1. Principles of Surgical Oncology Section 1: General Issues Steven A. Rosenberg Surgery is the oldest treatment for cancer and, until recently, was the only treatment that could cure patients with cancer. The surgical treatment of cancer has changed dramatically over the past several decades. Advances in surgical techniques and a better understanding of the patterns of spread of individual cancers have allowed surgeons to perform successful resections for an increased number of patients. Improvements in radiation therapy and the development of systemic treatments that can control microscopic disease have prompted surgeons to reassess the magnitude of surgery necessary. The surgeon has a central role in the prevention, diagnosis, treatment, palliation, and rehabilitation of the cancer patient. The principles underlying each of these roles of the surgical oncologist are discussed in this chapter. Historical Perspective Although the earliest discussions of the surgical treatment of tumors are found in the Edwin Smith papyrus from the Egyptian Middle Kingdom (circa 1600 BC), the modern era of elective surgery for visceral tumors began in frontier America in 1809. 1,2 Ephraim McDowell removed a 22-pound ovarian tumor from a patient, Mrs. Jane Todd Crawford, who survived for 30 years after the operation. This procedure, the first of 13 ovarian resections performed by McDowell, was the first elective abdominal operation and provided a stimulus to the development of elective surgery. The surgical treatment of increasing numbers of cancer patients depended on two subsequent developments in surgery. The first of these was the introduction of general anesthesia by two dentists, Dr. William Morton and Dr. Crawford Long. The first major operation using general ether anesthesia was the excision of the submaxillary gland and part of the tongue, performed by Dr. John Collins Warren on October 16, 1846, at the Massachusetts General Hospital. The second major development resulted from the introduction of the principles of antisepsis by Joseph Lister in 1867. Based on the concepts of Pasteur, Lister introduced carbolic acid in 1867 and described the principles of antisepsis in an article in the Lancet that same year.
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1. Principles of Surgical OncologySection 1: General IssuesSteven A. RosenbergSurgery is the oldest treatment for cancer and, until recently, was the only treatment that could cure patients with cancer. The surgical treatment of cancer has changed dramatically over the past several decades. Advances in surgical techniques and a better understanding of the patterns of spread of individual cancers have allowed surgeons to perform successful resections for an increased number of patients. Improvements in radiation therapy and the development of systemic treatments that can control microscopic disease have prompted surgeons to reassess the magnitude of surgery necessary. The surgeon has a central role in the prevention, diagnosis, treatment, palliation, and rehabilitation of the cancer patient. The principles underlying each of these roles of the surgical oncologist are discussed in this chapter.Historical PerspectiveAlthough the earliest discussions of the surgical treatment of tumors are found in the Edwin Smith papyrus from the Egyptian Middle Kingdom (circa 1600 BC), the modern era of elective surgery for visceral tumors began in frontier America in 1809.1,2 Ephraim McDowell removed a 22-pound ovarian tumor from a patient, Mrs. Jane Todd Crawford, who survived for 30 years after the operation. This procedure, the first of 13 ovarian resections performed by McDowell, was the first elective abdominal operation and provided a stimulus to the development of elective surgery.The surgical treatment of increasing numbers of cancer patients depended on two subsequent developments in surgery. The first of these was the introduction of general anesthesia by two dentists, Dr. William Morton and Dr. Crawford Long. The first major operation using general ether anesthesia was the excision of the submaxillary gland and part of the tongue, performed by Dr. John Collins Warren on October 16, 1846, at the Massachusetts General Hospital. The second major development resulted from the introduction of the principles of antisepsis by Joseph Lister in 1867. Based on the concepts of Pasteur, Lister introduced carbolic acid in 1867 and described the principles of antisepsis in an article in the Lancet that same year.These developments freed surgery from pain and sepsis and greatly increased its use for the treatment of cancer. In the decade before the introduction of ether, only 385 operations were performed at the Massachusetts General Hospital. By the last decade of the 19th century, more than 20,000 operations per year were performed at that hospital.3
Table 20.1.1 lists selected milestones in the history of surgical oncology. Although this list does not include all the important developments, it indicates the tempo of the application of surgery to cancer treatment.4 Major figures in the evolution of surgical oncology included Albert Theodore Billroth, who, in addition to developing meticulous surgical techniques, performed the first gastrectomy, laryngectomy, and esophagectomy. In the 1890s, William Stewart Halsted elucidated the principles of en bloc resections for cancer, exemplified by the radical mastectomy. Examples of radical resections for cancers of individual organs include the radical prostatectomy performed by Hugh Young in 1904, the radical hysterectomy performed by Ernest Wertheim in 1906, the abdominoperineal resection for cancer of the rectum performed by W. Ernest Miles in 1908, and the first successful pneumonectomy performed for cancer by Evarts Graham in 1933. Modern technical innovations continue to extend the surgeon's capabilities. Recent examples include the development of microsurgical techniques that enable the performance of free graft
procedures for reconstruction, automatic stapling devices, sophisticated equipment that allows for a wide variety of endoscopic surgery, and major improvements in postoperative management and critical care of patients that have improved the safety of major surgical therapy.
Anesthesia for Oncologic SurgeryModern anesthetic techniques have greatly increased the safety of major oncologic surgery. Regional and general anesthesia play important roles in a wide variety of diagnostic techniques, in local therapeutic maneuvers, and in major surgery.Anesthetic techniques may be divided into those for regional and those for general anesthesia. Regional anesthesia involves a reversible blockade of pain perception by the application of local anesthetic drugs. These agents generally work by preventing the activation of pain receptors or by blocking nerve conduction. Agents commonly used for local and topical anesthesia for biopsy procedures in cancer patients are listed in Tables 20.1.2 and 20.1.3.5 Topical anesthesia refers to the application of local anesthetics to the skin or mucous membranes. Good surface anesthesia of the conjunctiva and cornea, oropharynx and nasopharynx, esophagus, larynx, trachea, urethra, and anus can result from the application of these agents.
Determination of Operative RiskAs with any treatment, the potential benefits of surgical intervention in cancer patients must be weighed against the risks of surgery. The incidence of operative mortality is of major importance in formulating therapeutic decisions and varies greatly in different patient situations (Table 20.1.4). The incidence of operative mortality is a complex function of the basic disease process that involves surgical factors, anesthetic technique, operative complications, and, most importantly, the general health status of patients and their ability to withstand operative trauma.In an attempt to classify the physical status of patients and their surgical risks, the American Society of Anesthesiologists (ASA) has formulated a general classification of physical status that appears to correlate well with operative mortality.7 Patients are classified into five groups depending on their general health status (as shown in Table 20.1.5).Operative mortality usually is defined as mortality that occurs within 30 days of a major operative procedure. In oncologic patients, the basic disease process is a major determinant of operative mortality. Patients undergoing palliative surgery for widely metastatic disease have a high operative mortality rate even if the surgical procedure can alleviate the symptomatic problem. Examples of these situations include surgery for intestinal obstruction in patients with widespread ovarian cancer and surgery for gastric outlet obstruction in patients with cancer of the head of the pancreas. These simple palliative procedures are associated with mortality rates up to 20% because of the debilitated state of the patient and the rapid progression of the underlying disease.
Table 20.1.4 Determinants of Operative RiskGeneral health statusSeverity of underlying illnessDegree to which surgery disrupts normal physiologic functionsTechnical complexity of the procedure (related to incidence of complications)
Type of anesthesia requiredExperience of personnel
Anesthesia-related mortality has decreased in the past four decades, largely because of the development of rigid practice standards and improved intraoperative monitoring techniques. A summary of the specific intraoperative monitoring methods used to achieve improved anesthetic safety is presented in Table 20.1.6.12 A study of 485,850 instances of anesthetic administration in 1986 in the United Kingdom revealed the risk of death from anesthesia alone to be approximately 1 in 185,000.9 In a retrospective review encompassing cases from 1976 through 1988, Eichhorn10 estimated anesthetic mortality in ASA class I and II patients to be 1 in 200,200. These are probably underestimates, because underreporting of anesthetic-related deaths is a problem in all studies. Most cancer patients undergoing elective surgery fall between physical status classes I and II; thus, an anesthetic mortality rate of 0.01% to 0.001% is a realistic estimate for this group.Anesthesia-related mortality is rare, and factors related to the patient's pre-existing general health status and disease are far more important indicators of surgical outcome. A study of the factors contributing to the risk of 7-day operative mortality after 100,000 surgical procedures yielded the findings shown in Table 20.1.7. The 7-day perioperative mortality in this study was 71.4 deaths per 10,000 cases, and the major determinants of death were the physical status of the patient, the emergent nature of the procedure, and the magnitude of the operation.The five most common causes of death after surgery are bronchopneumonia, congestive heart failure, myocardial infarction, pulmonary embolism, and respiratory failure. Perioperative pulmonary complications, therefore, are a major threat, and the patient-related risk factors associated with postoperative pulmonary complications are shown in Table 20.1.8.Patients with a recent myocardial infarction have a significantly higher incidence of reinfarction and cardiac death associated with surgery . Significant improvements have occurred as new techniques of anesthetic monitoring and hemodynamic support have been developed.
Cancer is often a disease of the elderly, and there is sometimes a tendency to avoid even curative major surgery for cancer in patients of advanced age. In the United States and in most Western countries, life expectancies for the elderly have increased substantially. The life expectancy in years of patients between the ages of 62 and 104 in the United States is shown in Table 20.1.10. The average life expectancies for 80-year-old men and women in the United States are 8 and 10.5 years, respectively. The expected survival of 90-year-old men and women is 4.7 and 6.0 years, respectively. Thus, even in the very old cancer patient, aggressive curative surgery can be warranted.19
Reports of most surgical series include an account of operative mortality and operative complications. These results, combined with a consideration of the general health status of the patient, allow a reasonable estimate of the operative mortality .
