UNIT 4.1/4.1G
SURGICAL
IMMUNOLOGY AND ORGAN TRANSPLANTATION
PART
A: SURGICAL IMMUNOLOGY
UNIT
OBJECTIVES:
Demonstrate an understanding of general immunological
principles and their application to surgical practice.
Demonstrate an understanding of the principles of care for patients with abnormal immune function who are undergoing general surgery procedures.
Demonstrate an understanding of the emerging field of molecular biology and the novel immune therapies having potential application to clinical surgery.
COMPETENCY-BASED
KNOWLEDGE OBJECTIVES:
Section
One: General Immunologic
Principles
1.
Describe the basic concepts of the human immune system, including:
a. Cells involved in
host defense
b. Central roles of
lymphocytes and macrophages
c. Their derivation
from pluripotent stem cells
2.
Summarize the major activities of the macrophage, its products of
secretion, and its role as the antigen-presenting cell (APC).
3.
Describe the ontogeny, function, and role in cellular immunity and
graft rejection of the T-lymphocyte; demonstrate understanding of the T-cell
receptor and its interaction with the human leukocyte antigen (HLA) complex.
4.
Summarize the events in T-cell activation, including the roles of CD4+
and CD8+ cells and the release of involved interleukins.
5.
Explain the development, differentiation, and function of B-lymphocytes
in the formation of antibodies; outline and describe the functional anatomy of
an immunoglobulin molecule.
6.
Describe
the immune functions of the spleen, liver, thymus, and bone marrow; summarize
the impact of their manipulation on the immune system.
7.
Describe
immunological changes which occur in the elderly patient compared to a younger
patient.
Section
Two: Defenses against Infection
1.
Describe the resident flora, mechanical barriers, local hormones, and
chemicals of the epithelium in the following tracts involved in the body's
defenses against infection:
a.
Gastrointestinal
b.
Respiratory
c.
Genitourinary
2. Describe the body's response to infection when:
a.
There has been no prior antigenic contact
b.
There has been prior contact
(1)
Passive and active immunization
(2)
T-cell memory activation
3.
Explain the therapeutic and prophylactic roles of intravenous
immunoglobulin and viral vaccines.
4.
Distinguish between several known congenital and acquired
immunodeficiency states, including sepsis and severe burns.
5.
Describe tests of cellular immune integrity, including skin and
laboratory tests of lymphocyte function.
Section
Three: Clinical Immunology
1.
Describe the mechanism of action and potential side effects of current
immunosuppressive agents; state the rationale for their use and timing in
transplantation and in other medical applications:
a. Prednisone
b. Cyclosporine
c. Azathioprine
d. Tacrolimus (FK5O6)
e.
Mycophenolatemofetil
(RS6144)
f.
Monoclonal
antibody (
2.
Differentiate between agents used to treat acute transplant rejection:
a. Steroids
b. Radiation therapy
c. Poly- and mono-
clonal antibodies
3.
Summarize the role and preparation of monoclonal antibodies in the
treatment of neoplastic lesions. Describe
their application to clinical pathology and diagnostic and therapeutic
oncology. Describe side effects and their treatment.
4.
Explain the preparation, quality control, and application of polyclonal
antibodies. Describe side effects and their treatment.
5.
Outline an approach to the management of infection in immunocompromised
patients resulting from:
a. Iatrogenic
immunosuppression secondary to drugs
b. Natural immune
deficiency states
c. Impaired immunity
secondary to cancer
6.
Formulate a plan for management of immunosuppression in patients with
severe surgical morbidity or complications.
Section
Four: Trends in Immunology and
Molecular Biology
1.
Recognize new and investigational immunosuppressive drugs used for
nontransplant medical conditions.
2.
Summarize the current rationale and clinical status of novel oncologic
treatments using biologic modifiers and immunomodulation; analyze their
potential limitations and side effects.
3.
Explain the manipulation of gene transplantation and
describe
several clinical applications currently being investigated.
4.
Discuss the growing importance of molecular biology and the basic
techniques of recombinant DNA technology to investigate problems in
immunology, oncology, and pathology.
5.
Explain the significance of transgenic animals, their creation, and
potential application to experimental and clinical transplantation.
COMPETENCY-BASED
PERFORMANCE OBJECTIVES:
1.
Participate in the perioperative management of immunosuppressive agents
in chronically-medicated patients undergoing general surgery.
2.
