay, and a quicker return to work, but higher long-term recurrence [31, 32]. If the purse-string suture is too deep, it can get into the rectal muscle, which can lead to serious complications. There have been reports of rectovaginal fistulas, pelvic abscesses, and even peritonitis and strictures [2].
DG-HAL, developed by Morinaga (Japan) in 1995, is to perform ligation of the distal branch of the superior rectal artery with the help of Doppler to detect the location of the artery so that the ligation will be accurate. From empirical experience, the hemorrhoids will shrink at 6 weeks’ follow-up.
Initial experience showed that for grade III and IV hemorrhoids, this procedure did not give satisfactory results, the recurrent rate was still high, so in 2005, the DG-HAL procedure was added with rectoanal repair (RAR), (Figure 10), namely, performing continuous sutures to fix the anal cushion proximally. To make sure that the anal cushion can move and be fixed proximally, the first stitch in the proximal part should include the rectal muscle and then submucosally. To avoid severe pain, the last suture to fix the anal cushions should be placed above 1 cm from the dentate line [33]. Figure 11a and b show hemorrhoids before and after DG-HAL-RAR.
DG-HAL-RAR a. Position of the probe to detect a branch of the superior rectal artery b. The number of arterial sutures varies from 5 to 8 and is not at the same level. c-d. Continues suturing for rectoanal repair. e. After the suture has been knotted, the final position. (Illustrated) by Kanaya).
a. Prior to surgery, Grade III Internal Hemorrhoid, and b. After DG-HAL-RAR. (personal collection).
The small meta-analysis of 3 RCT, by comparing 70 SH with 80 DG-HAL-RAR, the baseline homogenous (P = 0.40), showed no difference regarding success rate (p = 0.19), operation time (P = 0.55), postoperative complications (p = 0.11), and recurrence rate (P = 0.46), and the only difference is postoperative pain. DG-HAL causes less postoperative pain (P < 0.00001) [34]. A 705-patient multicenter study in Brazil found that a one-year follow-up after DG-HAL-RAR was significantly better in grades II and III compared to grade IV. Recurrence of prolapse, recurrence of bleeding, and thrombosis of grade II-III versus grade IV were 2.36% vs 26.54%, 1.01% vs 7.96%, and 1.35% vs 10.61%, respectively [35].
It should be noted that several conditions can contribute to increased pain after DG-HAL-RAR, namely the additional excision of thrombus of internal and external hemorrhoids, the presence of anal fissures, or laceration of the anal canal of the skin. This encourages caution during probe insertion. Additional local anesthetic infiltration will help to reduce postoperative pain [36]. In the case of large grade III and IV internal hemorrhoids, additional minimucosal excision is advised if any nodule remains after DG-HAL-RAR [37].
In developing countries, cases of large circular Grade IV internal hemorrhoids occur very often (Figure 12a). Since the Whitehead procedure has already been abandoned due to its complications, the Morgan Milligan procedure is the only choice. However, after removing 3 main piles, the normal mucosal bridges are still prominent (Figure 12b). The addition of DG-HAL-RAR to prominent mucosal bridges gives a good result (Figure 12c). Followed up for 17 months, with a good appearance and no complaints (Figure 12d) [38].
a. large circular Grade IV internal hemorrhoid, b. normal mucosal bridges are still visible after removal of three main piles (Milligan-Morgan Procedure). c. After DG-HAL-RAR of prominent visible mucosal bridges. d. 17 months postoperatively. (Personal collection).
For patients with instrumentation or surgery that only repositions the anal cushion, no special treatment is needed. Consuming high fiber and drinking lots of water will facilitate defecation, which is the standard for managing hemorrhoids, either conservatively or operatively, and also must be carried out postoperatively. The administration of analgesia is more tailored to the patient\'s needs because excision hemorrhoidectomy causes greater pain, so the need for analgesics is extra [2, 3]. Flavonoids, in this case, MPFF given post-surgery, have been proven by a meta-analysis of RCTs to reduce the risk of bleeding and post-surgical pain [14].
For excision hemorrhoidectomy, because the wound in the anal area, it requires special care. The anal area is a dirty area due to contamination with feces. Because of the pain, the patient will prefer not to wipe cleanly after defecation. Soaking in warm water with disinfectant will greatly help to clean the wound from contaminants, thereby helping reduce infection and speed healing. Soaking in warm water is also beneficial for reducing pain [8].