Roles for SurgeryPrevention of Cancer
All surgical oncologists should be aware of the high-risk situations that require surgery to prevent subsequent malignant disease. Some underlying conditions or congenital or genetic traits are associated with an extremely high incidence of subsequent cancer. When these cancers are likely to occur in nonvital organs, it is necessary to remove the potentially involved organ to prevent subsequent malignancy.20 Examples of diseases associated with a high incidence of cancer that can be prevented by prophylactic surgery are presented in Table 20.1.11 and are considered in more detail in Chapter 31. An excellent illustration is presented by patients with the genetic trait for multiple polyposis of the colon. If colectomy is not performed in these patients, approximately half will develop colon cancer by the age of 40. By age 70, virtually all patients with multiple polyposis will develop colon cancer.20 It is therefore advisable for all patients containing the mutant gene for multiple polyposis to undergo prophylactic colectomy before age 20 to prevent these cancers. Approximately 40% of patients with ulcerative colitis who have total colonic involvement ultimately die of colon cancer if they survive the ulcerative colitis.21 Three percent of children with ulcerative colitis develop cancer of the colon by the age of 10, and 20% develop cancer during each ensuing decade.22 Colectomy is indicated for patients with ulcerative colitis if the chronicity of this disease is well established. Patients with multiple endocrine neoplasia type 2A can be screened using polymerase chain reaction–based direct DNA testing for mutations in the RET protooncogene. This is the preferred method for screening kindred with multiple endocrine neoplasia type 2A to identify individuals in whom total thyroidectomy is indicated, regardless of the plasma calcitonin levels.23 A more complex example of the role of surgery in cancer prevention involves women at high risk for breast cancer. Because the risk of cancer in some women is increased substantially over the normal risk (but does not approach 100%), counseling that explains the benefits and risks of prophylactic mastectomy is an important part of the care of these patients. Genetic tests for the presence of BRCA1 and BRCA2 mutations provide valuable information. Statistical techniques can provide approximations of the risk for patients, depending on the frequency of disease in the family history, the age at the first pregnancy, and the presence of fibrocystic disease.Diagnosis of CancerThe major role of surgery in the diagnosis of cancer lies in the acquisition of tissue for exact histologic diagnosis. The principles underlying the biopsy of malignant lesions vary, depending on the natural history of the tumor under consideration.
Treatment of CancerSurgery can be a simple, safe method to cure patients with solid tumors when the tumor is confined to the anatomic site of origin. The extension of the surgical resection to include areas of regional spread can cure some patients, although regional spread often is an indication of undetectable distant micrometastases.The role of surgery in the treatment of cancer patients can be divided into six areas: (1) definitive surgical treatment for primary cancer, selection of appropriate local therapy, and integration of surgery with other adjuvant modalities; (2) surgery to reduce the bulk of disease (e.g., ovarian cancer); (3) surgical resection of metastatic disease with curative intent (e.g., pulmonary metastases in sarcoma patients, hepatic metastases from colorectal cancer); (4) surgery for the treatment of oncologic emergencies; (5) surgery for palliation; and (6) surgery for reconstruction and rehabilitation. In each area, integration with other treatment modalities can be essential for a successful outcome.Resection of the Primary Cancer
Three major challenges confront the surgical oncologist in the definitive treatment of solid tumors: accurate identification of patients who can be cured by local treatment alone; development and selection of local treatments that provide the best balance between local cure and the impact of treatment morbidity on the quality of life; and development and application of adjuvant treatments that can improve the control of locally invasive and distant metastatic disease. The selection of the appropriate local therapy to be used in cancer treatment varies with the individual cancer type and the site of involvement. In many instances, definitive surgical therapy that encompasses a sufficient margin of normal tissue is sufficient local therapy. The treatment of many solid tumors falls into this category, including the wide excision of primary melanomas in the skin, which can be cured locally by surgery alone in approximately 90% of cases. The resection of colon cancers with a 5-cm margin from the tumor results in anastomotic recurrences in fewer than 5% of cases. In other instances, surgery is used to obtain histologic confirmation of diagnosis, but primary local therapy is achieved through the use of a nonsurgical modality, such as radiation therapy. Examples include the treatment of Ewing's sarcoma in long bones and the treatment of selected primary malignancies in the head and neck. In each instance, selection of the definitive local treatment involves careful consideration of the likelihood of cure balanced against the morbidity of the treatment modality.
The magnitude of surgical resection is modified in the treatment of many cancers by the use of adjuvant treatment modalities. Rationally integrating surgery with other treatments requires a careful consideration of all effective treatment options. It is knowledge of this rapidly changing field that most distinctly separates the surgical oncologist from the general surgeon.In some instances, the availability of effective adjuvant modalities has led to a decrease in the magnitude of surgery. The evolution of treatment for childhood rhabdomyosarcoma is a striking example of the successful integration of adjuvant therapies with surgery in the treatment of cancer.24,25 Child hood rhabdomyosarcoma is the most common soft tissue sarcoma in infants and children. Before 1970, surgery alone was used almost exclusively, and 5-year survival rates of 10% to 20% were commonly reported. Local surgery alone failed in patients with rhabdomyosarcomas of the prostate and extremities because of extensive invasion of surrounding tissues and the early development of metastatic disease. The failure of surgery alone to control local disease in patients with childhood rhabdomyosarcoma led to the introduction of adjuvant radiation therapy. This resulted in a marked improvement in local control rates that was further improved dramatically by the introduction of combination chemotherapy. Long-term cure rates are now in the range of 80%. Many other examples of the integration of surgery with other treatment modalities appear throughout this text.
Cytoreductive SurgeryIn some instances, the extensive local spread of cancer precludes the removal of all gross disease by surgery. The partial surgical resection of bulk disease in the treatment of selected cancers improves the ability of other treatment modalities to control residual gross disease that has not been resected.26,27 Studies that suggest the merit of this approach are discussed in Chapter 42.5 dealing with ovarian cancer.
Enthusiasm for cytoreductive surgery has led to the inappropriate use of surgery to reduce the bulk of tumor in some cases. Clearly, cytoreductive surgery is of benefit only when other effective treatments are available to control the residual disease that is unresectable. Except in rare palliative settings, there is no role for cytoreductive surgery in patients for whom little other effective therapy exists.
Metastatic DiseaseThe value of surgery in the cure of patients with metastatic disease tends to be overlooked. As a general principle, patients with a single site of metastatic disease that can be resected without major morbidity should undergo resection of that metastatic cancer. Some patients with limited metastases to lung or liver or brain can be cured by surgical resection. This approach is especially appropriate for cancers that do not respond well to systemic chemotherapy. The resection of pulmonary metastases from soft tissue and bony sarcomas can be curative in as many as 30% of patients. As effective systemic therapy is developed for the treatment of these diseases, cure rates may increase. Studies have shown that similar cure rates occur in patients with adenocarcinomas when resected metastatic disease in the lung is the sole clinical site of metastases. Small numbers of pulmonary metastases often are the only clinically apparent metastatic disease in patients with sarcomas. However, this is rare in the natural history of most adenocarcinomas. If solitary metastases to the lung do occur in patients with carcinoma of the colon or other adenocarcinomas, surgical resection is indicated.Similarly, resection of hepatic metastases, especially from colorectal cancer, in patients in whom the liver is the only site of known metastatic disease can lead to long-term cure in approximately 25%. This far exceeds the cure rates of any other available treatment.Resection for cure of solitary brain metastases should also be considered when the brain is the only site of known metastatic disease. The exact location and functional sequelae of resection should be considered when making this treatment decision.
2. MACAM MACAM BIOPSI Various techniques exist for obtaining tissues suspected of malignancy, including aspiration biopsy, needle biopsy, incisional biopsy, and excisional biopsyAspiration biopsy involves the aspiration of cells and tissue fragments through a needle that has been guided into the suspect tissue.
In needle biopsy, a core of tissue is obtained through a specially designed needle introduced into the suspect tissue. The core of tissue provided by needle biopsy is sufficient for the diagnosis of most tumor types. Soft tissue and bony sarcomas often present major difficulties in differentiating benign and reparative lesions from malignancies and often cannot be diagnosed accurately. If these latter lesions are considered in the diagnosis, attempts should be made to obtain larger amounts of tissue than are possible from a needle biopsy.Incisional biopsy refers to removal of a small wedge of tissue from a larger tumor mass. Incisional biopsies often are necessary for diagnosis of large masses that require major surgical procedures for even local excision. Excisional biopsy refers to excision of the entire suspected tumor tissue with little or no margin of surrounding normal tissue. Care should be
taken to avoid contaminating new tissue planes or further compromising the ultimate surgical procedure.The following principles guide the performance of all surgical biopsies:
Needle tracks or scars should be placed so that they can be conveniently removed as part of the subsequent definitive surgical procedure. Placement of biopsy incisions is extremely important, and misplacement often can compromise subsequent care. Incisions on the extremity generally should be placed longitudinally so as to make the removal of underlying tissue and subsequent closure easier.
Care should be taken to avoid contaminating new tissue planes during the biopsy procedure. The development of large hematomas after biopsy can lead to tumor spread and must be scrupulously avoided by securing excellent hemostasis during the biopsy. For biopsies on extremities, the use of a tourniquet may help to control bleeding. Instruments used in a biopsy procedure are another potential source of contamination of new tissue planes. It is not uncommon to take biopsy samples from several suspected lesions at one time. Care should be taken to avoid using instruments that may have come in contact with a tumor when obtaining tissue from a potentially uncontaminated area.
Adequate tissue samples must be obtained to meet the needs of the pathologist. For the diagnosis of selected tumors, electron microscopy, tissue culture, or other techniques may be necessary. Sufficient tissue must be obtained for these purposes if diagnostic difficulties are anticipated.
When knowledge of the orientation of the biopsy specimen is important for subsequent treatment, it is important to mark distinctive areas of the tumor to facilitate subsequent orientation of the specimen by the pathologist. Certain fixatives are best suited to specific types or sizes of tissue. If all biopsy specimens are placed in formalin immediately, the opportunity to perform valuable diagnostic tests may be lost. The handling of excised tissue is the surgeon's responsibility.
Placement of radiopaque clips during biopsy and staging procedures is sometimes important to delineate areas of known tumor and to guide the subsequent delivery of radiation therapy to these areas
3. Terapi Paliatif
PalliationSurgical resection often is required for the relief of pain or functional abnormalities. The appropriate use of surgery in these settings can improve the quality of life for cancer patients. Palliative surgery may include procedures to relieve mechanical problems, such as intestinal obstruction, or the removal of masses that are causing severe pain or disfigurement. A study by Krouse et al.28 has emphasized the role of surgery in the palliative treatment of cancer patients.
