CHAPTER 1THEORY: ESOPHAGEAL CANCER1.1 IntroductionThe American Cancer Societys estimates for esophageal cancer in the United States for 2013 areabout 17,990 new esophageal cancer cases diagnosed (14,440 in men and 3,550 in women),andabout 15,210 deaths from esophageal cancer (12,220 in men and 2,990 in women).This disease is 3 to 4 times more common among men than among women. The lifetime risk ofesophageal cancer in the United States is about 1 in 125 in men and about 1 in 435 in women.Overall, the rates of esophageal cancer in the United States have been fairly stable for manyyears. It was once much more common in African Americans than in whites. But it is now aboutequally as common, as rates have fallen in African Americans and increased slightly in whitesover the past few decades. Squamous cell carcinoma is the most common type of cancer of theesophagus among African Americans, while adenocarcinoma is more common in whites. Cancerof the esophagus is much more common in some other countries. For example, esophageal cancerrates in Iran, northern China, India, and southern Africa are 10 to 100 times higher than in theUnited States. The main type of esophageal cancer in these countries is squamous cell carcinoma.Although many people with esophageal cancer will go on to die from this disease, treatment hasimproved and survival rates are getting better. During the 1960s, fewer than 5% of patientssurvived at least 5 years after diagnosis. Now, about 20% of patients survive at least 5 years afterdiagnosis. This includes patients with all stages of esophageal cancer at the time of diagnosis.Survival rates for people with early stage cancer are higher.1.2 Anatomy of EsophagusThe esophagus is a hollow, muscular tube that connects the throat to the stomach. It lies behindthe trachea (windpipe) and in front of the spine. Food and liquids that are swallowed travelthrough the inside of the esophagus (called the lumen) to reach the stomach. In adults, theesophagus is usually between 10 and 13 inches long and is about ¾ of an inch across at itssmallest point.
1.3 Histology of EsophagusMucosa: This is the layer that lines the inside of the esophagus. The mucosa has 3 parts:• The epithelium forms the innermost lining of the esophagus and is normally made upof flat, thin cells called squamous cells. This is where most cancers of the esophagusstart.• The lamina propria is a thin layer of connective tissue right under the epithelium.• The muscularis mucosa is a very thin layer of muscle under the lamina propria.Submucosa: This is a layer of connective tissue just below the mucosa that contains blood vesselsand nerves. In some parts of the esophagus, this layer also contains glands that secrete mucus.Muscularispropria: This is a thick band of muscle under the submucosa. This layer of musclecontracts in a coordinated, rhythmic way to push food along the esophagus from thethroat to thestomach.Adventitia: This is the outermost layer of the esophagus, which is formed by connective tissue.The upper part of the esophagus has a special area of muscle at its beginning that relaxes to openthe esophagus when it senses food or liquid coming toward it. This muscle is called the upperesophageal sphincter.The lower part of the esophagus that connects to the stomach is called the gastroesophageal (GE)junction. A special area of muscle near the GE junction, called the lower esophageal sphincter,controls the movement of food from the esophagus into the stomach and it keeps the stomachsacid and digestive enzymes out of the esophagus.Reflux and Barrett’s EsophagusThe stomach has strong acid and enzymes that digest food. The epithelium (inner lining) of thestomach is made of gland cells that release acid, enzymes, and mucus. These cells have specialfeatures that protect them from the stomachs acid and digestive enzymes.
In some people, acid escapes from the stomach back into the esophagus. The medical term forthis is gastroesophageal reflux disease (GERD), or just reflux. In many cases, reflux can causesymptoms such as heartburn or a burning feeling spreading out from the middle of the chest. Butsometimes, reflux can occur without any symptoms at all.If reflux of stomach acid into the lower esophagus continues for a long time, it can damage thelining of the esophagus. This causes the squamous cells that usually line the esophagus to bereplaced with gland cells. These gland cells usually look like the cells that line the stomach andthe small intestine and are more resistant to stomach acid. The presence of gland cells in theesophagus is known as Barretts (or Barrett) esophagus. People with Barretts esophagus are muchmore likely to develop cancer of the esophagus. These people require close medical follow-up inorder to find cancer early. Still, although they have a higher risk, most people with Barrettsesophagus do not go on to develop cancer of the esophagus1.4 Esophageal CancerCancer of the esophagus (also referred to as esophageal cancer) starts in the inner layer (themucosa) and grows outward (through the submucosa and the muscle layer). Since 2 types of cellscan line the esophagus, there are 2 main types of esophageal cancer: squamous cell carcinomaand adenocarcinoma.The esophagus is normally lined with squamous cells. The cancer starting in these cells is calledsquamous cell carcinoma. This type of cancer can occur anywhere along the esophagus. At onetime, squamous cell carcinoma was by far the more common type of esophageal cancer in theUnited States. This has changed over time, and now it makes up less than half of esophagealcancers in this country.Cancers that start in gland cells are called adenocarcinomas. This type of cell is not normally partof the inner lining of the esophagus. Before an adenocarcinoma can develop, gland cells mustreplace an area of squamous cells, which is what happens in Barretts esophagus. This occursmainly in the lower esophagus, which is the site of most adenocarcinomas. Cancers that start atthe area where the esophagus joins the stomach (the GE junction), which includes about the first2 inches of the stomach (called the cardia), tend to behave like esophagus cancers (and are treatedlike them, as well), so they are grouped with esophagus cancers
1.4.1 Risk FactorThere are several risks factor such as:Age: Less than 15% of cases are found in people younger than age 55.Gender: Compared with women, men have more than a 3-fold higher rate of esophageal cancer.Gastroesophageal reflux diseaseBarretts esophagus: The risk of cancer is highest if dysplasia is present or if other people infamily also have Barrett’s.Tobacco and alcohol: The link to squamous cell esophageal cancer is even stronger. Drinkingalcohol also increases the risk of esophageal cancer. The chance of getting esophageal cancergoes up with higher intake of alcohol.Obesity: This is in part explained by the fact that people who are obese are more likely to haveesophageal reflux.Diet: A diet high in fruits and vegetables is linked to a lower risk of esophageal cancer. Drinkingvery hot liquids frequently may increase the risk for the squamous cell type of esophageal cancerdue to long-term damage the liquids do to the cells lining the esophagus. Overeating, which leadsto obesity, increases the risk of the adenocarcinoma of the esophagus.Achalasia: People with achalasia have a risk of esophageal cancer that is many times normal. Onaverage, the cancers are found about 15-20 years after the achalasia is diagnosed.Tylosis: This is a rare, inherited disease that causes excess growth of the top layer of skin on thepalms of the hands and soles of the feet. People with tylosis need to be watched closely to try tofind esophageal cancer early. Often this requires regular monitoring with an upper endoscopyEsophageal webs: A web is a thin membrane extending out from the inner lining of theesophagus that causes an area of narrowing. Most esophageal webs do not cause any problems,but larger webs may cause food to get stuck in the esophagus, which can lead to problemsswallowing. When an esophageal web is found along with anemia, tongue irritation (glossitis),brittle fingernails, and a large spleen it is called Plummer-Vinson syndrome. Another name for
this is Paterson-Kelly syndrome. About 1 in 10 patients with this syndrome eventually developsquamous cell cancer of the esophagus.Workplace exposures: Exposure to chemical fumes in certain workplaces may lead to anincreased risk of esophageal cancer. For example, exposure to the solvents used for dry cleaningmay lead to a greater risk of esophageal cancer. Some studies have found that dry cleaningworkers may have a higher rate of esophageal cancer.Injury to the esophagus: Lye is a chemical found in strong industrial and household cleanerssuch as drain cleaners. Lye is a corrosive agent, meaning it can burn and destroy cells. Sometimessmall children mistakenly drink from a lye-based cleaner bottle. The lye causes a severe chemicalburn in the esophagus. As the injury heals, the scar tissue can cause an area of the esophagus tobecome very narrow (called a stricture). People with these strictures have an increased rate of thesquamous cell type of esophageal cancer as adults. The cancers occur on average about 40 yearsafter the lye was swallowed.History of certain other cancers:People who have had certain other cancers, such as lungcancer, mouth cancer, and throatcancer have a high risk of getting squamous cell carcinoma ofthe esophagus as well. This may be because all of these cancers can be caused by smoking.Human papilloma virus: Genes from human papilloma virus (HPV) have been found in up toone-third of esophagus cancer tumors from patients living in Asia and South Africa. Signs ofHPV infection have not been found in esophagus cancers from patients living in the other areas,including the US. HPV is a group of more than 100 related viruses. They are called papillomaviruses because some of them cause a type of growth called a papilloma (or wart). Infection withcertain types of HPV is linked to a number of cancers, including throat cancer, anal cancer, andcervical cancer1.4.2 Diagnosis of Esophageal Cancer22.214.171.124 Sign and SymptomsDysphagia: The most common symptom of esophageal cancer is a problem swallowing. This isoften mild when it starts, and then gets worse over time as the opening inside the esophagus getsnarrower. Dysphagia is commonly a late symptom caused by a large cancer. When swallowing
becomes difficult, people often change their diet and eating habits without realizing it. They takesmaller bites and chew their food more carefully and slowly. As the cancer grows larger, theproblem gets worse. People then may start eating softer foods that can pass through theesophagus more easily. They may avoid bread and meat, since these foods typically get stuck.The swallowing problem may even get bad enough that some people stop eating solid foodcompletely and switch to a liquid diet. If the cancer keeps growing, at some point even liquidswill not be able to pass. To help pass food through the esophagus, the body makes more saliva.This causes some people to complain of bringing up lots of thick mucus or saliva.Chest Pain: Sometimes, people complain of pain or discomfort in the middle part of their chest.Some people describe a feeling of pressure or burning in the chest. These symptoms are moreoften caused by problems other than cancer, such as heartburn, and so they are rarely seen as asignal that a person may have cancer. Swallowing may become painful when the cancer is largeenough to limit the passage of food through the esophagus. Pain may be felt a few seconds afterswallowing, as food or liquid reaches the tumor and has trouble getting past it.Weight Loss: About half of patients with esophageal cancer lose weight (without trying to). Thishappens because their swallowing problems keep them from eating enough to maintain theirweight. Other factors include a decreased appetite and an increase in metabolism from the cancer.Other symptoms are: Hoarseness, chronic cough, hiccups, pneumonia, bone pain, and bleedinginto the esophagus.126.96.36.199 Imaging TestsBarium Swallow: A barium swallow test can show any irregularities in the normally smoothsurface of the inner lining of the esophagus. Even small, early cancers can often be seen usingthis test. Tumors grow out from the lining of the esophagus and stick out into the lumen (the openarea of the tube). They cause the barium to coat that area of the esophagus unevenly. Earlycancers can look like small round bumps or flat, raised areas (called plaques), while advancedcancers look like large irregular areas and cause a narrowing of the width of the esophagus. Thistest can also be used to diagnose one of the more serious complications of esophageal cancercalled a tracheo-esophageal fistula.