Changes in diet, method of defecation, and control of identified risk factors for the patients (chronic cough, shortness of breath, constipation, urinary difficulties, weight lifting, etc.) are important factors in preventing recurrence [8].
Hemorrhoids are frequently encountered in clinical practice, and physicians must be well-versed in the pathogenesis, risk factors, correct diagnosis, and correct management for patients to receive the best care and recover. The anal cushion sliding theory is now well accepted in the pathogenesis of hemorrhoids and is mostly related to constipation. Therefore, in the management of hemorrhoids, prevention or treatment of constipation has an important place. The first choice for preventing or treating constipation is to eat a high-fiber diet and drink plenty of water. Flavanoids, as oral medication, can be added since they have already been demonstrated to reduce hemorrhoid signs and symptoms. In the case of grades I, II, or small grades III, which fail in medicamentous treatment, instrumentation can be offered, and rubber band ligation is the best choice due to its effectiveness and low price. Surgery is the treatment of choice in emergency cases (thrombosis, strangulation, or bleeding that fails with other treatments) and in cases of grade III and IV that fail nonsurgical management. The gold standard of hemorrhoid surgery is excisional surgery, namely Morgan Milligan and Ferguson. Ferguson is slightly superior to Morgan Milligan regarding postoperative pain, bleeding, and speed of healing. Since excisional surgery is painful, nowadays it offers anal cushion preserving surgery. They are stapler hemorrhoidopexy (SH), hemorrhoidal artery ligation, and rectoanal repair under the guidance of Doppler (DG HAL-RAR). Both methods were comparable regarding the length of operative time, bleeding complications, and recurrence. But only regarding postoperative pain, DG HAL-RAR was superior to SH. DG HAL-RAR and SH also had less postoperative pain but higher recurrence compared to excisional surgery. Based on its advantages and disadvantages, let the patient choose the method of surgery.
IntechOpen’s Academic Editors and Authors have received funding for their work through many well-known funders, including: the European Commission, Bill and Melinda Gates Foundation, Wellcome Trust, Chinese Academy of Sciences, Natural Science Foundation of China (NSFC), CGIAR Consortium of International Agricultural Research Centers, National Institute of Health (NIH), National Science Foundation (NSF), National Aeronautics and Space Administration (NASA), National Institute of Standards and Technology (NIST), German Research Foundation (DFG), Research Councils United Kingdom (RCUK), Oswaldo Cruz Foundation, Austrian Science Fund (FWF), Foundation for Science and Technology (FCT), Australian Research Council (ARC).
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\n\n\r\n\tThis book series will offer a comprehensive overview of recent research trends as well as clinical applications within different specialties of dentistry. Topics will include overviews of the health of the oral cavity, from prevention and care to different treatments for the rehabilitation of problems that may affect the organs and/or tissues present. The different areas of dentistry will be explored, with the aim of disseminating knowledge and providing readers with new tools for the comprehensive treatment of their patients with greater safety and with current techniques. Ongoing issues, recent advances, and future diagnostic approaches and therapeutic strategies will also be discussed. This series of books will focus on various aspects of the properties and results obtained by the various treatments available, whether preventive or curative.
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He received his Ph.D. in Plant Stress Physiology and Antioxidant Metabolism from Ehime University, Japan, with a scholarship from the Japanese Government (MEXT). Later, he completed his postdoctoral research at the Center of Molecular Biosciences, University of the Ryukyus, Japan, as a recipient of the Japan Society for the Promotion of Science (JSPS) postdoctoral fellowship. He was also the recipient of the Australian Government Endeavour Research Fellowship for postdoctoral research as an adjunct senior researcher at the University of Tasmania, Australia. Dr. Hasanuzzaman’s current work is focused on the physiological and molecular mechanisms of environmental stress tolerance. Dr. Hasanuzzaman has published more than 150 articles in peer-reviewed journals. He has edited ten books and written more than forty book chapters on important aspects of plant physiology, plant stress tolerance, and crop production. According to Scopus, Dr. Hasanuzzaman’s publications have received more than 10,500 citations with an h-index