Apa Itu Terapi Paliatif? Ketika dokter menyarankan pasien kanker yang sudah parah atau stadium lanjut untuk pulang atau dirawat di rumah, tak sedikit keluarga pasien yang marah dan menuding dokter tak bertanggungjawab. Padahal dokter akan mengatakan itu jika sudah tidak bisa berbuat banyak dan perawatan paliatiflah yang diperlukan.
Apa Itu Paliatif?Paliatif berasal dari bahasa Latin''palliare” yang berarti untuk menyelubungi. Perawatan paliatif adalah pendekatan yang bertujuan memperbaiki kualitas hidup pasien dan keluarga yang menghadapi masalah yang berhubungan dengan penyakit yang dapat mengancam jiwa, melalui pencegahan dan peniadaan melalui identifikasi dini dan penilaian yang tertib serta penanganan nyeri dan masalah-masalah lain, fisik, psikososial dan spiritual (WHO 2002).Perawatan paliatif adalah perawatan kesehatan terpadu yang bersifat aktif dan menyeluruh, dengan pendekatan multidisiplin yang terintegrasi. Tujuannya untuk mengurangi penderitaan pasien, memperpanjang umurnya, meningkatkan kualitas hidupnya, juga memberikan support kepada keluarganya. Meski pada akhirnya pasien meninggal, yang terpenting sebelum meninggal dia sudah siap secara psikologis dan spiritual, serta tidak stres menghadapi penyakit yang dideritanya. Jadi, tujuan utama perawatan paliatif bukan untuk menyembuhkan penyakit dan yang ditangani bukan hanya penderita, tetapi juga keluarganya.
Untuk Siapa?Dulu perawatan ini hanya diberikan kepada pasien kanker yang secara medis sudah tidak dapat disembuhkan lagi, tetapi kini diberikan pada semua stadium kanker dan berbagai kelainan yang bersifat kronis, penyakit degeneratif, penyakit paru obstruktif kronis, cystic fibrosis, stroke, Parkinson, gagal jantung / heart failure, penyakit genetika dan penyakit infeksi seperti HIV/AIDS. Penyakit-penyakit tersebut memerlukan perawatan paliatif, disamping kegiatan promotif, preventif, kuratif, dan rehabilitatif.
Prinsip PaliatifMenurut dr. Maria A. Witjaksono, dokter Palliative Care Rumah Sakit Kanker Dharmais, Jakarta, prinsip-prinsip perawatan paliatif adalah sebagai berikut:1. Menghargai setiap kehidupan.2. Menganggap kematian sebagai proses yang normal.3. Tidak mempercepat atau menunda kematian.4. Menghargai keinginan pasien dalam mengambil keputusan.5. Menghilangkan nyeri dan keluhan lain yang menganggu.6. Mengintegrasikan aspek psikologis, sosial, dan spiritual dalam perawatan pasien dan keluarga.7. Menghindari tindakan medis yang sia-sia.8. Memberikan dukungan yang diperlukan agar pasien tetap aktif sesuai dengan kondisinya sampai akhir hayat.9. Memberikan dukungan kepada keluarga dalam masa duka cita.
Di Indonesia perawatan paliatif baru dimulai pada tanggal 19 Februari 1992 di RS Dr. Soetomo (Surabaya), disusul RS Cipto Mangunkusumo (Jakarta), RS Kanker Dharmais (Jakarta), RS Wahidin Sudirohusodo (Makassar), RS Dr. Sardjito (Yogyakarta), dan RS Sanglah (Denpasar).
Perawatan paliatif terdapat dalam berbagai macam.Home Caredilakukan dengan melakukan kunjungan ke rumah-rumah penderita, terutama yang karena alasan-alasan tertentu tidak dapat datang ke rumah sakit. Kunjungan dilakukan oleh tim yang terdiri atas dokter paliatif, psikiater, perawat, dan relawan, untuk memantau dan memberikan solusi atas masalah-masalah yang dialami penderita kanker dan keluarganya, bukan hanya menyangkut masalah medis/biologis, tetapi juga masalah psikis, sosial, dan spiritual. Perawatan paliatif membolehkan pasien di rawat di rumah didampingi keluarga tercinta. Saat di rawat di rumah, pasien biasanya akan merasa lebih nyaman dan bisa membantu meringankan beban dan pikiran sehingga lebih siap menghadapi penyakitnya.Day Caremerupakan layanan untuk tindakan medis yang tidak memerlukan rawat inap, misalnya perawatan luka, kemoterapi, dsb.Respite Caremerupakan layanan yang bersifat psikologis. Di sini penderita maupun keluarganya dapat berkonsultasi dengan psikolog atau psikiater, bersosialisasi dengan penderita kanker lain, mengikuti terapi musik, atau sekedar bersantai dan beristirahat. Bisa juga menitipkan penderita kanker (selama jam kerja), jika pendamping atau keluarga yang merawatnya ada keperluan lain.
Menurut Prof. R. Sunaryadi Tejawinata dr., SpTHT (K), FAAO, PGD.Pall.Med (ECU) –Kepala Pusat Pengembangan Paliatif & Bebas Nyeri RSU Dr. Soetomo periode 1992-2006– salah satu aspek penting dalam perawatan paliatif adalah kasih, kepedulian, ketulusan, dan rasa syukur. Begitu pentingnya aspek ini, sampai melebihi pentingnya penanganan nyeri yang mutlak harus dilakukan dalam perawatan paliatif.
Masyarakat menganggap perawatan paliatif hanya untuk pasien dalam kondisi terminal
yang akansegera meninggal. Namun konsep baru perawatan paliatif menekankan pentingnya integrasiperawatan paliatif lebih dini agar masalah fisik, psikososial dan spiritual dapat diatasi dengan baik.Perawatan paliatif adalah pelayanan kesehatan yang bersifat holistik dan terintegrasi denganmelibatkan berbagai profesi dengan dasar falsafah bahwa setiap pasien berhak mendapatkan perawatan terbaik sampai akhir hayatnya.
4. Pemeriksaan Penunjang Kanker
Biologic Aspects of Radiation OncologyMechanisms and Consequences of Radiation-Induced DNA DamageRadiation is administered to cells either in the form of photons (i.e., x-rays and gamma rays) or particles (protons, neutrons, and electrons). When photons or particles interact with biological material they result in ionizations that can either directly interact with subcellular structures or they can interact with water, the major constituent of cells, and generate free radicals that can then interact with subcellular structures (Fig. 21.1).The direct effects of radiation are the consequence of the DNA in chromosomes absorbing energy that leads to ionizations. This is the major mechanism of DNA damage induced by protons and neutrons and is termed high linear energy transfer (Fig. 21.2). In contrast, the interaction of photons with other molecules such as water results in the production of free radicals, some of which possess a lifetime long enough to be able to diffuse to the nucleus and interact with DNA in the chromosomes. This is the major mechanism of DNA damage induced by x-rays and has been termed low linear energy transfer.1
A free radical generated through the interaction of photons with other molecules that possess an unpaired electron in their outermost shell (e.g., hydroxyl radicals) can abstract a hydrogen molecule from a macromolecule such as DNA to generate damage. Cells that have increased levels of free radical scavengers such as glutathione would have less DNA damage induced by x-rays, but have similar levels of DNA damage induced by protons that are directly absorbed by chromosomal DNA. Furthermore, a low oxygen environment would also protect cells from x-ray–induced damage as there would be fewer radicals available to induce DNA damage in the absence of oxygen, but this environment would have little impact on DNA damage induced by protons.2
Ionizing radiation causes base damage, single-strand breaks, double-strand breaks, and sugar damage, as well as DNA-DNA, and DNA-protein cross links. The critical target for ionizing radiation-induced cell inactivation and cell killing is the DNA double-strand break.3,4 In eukaryotic cells, DNA double-strand breaks can be repaired by two processes: homologous recombination repair (HRR) that requires an undamaged DNA strand as a participant in the repair, and nonhomologous end joining (NHEJ) that mediates end-to-end joining.5 In lower eukaryotes such as yeast, homologous recombination repair is the predominant pathway used for repairing DNA double-strand breaks, whereas mammalian cells use both homologous and nonhomologous recombination to repair their DNA. Double-strand break repair by HRR is considered an error-free process because the repair is mediated by using the DNA sequence from the undamaged homologous chromosome as a template for repair. In mammalian cells, the choice of repair is biased by the phase of the cell cycle and by the abundance of repetitive DNA. HRR is used primarily in the late S-
phase/G2 phases of the cell-cycle, and NHEJ predominates in the G1-phase of the cell-cycle (Fig. 21.3). NHEJ is error-prone and probably contributes to the formation of mutagenic lesions induced in DNA by ionizing radiation. NHEJ and HRR are not mutually exclusive, and both have been found to be active in the late S/G2 phase of the cell cycle, indicating that factors in addition to cell-cycle phase are important in determining which mechanism will be used to repair DNA strand breaks.