Plan and perform elective surgery in immunosuppressed patients with
attention to minimizing infectious risks; perform emergent surgical
intervention (treatment of perforated viscous) in similar high-risk patients.
3.
Optimize patients' immune state secondary to systemic compromise
following major surgery, burns, trauma, and malnutrition.
4.
Recognize and treat wound infections and other complex disorders in
chronically immunosuppressed patients undergoing elective and emergent
surgery.
5.
Monitor drug levels and side effects in immunosuppressants.
6.
Participate in the care of patients receiving immunostimulatory
medications (e.g., IV immunoglobulin [IVIG], granulocyte stimulating factor).
7.
Describe differences in survival rate which occur in elderly patients
compared to younger patients. Consider
the following factors:
a.
Differences
in work-ups that occur in elderly patients.
b.
Complications
in elderly versus younger patients
PART B:
ORGAN TRANSPLANTATION
UNIT
OBJECTIVES:
Demonstrate an understanding of the history of clinical transplantation and interpret the guidelines for preparing patients for organ transplantation.
Demonstrate a working understanding of the
fundamental immunologic principles governing organ transplantation and
immunosuppression.
Demonstrate understanding of the potential metabolic,
physiologic, and malignant side effects of immunosuppressants.
COMPETENCY-BASED
KNOWLEDGE OBJECTIVES:
Section
One: Background/Preparation
1.
Demonstrate a working knowledge of the history and evolution of
clinical transplantation, including:
a.
Early vascular surgery
b.
Concept of tolerance
c.
First successful organ transplants
d.
Introduction of immunosuppressive agents
2.
Describe the anatomic and biologic terms associated with organ
transplantation, donor and recipient relationships, and grafting between
species.
3.
Explain the human leukocyte antigen (HLA) complex, including its
genetic location and composition, pattern of inheritance, and the difference
between Class I and II antigens of the major histocompatability complex (MHC).
Consider these aspects:
a. Serological
determination HLA
b. Molecular methods
of HLA
c. Crossmatching
4.
Discuss the role of tissue typing in the identification and preparation
of patients for organ transplantation to include:
a.
Natural, pre-formed antibodies
b.
Acquired antibodies
c.
The role of panel reactive antibody (PRA)(sensitization)
d.
The effect of tissue typing compatibility on graft survival
5. Discuss
advanced age as a positive consideration in solid organ transplantation
by considering the importance of:
a.
Physiologic
status vs. absolute age in years
b.
Rates
of organ rejection and its severity among the elderly
c.
Elderly
compliance with medical regimens
d.
Extended
life expectancy
6.
Compare the 5-year survival for patients aged 60 and older receiving a
renal transplant with those undergoing dialysis.
7.
Define the criteria for organ and tissue donation; apply these criteria
to critically ill patients.
8.
Explain the clinical definition of brain death, including a discussion
of the available laboratory and radiologic studies to support the clinical
criteria.
9.
Analyze and formulate a plan for management of the organ donor.
10.
Outline the development of organ preserving solutions and techniques,
and describe
the currently practiced methods for handling and storing vascularized organs.
Section Two: Clinical
Transplantation
1.
Discuss the current method for the allocation of organs for
transplantation, including consideration of the need, availability, and
philosophical biases surrounding organ donation. (Be prepared to utilize the
algorithm for assigning organs based on the results of HLA typing, PRA, blood
type, age, and time-waiting.)
2.
Explain the united organ sharing (UNOS) method for assigning organs to
potential recipients. Discuss how local procurement agencies function to
optimize the donor organ pool and facilitate coordination of organ harvesting
and their subsequent distribution.
3.
Analyze and outline the indications for kidney, pancreas, heart, and
lung transplant; relate the relative frequency of these operations as well as
rates of patient and graft survival.
4.
Specify the various drug schemes for induction, maintenance, and
rejection therapy, including new "rescue" therapies.
5.
Describe the mechanism of action, dosing schedule, and side effects of
the following immunosuppressive drugs:
a. Azathioprine
b. Prednisone
c. Anti-lymphocyte
globulin
d. Cyclosporine
e. Anti-T3 monoclonal
antibody
f. Tacrolimus (FK506)
g.
Anti
IL-2R
h.
Mycophenolate
mofetil
i. Rapamycin
6.
Analyze the short- and long- term risks of chronic immunosuppression:
a. Opportunistic
infections d.
Lymphoproliferative disease
b. Cardiovascular
problems e.
Rejection
c. Autoimmune diseases
7.