of 53. He has been named a Highly Cited Researcher by Clarivate. He is an editor and reviewer for more than fifty peer-reviewed international journals and was a recipient of the “Publons Peer Review Award” in 2017, 2018, and 2019. He has been honored by different authorities for his outstanding performance in various fields like research and education, and he has received the World Academy of Science Young Scientist Award (2014) and the University Grants Commission (UGC) Award 2018. He is a fellow of the Bangladesh Academy of Sciences (BAS) and the Royal Society of Biology.",institutionString:"Sher-e-Bangla Agricultural University",institution:{name:"Sher-e-Bangla Agricultural University",country:{name:"Bangladesh"}}},{id:"213308",title:"Associate Prof.",name:"Manuel Víctor",middleName:null,surname:"López-González",slug:"manuel-victor-lopez-gonzalez",fullName:"Manuel Víctor López-González",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/213308/images/10301_n.jpg",biography:null,institutionString:null,institution:{name:"University of Malaga",country:{name:"Spain"}}},{id:"169212",title:"Prof.",name:"Pavol",middleName:null,surname:"Svorc",slug:"pavol-svorc",fullName:"Pavol Svorc",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/169212/images/system/169212.jpg",biography:"Dr. Pavol Švorc is an Associate Professor, Doctor of the Natural Sciences, Philosophe Doctor. In 1982 he became a Doctor of the Natural Sciences from General Biology, Natural Faculty, Šafarik’s University in Košice. In 1995 he received a PhD. – Physiology and Patophysiology, Natural Faculty Šafarik’s University in Košice. In 2005 he became an Associate Professor from Normal and Patological Physiology, Medical Faculty, Šafarik’s University in Košice. From 1982 to 1983 Dr.Švorc worked as an independent specialist in the local museum in Poprad, Slovakia. In 1983 he started working as a lecturer at the Department of Physiology, Šafarik’s University in Kosice, Slovakia. From\r\n2011 until 2014 he was a Head of the Institute of Physiology and Pathophysiology, Medical Faculty, University of Ostrava, Czech Republic. His research interest includes:\r\nChronobiology of cardiovascular system, respiratory system and autonomic nervous system.",institutionString:"Pavol Josef Safarik University",institution:{name:"University of Pavol Jozef Šafárik",country:{name:"Slovakia"}}},{id:"187859",title:"Prof.",name:"Kusal",middleName:"K.",surname:"Das",slug:"kusal-das",fullName:"Kusal Das",position:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bSBDeQAO/Profile_Picture_1623411145568",biography:"Kusal K. Das is a Distinguished Chair Professor of Physiology, Shri B. M. Patil Medical College and Director, Centre for Advanced Medical Research (CAMR), BLDE (Deemed to be University), Vijayapur, Karnataka, India. Dr. Das did his M.S. and Ph.D. in Human Physiology from the University of Calcutta, Kolkata. His area of research is focused on understanding of molecular mechanisms of heavy metal activated low oxygen sensing pathways in vascular pathophysiology. He has invented a new method of estimation of serum vitamin E. His expertise in critical experimental protocols on vascular functions in experimental animals was well documented by his quality of publications. He was a Visiting Professor of Medicine at University of Leeds, United Kingdom (2014-2016) and Tulane University, New Orleans, USA (2017). For his immense contribution in medical research Ministry of Science and Technology, Government of India conferred him 'G.P. Chatterjee Memorial Research Prize-2019” and he is also the recipient of 'Dr.Raja Ramanna State Scientist Award 2015” by Government of Karnataka. He is a Fellow of the Royal Society of Biology (FRSB), London and Honorary Fellow of Karnataka Science and Technology Academy, Department of Science and Technology, Government of Karnataka.",institutionString:"BLDE (Deemed to be University), India",institution:null},{id:"243660",title:"Dr.",name:"Mallanagouda Shivanagouda",middleName:null,surname:"Biradar",slug:"mallanagouda-shivanagouda-biradar",fullName:"Mallanagouda Shivanagouda Biradar",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/243660/images/system/243660.jpeg",biography:"M. S. Biradar is Vice Chancellor and Professor of Medicine of\nBLDE (Deemed to be University), Vijayapura, Karnataka, India.\nHe obtained his MD with a gold medal in General Medicine and\nhas devoted himself to medical teaching, research, and administrations. He has also immensely contributed to medical research\non vascular medicine, which is reflected by his numerous publications including books and book chapters. Professor Biradar was\nalso Visiting Professor at Tulane University School of Medicine, New Orleans, USA.",institutionString:"BLDE (Deemed to be University)",institution:{name:"BLDE University",country:{name:"India"}}},{id:"289796",title:"Dr.",name:"Swastika",middleName:null,surname:"Das",slug:"swastika-das",fullName:"Swastika Das",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/289796/images/system/289796.jpeg",biography:"Swastika N. Das is Professor of Chemistry at the V. P. Dr. P. G.