The Effect of Radiation on Cell SurvivalThe classic response used to describe cells exposed to ionizing radiation is cell inactivation as cells exposed to radiation cease dividing, but do not necessarily disappear. We now know that this “inactivation†� is the result of a DNA damage-induced inhibition of cell-cycle progression termed senescence. Senescent cells are reproductively inactive, but are metabolically active and secrete factors that influence the proliferation and survival of neighboring cells. The potential consequences of cells exposed to ionizing radiation are normal cell division, DNA damage-induced senescence, DNA damage-induced apoptosis, or mitotic-linked cell death (Fig. 21.5). These manifestations of DNA damage can occur rapidly within one or two cell divisions or can manifest at later times after many cell divisions.7 Effects that occur at later times have been termed delayed reproductive cell death and are probably not the result of DNA damage per se, but of secreted factors.8 This phenomenon is still poorly understood, but could have important clinical implications. Radiation-induced cell killing is quantified by measuring the reproductive ability of a single cell to divide into a colony of 50 or more cells.9 By comparing the number of colonies that form on an irradiated plate with the number of colonies that form on an unirradiated plate, one can determine the effect of radiation dose on cell reproductive viability. Thus, a survival curve reflects the sum total of events previously described that lead to an impairment in a cell's reproductive viability.7 Typically, the surviving fraction of cells is plotted on a logarithmic scale and the absorbed dose is plotted on a linear scale. The survival curve for simple prokaryotic species such as bacteria exhibits an exponential decrease in survival as dose increases. This killing is random because the dose-response curve generated from the progeny of a surviving bacterial colony will have the same exponential shape as the original survival curve. In contrast to analogous experiments performed with chemotherapy, none of the surviving colonies from cells exposed to radiation have decreased sensitivity, indicating that radiation does not select for resistant variants.
radiation plays an important part in palliative treatment. Perhaps most importantly, emergency irradiation can begin to reverse the devastating effects of spinal cord compression and of superior vena cava syndrome. A single 8-Gy fraction is highly effective for many patients with bone pain from a metastatic lesion. Some have advocated the use of body stereotactic radiation to treat vertebral body metastases in patients who have a long projected survival or who need retreatment after previous radiation,139 but the role of stereotactic body radiotherapy is still being defined in this setting. Stereotactic treatment can relieve symptoms from a small number of brain metastasis, and fractionated whole-brain radiation can mitigate the effects of multiple metastases. Bronchial obstruction can
often be relieved by a brief course of treatment as can duodenal obstruction from pancreatic cancer. Palliative treatment is usually delivered in a smaller number of larger radiation fractions (see “Fractionation†�) because the desire to simplify the treatment for a patient with limited life expectancy outweighs the somewhat increased potential for late side effects.Palliative radiation therapy differs substantially from radical treatment. In contrast toradical therapy, in which the goal is to eradicate the tumor even if treatment produces significant morbidity, in palliative treatment the goal is to weigh carefully any anticipated toxicity against the potential benefit. In this respect, radiation therapy differs substantially from chemotherapy, in which the toxicity of palliative treatment and radical treatment are often similar. In addition, the planning of a course of palliative therapy for metastatic disease should involve the best estimate of subsequent possible sites of metastasis. For instance, it might be unwise in planning a second course of spine radiation to leave a single vertebral body untreated between the two treated fields, as it will be very difficult to treat a metastasis in that remaining vertebral body without overlapping a region of previous treatment. Such overlap might subject the patient to a high risk of transverse myelitis, a devastating complication.5. Terapi non bedah
Chemotherapy, which includes newly developed targeted treatments, is the principle tool of the medical oncologist. The development of effective combination chemotherapy programs for childhood leukemia, advanced Hodgkin's lymphoma, and diffuse large B-cell lymphomas in the 1960s provided curative therapeutic strategies for patients with advanced malignancies of all types. These advances confirmed the principle that chemotherapy could indeed cure advanced cancer and provided the rationale for using chemotherapy in the adjuvant setting following surgical resection and for integrating chemotherapy into combined modality programs with surgery and radiation therapy in locally advanced disease. The principal obstacles to the clinical efficacy of chemotherapy have been toxicity to the normal tissues of the body and the development of cellular drug resistance. The development and application of molecular techniques to analyze gene expression of normal and malignant cells at the level of DNA, RNA, and protein has helped to identify some of the critical mechanisms through which chemotherapy exerts its antitumor effects and activates the program of cell death. The advances in molecular technology have also provided insights into the molecular and genetic events within cancer cells that can confer chemosensitivity to drug treatment. This enhanced understanding of the molecular pathways by which chemotherapy exerts its cytotoxic activity and by which genetic instability can result in resistance to drug therapy has provided a rationale for the development of innovative therapeutic strategies in which molecular, genetic, and biologic therapies can be used in combination to directly attack these novel targets. As such, chemotherapy has now evolved into more specific targeted treatment. The implementation of such novel treatment approaches provides an important paradigm shift as to how chemotherapy is administered. The long-term goal of these research efforts is to improve the clinical outcome for cancer patients undergoing treatment, especially those with cancers that traditionally have been resistant to conventional chemotherapy.Historical Perspective
The systemic treatment of cancer has its roots in the initial work of Paul Ehrlich, who coined the term chemotherapy. The use of in vivo rodent model systems to develop antibiotics for treating infectious diseases led Clowes and colleagues at Roswell Park Memorial Institute, in the early 1900s, to develop inbred rodent lines bearing transplanted tumors to screen potential anticancer drugs. This in vivo system provided the foundation for mass screening of novel compounds.1 Alkylating agents represent the first class of chemotherapeutic drugs to be used in the clinical setting. Of note, application of this class of compounds was a direct product of the secret gas program of the United States during both world wars, and was based on the astute observation that exposure to mustard gas resulted in bone marrow and lymphoid hypoplasia. This experience led to the first clinical use of nitrogen mustard in a patient with non-Hodgkin's lymphoma in 1942. Subsequent treatment with this alkylating agent resulted in dramatic regressions in advanced lymphomas and thereby generated significant excitement in the field of cancer pharmacology.At about the same time, Sidney Farber reported that folic acid had a significant proliferative effect on leukemic cell growth in children with lymphoblastic leukemia. These observations led to the development of folic acid analogs as cancer drugs to inhibit cellular folate metabolism. This work initiated the era of cancer chemotherapy. In fact, the entire class of antimetabolites, including antifolates, fluoropyrimidines, deoxycytidine analogs, and the purine analogs were all designed with the expectation that they would target critical biochemical pathways involved in de novo pyrimidine and purine metabolism, respectively, and thereby inhibit cancer cell proliferation and growth. Indeed, these compounds represent the very first examples of targeted anticancer agents to be developed for clinical application. Current targeted treatments, in contrast, focus on elements of the cellular signaling apparatus uncovered since then. Clinical Application of Chemotherapy
Presently, chemotherapy is used in four main clinical settings: (i) primary induction treatment for advanced disease or for cancers for which there are no other effective treatment approaches (Tables 22.1.1 and 22.1.2); (ii) as the primary or neoadjuvant treatment for patients with localized disease for whom local forms of therapy, such as surgery, radiation, or both, are ineffective by themselves (Table 22.1.3); (iii) adjuvant treatment, either concurrent or following local methods of treatment, including surgery, radiation therapy, or both (Table 22.1.4); and (iv) direct instillation into sanctuary sites or site-directed perfusion of specific regions of the body directly affected by the cancer.Primary induction chemotherapy refers to drug therapy administered as the first treatment for patients who present with advanced cancer for which no alternative treatment exists.2,3 This approach applies for patients with advanced, metastatic disease. Studies involving a wide range of solid tumor types have shown that chemotherapy confers survival benefit when compared with only supportive care in patients with advanced disease, which provides sound rationale for the early initiation of drug treatment. Cancer chemotherapy can be curative in a small but significant subset of patients who present with advanced disease. In adults, these curable cancers include Hodgkin's and non-Hodgkin's lymphoma, acute lymphoblastic and myelogenous leukemia, germ cell cancer, ovarian and localized small-cell lung cancers, and choriocarcinoma. In pediatric patients, the major curable cancers include the acute leukemias, Burkitt's lymphoma, Wilms' tumor, and embryonal rhabdomyosarcoma.
Neoadjuvant chemotherapy refers to the use of chemotherapy as the primary treatment in patients who present with localized cancer for which local therapies, such as surgery and/or radiation, exist but are less than completely effective.4 For chemotherapy to be used as the initial treatment for a cancer that would be partially curable by either surgery or radiation therapy, there generally is documented evidence for its clinical efficacy in the advanced disease setting. At present, neoadjuvant therapy is used to treat locally advanced anal cancer, bladder cancer, breast cancer, gastroesophageal cancer, head and neck cancer, non–small-cell lung cancer, rectal cancer, and osteogenic sarcoma among others. Clinical benefit is usually optimized when chemotherapy is administered in combination with radiation therapy, either concurrently or sequentially. One additional goal of neoadjuvant therapy is to reduce the size of the primary tumor such that it allows the surgeon a better chance of complete resection while reducing the potential spread of micrometastatic spread. Moreover, in the case of laryngeal cancer, anal cancer, osteosarcoma, and bladder cancer, neoadjuvant chemotherapy may allow for preservation of vital organs such as the larynx, anal sphincter, limbs, and bladder, respectively. One of the most important roles for cancer chemotherapy is as an adjuvant to local treatment modalities such as surgery and radiation therapy, and this approach has been termed adjuvant chemotherapy.5 The development of disease recurrence, either locally or systemically, after surgery, radiation, or both is mainly due to the spread of occult micrometastases. Thus, the goal of adjuvant therapy is to eradicate micrometastases to reduce the incidence of both local and systemic recurrence and to improve the overall survival of patients. In general, chemotherapy regimens with clinical activity against advanced disease are used in the adjuvant setting and may have curative potential after surgical resection of the primary tumor, provided the appropriate dose and schedule are used. Several well-conducted randomized phase 3 clinical studies have documented efficacy of adjuvant chemotherapy in prolonging disease-free and overall survival in patients with breast cancer, colon cancer, gastric cancer, non–small-cell lung cancer, ovarian cancer, head and neck cancer, and cervical cancer, Wilms' tumor, and osteogenic sarcoma. There is also evidence to support the use of adjuvant chemotherapy in patients with anaplastic astrocytomas. Patients with primary malignant melanoma at high risk of metastases derive benefit in terms of improved disease-free survival and overall survival from adjuvant treatment with the biologic agent interferon-α, although this treatment must be given for 1 year for optimal clinical efficacy. Finally, the antiestrogens tamoxifen and anastrozole are effective adjuvant agents in postmenopausal women whose breast tumors express the estrogen receptor. Because both agents are cytostatic rather than cytocidal, they must be administered on a prolonged basis, and the standard recommended treatment length is now for 2 to 3 years, followed by the use of an aromatase inhibitor exemestane for a total treatment duration of 5 years.