Evaluate the diagnostic maneuvers to detect hyperacute, acute, and
chronic organ rejection.
COMPETENCY-BASED
PERFORMANCE OBJECTIVES:
1.
Evaluate potential candidates for living-related and cadaveric
vascularized organ transplantation, including:
a.
Clinical suitability
b.
Strength of social support
c.
Expected graft and patient survival
2.
Participate in the pre- and post- operative surgical management of
patients after vascularized organ transplant.
3.
Assist/perform kidney, pancreas, and heart transplantation.
4.
Participate in the perioperative management of immunosuppressive drug
therapy, including monitoring drug levels and treating potential toxicities.
5.
Participate in the evaluation of patients suspected of organ rejection
to include:
a.
Laboratory and radiologic testing
b.
Administration of immunosuppressive (IS) agents
c.
Following patients for potential acute and chronic side effects
6.
Participate in the preparation and handling of multiple organ harvest
in the brain dead patient.
7.
Define
suitability characteristics of organs for transplantation.
8.
Formulate
a response to these ethical questions:
a.
Should
an individual with renal disease, who is 70-75 years old, have access to the
scarce resource of cadaver kidneys?
b.
Should
the surgeon reasonably consider renal transplantation in older recipients when
the nephrologist contends that dialysis is the preferred method of treatment?
9.
Manage postoperative surgical complications, including wound infection,
anastomotic stenoses and leaks, and lymphocele formation.
The Surgical
Immunology and Organ Transplantation unit was revised by Carl E. Haisch, MD
from the Curriculum, third edition.
SELECTED
BIBLIOGRAPHY:
Albrechtsen
D, Leivestad T, Sodal G, et al. Kidney transplantation in patients older than
70 years of age. Transplant Proc
1995;27:986-988.
Bromberg JS, Punch JD, Merion RM, et al.
Transplantation and immunology. In:
Cecka JM, Terasaka PI. Optimal use of older donor
kidneys: older recipients. Transplant
Proc 1995;27:801-802.
Diethelm
AG, Deierhoi MH, Barber WH, et al. Organ transplantation in clinical surgery.
In:
Faubert PF, Porush JG. Renal Disease in the Elderly (2nd ed).
Flye MW. Atlas
of Organ Transplantation.
Ghobrial RM, Kahan BD. Physiologic basis of
transplantation. In: Miller TA
(ed), Modern Surgical Care: Physiologic
Foundations and Clinical Applications (2nd ed).
Greenfield LJ, Mulholland M, Oldham KT,
Zelenock
GB, Lillemoe KD (eds). Transplantation and immunology. Surgery:
Scientific Principles and Practice (3rd
ed).
Haisch CE, Verbanac KM. Immunity and the
immunocompromised patient. In:
Miller TA (ed), Modern Surgical Care:
Physiologic Foundations and Clinical Applications (2nd ed).
Kahan
BD, Ponticelli C. Principles and Practice of Renal Transplantation.
Morris PJ. Kidney Transplantation:
Principles and Practice (5th ed).
Richie
RE, Pierson RN, III, Fox M, et al. Solid organ transplantation. In:
Adkins RB, Jr., Scott HW, Jr. (eds), Surgical
Care for the Elderly (2nd ed).
Rohrer
RJ. Basic immunology for surgeons. In:
O’Leary JP (ed), The Physiologic Basis
of Surgery (2nd ed).
Schaubel D, Desmeules M, Mao Y, et al.
Survival experience among elderly end-stage renal disease patients—a
controlled comparison of transplantation and dialysis. Transplantation
1995;60:1389-1394.
Vivas CA, Hickey DP, Jordan ML, et al. Renal
transplantation in patients 65 years old or older. J Urol 1992;147:990-993.
Web
reference
http://www.unos.org
UNIT 4.2/4.2G
SURGICAL
ONCOLOGY
UNIT
OBJECTIVES:
Demonstrate understanding of the biology, pathology,
diagnosis, treatment, and prognosis of neoplastic diseases.
Demonstrate
proficiency in diagnosis, preparation, operative treatment, and total
management of the cancer patient,
including
long-term follow-up care.
Understand surgical options of curative and palliative care for cancer patients.
Understand the network of community resources and their functions, available to patients at end of life.
COMPETENCY-BASED
KNOWLEDGE OBJECTIVES:
Junior Level:
1.
Discuss frequency/death rates of the top five benign and malignant
neoplasms in men, women, and children in the
2.