\nHalakatti College of Engineering and Technology, BLDE (Deemed\nto be University), Vijayapura, Karnataka, India. She obtained an\nMSc, MPhil, and PhD in Chemistry from Sambalpur University,\nOdisha, India. Her areas of research interest are medicinal chemistry, chemical kinetics, and free radical chemistry. She is a member\nof the investigators who invented a new modified method of estimation of serum vitamin E. She has authored numerous publications including book\nchapters and is a mentor of doctoral curriculum at her university.",institutionString:"BLDEA’s V.P.Dr.P.G.Halakatti College of Engineering & Technology",institution:{name:"BLDE University",country:{name:"India"}}},{id:"248459",title:"Dr.",name:"Akikazu",middleName:null,surname:"Takada",slug:"akikazu-takada",fullName:"Akikazu Takada",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/248459/images/system/248459.png",biography:"Akikazu Takada was born in Japan, 1935. After graduation from\nKeio University School of Medicine and finishing his post-graduate studies, he worked at Roswell Park Memorial Institute NY,\nUSA. He then took a professorship at Hamamatsu University\nSchool of Medicine. In thrombosis studies, he found the SK\npotentiator that enhances plasminogen activation by streptokinase. He is very much interested in simultaneous measurements\nof fatty acids, amino acids, and tryptophan degradation products. By using fatty\nacid analyses, he indicated that plasma levels of trans-fatty acids of old men were\nfar higher in the US than Japanese men. . He also showed that eicosapentaenoic acid\n(EPA) and docosahexaenoic acid (DHA) levels are higher, and arachidonic acid\nlevels are lower in Japanese than US people. By using simultaneous LC/MS analyses\nof plasma levels of tryptophan metabolites, he recently found that plasma levels of\nserotonin, kynurenine, or 5-HIAA were higher in patients of mono- and bipolar\ndepression, which are significantly different from observations reported before. In\nview of recent reports that plasma tryptophan metabolites are mainly produced by\nmicrobiota. He is now working on the relationships between microbiota and depression or autism.",institutionString:"Hamamatsu University School of Medicine",institution:{name:"Hamamatsu University School of Medicine",country:{name:"Japan"}}},{id:"137240",title:"Prof.",name:"Mohammed",middleName:null,surname:"Khalid",slug:"mohammed-khalid",fullName:"Mohammed Khalid",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/137240/images/system/137240.png",biography:"Mohammed Khalid received his B.S. in Chemistry in July 2000, and his Ph.D. in Physical Chemistry in 2007 from the University of Khartoum, Sudan. In 2009 he joined the Dr. Ron Clarke research group at the School of Chemistry, Faculty of Science, University of Sydney, Australia as a postdoctoral fellow where he worked on the Interaction of ATP with the phosphoenzyme of the Na+, K+-ATPase, and Dual mechanisms of allosteric acceleration of the Na+, K+-ATPase by ATP. He then worked as Assistant Professor at the Department of Chemistry, University of Khartoum, and in 2014 was promoted to Associate Professor ranking. In 2011 he joined the staff of the Chemistry Department at Taif University, Saudi Arabia, where he is currently active as an Assistant Professor. His research interests include:\r\n(1) P-type ATPase Enzyme Kinetics and Mechanisms; (2) Kinetics and Mechanism of Redox Reactions; (3) Autocatalytic reactions; (4) Computational enzyme kinetics; (5) Allosteric acceleration of P-type ATPases by ATP; (6) Exploring of allosteric sites of ATPases and interaction of ATP with ATPases located in the cell membranes.",institutionString:"Taif University",institution:{name:"Taif University",country:{name:"Saudi Arabia"}}},{id:"63810",title:"Prof.",name:"Jorge",middleName:null,surname:"Morales-Montor",slug:"jorge-morales-montor",fullName:"Jorge Morales-Montor",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/63810/images/system/63810.png",biography:"Dr. Jorge Morales-Montor was recognized with the Lola and Igo Flisser PUIS Award for best graduate thesis at the national level in the field of parasitology. He received a fellowship from the Fogarty Foundation to perform postdoctoral research stay at the University of Georgia. He has 153 journal articles to his credit. He has also edited several books and published more than fifty-five book chapters. He is a member of the Mexican Academy of Sciences, Latin American Academy of Sciences, and the National Academy of Medicine. He has received more than thirty-five awards and has supervised