Barium swallow demonstrating stricture due tocancerBarium swallow demonstrating an endoluminalmass in the mid esophagusComputed Tomography (CT) Scan: CT scans are not usually used to make the initial diagnosisof esophageal cancer, but they can help see how far it has spread. CT scans often can show wherethe cancer is in the esophagus. These scans can also show the nearby organs and lymph nodes(bean-sized collections of immune cells to which cancers often spread first), as well as distantareas of cancer spread.Magnetic resonance imaging (MRI) scan: Like CT scans, MRI scans provide detailed imagesof soft tissues in the body. But MRI scans use radio waves and strong magnets instead of X-rays.The energy from the radio waves is absorbed and then released in a pattern formed by the type oftissue and by certain diseases. A computer translates the pattern of radio waves given off by thetissues into a very detailed image of parts of the body. A contrast material might be injected intoa vein. MRI scans are very helpful in looking at the brain and spinal cord, but they are not oftenneeded to assess spread of esophageal cancer.Positron emission tomography (PET) scan: For a PET scan, a form of radioactive sugar(known as fluorodeoxyglucose or FDG) is injected into the blood. The amount of radioactivityused is very low. Cancer cells in the body are growing rapidly, so they absorb large amounts of
the radioactive sugar. The picture is not finely detailed like a CT or MRI scan, but it provideshelpful information about whole body.EndoscopyUpper endoscopy: Performing esophagogastroduodenoscopy allows direct visualization andbiopsies of the tumor.Endoscopy demonstrating intraluminalesophageal cancerChest CT scan showing invasion of the tracheaby esophageal cancerEndoscopic ultrasound: This is actually a type of imaging test that involves the use of endoscopy.Ultrasound tests use sound waves to take pictures of parts of the body. They use no radiation andare very safe. For an endoscopic ultrasound, the probe that gives off the sound waves is at the endof an endoscope, which is passed down the throat and into the esophagus. This allows the probeto get very close to the cancer. This is done with local anesthesia and light sedation.This test is very useful in determining the size of an esophageal cancer and how far it has growninto nearby tissues. It can also help determine if nearby lymph nodes might beaffected by thecancer. If enlarged lymph nodes are seen on the ultrasound and not beside the tumor, the doctormay use a thin, hollow needle to get biopsy samples of them. This helps to decide if the tumorcan be surgically removed.Bronchoscopy: This exam may be done for cancer in the upper part of the esophagus to see if ithas spread to the windpipe (trachea) or the tubes leading from the trachea into the lung (bronchi).
If abnormal areas are seen, small instruments can be passed down the bronchoscope to takebiopsy samples.Laparoscopy and thoracoscopy have a greater than 92% accuracy in staging regional nodes.Lab testing of biopsy samplesAn area seen on endoscopy or on an imaging test may look like cancer, but the only way to knowfor sure is to do a biopsy.This is most often done during an endoscopy exam. A doctor called apathologist then looks at the tissue under a microscope to see if any cancer cells are present. Ifthere is cancer, the pathologist will determine the type (adenocarcinoma or squamous cell) andthe grade of the cancer (how abnormal the patterns of cells look under the microscope).HER2 testing: If esophageal cancer is found but is too advanced for surgery, samples may betested for the HER2 gene or protein. Some people with esophageal cancer have too much of aprotein called HER2 on the surface of their cancer cells, which helps the cells grow. However, adrug that targets the HER2 protein, known as trastuzumab (Herceptin®), may help treat thesecancers when used along with chemotherapy. Only cancers that have too much of the HER2 geneor protein are likely to be affected by this drug, which is why doctors may test tumor samples forit.Other tests are: blood test, complete blood count (CBC) to look for anemia (which could becaused by internal bleeding). A stool sample may be checked to see if it contains occult (unseen)blood. Also check for liver and kidney functions are normal.1.4.3 StagingEsophageal cancer staging was changed in the last edition of the Union for International CancerControl/American Joint Cancer Committee (UICC/AJCC) manual in 2009. All esophagealtumors and tumors with epicenters within 5 cm of the esophagogastric junction that also extendinto the esophagus are classified and staged according to the esophageal scheme. All other tumorswith an epicenter in the stomach greater than 5 cm from the esophagogastric junction or thosewithin 5 cm of the esophagogastric junction without extension into the esophagus are stagedusing the gastric carcinoma scheme.
Conventional staging tools such as esophagoscopy or barium esophagogram can demonstrateonly intraluminal disease extent, and CT scan of the chest is relatively insensitive, except for thepresence of extensive local disease. Esophageal ultrasound allows the visualization of both theesophageal wall and local lymph nodes. As such, it allows a clinical determination of both T andN stage in most patients.Survival rates are not readily available for each stage in the AJCC staging system for esophagealcancer. The survival rates below come from the National Cancer Institutes Surveillance,Epidemiology, and End Results (SEER) database, and are based on patientswho were diagnosedwith esophageal cancer between 2002 and 2008. The SEER database does not divide survivalrates by AJCC stage. Instead, this database divides cancers into 3 larger, summary stages:• Localized means that the cancer is only growing in the esophagus. It includes AJCCstage I and some stage II tumors (such as those that are T1, T2, or T3, N0, M0). Stage0 cancers are not included in these statistics.• Regional means that the cancer has spread to nearby lymph nodes or tissues. Thisincludes T4 tumors and cancers with lymph node spread (N1, N2, or N3).• Distant means that the cancer has spread to organs or lymph nodes away from thetumor, and includes all M1 (stage IV) cancers.Stage 5-Year Relative Survival Rates are: Localized 38%, regional 20% and distant 3%These survival rates for esophageal cancer do not separate squamous cell carcinomas fromadenocarcinomas, although adenocarcinomas are generally thought to have a slightly betterprognosis (outlook) overall.
