CANCER SURGERY
Educational Objectives
| The goal of this program is to improve the surgical management of soft tissue sarcomas (STS), thyroid cancer, and neoplasms
of the foregut. After hearing and assimilating this program, the clinician will be better able to:
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 | 1. Recognize the risk factors and genetic features of STS, diagnose extremity STS tumors, and choose optimal methods
of surgical resection with or without radiation therapy.
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| 2. Describe the goals of surgery for thyroid cancer.
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| 3. Evaluate the role of central lymph node dissection in treating thyroid cancer.
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| 4. Implement the revised guidelines of the American Thyroid Association for thyroid cancer surgery.
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| 5. Manage neoplasms of the foregut using minimally invasive surgical techniques and limit recurrence.
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Faculty Disclosure
In adherence to ACCME Standards for Commercial Support, Audio-Digest requires all faculty and members of the planning
committee to disclose relevant financial relationships within the past 12 months that might create any personal conflicts of interest.
Any identified conflicts were resolved to ensure that this educational activity promotes quality in health care and not a
proprietary business or commercial interest. For this program, Dr. Doherty disclosed a consulting relationship with Medtronic
and 3M Health Information Systems. Drs. Quinn and Greene and the planning committee reported nothing to disclose.
Acknowledgements
Dr. Quinn’s lecture was recorded at Current Concepts in General Surgery and Trauma, held September 5-7, 2007, in
Albuquerque, NM, and sponsored by the University of New Mexico Health Science Center, Department of Surgery,
and Office of Continuing Medical Education. Dr. Doherty’s lecture was recorded at 36th Annual Phoenix Surgical
Symposium, held February 13-16, 2008, in Phoenix, AZ, and sponsored by Banner Health and The Phoenix Surgical
Society. Dr. Greene’s lecture was recorded at Surgery of the Foregut, held February 18-20, 2008, Coral Gables, FL,
and sponsored by the Section of Minimally Invasive Surgery, and the Bariatric Institute of Cleveland Clinic Florida
in conjunction with the European Surgical Institute, the Federation of Latin American Surgeons, and the Association
of Latin American Endoscopic Surgeons. The Audio-Digest Foundation thanks the speakers and sponsors for their
cooperation in the production of this program.
| CONTEMPORARY MANAGEMENT OF EXTREMITY SOFT TISSUE SARCOMAS —Robert H. Quinn, MD, Associate
Professor, Department of Orthopaedics and Rehabilitation, Division of Orthopaedic Oncology, University of New Mexico
School of Medicine, Albuquerque
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| Background: incidence in United States—soft tissue sarcomas (STS) rare; ≈8600 new cases (0.63% of new cancers)
and ≈3660 deaths per year (1.15% of cancer deaths); sites—most common in extremities (60%), then trunk, retroperineum,
and head and neck; histologic subtypes—>50 total, including malignant fibrohistiocytoma (MFH; most common),
liposarcoma, leiomyosarcoma, synovial sarcoma, and malignant peripheral nerve sheath tumors
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| Epidemiology: risk factors—exposure to high-dose (ie, therapeutic) radiation causes dose-dependent, 8- to 50-fold increase
in rate after 5-yr to 10-yr latency; must occur within irradiated field; exposure to herbicides (eg, phenoxyacetic acids)
and wood preservatives (eg, chlorophenols); exposure to Agent Orange no longer considered risk factor; chronic
lymphedema increases incidence
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| Genetics: amplification of oncogenes—eg, MDM2, N-myc, c-erB2, ras family, correlated with adverse outcomes; inactivation
of tumor suppressor genes—eg, retinoblastoma (Rb); p53 mutations (seen in 30%-60%); patients with germline
mutations in p53 (Li-Fraumeni syndrome) have high incidence of STS; chromosomal translocations—may code
for oncoproteins (eg, Ewing’s sarcoma has EWS-FLI1 fusion, clear cell sarcoma has EWS-ATF1 fusion, myxoid liposarcoma
has TLS-CHOP fusion, alveolar rhabdomyosarcoma has PAX3-FKHR fusion, synovial sarcoma has SSX-SYT fusion);
with exception of Ewing’s sarcoma, translocation expressed in low percentage of tumors
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| Detection: imaging—magnetic resonance imaging (MRI) for extremities, pelvis, and spine; computed tomography (CT)
gold standard for retroperitoneum and thorax; staging chest CT used when tumor >5 cm and/or high-grade (speaker