Imunoterapi
Recent progress in understanding basic aspects of cellular immunology and tumor–host immune interactions have led to the development of effective immune-based therapies
capable of mediating the rejection of metastatic cancer in humans. Early studies of allografts and transplanted syngeneic tumors in mice demonstrated that it was the cellular arm of the immune response rather than the action of antibodies (humoral immunity) that was responsible for tissue rejection. Thus most modern studies of the immunotherapy of solid tumors have emphasized attempts to increase levels of immune lymphocytes capable of recognizing cancer antigens and destroying established cancers. Although antibodies that recognize growth factors on the surface of tumors can contribute to tumor regression, these antibodies appear to act primarily by interfering with growth signals rather than by the direct destruction of tumor cells, and this will be considered elsewhere in this text.Evidence for specific tumor recognition by cells of the immune system was obtained in experiments first conducted in the 1940s using murine tumors generated or induced by the mutagen methylcholanthrene (MCA). Mice that received a surgical resection of previously inoculated tumors could be protected against a subsequent tumor challenge; however, while these mice were protected against challenge with the immunizing tumor, either no or limited protection was observed against challenge with additional MCA tumors. Subsequent observations indicated that CD8+ cytotoxic T cells were the cells that were primarily responsible for mediating the rejection of MCA-induced tumors as well as other tumors. These findings led to the identification in the 1980s of genes that encoded tumor rejection antigens expressed on murine tumors as well as the subsequent identification of antigens recognized by human tumor reactive T cells. The observation that many human tumor antigens represented widely expressed, nonmutated gene products led to the expectation that effective vaccine therapies could be developed for the treatment of cancer patients. The results of vaccination therapies that boost the immune response of individuals with cancer have, however, to this point been disappointing. Vaccination with virus like particles expressing human papilloma virus (HPV) proteins are successful in preventing the establishment of cervical cancer; however, this vaccine works by preventing viral infection. In spite of the presence of highly immunogenic HPV epitopes on cervical cancers, vaccination appears to be ineffective for the treatment of patients with existing disease that results from infection with this virus. Immune-based therapies have been developed, however, that are capable of resulting in the regression of large, established tumor metastases in the human. In a current clinical protocol involving the adoptive transfer of melanoma reactive T cells, objective clinical responses have been observed in approximately 50% of treated patients. Intensive studies are under way to better understand the basic mechanisms that regulate immune responses to tumor in order to design more effective immunotherapies for patients with cancer.Approaches to the Identification of Human Tumor AntigensThree major approaches have been used to identify the molecular nature of antigens that are naturally processed and presented on tumor cells, which to date comprise more than 100 antigenic proteins and/or epitopes (Table 23.1). Most antigens have been identified using T cells with the ability to recognize intact cancer cells, as assessed by either specific cytokine release or lysis when T cells and cancer cells are cocultured. These T cells can be derived by repeated in vitro sensitization with tumor cells or by the culture of tumor infiltrating lymphocytes (TIL). These antitumor T cells can be used to screen tumor cDNA libraries transfected into target cells containing the appropriate restriction element. Alternatively, peptides can be eluted from cancer cells and used to pulse histocompatibility leukocyte antigen (HLA) matched target cells that are then tested for recognition by the antitumor T cells. To identify HLA class II–restricted tumor antigens, cellular proteins can
be fractionated and fed to anaphase-promoting complexes (APCs) until a single protein species is identified.A second approach to identify cancer antigens uses a “reverse immunology†� method in which putative antigens are used to generate tumor reactive T cells by repeated in vitro sensitization with candidate peptides from proteins that were primarily identified through the use of previously described peptide major histocompatibility complex (MHC) binding motifs. For example, the HLA binding motif for the HLA-A2 class I molecule, which is expressed by approximately 50% of Caucasians, consists of an optimal methionine, leucine, or isoleucine anchor residue at position two and a valine at the carboxy-terminal anchor residue position, generally position nine or ten.1 The peptide reactive T cells are then tested for the ability to recognize intact cancer cells to determine whether the identified peptides are naturally processed and presented on the surface of cancer cells. Alternatively, mice transgenic for human MHC molecules can be immunized with candidate antigens and the murine T cells used to test for cancer cell recognition. Only a small percentage of the potential epitopes are naturally presented on the cell surface at sufficient levels to allow detection by T cells. Peptides that are presented on the cell surface in association with class I molecules appear to be processed in the proteosome, a multisubunit catalytic complex that is responsible for generating the carboxy-terminus of processed peptides (Fig. 23.1).2 Thus, although it has been surprisingly easy to use these techniques to generate T cells against individual peptides, only a limited number of these peptides are naturally presented on the surface of tumor cells.
All tumor antigens are recognized by T-cell receptors that recognize peptides presented on cell surface MHC molecules. CD8+ T cells recognize peptides on class I MHC and CD4+ T cells recognize peptides on class II MHC molecules (Fig. 23.2).A third approach to the identification of tumor antigens is a method that has been termed SEREX (serological analysis of recombinant cDNA expression libraries).3 This method, which utilizes antisera from cancer patients to screen cDNA libraries constructed from tumor cells, has resulted in the identification of thousands of target molecules (online list available at http://www2.licr.org/CancerImmunomeDB/).4 Although some of the proteins identified using this technique are expressed in a tumor-specific manner, many of the proteins identified using this technique are expressed in normal tissues but appear to be overexpressed in tumor cells. Normal proteins released from large masses of necrotic and apoptotic tumor cells may also be processed by dendritic cells (DC), which may also lead to the generation of antibodies against intracellular products that are normally sequestered from the immune system.
Three Main Approaches to Cancer Immunotherapy1. Nonspecific stimulation of immune reactions (a) Stimulate effector cells (b) Inhibit regulatory cells2. Active immunization to enhance anti-tumor reactions (cancer vaccines)3. Passively transfer activated immune cells with antitumor activity (adoptive immunotherapy)
Whole Cell Vaccines
Clinical trials employing whole tumor cells as vaccines represents can theoretically activate cells reactive against multiple antigenic targets, and early model studies have demonstrated the ability of autologous tumor cell vaccination to protect mice from subsequent tumor inoculation.107,108 In a trial comparing treatment with a combination of an allogeneic melanoma vaccine with the adjuvant DETOX, there was no significant increase in relapse-free survival when compared to patients randomized to observation without further therapy.109 Treatment with a combination of three irradiated allogeneic melanoma cells with BCG (Canvaxin trial) resulted in an overall survival rate of 49%, as opposed to a rate of 37% in patients who did not receive the vaccine.110 Further evaluation of this approach in phase III trials, however, showed no significant difference in survival of patients with stage III or IV melanoma receiving this treatment compared to controls receiving BCG alone.111
Gene modified cells have been evaluated for their effectiveness in cancer therapy protocols. In a murine model system, mice that were immunized with B16 melanoma cells transduced with genes encoding ten cytokines were examined for their resistance to a subsequent inoculation of the wild type B16 tumor.112 The results indicated that tumors transduced with the GM-CSF gene provided significant protection against B16 tumor challenge, and a lower level of protection was observed in mice immunized with IL-4 and IL-6 transduced tumors. In a clinical trial involving immunization of patients with autologous renal carcinoma cells that had been transduced with the GM-CSF gene, immune responses against the parental renal carcinomas were observed, as measured by delayed-type hypersensitivity (DTH) responses, and an objective clinical response was observed in one out of the 16 fully evaluable patients.113 Immunization of melanoma patients with allogeneic irradiated melanomas transduced with GM-CSF analysis of DTH responses provided evidence for priming of reactivity against autologous tumor cells in 17 out of 25 patients, and one complete and one partial response was observed,114 but again it is difficult to evaluate the effectiveness of this approach in this relatively small trial.
6. Peran Nutrisi, Suportif, psikologi pada penderita neoplasma
Nutrition SupportAlessandro LavianoRobert A. MeguidMichael M. MeguidDuring the past few years, significant breakthroughs in the field of tumor biology and genomics enhanced our ability to effectively treat cancer patients. However, although many tumors can now be treated, only a few patients with advanced disease are likely to be cured. Consequently, nutritional support has become critical for oncologists who aim to maintain quality of life during cancer treatment and palliative care. Cancer patients often lose appetite and body weight either due to the disease itself or its treatment. Thus, malnutrition is frequently observed in cancer patients. However, weight loss caused by cancer differs from that observed during simple starvation, which is characterized by preservation of lean body mass. Weight loss in cancer patients does not solely result from anorexia and reduced food intake, but largely due to the profound derangements in metabolism induced by the inflammatory response to tumor growth (Table 64.2.1). This, in turn, prevents optimal nutrient utilization.The etiology of cancer-associated malnutrition appears to be related to the pathological loss of inhibitory control of central and peripheral catabolic pathways, whose increased activities
are not counterbalanced by the increased central and peripheral anabolic drive.1 The molecular mechanisms responsible for these metabolic derangements are being increasingly elucidated, leading to novel, pathogenesis-based therapeutic approaches currently being tested.