1.4.4 Treatment of Esophageal CancerGeneral treatment informationThe main options for treatment of cancer of the esophagus include:• Surgery• Radiation• Chemotherapy• Targeted therapy• Endoscopic treatmentsEndoscopic treatments, such as endoscopic mucosal resection, radiofrequency ablation, andphotodynamic therapy, may be used for early cancers and pre-cancers of the esophagus. Some of
these treatments can also be used as palliative treatment when all the cancer cannot be removed.Palliative treatment is meant to relieve symptoms, such as pain and trouble swallowing, but it isnot expected to cure the cancer.Esophagectomy: Often a small part of the stomach is removed as well. The upper part of theesophagus is then connected to the remaining part of the stomach. Part of the stomach is pulledup into the chest or neck to become the new esophagus. How much of the esophagus is removeddepends upon the stage of the tumor and where its located. If the cancer is in the lower part ofthe esophagus (near the stomach) or at the place where the esophagus and stomach meet (thegastroesophageal or GE junction), the surgeon will remove part of the stomach, the part of theesophagus containing the cancer, and about 3 to 4 inches of normal esophagus above this. Thenthe stomach is connected to what is left of the esophagus either high in the chest or in the neck.If the tumor is in the upper or middle part of the esophagus, most of the esophagus will need to beremoved to be sure to get enough tissue above the cancer. The stomach will then bebrought upand connected to the esophagus in the neck. If the stomach cannot be used to replace theesophagus, the surgeon may use a piece of the intestine instead. When a piece of intestine is used,it must be moved without damaging its blood vessels. If the vessels are damaged, not enoughblood will get to that piece of intestine, and the tissue will die.Esophagectomy may be done using either of 2 main types of techniques. The standard, opentechnique uses one or more large incisions (cuts) in the neck, chest, or abdomen to perform thesurgery. In minimally invasive surgery, the surgeon operates through several smaller incisionsusing special long, thin surgical instruments.Open esophagectomy: Many different approaches can be used in operating on esophageal cancer.For a transthoracic esophagectomy, the esophagus is removed with the main incisions in theabdomen and the chest. If the main incisions are in the abdomen and neck, it is called atranshiatalesophagectomy. Some approaches use incisions in the neck, chest, and abdomen.Minimally invasive esophagectomy: For some early (small) cancers, the esophagus can beremoved through several small incisions instead of 1 or 2 large incisions. The surgeon puts ascope (like a tiny telescope) through one of the incisions to see everything during the operation.Then the surgical instruments go in through other small incisions. In order to do this type of
procedure well, the surgeon needs to be highly skilled and have a great deal of experienceremoving the esophagus this way. Because it uses smaller incisions, minimally invasiveesophagectomy may allow the patient to leave the hospital sooner and recover faster.Lymph node removal: For either type of esophagectomy, nearby lymph nodes are removedduring the operation as well. These are then checked to see if they contain cancer cells. If thecancer has spread to lymph nodes, the outlook is not as good, and the doctor may recommendother treatments (like chemotherapy and/or radiation) after surgery.Radiation therapy for cancer of the esophagus: Radiation therapy is the use of high-energyradiation to kill cancer cells. It is often combined with other types of treatment, such aschemotherapy (chemo) and/or surgery, to treat esophageal cancer. Radiation therapy may beused:• As part of the primary (main) treatment of esophageal cancer in some patients,typically along with chemo. This is often used for people who cant have surgery dueto poor health.• Before surgery (usually along with chemo), to try to shrink the cancer and make iteasier to remove (called neoadjuvant treatment).• After surgery (usually along with chemo), to try to kill any areas of cancer cells thatmay have been left behind but are too small to see. This is known as adjuvant therapy.• To ease the symptoms of advanced esophageal cancer such as pain, bleeding, ortrouble swallowing. This is called palliative therapy.There are 2 main types of radiation therapy:External-beam radiation therapy: This type of treatment focuses radiation from outside thebody on the cancer. This is the type of radiation therapy most often used when the intent is to tryto cure esophageal cancer.. Radiation therapy is much like getting an x-ray, but the radiation isstronger. The procedure itself is painless. Each treatment lasts only a few minutes. Most often,radiation treatments are given 5 days a week for several weeks.Internal radiation therapy (brachytherapy): For this type of treatment, the doctor placesradioactive material very close to the cancer through an endoscope. The radiation travels only a
short distance, so it reaches the tumor but has little effect on nearby normal tissues. Theradioactive source is then removed a short time later. Brachytherapy can be given 2 ways;forhigh-dose rate (HDR) brachytherapy, the doctor leaves the radioactive material near the tumor fora few minutes at a time, which may require several treatments. In low-dose rate (LDR)brachytherapy, a lower dose of radiation is put near the tumor for longer periods (1 or 2 days) at atime. This requires that the patient stay in the hospital during treatment, but it can usually becompleted in only 1 or 2 treatments. Brachytherapy is most often used with more advancedesophageal cancers to shrink tumors so a patient can swallow more easily. This technique cannotbe used to treat a very large area, so it is better used as a way to relieve symptoms (and not to tryto cure the cancer).Chemotherapy for cancer of the esophagus: Chemotherapy (chemo) uses drugs that are giventhrough a vein or by mouth to treat cancer. These drugs enter the bloodstream and reach all areasof the body, making this treatment useful for cancer that has spread. Depending on the type andstage of esophageal cancer, chemo may be given:• As part of the main (primary) treatment, along with radiation therapy.• Before surgery (usually along with radiation therapy) to try to shrink the cancer andmake it easier to remove. This is called neoadjuvant treatment.• After the cancer has been removed by surgery (usually along with radiation therapy)to try to kill any small areas of tumor cells that may have been left behind. This isknown as adjuvant treatment.• Alone or with radiation to help control symptoms like pain or trouble swallowingwhen the cancer cant be cured. This is called palliative treatment.Chemo by itself rarely cures esophageal cancer. It is often given together with radiation therapy.This combination (called chemoradiation or chemoradiotherapy) can be useful for large tumorsthat couldnt be removed otherwise. It can shrink the tumor enough for surgery to be an option.Chemoradiation is also often used before surgery for smaller tumors. Using chemoradiationbefore surgery can help people live longer than using surgery alone. Chemoradiation is alsosometimes given after surgery, but it isn’t clear that it is as helpful as giving it before surgery.
In some cases, chemoradiation may be used as the only treatment. This may be a good choice forpatients who cannot have surgery because they have other major health problems. Thismay alsobe an option for some patients who could have surgery.Chemo is given in cycles, with each period of treatment followed by a rest period to allow thebody time to recover. Each chemo cycle typically lasts for a few weeks. Many different chemodrugs can be used to treat esophageal cancer. Common regimens are:• Carboplatin and paclitaxel (Taxol®) (which may be combined with radiation)• Cisplatin and 5-fluorouracil (5-FU) (often combined with radiation)• ECF: epirubicin (Ellence®), cisplatin, and 5-FU (especially for gastroesophagealjunction tumors)• DCF: docetaxel (Taxotere®), cisplatin, and 5-FU• Cisplatin with capecitabine (Xeloda®)Other chemo drugs that have been used to treat cancer of the esophagus include oxaliplatin,doxorubicin (Adriamycin®), bleomycin, mitomycin, methotrexate, vinorelbine (Navelbine®),topotecan, and irinotecan (Camptosar®). For some esophagus cancers, chemo may be used alongwith the targeted drug trastuzumab(Herceptin®).Targeted therapy for cancer of the esophagus: As researchers have learned more about thechanges in cells that cause cancer, they have been able to develop newer drugs that specificallytarget these changes. Targeted drugs work differently from standard chemotherapy drugs. Theyoften have different (and less severe) side effects. A small number of esophagus cancers have toomuch of a protein called HER2 on the surfaceof their cells. This protein may help the cancer cellsto grow. Having too much of this protein is caused by having too many copies of the HER2 gene.A drug that targets the HER2 protein, known as trastuzumab (Herceptin), may help treat thesecancers when used along with chemotherapy. If you have esophageal cancer and cannot havesurgery, your doctor may have your tumor biopsy samples tested for the HER2 protein or gene.Only cancers that have too much of the HER2 protein or gene are likely to be affected by thisdrug.
Trastuzumab is given by injection into a vein (IV) once every 3 weeks along with chemo. Theoptimal length of time to give it is not yet known. Most of the side effects of trastuzumab arerelatively mild and may include fever and chills, weakness, nausea, vomiting, cough, diarrhea,and headache. These occur less often after the first dose. Less often, this drug can cause heartdamage, leading to the heart muscle becoming weak. That is why this drug is not often given withcertain chemo drugs called anthracyclines, such as epirubicin (Ellence) or doxorubicin(Adriamycin), because it may further increase the risk of heart damage if they are given together.Endoscopic treatments for cancer of the esophagus: Several types of treatment for esophagealcancer can be done by passing an endoscope (a long, flexible tube) down the throat and into theesophagus. Some of these treatments may be used to try to cure very early stage cancers, or evento prevent them from developing by treating Barretts esophagus or dysplasia. Other treatmentsare used mainly to help relieve symptoms from more advanced esophageal cancers that cant beremoved. Endoscopic mucosal resectionEndoscopic mucosal resection (EMR) is a technique where the inner lining of the esophagus isremoved with instruments attached to the endoscope. EMR can be used for dysplasia (precancer)and some very early focal (single, small tumors) cancers of the esophagus. After the abnormaltissue is removed, patients take drugs called proton pump inhibitors to suppress acid productionin the stomach. This can help keep the disease from returning.Photodynamic therapy: Photodynamic therapy (PDT) is a method that can be used to treatesophageal pre-cancer (dysplasia) and some early esophageal cancers. These may be found whenBarretts esophagus is biopsied. PDT can also be used to help with symptoms for some cancersthatare too advanced to be removed. For this technique, a light-activated drug called porfimersodium (Photofrin®) is injected into a vein. Over the next couple of days, the drug is more likelyto collect in cancer cells than in normal cells. A special type of laser light is then focused on thecancer through an endoscope. This light causes changes in the drug that has collected inside thecancer cells, changing it into a new chemical that can kill cancer cells. The dead cells may thenbe removed a few days later during an upper endoscopy. This process can be repeated if needed.The advantage of PDT is that it can kill cancer cells with very little harm to normal cells. Butbecause the chemical must be activated by light, it can only kill cancer cells near the inner