numerous bachelor’s, master’s, and Ph.D. students. Dr. Morales-Montor is the past president of the Mexican Society of Parasitology.",institutionString:"National Autonomous University of Mexico",institution:{name:"National Autonomous University of Mexico",country:{name:"Mexico"}}},{id:"217215",title:"Dr.",name:"Palash",middleName:null,surname:"Mandal",slug:"palash-mandal",fullName:"Palash Mandal",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/217215/images/system/217215.jpeg",biography:null,institutionString:"Charusat University",institution:null},{id:"49739",title:"Dr.",name:"Leszek",middleName:null,surname:"Szablewski",slug:"leszek-szablewski",fullName:"Leszek Szablewski",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/49739/images/system/49739.jpg",biography:"Leszek Szablewski is a professor of medical sciences. He received his M.S. in the Faculty of Biology from the University of Warsaw and his PhD degree from the Institute of Experimental Biology Polish Academy of Sciences. He habilitated in the Medical University of Warsaw, and he obtained his degree of Professor from the President of Poland. Professor Szablewski is the Head of Chair and Department of General Biology and Parasitology, Medical University of Warsaw. Professor Szablewski has published over 80 peer-reviewed papers in journals such as Journal of Alzheimer’s Disease, Biochim. Biophys. Acta Reviews of Cancer, Biol. Chem., J. Biomed. Sci., and Diabetes/Metabol. Res. Rev, Endocrine. He is the author of two books and four book chapters. He has edited four books, written 15 scripts for students, is the ad hoc reviewer of over 30 peer-reviewed journals, and editorial member of peer-reviewed journals. Prof. Szablewski’s research focuses on cell physiology, genetics, and pathophysiology. He works on the damage caused by lack of glucose homeostasis and changes in the expression and/or function of glucose transporters due to various diseases. He has given lectures, seminars, and exercises for students at the Medical University.",institutionString:"Medical University of Warsaw",institution:{name:"Medical University of Warsaw",country:{name:"Poland"}}},{id:"173123",title:"Dr.",name:"Maitham",middleName:null,surname:"Khajah",slug:"maitham-khajah",fullName:"Maitham Khajah",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/173123/images/system/173123.jpeg",biography:"Dr. Maitham A. Khajah received his degree in Pharmacy from Faculty of Pharmacy, Kuwait University, in 2003 and obtained his PhD degree in December 2009 from the University of Calgary, Canada (Gastrointestinal Science and Immunology). Since January 2010 he has been assistant professor in Kuwait University, Faculty of Pharmacy, Department of Pharmacology and Therapeutics. His research interest are molecular targets for the treatment of inflammatory bowel disease (IBD) and the mechanisms responsible for immune cell chemotaxis. He cosupervised many students for the MSc Molecular Biology Program, College of Graduate Studies, Kuwait University. Ever since joining Kuwait University in 2010, he got various grants as PI and Co-I. He was awarded the Best Young Researcher Award by Kuwait University, Research Sector, for the Year 2013–2014. He was a member in the organizing committee for three conferences organized by Kuwait University, Faculty of Pharmacy, as cochair and a member in the scientific committee (the 3rd, 4th, and 5th Kuwait International Pharmacy Conference).",institutionString:"Kuwait University",institution:{name:"Kuwait University",country:{name:"Kuwait"}}},{id:"195136",title:"Dr.",name:"Aya",middleName:null,surname:"Adel",slug:"aya-adel",fullName:"Aya Adel",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/195136/images/system/195136.jpg",biography:"Dr. Adel works as an Assistant Lecturer in the unit of Phoniatrics, Department of Otolaryngology, Ain Shams University in Cairo, Egypt. Dr. Adel is especially interested in joint attention and its impairment in autism spectrum disorder",institutionString:"Ain Shams University",institution:{name:"Ain Shams University",country:{name:"Egypt"}}},{id:"94911",title:"Dr.",name:"Boulenouar",middleName:null,surname:"Mesraoua",slug:"boulenouar-mesraoua",fullName:"Boulenouar Mesraoua",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/94911/images/system/94911.png",biography:"Dr Boulenouar Mesraoua is the Associate Professor of Clinical Neurology at Weill Cornell Medical College-Qatar and a Consultant Neurologist at Hamad Medical Corporation at the Neuroscience Department; He graduated as a Medical Doctor from the University of Oran, Algeria; he then moved to Belgium, the City of Liege, for a Residency in Internal Medicine and Neurology at Liege University; after getting the Belgian Board of Neurology (with high marks), he went to the National Hospital for Nervous Diseases, Queen Square, London, United Kingdom for