The goals of nutrition support in cancer are (1) to maintain or improve nutritional status to allow for initiation and completion of aggressive anticancer therapies and (2) to increase functional capacity and quality of life, even in advanced cases. The issue of quality of life in cancer patients is of paramount importance because patients are more concerned with their ability to function as close to normal as possible and to maintain a good quality of life than being preoccupied with their ultimate mortality.2 In this respect, it should be emphasized that when body weight, and particularly lean body mass, is lost, function and quality of life suffer.3 In particular, it has been assessed in cancer patients that 50% of the quality of life function scores are determined by nutritional intake and weight loss.4
Not only tumor growth but also cancer treatments, including surgery, chemotherapy, and radiation therapy, interfere with the patient's ability to taste, ingest, swallow, or digest food. Anorexia and reduced food intake are frequently presenting symptoms of a tumor. Surgery and radiation of the gastrointestinal tract may affect the digestion and absorption of nutrients. Drugs may cause nausea and diarrhea. Although many new agents have been developed to combat these symptoms, their prevalence is still high.In summary, cancer-associated malnutrition is the result of a deadly combination of anorexia, with its attendant reduced food intake, and alterations of host metabolism, exacerbating weight loss and impeding its reversal with nutrient supplementation.AnorexiaOne of the most distressing symptoms presenting a significant challenge to the cancer patient is the progressive development of anorexia and reduced food intake.5,6 Anorexia is defined as the loss of the desire to eat and may result from the occurrence of changes in smell, generalized alterations of taste (i.e., dysgeusia), specific alterations of taste (e.g., meat aversion), early satiety, or nausea and vomiting. Anorexia may be the presenting symptom of cancer, occurring independently from cancer treatment, but it is frequently associated with antineoplastic therapy as a side effect of chemo- and radiation therapy.The pathogenesis of cancer-associated anorexia appears to be related to the inability of the neuroregulation of energy homeostasis due to locoregional inflammation. This results in the impairment of normal metabolic regulation via hormones, peptides, and other neural signaling arising form peripheral tissues.7
As a result, the brain is persistently set in an anorexigenic mode, which induces the suppression of appetite, and is not influenced by the usual peripheral signals indicating the progressive depletion of energy stores. The diagnosis of anorexia can either be made by assessing the presence of specific symptoms (i.e., changes in taste and smell, meat aversion, nausea and vomiting, early satiety) or by using specific questionnaires. The North Central Cancer Treatment Group and the Functional Assessment of Anorexia Cachexia Therapy questionnaires comprise surveys including questions related to nutritional issues, including appetite, food intake, nausea and vomiting, body weight, and interest in food. Although the North Central Cancer Treatment Group questionnaire provides a “yes†� or “no†�
assessment of the presence of anorexia, the Functional Assessment of Anorexia Cachexia Therapy questionnaire allows a quantitative assessment. When anorexia develops as a side effect of cancer treatment, it frequently results from the occurrence of nausea, vomiting, and dysgeusia. Drug-related toxicity is responsible for the nausea and vomiting occurring with chemotherapy, but a strong psychological component has also been reported. Indeed, patient expectation of developing nausea and vomiting during chemotherapy is a strong predictor of actual severe nausea.8 Thus, interventions designed to reduce the expectation of nausea by patients should be developed. Also, food aversion patterning may develop during chemo- and radiation therapy (i.e., the distressing emotional association of specific tastes and smells with negative psychological experiences).7 Food aversion patterning may be responsible for vomiting when odors or tastes associated with chemotherapy are perceived. In this respect, during anorexigenic cancer treatments, it is important to suggest to patients not to eat their favorite foods to prevent the development of aversion to those foods.
Drugs such as vincristine and the taxanes have the strongest associations with dysgeusia. The pathogenesis of chemotherapy-induced dysgeusia is related to the excretion or secretion of drugs in saliva, thereby markedly altering taste and leading to food revulsion and avoidance. Not only may certain tastes be affected, but food consistency or texture may be a factor as well, requiring more chewing, which may increase saliva production, perpetuating the cycle. Multiple other mechanisms may be involved in dysgeusia, including zinc deficiency, morphologic changes in the lingual papillae, and even neuropathy. Dysgeusia may also be caused by depression, which may initially go unrecognized in cancer patients. Various attempts at treatment of dysgeusia have been made, but with little success. Each patient must experiment to find foods that are associated with the least alteration in taste. Different tastes can be tested using sugar for sweet, lemon juice for sour, salt (for salt), and aspirin or quinine for bitter. Usually, foods that can be swallowed with little chewing and therefore little saliva production are tolerated best. Attempts at dietary supplementation with elements such as zinc, folic acid, α-lipoic acid, and the B vitamins may alleviate some metallic tastes but are only mildly helpful. Zinc seems to work best with a “sweet†� dysgeusia, but drugs often give a more metallic taste, and the best treatment for dysgeusia remains withdrawal of the offending drug. After drug cessation, the taste usually returns to normal over a 2-month period. Perhaps a more effective regimen is nutritional counseling to give patients a goal of their necessary daily protein and calorie intake. This allows them to overcome the dysgeusia and avoid weight loss and muscle depletion and maintain an element of control in their management. Patients, with the aid of caregivers, must continually experiment to find foods that are palatable and provide the necessary amounts of nutrients.
Weight Loss and Cancer CachexiaMost cancer patients lose weight as a result of their disease and/or aggressive therapeutic regimens. The amount of weight loss varies with the type of cancer, pancreatic cancer being
among the worst. Loss in excess of 10% of baseline body weight over 6 months is defined as critical weight loss. If weight loss in cancer patients was secondary to anorexia and/or gastrointestinal tract obstruction, and thus due to reduced food intake, then these issues could be resolved with proper nutritional counseling and support. Unfortunately, cancer patients lose body weight, and particularly lean body mass, due to the inflammatory changes brought about by the tumor's presence.9 Direct effects of cytokines and other inflammatory mediators, the acute-phase response, and proteolysis are difficult to reverse with traditional nutritional support because the ensuing weight loss is not the result of starvation. This peculiar malnutrition syndrome is known as cancer cachexia (Fig. 64.2.1). Lundholm et al.10 highlighted the negative role of inflammation and metabolic derangement in cancer cachexia and showed that an integrated metabolic support, including nutritional support, anti-inflammatory drugs, and erythropoietin, improves survival in advanced cancer patients.
Although a consensus definition does not exist, cancer cachexia could be defined as a profound destructive process characterized by skeletal muscle wasting and harmful abnormalities in fat and carbohydrate metabolism in spite of adequate caloric and nutrient intake (Table 64.2.2). Generally acknowledged criteria for the diagnosis of cachexia have not yet been established. Fearon et al.,11 however, showed that the association of weight loss, reduced food intake, and systemic inflammation, as defined by increased levels of C-reactive protein, identifies patients with both adverse function and prognosis.Multiple factors interact to produce cancer cachexia, including tumor products, hormones, and inflammatory mediators.12 This interaction promotes gluconeogenesis, limits anabolism, and increases catabolism. The pathogenesis of cancer cachexia is mediated by the induction of an inflammatory response to the growing tumor. Many host-derived inflammatory mediators involved in cancer cachexia have been identified. The cytokines tumor necrosis factor-α, interleukin-1, interleukin-6, and interferon-γ appear to play a significant role in this.13 Because elevated levels of these cytokines are rarely found in the blood of cancer patients, the effect may be more from paracrine than from systemic production.Additional mediators of cancer cachexia include two peptides produced by the tumor and known to influence protein and lipid metabolism, the proteolysis-inducing factor and the lipid-mobilizing factor, respectively. Proteolysis-inducing factor activates the ubiquitin proteolytic pathway, resulting in proteolysis; while lipid-mobilizing factor promotes breakdown of adipose tissue into fatty acids.9 The synergy between host-derived and tumor-derived factors increases the activity of the muscle ubiquitin-proteasome system,12 which is not counterbalanced by a similar increase of protein synthesis, with the net result of progressive muscle wasting.
Nutrition Support for Weight Loss and Cancer CachexiaNutritional interventions are valuable to cancer patients when they are easily user-friendly, promote preservation of lean body mass, and aim to maintain function and quality of life. Several new reports have examined supplements and additives for use in cancer patients to maintain lean body mass. Nutritional counseling must be the foundation of any program designed to raise energy or protein intake.The best therapeutic option for cancer cachexia is effective treatment of the underlying disease.14 If this cannot be achieved, then specialized nutritional support should be developed that aims at maintaining body weight, in particular lean body mass, by counteracting the negative effects on metabolism and eating behavior of the increased inflammatory response. Indeed, preserving lean body mass in cancer patients influences not only their morbidity but also their quality of life.15
The first step in the multimodal nutritional support of cancer patients is nutritional counseling. Early, intensive, individualized nutritional counseling has consistently been shown to be effective in preserving body weight and physical function in cancer patients.16 It should be emphasized that the key to success of this approach is strict adherence to patients' needs and frequent monitoring of results. Therefore, the efficacy of nutritional counseling in cancer patients relies on the presence of a well-trained and specialized nutrition support team, particularly when considering that in many cancer patients body weight stabilization cannot be achieved by a daily energy intake lower than 30 kcal/kg of body weight.5
Pharmacologic agents, such as the steroid megestrol acetate, have been used to increase appetite but are associated with fat gain rather than increase in lean body mass.17 Likewise, corticosteroids may also increase appetite but are actually catabolic agents that induce muscle breakdown, especially in inactive, fatigued cancer patients.17 Dronabinol, a derivative of cannabis, which stimulates the endocannabinoid system, has not been proven effective in improving appetite in cancer patients.17
More recently, the identification of the prophagic effects of the peptide hormone ghrelin and the increased understanding of the role in cancer anorexia-cachexia of the hypothalamic anorexigenic melanocortin system suggest the use of exogenous ghrelin or antimelanocortin peptides as anticachexia agents. Preliminary experimental and clinical studies appear promising, but larger trials are needed before their use can be routinely applied.18,19 Considering the central role of proteolysis-inducing factor and cytokines in triggering muscle wasting, it has been postulated that inhibition of their synthesis and activity may decrease proteolysis. The omega-3 fatty acid eicosapentaenoic acid (EPA) has been shown to have antitumor and anticachectic effects. Although the impact on cancer cachexia of supplemental fish oil capsules is questionable,20,21 the use of oral nutritional supplements enriched with EPA, at a dose of 2 to 3 g/day, appears to ameliorate lean body mass wasting.15,22
The supplementation of essential amino acids, and particularly of branched-chain amino acids (BCAA), has been shown to ameliorate cancer anorexia and stimulate protein synthesis, thereby maintaining muscle and lean body mass.23 These effects appear to be secondary to the inhibitory influence of BCAA, and in particular of leucine, on brain serotonergic neurotransmission, yielding to improved appetite, and on the ubiquitin–proteasome system, the main proteolytic system involved in cancer cachexia.23 Similar to the results observed with the supplementation of leucine, the use of β-hydroxy-β-methylbutyrate, a leucine metabolite, promotes deposition of lean body mass in cancer patients.23
Arginine plasma levels have been found to be reduced in cancer patients, suggesting a possible deficiency of this amino acid.24 However, its use in cancer patients has not been tested in large clinical trials. Anabolic agents have also been used to increase muscle mass and weight gain in cancer patients, with conflicting results.17 It is important to consider the possible side effects, including tumor growth stimulation, before prescribing anabolic agents to cancer patients.Branched-chain amino acids, EPA, and arginine represent a class of nutrients receiving much attention because of their influence on deranged host metabolism when administered at pharmacologic doses. These nutrients with pharmacologic properties have been termed “nutraceuticals,†� and their identification is progressively changing and enhancing the nutrition–metabolic support of cancer patients.Based on the available evidence, it appears advisable to use a hypercaloric (30 to 35 kcal/kg of body weight), high-protein diet rich in BCAAs (approximately 10 to 15 g/d, 50% of which should be leucine), and EPA (2 to 3 g/d) for patients with cachexia who can tolerate oral feeding. These nutrients can easily be incorporated into a daily routine with appropriate Use of Glutamine and ArginineUnder physiologic conditions, a sufficient amount of glutamine is endogenously produced to meet the body's demand. In conditions of stress, the amount of glutamine produced is no longer sufficient, and a glutamine deficit may occur without supplementation. Therefore, glutamine is considered a conditionally essential amino acid. Glutamine is the preferential substrate of rapidly dividing cells, including bone marrow and gut mucosa. Therefore, its supplementation may be beneficial in patients receiving high-dose chemotherapy who develop mucositis. Clinical studies indicate that provision of glutamine, either orally or parenterally, in patients undergoing bone marrow transplantation, improves nitrogen balance and reduces complications.34
Arginine has immunomodulatory effects that are beneficial to cancer patients. Arginine supplementation in combination with omega-3 fatty acids is effective in reducing surgical morbidity and hospitalization costs.47 However, concern exists that as a precursor to nitric oxide, its use in septic patients may be contraindicated. However, no specific studies have tested this.