surface of the esophagus – those that can be reached by the light. This light cannot reach cancersthat have spread deeper into the esophagus or to other organs.Radiofrequency ablation (RFA): This procedure can be used to treat dysplasia in areas ofBarretts esophagus. It may lower the chance of cancer developing in that area. In this procedure,a balloon containing many small electrodes is passed into an area of Barretts esophagus throughan endoscope. The balloon is then inflated so that the electrodes are in contact with the innerlining of the esophagus. Then an electrical current is passed through it, which kills the cells in thelining by heating them. Over time, normal cells will grow in to replace the Barretts cells. Thepatient needs to stay on drugs to block stomach acid production after the procedure. Endoscopy(with biopsies) then is done periodically to watch for any further changes in the lining of theesophagus. RFA rarely causes strictures (narrowing) or bleeding in the esophagus.Laser ablation: This technique can be used to help open up the esophagus when it is blocked byan advanced cancer. This can help improve problems swallowing. In this treatment, a laser beamis aimed at the cancer through the tip of an endoscope. The laser opens up the esophagus byvaporizing and coagulating cancerous tissue. The laser used is called a neodymium: yttrium-aluminum-garnet (Nd:YAG) laser. Most patients will benefit from laser endoscopy, but thecancer often grows back, so the procedure may need to be repeated every month or two.Argon plasma coagulation: This technique is similar to laser ablation, but it uses argon gas anda high-voltage spark delivered through the tip of an endoscope. The spark causes the gas to reachvery high temperatures, which can then be aimed at the tumor. This approach is used to helpunblock the esophagus when the patient has trouble swallowing. Electrocoagulation(electrofulguration).This method involves passing a probe down into the esophagus through anendoscope and then burning the tumor off with electric current. In some cases, this treatment canhelp relieve esophageal blockage.Esophageal stent: A stent is a device made of mesh material. Most often stents are made out ofmetal, but they can also be made out of plastic. Using endoscopy, a stent can be placed into theesophagusacross the length of the tumor. Once in place, it self-expands (opens up) to become atube that helps hold the esophagus open. The success of the stent depends on the type of stent that
is used and where it is placed. Stents will relieve trouble swallowing in most patients that aretreated. They are often used after other treatments to help keep the esophagus open.References:1. American Cancer Society. Cancer Facts and Figures 2013. Atlanta, Ga: American CancerSociety; 2013.2. American Joint Committee on Cancer. AJCC Cancer Staging Manual. 7th ed. New York,NY: Springer; 2010:103–1113. National Cancer Institute. Physician Data Query (PDQ). Esophageal Cancer Treatment.7/13/2012. Accessed atwww.cancer.gov/cancertopics/pdq/treatment/esophageal/HealthProfessional on May 17,2013.4. Keith M Baldwin, DO. Esophageal cancer. Attending Surgical Oncologist, RogerWilliams Medical Center, Boston University School of Medicine. Accessed athttp://emedicine.medscape.com/article/277930
CHAPTER 2THEORY: DOUBLE-LUMEN ENDOTRACHEAL TUBE AND GENERALANESTHESIA2.1 Double-Lumen Endotracheal Tube2.1.1 IntroductionDouble-lumen endotracheal tube placement is performed to achieve lung separation.However, thoracic surgeons may require lung separation and one-lung ventilation to performcertain procedures and provide optimal surgical exposure.For double-lumen endotracheal tube placement, the anesthesiologist places a tube withtwo lumens through which to ventilate the lungs. This double-lumen tube is placed in the trachea,with one lumen in either the left or right bronchial main stem; the other lumen remains in thetrachea. This allows the clinician to ventilate both lungs or the right/left lung independently. Theoperative lung is referred to as the surgical lung or nondependent lung. The image below depictsa double-lumen endotracheal tube.Double-lumen endotracheal tubeOf the three methods of lung separation—double-lumen endotracheal tube placement,bronchial blocker, and single-lumen endobronchial tube placement—double-lumen endotrachealtube placement is the most common way of separating the two lungs. It is not only quicker thanthe other two methods, but it allows for access into an isolated lung, suctioning from the isolatedlung, and application of continuous positive airway pressure if required to improve oxygenation.Ventilation of either or both lungs can be easily achieved. In addition, even though a
fiberopticscope is very helpful with double-lumen endotracheal tube placement, it is notabsolutely required, which can also be an advantageous in some situations.However, double-lumen endotracheal tubes may be challenging to place in patients withdifficult airways. Double-lumen endotracheal tubes are not meant for postoperative ventilation. Inaddition, because of their significantly larger size and stiffness, they have a higher propensity fortrauma after insertion, which may result in postoperative hoarseness and/or vocal cord lesions.2.1.2 Indicationa. Absolute IndicationsSeparation of the two lungs for any of the absolute indications discussed here should beconsidered a lifesaving maneuver because failure to separate the lungs under any ofthese conditions could result in a life-threatening complication or situation. Absoluteindications are as follows:Isolation of each lung to prevent contamination of a healthy lung (eg, infection,massive hemorrhage)Control of distribution of ventilation to only one lung (eg,bronchopleural/bronchopleural cutaneous fistulas, unilateral cyst or bullae, majorbronchial trauma/disruption)Unilateral lung lavageVideo-assisted thoracoscopic surgery (VATS)b. Relative IndicationsThere are a large number of relative indications for separation of the lungs, and they areall for the purpose of facilitating surgical exposure by collapsing the lung in theoperative hemithorax. Relative indications are as follows:Thoracic aortic aneurysmPneumonectomyLung volume reductionMinimally invasive cardiac surgery
Upper lobectomyEsophageal proceduresLobectomy (middle and lower lobes)Mediastinal mass resectionThymectomyBilateral sympathectomies2.1.3 Techniquea. Tube Insertion• Several methods can be used to insert the double-lumen endotracheal tube: underdirect laryngoscopy, via tube exchanger, or over fiberoptic bronchoscope.• During placement, a curved laryngoscope blade is used to intubate the airway. Thedistal, bronchial (blue) tube is held with the tip directed upward. As it passesthrough the glottis, the stylet is removed. At this point, the tube is advanced androtated 90 degrees (towards the side to be intubated) and advanced until resistance isfelt; this depth is usually between 28-30 cm.• At this point, the tracheal (white) cuff is inflated, breath sounds are auscultated, andend-tidal CO2 is noted on the capnogram to tell the clinician that the tube is in theairway. At this point, correct tube placement is confirmed by direct visualization viabronchoscopy.• The flexible, fiberoptic bronchoscope is passed down the tracheal lumen. Theclinician will deflate the tracheal cuff and pull back until the carina is seen. At thispoint, tracheal cartilaginous rings are anterior and the tracheal membrane isposterior. Advance the tube until the bronchial blue tip enters the left main stem.• At this point, inflate the blue balloon with 1-3 mL of air until the blue cuff is visiblein the left main stem. A portion of the blue cuff should be seen seated in the leftmain stem.• After placement, the patient is positioned laterally on the operating room table.After positioning, the tube should be checked again to validate that it has notmoved. The tube can either become malpositioned by coming out or advancing to adeeper level.
• When patient position is changed to lateral, the tube can be displaced, mainly due toextension of the neck.• The clinician should check position periodically throughout the surgery.b. Position Verification• There are multiple methods available to confirm placement, including radiographicverification, auscultation, fiberoptic visualization, and various clinical tests such asselective capnography and use of underwater seal. Auscultation and fiberopticexamination are used most commonly.Auscultation• Auscultation is a widely available first-line test. After placement of the double-lumen endotracheal tube, the tracheal cuff is inflated and ventilation is attempted.The patient should have bilateral breath sounds and end-tidal CO2 should be notedon capnogram. This tells the clinician that the tube is in the airway.• Next, the tracheal lumen is clamped and opened. The bronchial cuff is inflated withminimal volume to stop the leak (usually about 2 mL of air). At this point,confirmation of separation of lungs can be done with air bubble leak test. One-sidedbreath sounds should be heard, only over the desired lung field.• Next, with the bronchial cuff up, the tracheal lumen is unclamped and reconnected,the bronchial lumen is clamped, and ventilation is attempted through tracheallumen. If the tube is positioned correctly, breath sounds should be heard overcontralateral hemithorax. Then the bronchial lumen is unclamped and reconnectedand bilateral breath sounds should be audible again. This concludes auscultation forcorrect placement.Fiberoptic Bronchoscope• The fiberoptic bronchoscope first is advanced through the tracheal lumen to confirmthat the bronchial tube is placed in the desired bronchus. For the left bronchus, thecuff should be ideally placed 5 mm below the carina. It is crucial to identify theright bronchus. The right main bronchus gives off the right upper lobe bronchus,which is the only one that has 3 orifices in it. Then examination through the
bronchial tube is done to assure tube patency and determine margin of safety.Therefore, orifices to both upper and lower lobes must be identified. Identificationof those bronchi confirms correct placement of a left-sided tube.2.2 General AnesthesiaGeneral anesthesia uses intravenous and inhaled agents to allow adequate surgical accessto the operative site. A point worth noting is that general anesthesia may not always be the bestchoice; depending on a patient’s clinical presentation, local or regional anesthesia may be moreappropriate.Anesthesia providers are responsible for assessing all factors that influence a patientsmedical condition and selecting the optimal anesthetic technique accordingly. Attributes ofgeneral anesthesia include the following:Advantages• Reduces intraoperative patient awareness and recall• Allows proper muscle relaxation for prolonged periods of time• Facilitates complete control of the airway, breathing, and circulation• Can be used in cases of sensitivity to local anesthetic agent• Can be administered without moving the patient from the supine position• Can be adapted easily to procedures of unpredictable duration or extent• Can be administered rapidly and is reversibleDisadvantages• Requires increased complexity of care and associated costs• Requires some degree of preoperative patient preparation• Can induce physiologic fluctuations that require active intervention• Associated with less serious complications such as nausea or vomiting, sore throat,headache, shivering, and delayed return to normal mental functioning• Associated with malignant hyperthermia, results in acute and potentially lethaltemperature rise, hypercarbia, metabolic acidosis, and hyperkalemiaNowadays, the risk caused by anesthesia to a patient undergoing routine surgery is verysmall. Mortality attributable to general anesthesia is said to occur at rates of less than 1:100,000.Minor complications occur at predicable rates, even in previously healthy patients.