a fellowship in Clinical Neurophysiology, under Pr Willison ; Dr Mesraoua had also further training in Epilepsy and Continuous EEG Monitoring for two years (from 2001-2003) in the Neurophysiology department of Zurich University, Switzerland, under late Pr Hans Gregor Wieser ,an internationally known epileptologist expert. \n\nDr B. Mesraoua is the Director of the Neurology Fellowship Program at the Neurology Section and an active member of the newly created Comprehensive Epilepsy Program at Hamad General Hospital, Doha, Qatar; he is also Assistant Director of the Residency Program at the Qatar Medical School. \nDr B. Mesraoua's main interests are Epilepsy, Multiple Sclerosis, and Clinical Neurology; He is the Chairman and the Organizer of the well known Qatar Epilepsy Symposium, he is running yearly for the past 14 years and which is considered a landmark in the Gulf region; He has also started last year , together with other epileptologists from Qatar, the region and elsewhere, a yearly International Epilepsy School Course, which was attended by many neurologists from the Area.\n\nInternationally, Dr Mesraoua is an active and elected member of the Commission on Eastern Mediterranean Region (EMR ) , a regional branch of the International League Against Epilepsy (ILAE), where he represents the Middle East and North Africa(MENA ) and where he holds the position of chief of the Epilepsy Epidemiology Section; Dr Mesraoua is a member of the American Academy of Neurology, the Europeen Academy of Neurology and the American Epilepsy Society.\n\nDr Mesraoua's main objectives are to encourage frequent gathering of the epileptologists/neurologists from the MENA region and the rest of the world, promote Epilepsy Teaching in the MENA Region, and encourage multicenter studies involving neurologists and epileptologists in the MENA region, particularly epilepsy epidemiological studies. \n\nDr. Mesraoua is the recipient of two research Grants, as the Lead Principal Investigator (750.000 USD and 250.000 USD) from the Qatar National Research Fund (QNRF) and the Hamad Hospital Internal Research Grant (IRGC), on the following topics : “Continuous EEG Monitoring in the ICU “ and on “Alpha-lactoalbumin , proof of concept in the treatment of epilepsy” .Dr Mesraoua is a reviewer for the journal \"seizures\" (Europeen Epilepsy Journal ) as well as dove journals ; Dr Mesraoua is the author and co-author of many peer reviewed publications and four book chapters in the field of Epilepsy and Clinical Neurology",institutionString:"Weill Cornell Medical College in Qatar",institution:{name:"Weill Cornell Medical College in Qatar",country:{name:"Qatar"}}},{id:"282429",title:"Prof.",name:"Covanis",middleName:null,surname:"Athanasios",slug:"covanis-athanasios",fullName:"Covanis Athanasios",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/282429/images/system/282429.jpg",biography:null,institutionString:"Neurology-Neurophysiology Department of the Children Hospital Agia Sophia",institution:null},{id:"190980",title:"Prof.",name:"Marwa",middleName:null,surname:"Mahmoud Saleh",slug:"marwa-mahmoud-saleh",fullName:"Marwa Mahmoud Saleh",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/190980/images/system/190980.jpg",biography:"Professor Marwa Mahmoud Saleh is a doctor of medicine and currently works in the unit of Phoniatrics, Department of Otolaryngology, Ain Shams University in Cairo, Egypt. She got her doctoral degree in 1991 and her doctoral thesis was accomplished in the University of Iowa, United States. Her publications covered a multitude of topics as videokymography, cochlear implants, stuttering, and dysphagia. She has lectured Egyptian phonology for many years. Her recent research interest is joint attention in autism.",institutionString:"Ain Shams University",institution:{name:"Ain Shams University",country:{name:"Egypt"}}},{id:"259190",title:"Dr.",name:"Syed Ali Raza",middleName:null,surname:"Naqvi",slug:"syed-ali-raza-naqvi",fullName:"Syed Ali Raza Naqvi",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/259190/images/system/259190.png",biography:"Dr. Naqvi is a radioanalytical chemist and is working as an associate professor of analytical chemistry in the Department of Chemistry, Government College University, Faisalabad, Pakistan. Advance separation techniques, nuclear analytical techniques and radiopharmaceutical analysis are the main courses that he is teaching to graduate and post-graduate students. In the research area, he is focusing on the development of organic- and biomolecule-based radiopharmaceuticals for diagnosis and therapy of infectious and cancerous diseases. Under the supervision of Dr. Naqvi, three students have completed their Ph.D. degrees and 41 students have completed their MS degrees. He has completed three research projects and is currently working on 2 projects entitled “Radiolabeling of fluoroquinolone derivatives for the diagnosis of deep-seated bacterial infections” and “Radiolabeled minigastrin peptides for diagnosis and therapy of NETs”. He has published about 100 research articles in international reputed journals and 7 book chapters. Pakistan Institute of Nuclear Science & Technology (PINSTECH) Islamabad, Punjab Institute of Nuclear Medicine (PINM), Faisalabad and Institute of Nuclear Medicine and Radiology (INOR) Abbottabad are the main collaborating institutes.",institutionString:"Government College University",institution:{name:"Government College University, Faisalabad",country:{name:"Pakistan"}}},{id:"58390",title:"Dr.",name:"Gyula",middleName:null,surname:"Mozsik",slug:"gyula-mozsik",fullName:"Gyula Mozsik",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/58390/images/system/58390.png",biography:"Gyula Mózsik MD, Ph.D., ScD (med), is an emeritus professor of Medicine at the First Department of Medicine, Univesity of Pécs, Hungary. He was head of this department from 1993 to 2003. His specializations are medicine, gastroenterology, clinical pharmacology, clinical nutrition, and dietetics. His research fields are biochemical pharmacological examinations in the human gastrointestinal (GI) mucosa, mechanisms of retinoids, drugs, capsaicin-sensitive afferent nerves, and innovative pharmacological, pharmaceutical, and nutritional (dietary) research in humans. He has published about 360 peer-reviewed papers, 197 book chapters, 692 abstracts, 19 monographs, and has edited 37 books. He has given about 1120 regular and review lectures. He has organized thirty-eight national and international congresses and symposia. He is the founder of the International Conference on Ulcer Research (ICUR); International Union of Pharmacology, Gastrointestinal Section (IUPHAR-GI); Brain-Gut Society symposiums, and gastrointestinal cytoprotective symposiums. He received the Andre Robert Award from IUPHAR-GI in 2014. Fifteen of his students have been appointed as full professors in Egypt, Cuba, and Hungary.",institutionString:"University of Pécs",institution:{name:"University of Pecs",country:{name:"Hungary"}}},{id:"277367",title:"M.Sc.",name:"Daniel",middleName:"Martin",surname:"Márquez López",slug:"daniel-marquez-lopez",fullName:"Daniel Márquez López",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/277367/images/7909_n.jpg",biography:"Msc Daniel Martin Márquez López has a bachelor degree in Industrial Chemical Engineering, a Master of science degree in the same área and he is a PhD candidate for the Instituto Politécnico Nacional. His Works are realted to the Green chemistry field, biolubricants, biodiesel, transesterification reactions for biodiesel production and the manipulation of oils for therapeutic purposes.",institutionString:null,institution:{name:"Instituto Politécnico Nacional",country:{name:"Mexico"}}},{id:"196544",title:"Prof.",name:"Angel",middleName:null,surname:"Catala",slug:"angel-catala",fullName:"Angel Catala",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/196544/images/system/196544.jpg",biography:"Angel Catalá studied chemistry at Universidad Nacional de La Plata, Argentina, where he received a Ph.D. in Chemistry (Biological Branch) in 1965. From 1964 to 1974, he worked as an Assistant in Biochemistry at the School of Medicine at the same university. From 1974 to 1976, he was a fellow of the National Institutes of Health (NIH) at the University of Connecticut, Health Center, USA. From 1985 to 2004, he served as a Full Professor of Biochemistry at the Universidad Nacional de La Plata. He is a member of the National Research Council (CONICET), Argentina, and the Argentine Society for Biochemistry and Molecular Biology (SAIB). His laboratory has been interested for many years in the lipid peroxidation of biological membranes from various tissues and different species. Dr. Catalá has directed twelve doctoral theses, published more than 100 papers in peer-reviewed journals, several chapters in books, and edited twelve books. He received awards at the 40th International Conference Biochemistry of Lipids 1999 in Dijon, France. He is the winner of the Bimbo Pan-American Nutrition, Food Science and Technology Award 2006 and 2012, South America, Human Nutrition, Professional Category. In 2006, he won the Bernardo Houssay award in pharmacology, in recognition of his meritorious works of research. Dr. Catalá belongs to the editorial board of several journals including Journal of Lipids; International Review of Biophysical Chemistry; Frontiers in Membrane Physiology and Biophysics; World Journal of Experimental Medicine and Biochemistry Research International; World Journal of Biological Chemistry, Diabetes, and the Pancreas; International Journal of Chronic Diseases & Therapy; and International Journal of Nutrition. He is the co-editor of The