Describe trends of increasing, decreasing, and high incidence for
certain solid neoplasms.
3.
Explain
the implications of the heterogeneous cellular makeup of most solid neoplasms
with reference to clinical behavior and response to adjuvant treatment.
4.
Discuss
the mechanisms of cellular apoptosis and the potential feasibility for
therapeutic applications.
5.
Identify genetic factors associated with neoplastic disease in regard
to known proto-oncogenes.
6.
Define current theories of carcinogenesis.
7.
Summarize the tenets of tumor biology, including the biochemical events
of invasion and metastasis; describe the natural history of these lesions.
8.
Identify and differentiate between the diagnostic features of benign
versus malignant neoplasms (gross and microscopic).
9.
Predict patterns of presentation of malignant neoplasms.
10.
Describe the characteristics of the various staging systems and explain
their use in evaluating malignant neoplasms.
11.
Outline the appropriate usage of tumor markers, tumor excretory
metabolites, and diagnostic cytologic techniques.
12.
Describe the principles of surgical technique for operative procedures
designed for cure of malignant diseases and their application to endoscopic
operative techniques.
13.
Summarize the nutritional requirements for cancer patients, and
describe how they differ from those recommended for a healthy patient.
14.
Describe indications for curative versus palliative treatment, and
formulate therapeutic plans for each approach.
15.
Outline the status of the current predominant investigative work in
cancer immunotherapy.
16.
Explain the rationale for the use of heat shock proteins in conjunction
with immunology.
17.
Summarize current techniques of genetic screening for cancer.
18.
Describe the biologic rationale, mechanisms, and current status of gene
therapy for malignancy.
19.
Describe the enzymatic determinants of prognosis for epithelial derived
cancers and their biologic sources.
20.
Discuss the economic and psychosocial issues associated with malignant
disease, and analyze how they affect the management of patients with cancer,
including:
a.
Ethics of cancer management
b.
Rehabilitation
c.
Home care resources
d.
Patient support groups
e.
Family support groups
f.
Enterostomal therapy
g.
Cost containment
h.
Pre-admission procedures and authorization
i.
Conservation of in-patient resources
j.
Special problems of the elderly
k.
Tumor registry data
21.
Identify available social service and community agency resources to
address the issues listed in #20 above.
Senior Level:
1.
Apply clinical screening for common malignancies. Recognize typical
presentations and clinical manifestations for different types of neoplasms.
2.
Describe the stimuli for and the biologic events in angiogenesis and
the potential therapeutic implications thereof.
3.
Discuss the known facts relative to tumor suppressive genes and the
implications of mutations.
4.
Stage specific neoplasms both clinically and pathologically, including
the tumor, nodes, and metastasis system (TNM).
5.
Relate tumor staging to prognosis.
6.
Describe differences in presentation, treatment, and outcomes for
malignancy in older patients.
7.
Compare each applicable treatment modality to the prognosis for tumors
within the scope of general surgery.
8.
Apply post-treatment screening/surveillance for common malignancies.
9.
Discuss the known facts relative to tumor recurrence after local
resection of a primary lesion of the breast and colon with regard to survival.
10.
Identify margins of resection and how this relates to local recurrence.
11.
Describe the indications for and actions of pharmacologic support in
the postoperative state.
12.
Describe the indications and means for implementing nutritional support
in the pre- and post- operative cancer patient.
13.
Explain the fundamental principles of radiation oncology and detail its
application as a primary therapy for the treatment of selected benign and
malignant lesions.
14.
Summarize the indications and appropriate modalities for adjuvant
therapy within the scope of general surgery, including chemotherapy, radiation
therapy, immunotherapy, and gene therapy.
15.
Describe radioimmunoguided surgery (RIGS) and its clinical
applications.
16.
Explain the rationale and methodology employed in lymphatic mapping and
sentinel node biopsies along with the expected level of positive findings.
17.
Understand the surgical options for venous access and oncologic care,
and their risks/complications.
18.
Describe the criteria and necessary procedures for intraoperative
monitoring of cardiovascular and pulmonary functions of the cancer patient.
19.
Analyze and explain an holistic approach to the treatment of patients
with cancer.
20.
Analyze the medical preparation of patients for cancer surgery to
include the correction of metabolic and nutritional deficits.
21.
Indicate the potential alterations in pulmonary function in the elderly
patient which may affect preoperative preparation and postoperative
management.
22.
Identify the indications of anticipated need in elderly patients for:
a.
Postoperative
urinary tract decompression
b.