2.2.1 Preparation for General AnesthesiaSafe and efficient anesthetic practices require certified personnel, appropriate medicationsand equipment, and an optimized patient.Minimum infrastructure requirements for general anesthesia include a well-lit space ofadequate size; a source of pressurized oxygen (most commonly piped in); an effective suctiondevice; standard ASA (American Society of Anesthesiologists) monitors, including heart rate,blood pressure, ECG, pulse oximetry, capnography, temperature; and inspired and exhaledconcentrations of oxygen and applicable anesthetic agents.Beyond this, some equipment is needed to deliver the anesthetic agent. This may be assimple as needles and syringes, if the drugs are to be administered entirely intravenously. In mostcircumstances, this means the availability of a properly serviced and maintained anesthetic gasdelivery machine.An array of routine and emergency drugs, including Dantrolene sodium (the specifictreatment for malignant hyperthermia), airway management equipment, a cardiac defibrillator,and a recovery room staffed by properly trained individuals completes the picture.2.2.2 Preparing the patientPreoperative evaluation allows for proper laboratory monitoring, attention to any new orongoing medical conditions, discussion of any previous personal or familial adverse reactions togeneral anesthetics, assessment of functional cardiac and pulmonary states, and development ofan effective and safe anesthetic plan. It also serves to relieve anxiety of the unknown surgicalenvironment for patients and their families. Overall, this process allows for optimization of thepatient in the perioperative setting.Physical examination associated with preoperative evaluations allow anesthesia providersto focus specifically on expected airway conditions, including mouth opening, loose orproblematic dentition, limitations in neck range of motion, neck anatomy, and Mallampatipresentations. By combining all factors, an appropriate plan for intubation can be outlined andextra steps, if necessary, can be taken to prepare for fiberoptic bronchoscopy, videolaryngoscopy, or various other difficult airway interventions.
Airway managementPresence of obesity, large breasts, short muscular neck, receding jaw, prominent upper incisorand high arched palate suggest difficult intubation.Predictive testsa. Mallampati Classification : indicatiors of difficult intubationMallampati classificationb. Cormack and Lehane Grading : used to grade the view at laryngoscopyc. Thyromental distance : measured form upper edge of thyroid cartilage to the chin with thehead fully extendedd. Cervical spine movement : Assesment of the full range of motion at atlanto-occipital joint(flexion, extension and rotation)When suspicion of an adverse event is high but a similar anesthetic technique must beused again, obtaining records and previous anesthetic records from previous operations or fromother institutions may be necessary.Other requirementsThe need for coming to the operating room with an empty stomach is to reduce the risk ofpulmonary aspiration during general anesthesia when a patient loses his or her ability tovoluntarily protect the airway.Patients should continue to take regularly scheduled medications up to and including themorning of surgery. Exceptions may include the following:
Anticoagulants to avoid increased surgical bleedingOral hypoglycemics (For example, metformin is an oral hypoglycemic agent that isassociated with the development of metabolic acidosis under general anesthesia.)Monoamine oxidase inhibitorsBeta blocker therapy (However, beta blocker therapy should be continued perioperativelyfor high-risk patients undergoing major noncardiac surgery)2.2.3 The process of anesthesiaa. PremedicationThis is the first stage of a general anesthetic and usually conducted in the surgicalward or in a preoperative holding area. The goal of premedication is to have the patient arrivein the operating room in a calm, relaxed frame of mind.The most commonly used premedication is midazolam, a short-acting benzodiazepine.In anticipation of surgical pain, nonsteroidal anti-inflammatory drugs or acetaminophen canbe administered preemptively. When a history of gastroesophageal reflux exists, H2 blockersand antacids may be administered. Drying agents (eg, atropine, scopolamine) are now onlyadministered routinely in anticipation of a fiberoptic endotracheal intubation.b. InductionThis is the critical part of the anesthesia process. This stage can be achieved byintravenous injection of induction agents (drugs that work rapidly, such as propofol), by theslower inhalation of anesthetic vapors delivered into a face mask, or by a combination ofboth.In addition to the induction drug, most patients receive an injection of an opioidanalgesic, such as fentanyl (a synthetic opioid many times more potent than morphine).Induction agents and opioids work synergistically to induce anesthesia. In addition,anticipation of events that are about to occur, such as endotracheal intubation and incision ofthe skin, generally raises the blood pressure and heart rate of the patient. Opioid analgesiahelps control this undesirable response.
The next step of the induction process is securing the airway. This may be a simplematter of manually holding the patients jaw such that his or her natural breathing isunimpeded by the tongue, or it may demand the insertion of a prosthetic airway device suchas a laryngeal mask airway or endotracheal tube. The major decision is whether the patientrequires placement of an endotracheal tube. Potential indications for endotracheal intubationunder general anesthesia may include the following:• Potential for airway contamination (full stomach, gastroesophageal [GE] reflux,gastrointestinal [GI] or pharyngeal bleeding)• Surgical need for muscle relaxation• Predictable difficulty with endotracheal intubation or airway access (eg, lateral orprone patient position)• Surgery of the mouth or face• Prolonged surgical procedureNot all surgery requires muscle relaxation. If surgery is taking place in the abdomenor thorax, an intermediate or long-acting muscle relaxant drug is administered in addition tothe induction agent and opioid. This paralyzes muscles indiscriminately, including themuscles of breathing. Therefore, the patients lungs must be ventilated under pressure,necessitating an endotracheal tube.Persons who, for anatomic reasons, are likely to be difficult to intubate are usuallyintubated electively at the beginning of the procedure, using a fiberoptic bronchoscope orother advanced airway tool.c. Maintenance phaseAt this point, the drugs used to initiate the anesthetic are beginning to wear off, andthe patient must be kept anesthetized with a maintenance agent. Anesthetic gas must beprovided. These may be inhaled as the patient breathes spontaneously or delivered underpressure by each mechanical breath of a ventilator.The maintenance phase is usually the most stable part of the anesthesia. As theprocedure progresses, the level of anesthesia is altered to provide the minimum amount ofanesthesia that is necessary to ensure adequate anesthetic depth. Traditionally, this has been a
matter of clinical judgment, but new processed EEG machines give the anesthesia provider asimplified output in real time, corresponding to anesthetic depth.If muscle relaxants have not been used, inadequate anesthesia is easy to spot. Thepatient moves, coughs, or obstructs his airway if the anesthetic is too light for the stimulusbeing given. If muscle relaxants have been used, then clearly the patient is unable todemonstrate any of these phenomena. In these patients, the anesthesia provider must rely oncareful observation of autonomic phenomena such as hypertension, tachycardia, sweating,and capillary dilation to decide whether the patient requires a deeper anesthetic. This requiresexperience and judgment.Excessive anesthetic depth, on the other hand, is associated with decreased heart rateand blood pressure, and, if carried to extremes, can jeopardize perfusion of vital organs or befatal. Short of these serious misadventures, excessive depth results in slower awakening andmore adverse effects.As the surgical procedure draws to a close, the patients emergence from anesthesia isplanned. Experience and close communication with the surgeon enable the anesthesiaprovider to predict the time at which the application of dressings and casts will be complete.In advance of that time, anesthetic vapors have been decreased or even switched off entirelyto allow time for them to be excreted by the lungs. Excess muscle relaxation is reversed usingspecific drugs and an adequate long-acting opioid analgesic to keep the patient comfortable inthe recovery room. If a ventilator has been used, the patient is restored to breathing byhimself, and, as anesthetic drugs dissipate, the patient emerges to consciousness.Removal of the endotracheal tube or other artificial airway device is only performedwhen the patient has regained sufficient control of his or her airway reflexes.d. ReversalIt is a process of discontinuation of anesthetic agents at the end of surgery to allowreturn of consciousness and recovery from muscle paralysis while maintaining analgesia.Volatile agents are discontinued first and later the nitrous oxide. Patient is given 100%oxygen. Wait for return of spontaneous breathing; this can be observed on capnography andcan also be felt with reservoir bag if patient is manually ventilated.