Psychological Issues in Cancer
The good physician treats the disease; the great physician treats the patient who has the disease.Coping, distress, and support are crucial psychological issues facing every cancer patient and his or her health care team. The diagnosis of cancer is a life-altering experience for anyone. The nature of the patient's response to it will affect mood, adherence to treatment, and the nature of his or her social support. Effective coping with the disease involves dealing with its direct and indirect effects, ranging from managing the details of medical appointments to handling existential dread. Facing the illness and its consequences requires acknowledging and managing strong but inevitable emotions that can interfere with medical care,1 family and vocational engagement, sleep, diet, and exercise.2
A wide range and prevalence of psychiatric and psychological problem affect patients and families before, during, and after cancer care and treatment. Recent studies in adults treated in outpatient cancer clinics demonstrate a 40% to 50% clinically relevant level of distress.3,4 Some of the more important factors are listed in Table 64.4.1.In addition, there are also physical symptoms of the cancer and its treatments that overlap with the somatic symptoms that are included in many psychiatric conditions. For example, it is often very difficult for even skilled clinicians to determine the extent to which fatigue, decreased appetite, or sleep problems are related to depression or anxiety versus certain types of cancer and targeted therapies. It is thus easy to misattribute the symptoms of a mood disorder to the cancer itself and fail to notice important opportunities for treatment. Despite the complexity involved in coping with serious medical and psychiatric problems, there are some guiding principles for understanding patient dynamics and potential psychological issues.
Factors in Psychological AssessmentPast psychiatric historyAge at diagnosisGenderType of cancerStage of cancerLocation of cancerHow the cancer was diagnosedTypes of cancer treatmentFamily coherenceMarital/partner statusBehavioral/previous coping strategiesReligion/spiritualityJob/employment statusMedical/psychiatric insuranceSubstance use or abuse
PainFinancesGenetic risks and testingSurvivorship resourcesPrinciples of Adaptive Coping with CancerStressors are best handled by: Facing rather than fleeing Altering perception Coping actively Expressing emotion Social supportCommon elements of group psychotherapeutic intervention include the following60:1. Social support. Psychotherapy, especially in groups, can provide a new social network with the common bond of facing similar problems. At a time when the illness makes a person feel removed from the flow of life, when many others withdraw out of awkwardness or fear, group psychotherapeutic support provides a new and important social connection. Indeed, the very thing that damages other social relationships is the ticket of admission to such groups, providing a surprising intensity of caring among members from the very beginning. Furthermore, members find that the process of giving help to others enhances their own sense of mastery of the role of “patient†� and increases their self-esteem, imbuing the experience of illness with a new meaning.2. Emotional expression. The expression of emotion is important in reducing social isolation and improving coping. Yet patients often believe that they are controlling the psychological and even physical impact of the disease by suppressing their emotional reaction to it. This attitude is often reinforced by friends and family who are made anxious by a display of appropriate fear or sadness in the patient, and by medical professionals as well, who perceive a patient's sadness as an indication of nihilism about treatment or loss of hope. Persistent negative affect as is seen in depression often elicits anger in those involved with the patient, since the patient seems unwilling rather than unable to modulate their feelings. However, normal anxiety and sadness related to having cancer is phasic and is better managed through expression and working through. Indeed there is evidence that emotional expression actually facilitates the resolution of long-term negative emotion.20,50 Encouragement of emotional expression can enhance intimacy in families, providing opportunities for direct expression of affection and concern. The use of the psychotherapeutic setting to deal with painful affect also provides an organizing context for handling its intrusion. When unbidden thoughts involving fears of dying and death intrude, they can be better managed by patients who know that there is a time and a place during which such feelings will be expressed, acknowledged, and dealt with. Furthermore, disease-related dysphoria is more intense when amplified by isolation, leaving the patient to feel that he or she is deservedly alone with the sense of anxiety, loss, and fear that he or she experiences. Being in a group where many others express similar distress normalizes their reactions, making them feel less alien and overwhelming.3. Detoxifying dying. Processing existential concerns by facing rather than avoiding issues such as dying and death, which could be considered likely to exacerbate depression, actually helps to reduce it. This approach encourages patients to face what they most fear and find some aspect of it they can do something about (e.g., control the process of dying when death is unavoidable). This helps patients to feel more active and less helpless, even in the
face of dying. Others have combined principles of cognitive therapy with a focus on existential concerns,65 finding it an effective approach to reduce symptoms of distress. Death anxiety in particular is intensified by isolation, in part because patients often conceptualize death in terms of separation from loved ones. This can be powerfully addressed by psychotherapeutic techniques that directly confront such concerns.66 Yalom66 has described the ultimate existential concerns as death, freedom, isolation, and meaninglessness. Rather than avoiding painful or anxiety-provoking topics in attempts to “stay positive,†� this form of group therapy addresses these concerns head-on with the intent of helping group members make better use of the time they have left. The goal is to help those facing the threat of death to see it from a new point of view. When worked through, life-threatening problems can come to seem real but not overwhelming. Facing even life-threatening issues directly can help patients shift from emotion-focused to problem-focused coping.4. Reorganizing life priorities and living in the present. The acceptance of the possibility of illness shortening life carries with it an opportunity for re-evaluating life's priorities. Facing the threat of death in a way that facilitates a sense of active coping can aid in making the most of what remains in life.67 This can help patients take control of those aspects of their lives they can influence, while grieving and relinquishing those they cannot. For cancer patients who are experiencing the traumatic stressor of anticipating their imminent death and its impact on their loved ones, adjustment may be mediated by changes from past- or future-focused orientation to a present-focused one that is more congruent with the reality of their foreshortened future. They learn to establish realistic priorities for the time they have left. In addition, progress in life goal reappraisal, reorganization of priorities, and perception of benefits may also mediate improvement in symptoms and enhance quality of life.68
5. Enhancing family support. Psychotherapeutic interventions can also be quite helpful in improving communication, identifying needs, increasing role flexibility, and adjusting to new medical social, vocational, and financial realities.69 The group format is especially helpful for such a task, in that problems expressing needs and wishes can be examined among group members as a model for clarifying communication in the family.6. Improving communication with physicians. Support groups can be quite useful in facilitating better communication with physicians and other health care professionals.2,70 Groups provide mutual encouragement to get questions answered, to participate actively in treatment decisions, and to consider alternatives carefully.7. Symptom control. Many group and individual psychotherapy programs teach specific coping skills designed to help patients reduce cancer-related symptoms such as anxiety, anticipatory nausea and vomiting, and pain. Techniques used include specific self-regulation skills such as self-hypnosis, meditation, biofeedback, and progressive muscle relaxation. Hypnosis is widely used for pain and anxiety control in cancer to attenuate the experience of pain and suffering and to allow painful emotional material to be examined.71 Group sessions that involve instruction in self-hypnosis provide an effective means of reducing pain and anxiety and consolidate the major themes of discussion in the group.72
Communication
The spoken language is most important tool in medicine; almost nothing happens in its absence. Physicians commonly train themselves to meet very high standards of expertise, but this everyday tool gets about as much respect as paperwork, and perhaps training in its use.1,2 Yet the most common complaint that patients have now and have had for decades past is that doctors do not talk to them. It has been repeatedly shown that patients who understand what is happening to them and why, are more cooperative and compliant with physician's suggested regimens. The implication is that what you say to patients really matters. Every word matters. Sometimes physicians say, “I can't watch every word,†�but that would be like a surgeon saying, “I can't watch my scalpel every moment.†We �are all so accustomed to talking and using words in our everyday life that we forget the impact of words on the listener. And we forget that doctor-patient communication is not ordinary conversation. The spoken language acts on the person and what acts on the person acts on every part of the person. In talking with patients, physicians themselves are the primary therapeutic agent. The vehicle through which virtually everything that physicians do to and with patients is the relationship between the patient and the physician. That relationship is best which is built on trust, and trust is best engendered by the truth. That is not the end of the story; it is the beginning.
7. Skrining dan deteksi dini neoplasma
--Deteksi dengan tumor marker
Penanda tumor atau tumor marker yakni suatu subtansi yang dapat ditemukan dalam tubuh karena adanya kanker. Biasanya ditemukan dalam darah atau urine, yang diproduksi langsung oleh sel – sel kanker atau tubuh sendiri sebagai respons terhadap adanya kanker atau kondisi lain. Mayoritas penanda tumor berupa protein.
Ada beberapa macam penanda tumor, bebrapa hanya teradpat pada satu jenis kanker, dan lainnya bisa terdapat dalam beberapa jenis kanker.