Nutritional
support
c.
Thromboembolism
prophylaxis
23.
Define and apply the criteria for palliative versus curative treatment
plans.
24.
Analyze and explain the rationale for combined adjuvant modalities in
the prevention and treatment of cancer recurrence.
25.
Apply proper clinical and demographic data to the tumor registry.
26.
Outline the indications for and initiate requests for appropriate
consultation.
27.
Demonstrate a working knowledge of prior research milestones, current
research efforts, and cancer research methodology.
COMPETENCY-BASED
PERFORMANCE OBJECTIVES:
Junior Level:
1.
Perform a complete history and physical examination on patients with
cancer.
2.
Formulate an appropriate differential cancer diagnosis, and record an
independent, written diagnosis for each cancer patient assigned.
3.
Excise benign lesions of skin, dermal appendages, and breast.
Demonstrate proper wound care and follow-up management.
4.
Excise skin cancers, demonstrating proper wound margins and appropriate
wound closure and follow-up management.
5.
Close wounds following major resections.
6.
Manage colostomies and ileostomies.
7.
Design an appropriate nutritional support program for a cancer patient
both pre- and post- operatively.
8.
First assist on colostomies, ileostomies, and wedge resections of lung
and liver.
9.
Perform lymph node biopsies, breast biopsies, and procedures of similar
magnitude.
10.
Cut en bloc gross surgical
specimens.
11.
Interpret frozen section slides with supervision.
12.
Perform nutritional assessments and plan nutritional support programs.
13.
Perform feeding gastrostomies and tube jejunostomies.
14.
Record clinical and pathological correlations by presenting the
clinical picture and operative findings on each assigned cancer patient.
15.
Perform all varieties of endoscopy (upper and lower gastrointestinal)
and bronchoscopy.
Senior Level:
1.
Demonstrate the capability for independent function in all aspects of
cancer patient management, including palliative care planning.
2.
Prepare and defend the preoperative assessment plan for the elderly
patient in preparation for:
a.
Gastric
resection
b.
c.
Pancreatic
resection (Whipple Procedure)
d. Mastectomy
3.
Stage specific neoplasms clinically and pathologically using the TNM
system.
4.
Prepare patients medically for cancer surgery, including correction of
nutritional and metabolic deficits.
5.
Specify and prepare management plans for nutritional support in the
elderly patient. Indicate
differences to be expected in requirements compared to patients less than 50
years of age.
6.
Assess the need and institute appropriate monitoring both pre- and
post- operatively.
7.
Use appropriate support from pharmacologic agents.
8.
Prepare an operative plan for treatment of malignant disease.
9.
Perform colostomies, colostomy closures, and bowel anastomoses of all
types.
10.
Demonstrate proficiency in the use and interpretation of operative and
endoscopic ultrasonography.
11.
Demonstrate proficiency in fine-needle and core biopsies of the breast.
12.
Demonstrate proficiency in endoscopic ultrasonography for detection of
hepatic metastases and depth of invasion of colorectal lesions.
13.
Demonstrate proficiency in gamma probe-directed or dye-directed
sentinel lymph node biopsy for breast cancer and melanoma.
14.
Assume responsibility for managing the psychosocial aspects of
neoplastic disease.
15.
Perform, with appropriate supervision, major resections in neck, chest,
abdomen, breast, and extremity, including complex operative procedures (e.g.,
Whipple procedures, construction of ileal loop bladder, major neck
dissections, segmental and lobar hepatic resections).
16.
Utilize appropriate social agencies and support groups in cancer
patient management.
17.
Assume teaching responsibilities for junior residents as assigned.
18.
Use laser therapy, photodynamic therapy, and cryotherapy when
indicated, observing proper precautions.
19. Participate
in a multidisciplinary tumor board.
The Surgical Oncology unit was revised by Rosa E. Cuenca, MD, from the Curriculum, third edition, by Douglas M. Evans, MD.
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RB, Doherty FJ, Mele FM, et al. Selected technologies and general surgery.
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Velanovich V. Preoperative screening based on
age, gender, and concomitant medical diseases. Surgery 1994;115:56-61.
Watters JM, Kirkpatrick SM, Hopbach D, et al.
Aging exaggerates the blood glucose response to total parental nutrition. Can
J Surg 1996;39:481-485.
Watters JM, Moulton SB, Clancy SM, et al.
Aging exaggerates glucose intolerance following injury. Trauma 1994;37:786-791.
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