Administer reversal agent such as neostigmine (anticholinesterase) or glycopyrrolateto counteract non-depolarizing muscle relaxant; atropine is usually given to counteract theparasympathetic effects of anticholinesterase.Reversal agent is given when there is evidence of spontaneous breathing effort.Patient’s tidal volume has to be ensured that it is adequate and able to control own airwaybefore attempting extubation.2.2.4 Postoperative CareThe anesthesia should conclude with a pain-free awakening and a management plan forpostoperative pain relief. This may be in the form of regional analgesia, oral, transdermal orparenteral medication. Minor surgical procedures are amenable to oral pain relief medicationsuch as paracetamol and NSAIDs such as ibuprofen. Moderate levels of pain require the additionof mild opiates such as tramadol. Major surgical procedures may require a combination ofmodalities to confer adequate pain relief.Parenteral methods include patient-controlled analgesia (PCA) involving a strong opiatesuch as morphine, fentanyl or oxycodone. To activate a syringe device, patient will press a buttonand receive a preset dose or bolus of the drug (eg: 1mg of morphine). The PCA device then locksout for a preset period to allow drug to take effect. If the patient becomes too sleepy or sedated,they make no more morphine requests.Shivering is a frequent occurs in the post operative period. Apart from causing discomfortand exacerbating post operative pain, shivering has been shown to increase oxygen consumption,cathecolamine release, cardiac output, heart rate, blood pressure and intra ocular pressure. Thereare number of techniques used to reduce this occurrence, such as increasing the ambienttemperature in theatre, using conventional or forced warm air blankets and using warmedintravenous fluids.2.2.5 Common Anesthetic DrugsThe main group of drugs commonly used in general anesthesia are broadly classified intoinduction agents, muscle relaxants, analgesics and reversal agents.Induction agents then are further classified into inhalational and parenteral/a. Inhalational Anaesthetic Agents
It exists as gaseous form (nitrous oxide) or volatile liquids (isoflurane). Halothaneis a halogenated alkane derivative. Other modern volatile agents are halogenated methylether derivatives (enflurane, isoflurane). Controllability is by pulmonary administrationand is delivered via vaporizers. The commonly used inhalational agents are liquids atroom temperature and therefore they need to be converted to the gaseous state foradministration to patients. Vaporizers is a device for producing a clinically useful andstable concentration of an anesthetic vapour in a carrier gas ( oxygen and nitrous oxide).The aim of inhalational anaesthesia is the development of an appropriate tension or partialpressure of anesthetic agent within the brain.Gaseous anaesthetic agents Nitrous oxide It is stored in steel cylinders as a liquid under pressure in equilibrium with thegas phase at normal room temperature. N2O is a colorless gas without appreciable odour or taste and non explosive. It is a potent analgesic but a weak anaesthetic agents It cause depress hematopoietic function ( megaloblasticanemia,thrombocytopenia and leucopenia), thus not advisable for administration of morethan 24 hours. It is widely used as an adjuvant to lower the MAC of volatile anesthetics. Withinhalation of 70% N2O / 30% O2 MAC value are reduced (~35%- 45%)Volatile Anesthetic agents HalothaneHalothane is a haloalkane and has a MAC value of 70%. It can be used forinduction of anesthesia in children. Halothane is a non specific Ca2+influx inhibitor and itmay cause bradycardia. It increases the automaticity of the heart and when combined withadrenaline it may cause tachyarrythmias. One of the important side effects is ha;othanehepatotoxicity. The diagnosis of halothane hepatitis is by exclusion. This may progressinto fulminant hepatic failure with a high mortality. Obese middle aged women having
repeat halothane exposures are at risk. Halothane hepatitis may occur following a singleexposure. IsofluraneIt causes a dose dependent reduction in blood pressure. The decrease in bloodpressure is due to vasodilatation and decreased total peripheral resistance. The heart rate isincreased via reflex mechanisms but arrhythmias are uncommon. Isoflurane does notaffect ventricular conduction and does not increase the excitability of ventricularmyocardium. Induction of anesthesia is difficult with isoflurane due to its pungent odourand preanesthetic concentration of isoflurane may cause an airway reflex stimulation, withincreased secretions and/or coughing and laryngospasm. SevofluraneIt is a new inhalational agent and more expensive than others. It has pleasantodour and can be used as induction agents in paediatric and adult patients. It has rapidonset of induction and recovery of anesthesia because it is less soluble in blood thanisoflurane. It has a mild negative inotropic effect. It also decreases systemic vascularresistance but does not cause reflex tachycardia. Sevoflurane is less arrythmogenic whencompared to halothane and it is suitable for daycare surgery.b. Intravenous induction agentsCriteria for ideal intravenous anesthetic agents: Induction of anesthesia should be rapid, smooth and safe It should have limited effects on cardiovascular and respiratory systems It should possess analgesic activity. Consciousness should return rapidly, smoothly and predictably.i. Sodium thiopental (Pentothal)Thiopental is the only intravenous barbiturate being used today and is classifiedunder an ultra short acting barbiturate. It is prepared as a 2.5% solution, water soluble,pH of 10.5 and stable for up to 1-2 weeks if refrigerated.
Mechanism of action: Depress the reticular activating system, reflecting the abilityof barbiturates to decrease the rate of dissociation of the inhibitory neurotransmitterGABA from its receptorsPharmacokinetics Short duration of action (5-10 minutes) following IV bolus reflects high lipidsolubility and redistribution from the brain to inactive tissues. Protein binding parallels lipids solubility, decreased protein binding increases drugsensitivity. Fat is the only compartment in which thiopental continues to accumulate 30minutes after injection Thiopental is metabolized in the liver slowly. Its hepatic excretion ratio is 0.15It has an anticonvulsant effect and is a useful drug for cerebral protection in headinjury. It also has an analgesics effect. In the presence of inadequate anaesthesia, airwaymanipulation may result in bronchospasm and laryngospasm. Cardiovascular effects ofbarbiturate include decrease in blood pressure due to vasodilatation and direct myocardialdepression. There is a compensatory increased in heart rate.It should be used cautiously in haemodynamically unstable patients and iscontraindicated in hypovolaemia and hypotensive patients. Induction dose is 3-5mg/kg ina healthy adult.ii. PropofolIt is 2,6-diisopropyl-phenol, under group of hindered phenol, an alkylphenolderivative. Formulated in a solution with 10% soy bean oil, hydrophobic nature. It hasrapid onset and short duration of action. Emergence and awakening are prompt andcomplete after even prolonged infusions.Mechanism of action: Propofol increases the inhibitory neurotransmissionmediated by gammaaminobutyric acid.
It has extensive metabolism by hepatic and extrahepatic. It has no cumulativeeffects, has antiemetic property and suitable for daycare surgery. It does nothasantianalgesic activity.Propofol is an ideal drug for total intravenous anesthesia. The target controlledinduction (TCI) and maintenance of anesthesia can be achieved nowadays with propofolby a special TCI pump. Propofol also can be used to provide sedation in ICU, for minorprocedures or in combination with regional anesthesia.Effects on organ systemCardiovascular: decrease in arterial blood pressure secondary to a drop in systemicvascular resistance, contractility, and preload. Hypotension is more pronounced than withthiopental. Propofol markedly impairs the normal arterial baroreflex response tohypotension.Respiratory: propofol causes profound respiratory depression. Propofol induceddepression of the upper airway reflexes exceeds that of thiopentalCerebral: decreases cerebral blood flow and intracranial pressure.Induction dose: 1.5-3 mg/ kg in a healthy adult.iii. KetamineIt is a phenicyclidine derivative. It produces dissociative anesthesia resulting incatatonia, amnesia and analgesia. Patient may appear awake and reactive but does notresponse to sensory stimuliMechanism of action: It acts on NMDA receptor. It blocks polysynaptic reflexes inthe spinal cord, inhibiting excitatory neurotransmitter effects. It has both anesthetic andanalgesic properties. It causes postoperative psychic phenomena- emergence delirium,vivid dreams, hallucination. Therefore it is not suitable for adults. These effects can beminimized by combination with benzodiazepines.Clinical usage:Induction of anesthesia in poor risk patients (eg: hypotension or bronchial asthma)As sole agent in dressing of burns, radiological procedures in children, masscasualties in the field.In the management of unresponsive severe bronchospasm
It is contraindicated in raised intracranial pressure, perforating eye surgery,hypertension, heart failure, recent myocardial infarction, aneurysm and valvular heartdisease.Dosage:o IV 1.5-2 mg/kg, onset 30 sec. duration 5-10min.o IM 10 mg/kg, onset 3-8min, duration 10-20minSystemic effects:Increase intracranial and intraocular pressuresPostoperative nausea and vomitingIncreased salivation. An antisialagogue is recommended before usedPreservation of airway reflexes and produces brochodilatationIncreased in cathecolamines secretionKetamine has cardiovascular effects: increases heart rate, blood pressure andpulmonary arterial pressure. It is most likely due to direct stimulation of the sympatheticnervous system.c. Neuromuscular blocking agentsMuscle relaxants are generally classified into two groups(depolarizing and non-depolarizing), depending on their mechanism of action.Depolarizing muscle relaxantsUsed to provide skeletal muscle relaxation to facilitate tracheal intubation andoptimal surgical condition. Ventilation must be provided as the diaphragmatic musclewould also be paralysed. There is no CNS activity and the problem of awareness beginwith introduction induction of muscle relaxants.Factors that influence inclusion of muscle relaxants in general anesthesia are typesof surgical procedures (anatomic location and patient position), anesthetic techniques andpatient factors (ASA class, obese, exreme of age).SuccinylcholineThe only depolariser drug that is used clinically. It consists of two molecules ofacetylcholine linked together. It acts on nicotinic receptors at neuromuscular junction
(NMJ) to cause sustained depolarization that prevents propagation of action potential. Thenet effect of SCh induced depolarization is uncoordinated skeletal muscle activity that isseen as fasciculation.It remains a useful muscle relaxants because of its rapid onset and short durationof muscular relaxation that cannot be achieved by any other available nondepolarisingmuscle relaxants.A dose of 1-2 mg/kg produces profound muscle relaxation within one minute. Fullrecovery is 10-12 minutes. It is used in emergency surgery as rapid sequence inductiontechnique and in situation of difficult airway management.Side effects It may cause cardiac dysarryhmias such as bradycardia especially in children. Hyperkalemia – at risk patients (burns, extensively trauma, unrecognized musculardystrophy and denervation injuries. Increased intragastric pressure (offset by even greater increase in loweroesophageal sphincter) Increased intraocular pressure (due to cycloplegic action of succinylcholine) Prolonged response in presence of atypical cholinesterase Increased intracranial pressure Muscle pain and myoglobinuriaNon depolarizing muscle relaxantActs on nicotinic receptors in a competitive fashion to produce neuromuscularblockade- absence od depolarization. Can be antagonized by anticholinesterase drugs.They are used to facilitate endotracheal intubation, controlled ventilation and maintenanceof muscle relaxation during surgical procedures.a. AtracuriumIt is an intermediate acting benzyliso-quinolinium type NDMR. Theintubation dose is 0.5-0.6mg/kg. It presents as 10mg/ml solution in 25mg or 50mgglass ampoules and is stored at 4 °C. Histamine release may occur in susceptiblepatients but anaphylactoid reaction is very rare.b. Vecuronium
It is an aminosteroid group and presents as freezed dried powder anddiluted with sterile water before used. There is no histamine release and devoid ofcardiovascular side effects. It does not antagonize fentanyl induced bradycardia. Itis metabolized by liver and also excreted unchanged in bile. The intubation dose is0.08-0.1 mg/kg.c. RocuroniumIt is an aminosteroid group. Its rapid onset of action makes it a potentialreplacement for SCh when rapid tracheal intubation is needed. Its duration ofaction is similar to vecuronium and has similar pharmacokinetic characteristic. Ithas minimal cardiovascular side effects and very low potential for histaminerelease. Dosage for endotracheal intubation is 0.6 mg/kg.d. PancuroniumIt is a long acting NDMR with a steroid structure (Bisaminoquaternarysteroid). It increases heart rate and blood pressure and cardiac output due tocardiac vagal blockade. Histamine release is very rare and bronchospasm isextremely uncommon.Assessment of neuromuscular blockade1. Clinical assessmenta. Ability to lift up head for 5 secondb. Hand grip for 5 secondc. Ability to produce vital capacity breath > 10 ml/kgd. Tongue protrusion2. Responses to electrical stimulation of a peripheral nerve stimulatorAnticholinesteraseAnticholinesterase is used to reverse non depolarizers. It inhibits the action ofacetylcholinesterase and increase the concentration of acetylcholine at the neuromuscularjunction. It also acts at parasympathetic nerve endings. Anticholinesterase increases acetylcholineat both nicotinic and muscarinic receptors. Muscarinic effects can be blocked by administrationof atropine or glycopyrolate.