Menurut dr. Kismardhani SpPK, Dokter Penanggungjawab Laboratorium Klinik Pramita Jl. Cik Ditiro No. 17 Yogyakarta, untuk melakukan pemeriksaan penanda tumor, dokter akan mengirim sampel darah atau urine pasien ke Laboratorium. Marker didapatkan dengan memeriksa darah atau urine menggunakan antibodi manusia yang akan bereaksi dengan protein spesifik tersebut.
Penanda Tumor ini digunakan untuk skrining dan deteksi awal kanker. Sementara skrining digunakan untuk memeriksa pasien yang tidak mempunyai gejala klinis. Deteksi Awal dilakukan untuk menemukan kanker apda stadium awal, sebelumnya terjadi penyebaran, dan masih berespons baik dengan terapi.
“ Penanda tumor yang sudah sangat dikenal yakni dengan pemeriksaan prostate-spesific antigen ( PSA ) dalam darah yang digunakan ( bersama dengan colok dubur ) untuk skrining kanker prostat, “ kata dr. Kismardhani.
Menurutnya, penanda tumor biasanya tidak digunakan untuk mendiagnosis kanker. Pada banyak kasus, kanker hanya didiagnosis dengan biopsi. Namun demikian, penanda tumor dapat membantu menentukan jenis Kanker dan membantu mendiagnosis penyebaran tumor ketika tumor primernya belum diketahui. Misal, seorang wanita dengan kanker pelvis dan abdomen, didapatinya penanda tumor CA 125 dengan kadar tinggi sangat menyokong dugaan kanker ovarium, walaupun tindakan pembedahan tidak dapat mengidentifikasi sumbernya. Hal ini menjadi sangat penting karena dapat menentukan terapi untuk jenis kanker ini.
Beberapa jenis kanker berkembang dan menyebar sangat cepat dibanding jenis lain. Tapi pada beberapa jenis Kanker ( misal kanker payudara ), beberapa akan berkembang dan menyebar lebih cepat dan sebagian lagi lebih atau kurang berespons terhadap terapi tertentu. Beberapa penanda tumor yang baru dapat membantu menunjukan agresivitas kanker seseorang atau seberapa baik responnya terhadap obat tertentu.
Satu hal terpenting dari manfaat penanda tumor, tandas dr. Kismardhani adalah untuk memonitoring terapi kanker, utamanya pasien stadium lanjut. Jika penanda tumor yang diperiksa spesifik dengan jenis kanker akan sangat mudah untuk mengetahui respons terapi daripada harus melakukan pemeriksaan foto thorax ulang, CT scan, bone scan atau pemeriksaan lain yang mahal.
Jika penanda tumor menurun kadanya, hampir selalu merupakan tanda keberhasilan terapi. Sebaliknya jika markernya meningkat, kemungkinan terapi harus diganti.
Marker juga digunakan untuk mewaspadai berulangnya ( relaps ) kanker setelah terapi inisial. Termasuk PSA ( untuk kanker prostat ), human chorionic gonadotropin ( HCG ) ( untuk tumor gestational trophoblast dan kanker sel germ pada ovarium dan testis ), serta Ca – 125 ( untuk kanker epitel ovarium ).
Beberapa wanita yang sudah mendapatkan terapi untuk tumor payudara selama bertahun – tahun harus melakukan pemeriksaan kada Ca 15-3. Hal ini kadang dapat mendeteksi
berulang kanker sebelum muncul gejala klinis atau terbukti dari pemeriksaan MRI. Hal yang sama pada carcinoembryonic antigen ( CEA ), untuk monitoring kanker colorectal.
Ada sejumlah Penanda tumor spesifik, antara lain :
ALPHA – FETOPROTEIN ( AFP ).
Sangat berguna untuk mengertahui responds terapi pada kanker hati ( Karsinoma Hepatoseluler ). Kada normal AFP biasanya kurang dari 20 ng/mL. Kadar AFP akan meningkat pada 2 dan 3 pasien dengan kanker hati. Kadar AFP meningkat bersama membesarnya tumor. Pada kebanyakan pasien dengan kanker hati, kadar AFP meningkat lebih dari 500 ng/mL. AFP meningkat pula pada hepatitis akut dan kronis, tapi jarang lebih dari 100 ng/mL. AFP juga meningkatk pada kanker testis tertentu ( jenis sel embryonal dan endodermal sinus ) dan digunakan untuk follow – up kanker tersebut. Peningkatan kadar AFP juga pada Kanker ovarium jenis tertentu yang jarang dan kanker testis yang disebut yolk sac tumor atau mixed germ cell cancer.
CA 15-3
Terutama untuk monitoring kanker payudara. Peningkatan kadar Ca 15-3 darah dijumpai pada kurang dari 10 % pasien dengan stadium awal dan sekitar 70 % pasien dengan stadium lanjut. Kadar biasanya turun seiring keberhasilan terapi. Kadar normal biasanya kurang dari 25 U/mL, tapi kadar sampai 100 U/mL kadang dijumpai pada wanita sehat.
8. Prinsip Modalitas terapi kanker
Selama ini di Indonesia ada lima (5) modalitas dalam terapi kanker yaitu:Modalitas Bedah, Radioterapi, Modalitas Kemoterapi, Modalitas TerapiHormon, Modalitas Terapi Target. Sementara di beberapa negara seperti Cina,Jepang, India, USA dan Jerman telah menggunakan modalitas keenam yaitucomplementary alternative medicine (seperti chiropractic, herbal, meditasi)sebagai pelengkap terapi.Modalitas BedahMetode bedah adalah metode terapi kanker yang paling lama. Bedah dapatdigunakan sebagai terapi kanker secara tunggal atau kombinasi dengan modalitaslainnya. Pasien kanker sering datang dengan status nutrisi yang buruk karenaanoreksia atau metabolisme katabolik akibat pertumbuhan tumor. Faktor inidapat memperlambat atau memperburuk kesembuhan setelah operasi. Pasiendapat mengalami neutropeni atau trombositopeni, yang dapat meningkatkanrisiko sepsis atau perdarahan. Oleh karena itu penilaian pre-operatif sangatpenting (Aft 2002; Hohenberger 2002; Rosenberg 1997).Peranan bedah onkologi ada tiga yaitu sebagai pencegahan kanker,diagnosis kanker, dan terapi kanker. Modalitas RadioterapiIradiasi dapat menghancurkan sel kanker karena laju metabolik selkanker lebih tinggi dan sel kanker tidak mempunyai kemampuan seperti sel
normal dalam perbaikan DNA yang rusak. Jenis radioterapi ada 2 yaitu radiasieksternal dan brakiterapi. Radiasi eksternal jika sumber radiasi berasal dari luartubuh. Sedangkan brakiterapi, jika sumber radiasi diletakkan di dalam/sedekatmungkin dari sel kanker (Hellman 1997).Efek samping radioterapi dapat akut dan delayed. Efek samping akutpaling sering terjadi, dapat diantisipasi dan terjadi dalam jangka waktu terbatas.Beratnya efek samping bergantung pada tipe iradiasi, region tubuh dan volumeiradiasi, dan kombinasi dengan terapi lainnya terutama dengan kemoterapi. Efeksamping radioterapi lebih lengkapnya dapat dilihat pada Tabel
Modalitas KemoterapiKemoterapi adalah pengobatan kanker dengan zat atau obat yangberkhasiat untuk membunuh sel kanker. Obat tersebut disebut sitostatika, artinyapenghambat kerja sel yang sedang tumbuh (proliferasi). Obat sitostatika dapatdiberikan secara sistemik (ke seluruh sistem tubuh), atau regional. Prinsipkemoterapi ada 3, yaitu membunuh/menghambat sel tumor induk dan anak sebarsecara sistemik, mengetahui mekanisme kerja obat sitostatika, dan mengetahuisifat biologi sel tumor (DeVita 1997; Ratain 1997). Tujuan pemberiankemoterapi ada 2 yaitu untuk tujuan kuratif dan paliatif. Tujuan kuratif artinyauntuk menyembuhkan penyakit. Sedangkan tujuan paliatif adalah untukmengurangi gejala penyakit dan untuk meningkatkan kualitas hidup penderitanya(DeVita 1997).
Modalitas Terapi HormonHormon adalah zat yang dikeluarkan oleh kelenjar endokrin, berfungsiuntuk perkembangan organ dan mengatur fungsi organ tersebut. Hormonmempunyai mekanisme feed back sehingga jumlah dalam tubuh dapatdipertahankan, sehingga fungsi organ tetap stabil. Kelainan genetik dapatmenyebabkan jumlah hormon meningkat/menurun dan kemudian mengganggufungsi organ (Hayes & Robertson 2002; Henderson 1997).Hormon terbukti berperan penting dalam menginduksi perkembanganberbagai jenis kanker seperti kanker payudara, endometrium, ovarium, prostat,tiroid, testis, dan tulang. Secara normal pertumbuhan dan fungsi normal organorgantersebut berada di bawah pengendalian hormon steroid atau hormonpolipeptida. Hormon dapat berperan dalam perkembangan kanker tanpamemerlukan suatu inisiator luar seperti kimiawi atau radiasi ionisasi (Hayes2002).Modalitas Terapi Target
Terapi target adalah usaha untuk mengurangi jumlah target yang
potensial untuk mendapatkan efek terapi, dari beberapa ratus target menjadi 20
atau 30 target. Hal ini dapat dilakukan dengan cara menghambat atau
menghentikan aktivasi proto-onkogen agar tetap dalam bentuk yang tidak
teraktivasi atau dengan cara mengunci protein penekan tumor dalam posisi yang
aktif. Cara kerja terapi target adalah dengan menutup reseptor yaitu reseptor
tirosin kinase, agar tidak dapat berikatan dengan ligan spesifik sehingga tidak
terjadi kaskade sinyal di bawahnya dan pada akhirnya tidak terjadi transkripsi.
Bentuk terapi target yaitu berupa antibodi monoklonal, yaitu antibodi spesifik
terhadap antigen yang diproduksi oleh hibridoma sel B untuk mendeteksi
molekul tertentu seperti antigen tumor. Antibodi monoklonal dapat mengenali
antigen spesifik tumor secara tepat sehingga dalam imunoterapi kanker diberi
julukan magic bullet (Clark 1996; Ross 2005).
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