Open Biology Journal and associate editor for Oxidative Medicine and Cellular Longevity.",institutionString:"Universidad Nacional de La Plata",institution:{name:"National University of La Plata",country:{name:"Argentina"}}},{id:"186585",title:"Dr.",name:"Francisco Javier",middleName:null,surname:"Martin-Romero",slug:"francisco-javier-martin-romero",fullName:"Francisco Javier Martin-Romero",position:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bSB3HQAW/Profile_Picture_1631258137641",biography:"Francisco Javier Martín-Romero (Javier) is a Professor of Biochemistry and Molecular Biology at the University of Extremadura, Spain. He is also a group leader at the Biomarkers Institute of Molecular Pathology. Javier received his Ph.D. in 1998 in Biochemistry and Biophysics. At the National Cancer Institute (National Institute of Health, Bethesda, MD) he worked as a research associate on the molecular biology of selenium and its role in health and disease. After postdoctoral collaborations with Carlos Gutierrez-Merino (University of Extremadura, Spain) and Dario Alessi (University of Dundee, UK), he established his own laboratory in 2008. The interest of Javier's lab is the study of cell signaling with a special focus on Ca2+ signaling, and how Ca2+ transport modulates the cytoskeleton, migration, differentiation, cell death, etc. He is especially interested in the study of Ca2+ channels, and the role of STIM1 in the initiation of pathological events.",institutionString:null,institution:{name:"University of Extremadura",country:{name:"Spain"}}},{id:"198499",title:"Dr.",name:"Daniel",middleName:null,surname:"Glossman-Mitnik",slug:"daniel-glossman-mitnik",fullName:"Daniel Glossman-Mitnik",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/198499/images/system/198499.jpeg",biography:"Dr. Daniel Glossman-Mitnik is currently a Titular Researcher at the Centro de Investigación en Materiales Avanzados (CIMAV), Chihuahua, Mexico, as well as a National Researcher of Level III at the Consejo Nacional de Ciencia y Tecnología, México. His research interest focuses on computational chemistry and molecular modeling of diverse systems of pharmacological, food, and alternative energy interests by resorting to DFT and Conceptual DFT. He has authored a coauthored more than 270 peer-reviewed papers, 32 book chapters, and 4 edited books. He has delivered speeches at many international and domestic conferences. He serves as a reviewer for more than eighty international journals, books, and research proposals as well as an editor for special issues of renowned scientific journals.",institutionString:null,institution:null},{id:"318757",title:"Associate Prof.",name:"Irina Alexandrovna",middleName:null,surname:"Savvina",slug:"irina-alexandrovna-savvina",fullName:"Irina Alexandrovna Savvina",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/318757/images/18742_n.jpg",biography:null,institutionString:null,institution:null}]}},subseries:{item:{id:"12",type:"subseries",title:"Human Physiology",keywords:"Anatomy, Cells, Organs, Systems, Homeostasis, Functions",scope:"Human physiology is the scientific exploration of the various functions (physical, biochemical, and mechanical properties) of humans, their organs, and their constituent cells. The endocrine and nervous systems play important roles in maintaining homeostasis in the human body. Integration, which is the biological basis of physiology, is achieved through communication between the many overlapping functions of the human body's systems, which takes place through electrical and chemical means. Much of the basis of our knowledge of human physiology has been provided by animal experiments. Because of the close relationship between structure and function, studies in human physiology and anatomy seek to understand the mechanisms that help the human body function. The series on human physiology deals with the various mechanisms of interaction between the various organs, nerves, and cells in the human body.",coverUrl:"https://cdn.intechopen.com/series_topics/covers/12.jpg",hasOnlineFirst:!1,hasPublishedBooks:!0,annualVolume:11408,editor:{id:"195829",title:"Prof.",name:"Kunihiro",middleName:null,surname:"Sakuma",slug:"kunihiro-sakuma",fullName:"Kunihiro Sakuma",profilePictureURL:"https://mts.intechopen.com/storage/users/195829/images/system/195829.jpg",biography:"Professor Kunihiro Sakuma, Ph.D., currently works in the Institute for Liberal Arts at the Tokyo Institute of Technology. He is a physiologist working in the field of skeletal muscle. He was awarded his sports science diploma in 1995 by the University of Tsukuba and began his scientific work at the Department of Physiology, Aichi Human Service Center, focusing on the molecular mechanism of congenital muscular dystrophy and normal muscle regeneration. 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