recommends for all patients because all STS can metastasize); x-ray possibly useful for lesions near bone and determining
mineralization; bone scan not helpful because metastatic bone involvement revealed in chest CT; angiography not
helpful unless tumor originates from blood vessel (eg, leiomyosarcoma)
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| Diagnosis: imaging—MRI occasionally helpful for diagnosis of certain tumors (eg, lipomas); heterogeneity may indicate
well differentiated, high-grade, or dedifferentiated tumor; calcification in CT or x-ray may indicate synovial or liposarcoma
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| Biopsy: fine-needle aspiration (FNA)—60% to 96% accuracy reported; often too few cells to determine grade (tumors
too heterogeneous); reported accuracy possibly biased, and studies inconclusive; FNA useful to detect recurrence and
metastasis; core-needle biopsy—provides more tissue and greater accuracy, but still possibly biased; incisional
biopsy—higher complication rate but higher diagnostic accuracy (98%-99%) and lower rate of repeat procedures; excisional
biopsy—useful for small easily accessible lesions in extremity or trunk; speaker recommends longitudinal excision
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| Prognosis and staging: determined by tumor depth, grade, and size; depth—patients with superficial tumors do better,
but deep STS more common; grade—metastatic potential 5% to 10% for low, 25% to 30% for intermediate, and 50% to
60% for high; size—metastatic potential 15% for tumors <5 cm, 30% for tumors ranging from 5 to 10 cm, 50% for 10 to
15 cm, 65% for >15 cm; tumor size at diagnosis 12 cm on average; patients 30 to 40 yr of age on average
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| Metastasis: site—usually lung; 5% lymph node (10%-20% for rhabdomyosarcoma, epithelioid, clear cell, MFH, synovial
and angiosarcomas); liver and peritoneum with retroperitoneal sarcoma; bone, brain, and liver, but rarely in isolation;
timing—80% within 2 to 3 yr, 98% within 5 yr
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| Surgery: amputation—still may be treatment of choice for some patients; resection (limb salvage)—National Institutes
of Health (NIH) recommends wide local excision with minimum 2-cm margin as standard of care (often difficult to
achieve such wide margins)
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| Radiation therapy: frequently necessary when margins <2 cm; high dose needed (60-70 Gy); cannot compensate for
inadequate surgery; covers 5- to 7-cm margin; preoperative use—covers smaller field; higher rate of wound complications;
shrinkage of tumor unlikely; intraoperative use—(eg, placement of brachytherapy catheters, and postoperative
afterloading) used more in retroperitoneal tumors; postoperative—larger field required; speaker favors postoperative
delivery because of lower rate of wound complications
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| Recurrence: older studies showed ≈10% local recurrence rate, regardless of method of surgery and/or radiation therapy
(eg, amputation, wide-margin surgery alone, wide-margin plus irradiation, minimal-margin plus irradiation with experienced
surgeon); current study shows 2.8% recurrence rate, even with minimal margins
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| Chemotherapy: only doxorubicin, dacarbazine (DTIC), and ifosfamide associated with rate of response >20%; meta-
analysis of 1500 patients showed time to recurrence and recurrence-free survival significantly better using doxorubicin
than control; only 4% overall survival in treated group, slightly better for tumors in extremity, but mortality from chemotherapy
approximately 10%; chemotherapy generally not indicated
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| Future therapy: biologic therapy—gastrointestinal stromal tumor (GIST) cells express c-Kit (CD117), transmembrane
glycoprotein receptor that regulates cell growth and survival; in-frame deletions or point mutations cause ligand-independent
activation; 54% response rate with 10% to 15% recurrence when tumors treated with selective c-Kit inhibitor,
ie, imatinib mesylate (Gleevec; ST1571)
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| Follow-up: chest CT—every 3 mo for 2 yr, then every 6 mo for 2 yr, then annually for 1 to 5 yr; MRI—every 3 to 12
mo for 5 to 10 yr; can be combined with CT
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| Pitfalls: one study showed patients with unplanned excision did as well as others after salvage surgeries and irradiation;
transverse incisions difficult to convert to longitudinal; STS can present as hematoma; fungating tumors require radiation
therapy and surgery
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| THYROID CANCER: HIGHLIGHTS OF AMERICAN THYROID ASSOCIATION GUIDELINES —Gerard M.