d. Opioid analgesicsFew examples of this drugs are morphine, pethidine, fentanyl and nalbuphine.This drugs act on opioid receptors and classified as full agonist, antagonist, or mixedagonist-antagonist depending on the actions on the opioid receptors. Three main receptorsare mu, kappa and delta.Morphine pharmacokinetics:Elimination halftimes for morphine following bolus administration is about 1.7-4.5hours. Following bolus administration onset time is relatively slow (15-30 minutes)because:1. morphine exhibits relatively low lipid solubility about 2.5% of fentanyl(Sublimaze)2. at physiological pH, morphine, a weak base with the pKa of about 8.0, isprimarily ionized. The ionized form does not favor passage through the lipidmembrane; accordingly, only about 10%-20% of molecules are un-ionized.Relatively high plasma clearance (15-40 ml/kg/minute) has implicated extrahepaticclearance mechanisms, most likely renal.Fentanyl (Sublimaze) pharmacokinetics:Fentanyl (Sublimaze) is significantly more lipid-soluble, compared morphine and,relative to morphine, has a more rapid onset of action (fentanyl (Sublimaze) is also aweak base and at physiological pH only about 10% of molecules are un-ionized).Clearance of about 10-20 ml/kg/minute is consistent with a primary hepaticmechanism. Fentanyl (Sublimaze)s short duration of action following bolusadministration is explained by rapid redistribution from brain to other compartmentssuch as skeletal muscle and fat. If, however, fentanyl (Sublimaze) is administered bycontinuous IV infusion or multiple IV dosing, other non-CNS compartments willsaturated and remaining CNS fentanyl will contribute to postoperative ventilatorydepression.
Action of opioid drugs:A. Central nervous system: Analgesia, sedation, euphoria, nausea, vomiting, miosis,depression of ventilation, pruritus and skeletal muscle rigidity.B. Respiratory system: bronchospasm in susceptible patients and depressed cough reflexC. Cardiovascular system: bradycardia (fentanyl) or tachycardia ( pethidine)D. Skin: pruritus may be due to histamine release or action on opioid receptor.E. Gastrointestinal tract: constipation, delays gastric emptying, increased tone of thecommon bile duct and sphincter of Oddi.F. Urinary tract: increased sphincter tone and retention of urine.Use of opioids in anesthesiasPremedication drugsInduction of anaesthesiaBlunt haemodynamic reactions to noxious stimulationIntraoperative analgesiaPostoperative analgesiaUsed in ICU as analgesia to facilitate mechanical ventilationDrug DosesMorphine 2.5 - 5 mg (IV), 15 - 30 mg (oral)Pethidine 50 to 100 mg S.C., I.M or in reduced doses I.V.repeated every 3 to 4 hoursFentanyl 25 - 50 µg (IV), 150 - 300 µg (oral)NaloxoneIt is an antagonist at all opioid receptors of pure opioid antagonist. It reverse all opioidactions including analgesia. It has short duration of action ( 1-4 hours) and has limited actionagainst partial or mixed actions opioids. Abrupt reversal of opioid analgesia can result insympathetic stimulation (tachycardia, ventricular irritability, hypertension and pulmonaryoedema).
Dosage : Bolus:o Adult: 0.04 mg IV in titrated bolus every 23 minutes until the desiredeffectso Child: 1-4mcg/kg titrated Continuous infusion: 5mcg/kg/hr IV will prevent respiratory depression withoutaltering the analgesia produced by neuraxial opioids.TramadolIt is an opioid agonist at mu receptor and inhibits noradrenaline reuptake and release of 5-hydroxytryptamine (monoaminergic pathways). It is given intravenously with the dose of 1-2mg/kg and also can be given orally (good bioavailability). It produces less respiratory depressionin equivalent dose if compared with morphine.Non opioidsUse of non steroidal anti-inflammatory drugs as analgesics (eg: Ketorolac, Diclofenac). Itblock synthesis of prostaglandins by inhibiting cyclooxygenase enzyme. It reduces pain byperipheral action and centrally by reducing input of nociceptive information in spinal cord.Ketorolac and Ketoprufenhas opioid sparing effects.Side effects: Reduced platelet aggregation may increase bleeding – it is not advisable for neurosurgicaland ophthalmic surgery. It may cause damage to gastric mucosa causing ulceration and bleeding. Bronchospasm – patients with asthma have an increased incidence of sensitivity to aspirin Renal failure- inhibition of renal prostaglandin synthesis may interfere with maintenanceof renal blood flow.Drug DosesVoltaren (Diclofenac) 100-200 mg dailyParacetamol 2 x 500mg 4-6 hourlySynflex Initially 550 mg then 275 mg6-8 hrly
CHAPTER 3CASE: PERIOPERATIVE ASSESSMENT3.1. Preoperative Assessment3.1.1. Case HistoryIDENTIFICATION DATAName : Rosli bin Ahmad TajudinSex : MaleAge : 45 years oldNationality/Tribe : Malaysian/MalayReligion : IslamAddress : Kangar, PerlisMarital Status : MarriedOccupation : Government OfficerAdmission Date :14thMay 2013CHIEF COMPLAINTThis 45-year old malay gentleman presented with a chief complaint of difficulty inswallowing for the past two months, worsening last week.HISTORY OF PRESENTING ILLNESSPatient suddenly developed difficulty in swallowing since two months ago. This is thefirst episode. Patient’s condition is progressively worsening. Initially, he was unable to take solidfood but later on, he could not tolerate fluid as well. He vomited out food particles and fluid aftereach meal. Patient also had loss of appetite and he lost around five to six kilogram body weight intwo months period.
Gastroscopy (OGDS) and tissue biopsy was done on 8thMay 2013 with the impression ofesophageal carcinoma. CT Scan done on 9thMay 2013 shows soft tissue mass at the midesophagus (2.8 cm length) which is causing stenosis of its lumen. On 13thMay 2013, BariumSwallow Test was carried out with the impression of persistent narrowing of distal esophaguswith irregular wall outline suggesting esophageal tumour.Otherwise, he has no regurgitation, no cough, no choking and aspiration, no painfulswallowing, no heartburn, no fever, no alteration of bowel habit, no shortness of breath, nohoarseness of voice, no abdominal pain, no upper respiratory tract infection and no urinary tractinfection.PAST MEDICAL HISTORYHe has no known of other medical condition.PAST SURGICAL HISTORYPatient had undergone oesophagogastroduodenoscopy (OGDS) on 8thMay 2013.ANAESTHETIC HISTORYPatient has never gone through any anaesthetic procedures.DRUG HISTORYPatient is not on any medication. There’s no history of drug or food allergy. Patientclaimed he is not taking any traditional medication or over the counter drugs.FAMILY HISTORYThere is no history of malignancy in the family. However, patient’s father has diabetesmellitus and his mother has hypertension.SOCIAL HISTORYPatient is a government officer, married with 4 children. Currently, he lives with his wifeand children. He is able to carry out activity of daily life independently. He is an active smoker
(20 sticks/day) for 20 years. He is non-alcoholic. There is no recent travel. He denied any high-risk behavior.3.1.2. Physical ExaminationGENERAL EXAMINATIONPatient is alert and conscious, lying comfortably on the bed. He does not look ill, not inpain, and not in respiratory distress. He has normal body build, and his hydration and nutritionalstatus is fair. There’s no gross deformity, no involuntary or abnormal movement, and there’s abranula attached at his left hand.VITAL SIGNSHEAD, NECK & EXTREMITIES EXAMINATIONOn general examination (extremities), the palm is moist, no pallor, no palmar erythemaand the temperature was normal. There’s no clubbing finger, and no bluish discoloration of thenail. No leukonychia or koilonychia noted. There’s no fine tremor or flapping tremor. There’salso no pedal edema at both lower extremities.Examination of the head did not reveal pallor of the conjunctiva, no jaundice of the sclera,no exophthalmus, no arcussenilis and no xanthelasma. There’s also no bluish discoloration of thelips and the tongue. The dental hygiene is good.Vital signs Value InterpretationTemperature 37°C AfebrileBlood pressure 135/80 mmHg NormalPulse rate 78 bpm NormalRespiratory rate 18x/minute NormalPain score 0/10 Not in painHeight 170 cm -Weight 61 kg -Body Mass Index 21 kg/m2Normoweight
For neck examination, on inspection, there’s no redness, no skin changes, no discharge,no surgical scar and no prominent vein and no increase in jugular venous pressure. On palpation,there is no increase in temperature and no palpable lymph nodes and no trachea deviation. Onauscultation, there’s no bruit can be heard.RESPIRATORY SYSTEM EXAMINATIONFrom airway assessment, patient was classified as Mallampati class I, and the thyromentaldistance was 6.5 cm or three fingers wide.Patient has no history or symptoms of upper respiratory tract infection. On examination;on inspection, the chest moved symmetrically with respiration, with abdominal-thoraco breathingpattern. The chest shape was normal and there was no deformity or scar noted on both anteriorand posterior chest wall. There were also no signs of respiratory distress. On palpation, the chestexpansion and tactile vocal fremitus were symmetrical on both anterior and posterior chest. Onpercussion, it was a symmetrical resonance sounds. On auscultation, no wheezing or crepitationheard. Air entry was equal on both sides.CARDIOVASCULAR SYSTEM EXAMINATIONThe peripheral pulses were palpable, equal and regular. There was no surgical scar seenon the chest. There was neither heave nor thrill can be palpated. Apex beat was palpable at leftmidclavicular line between 4thand 5thintercostal space. Normal 1stand 2ndheart sounds wereheard and there were no additional sounds or murmurs heard in the mitral, tricuspid, aortic andpulmonary area.ABDOMINAL EXAMINATIONOn inspection, the abdomen was not distended, moves with each respiration. Theumbilicus is centrally located. Otherwise, there is no surgical scar, no visible peristalsis orpulsation, no skin discolouration and no cough impulse.On palpation, the abdomen is soft and non-tender. No mass can be appreciated and nohepatomegaly or splenomegaly. The kidney was not ballotable.
The percussion gives tympanic sound, and there’s no shifting dullness. On auscultation,the bowel sound was present and no renal bruit heard.CENTRAL NERVOUS SYSTEM EXAMINATIONPatient was alert, and well oriented to person, time and place. Glasgow Coma Scale was15/15. Facial expression was symmetry. All cranial nerves were intact.MUSCULOSKELETAL SYSTEM EXAMINATIONPatient has a normal muscle bulk, strength, tone and power for both upper and lowerextremities. The shape of vertebral spine is normal. No deformities noted. Gait was normal.PHYSICAL STATUSASA score is 1. Patient was healthy with no systemic disease, and the surgery was anelective surgery.3.1.3. Investigation• Full blood count:
EKG:• Sinus rhythm• No ischemic changes• Interpretation: NormalChest X-Ray:• Lung: Normal• No cardiomegaly• Bones: Intact• Soft tissues: Normal• Trachea is not deviatedIndirect Laryngoscope:• Both vocal fold mobile equally• No anterior compression• Impression: Normal vocal cord3.1.4. SummaryA 45 years old malay gentleman, an active smoker, presented with difficulty inswallowing since the past 2 months, worsening one week before admission to the hospital.Initially he was unable to tolerate solid food but later on he could not take fluid as well. This isaccompanied by loss of appetite and weight loss. On physical examination, patient is clinicallystable and not dehydrated. Gastroscopy and tissue biopsy, CT scan, Barium Swallow Test resultsare suggestive of esophageal carcinoma. Otherwise, there’s no significant finding in any othersystem.
3.1.5. Preoperative Diagnosis• Esophageal Carcinoma3.1.6. Plan• Lower Esophagectomy + thoracotomy + pyloroplasty• To keep nil by mouth by 12 midnight (8 hours prior to surgery)• To inquire informed consent for the surgery and anaesthetic procedures• Send blood for blood crossmatch• To plan for general anaesthesia/intermittent positive pressure volume (double lumenintubation).3.2.Intraoperative AssessmentAnaesthesia : Balanced general anaesthesia with intermittent positive pressure ventilation(double lumen intubation)Fasting : Patient was kept nil by mouth 8 hours prior to operation.Premedication : Patient was given tablet midazolam 7.5 mg night before operation and in themorning prior to operation.3.2.1. AnaesthesiaProcedures :I. Preoperative assessment was done and consent was taken from the patient.II. GA machine was checked and anaesthetic drug was prepared before patient wasentered into the operation room.III. Intravenous assessed was established by inserting IV catheter 18G and patient waspreloaded with normal saline.IV. Procedures were done in a full aseptic technique, scrubbed, gloved and gowned.V. Patient was preoxygenated with 100% oxygen for 3 minutes at 8am.VI. Administration of intravenous Fentanyl 100mcg and intravenous Propofol 100mg.VII. Loss of consciousness was assessed by loss of eyelash reflex.VIII. Test ventilate before give muscle relaxant.
IX. Then, IV rocuroniumbromide 50mg was given and mask ventilate with oxygen andvolatile gas Sevoflurane 2% for 3minutes.X. Laryngoscopy and intubation were then performed by using double lumenendobronchial tube size 39mm, Cormack Lehane I, anchored at 29mm.XI. Post intubation, both lungs were tested for one sided lung ventilation and tube wasconfirmed further by fibreoptic bronchoscopy visualization.XII. Arterial line was inserted at right radial artery.XIII. Triple lumen catheter was inserted at right internal jugular vein.XIV. Other IV access available: right hand 16G branula, left hand 18G branulaXV. The vital sign which are oxygen saturation, brain tissue carbon dioxide, respiratoryrate, blood pressure, heart rate, any blood loss and urine output was monitored duringthe operation.XVI. Estimated blood loss is 500ml. Patient was given 7 pint fluid; 2 pint IV Voluven, 2pint IV Nacl 0.9%, 3 pint IV Hartman Solution. No blood transfusion was done duringthe operation.XVII. Anaesthesia was maintained with Sevoflurane and morphine 12mg.XVIII. Intra operatively patient was also given IV Ranitidine 50mg, IV Cefobid 1g, and IVFlagyl 500mgXIX. Post operatively, double lumen endobronchial tube was exchanged with portex ETTsize 8.0 mm, anchored at 21 mm.XX. Patient was sent to intensive care unit (ICU) for weaning, transfer by manual bagging.
Blood Pressure and Heart Rate :Blood pressure was monitored every 5 minutes during the whole operation procedure. Thesystole reading range was between 90 – 150 mmHg and diastolic pressure was between50 – 90mmHg. Heart rate was monitored every 5minutes and noted to be in normal rangewhich was within 70 – 90 beats per minutes.3.2.4. Summary:Patient was hemodynamically stable throughout the operation with 500mlestimated blood loss but no blood transfusion was needed. There is a tumor at the loweresophagus noted 1 cm above cardia measuring 3 X 3 cm. Proximal gastrectomy was done.Due to limited space over superior resectable margin, surgeon proceed with thoracotomyand single lung ventilation initiated. Lower end esophagectomy was done and proceed withproximal gastric and lower end esophagus anastomosis. Air leak test done – noleaking.Vagus nerve is preserved. Chest tube size 32 Fr was inserted. Right chest wallincision closed layer by layer. Patient was transferred to intensive care unit.3.3. Post Operative AssessmentAfter the operation, double lumen endobronchial tube was exchanged with endotrachealtube size 8 mm anchored at 21 mm.Patient was sent to the intensive care unit (ICU) for weaning, transferred with manualbagging.Non-invasive blood pressure (NIBP) monitor, ECG monitoring, pulse oximeter and DVTvenocuff prophylaxis were set-up.Patient was keep nil by mouth, put below radiant warmer to prevent hypothermia.Pain was minimal and there were no complaints of headache, nausea or vomiting.Otherwise, no other post-operative complications noted.
Vital Signs Reading InterpretationBlood pressure 111/89 mmHg NormalPulse rate 65 x/min NormalRespiratory rate 20x/ min NormalTemperature 37°C AfebrileSpO2 100% NormalPain score 2/10 Mild painPost-operative anaesthesia recovery scoreParameters Signs ScoreActivity Able to lift the head or has a good hand gripNone of the above10Respiration Able to breathe and cough easilyDyspnoeic or apnoeic10Circulation BP within 20% of pre-operative levelBP above or below 20% of pre-operativelevelPulse regular rate, within 20% of pre-operative levelPulse irregular, above or below 20% of pre-operative level1010Consciousness ArousableNot responding10Colour PinkDusky10Total score 3/6Note:Score 5 or more may be coming home with the conditions of operation/ action possibleScore 4 to the treatment room when the breathing value is 1
Score 3 or less to ICUOperative findings:Tumor at the lower esophagus noted 1 cm above cardia measuring 3 X 3 cm.Proximal gastrectomy was done.Thoracotomy and single lung ventilation initiated due to limited space over superiorresectable margin.Lower end esophagectomy was done and proceed with proximal gastric and lower endesophagus anastomosis. Air leak test done – no leaking.Vagus nerve is preserved.Noted multiple metastatic lymph nodes involving caeliac lymph nodes and metastaticnodules over the pancreas. No liver nodules.Plan:i. To put patient on CPAP PEEP setting.ii. To give IV morphine 3 mg/houriii. To give IV Dexmedetomidine (Precedex) 0.4 mcg/kg/houriv. To give IV pantoprazole 40 mgv. To give IV Sulfaperazone 2g twice dailyvi. Infuse 2 pints of dextrose 5% and 3 pints normal saline 0.9% in 24 hoursvii. Keep nil by mouth for 6-8 hours