Doherty, MD, Norman Thompson Professor, Department of Surgery, Chief, Division of Endocrine Surgery, Head, Section
of General Surgery, and Program Director, Department of Surgery, University of Michigan Medical School, Ann Arbor
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| Background: revision of American Thyroid Association (ATA) guidelines authorized in 2004; topics included role of preoperative
staging, appropriate surgery, role of postoperative staging systems, role of postoperative radioactive iodine remnant
ablation, role of thyrotropin suppression therapy, and roles of adjunctive external beam or chemotherapy in treatment
of thyroid cancer; main surgical controversy involves application of central neck lymph node (CLN) dissection
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| Goals of surgery: remove entire primary tumor, any disease extending beyond thyroid capsule, and any involved cervical
lymph nodes; minimize morbidity from treatment and disease; permit accurate staging; facilitate postoperative treatment
with radioactive iodine; permit long-term surveillance, and minimize risk for disease recurrence and metastasis
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| Study: evaluated baseline thyroglobulin (Tg) and level stimulated by recombinant thyrotropin (TSH) in patients with differentiated
thyroid cancer; best outcomes shown in patients with unmeasurable levels of Tg at baseline and no increase after
stimulation; had lowest likelihood of recurrence, and received least aggressive follow-up treatment
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| Main guidelines: total or near-total thyroidectomy recommended for most patients; lobectomy possibly sufficient for
small (≤15 mm), low-risk, isolated, intrathyroidal papillary carcinomas without nodal metastasis; consider routine central
compartment (level 6) LN dissection for patients with papillary thyroid carcinoma and suspected Hürthle cell carcinoma;
near-total or total thyroidectomy without central LN dissection possibly appropriate for follicular cancer and as alternative
for papillary and Hürthle cell cancers when followed by therapy with radioactive iodine; concern and controversy remain
about potential morbidity from more aggressive operation
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| Background: current data do not favor bilateral over unilateral dissections, but either better than no CLN dissection
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| Benefit: dissection limits recurrence, reduces need for further radioactive iodine therapy, and additional operations; study
results—195 patients with papillary thyroid cancer and routine dissection of level 6 CLNs had 1.6% observed disease-
specific mortality, compared to 8% to 11% expected after 13 yr; 5 of 8 patients who died had metastatic disease at diagnosis
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| Difficulty identifying positive CLNs at time of surgery: study results—found only 61 of 118 patients with involved CLNs
identifiable before return of pathology results; second study—positive nodes identified in only 64% of patients with involved
CLNs at time of surgery
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| Study using surrogate end point: among 447 patients who had clinically node-negative papillary thyroid cancer, 391 underwent
total thyroidectomy alone; subsequent 56 patients underwent total thyroidectomy with dissection of CLNs; all had
radioactive iodine ablation; study characteristics—not randomized; no contemporaneous controls; evaluated Tg levels
at 6 mo after treatment as surrogate for completeness of therapy; patients who underwent CLN dissections had more parathyroid
autografts (1.6 per patient); results— significant rate of temporary hypocalcemia, but unchanged rates of permanent
hypoparathyroidism (1 in 56 vs 2 in 391) and rate of permanent recurrent laryngeal nerve injury; mean Tg levels
at 6 mo in group with central neck dissection decreased from 9.3 to 0.41 ng/mL; 43% of patients in group without and
72% of patients with CLN dissection had low levels of Tg after stimulation, suggesting good prognosis; conclusions—
limited level 3 data to support survival benefit of central neck dissection; CLN dissection can significantly reduce serum
Tg and increase proportion of patients with undetectable Tg
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| Recommendations (from speaker and ATA committee): remove CLNs during thyroidectomy; new guidelines
expected to reflect wider role for CLN dissection; for papillary thyroid cancer >1 cm, use ultrasonography (US) to determine
extent of disease; perform thyroidectomy with minimal dissection and no lymphadenectomy (speaker disagrees
with recommendation and recommends total thyroidectomy with CLN dissection including radioactive iodine remnant
ablation for nearly all patients and long-term TSH suppressive therapy)
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| UPDATE ON LAPAROSCOPIC SURGERY FOR NEOPLASMS OF THE FOREGUT: ARE TROCAR SITE METASTASES
STILL A CONCERN ?—Frederick L. Greene, MD, Chair, Department of Surgery, Carolinas Medical Center,
Charlotte, NC
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| Introduction: large database shows only 1.5% to 2% rate of cancer recurrence at trocar site; minimally invasive surgery
(MIS) procedures safe and effective, but improvements needed in instrumentation, optics, and education; TNM staging
system important for determining therapeutic approach
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| Limiting port-site metastasis: approach to pneumoperitoneum important; turbulence, smoke, carbon dioxide, and exfoliation
may contribute to metastasis; careful tissue handling critical (eg, use of specimen bag); application of tumoricidal
agents, eg, povidone-iodine (Betadine), to trocar site possibly beneficial; speaker recommends devices used with HandPort
System inserted into abdominal wall to create barrier; reduction of intraperitoneal smoke depends on improvements in energy
sources; studies show patients who experience hypothermia during surgery (as most do) have higher likelihood of port-
site recurrence
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| Managing GIST: rare neoplasms derived from interstitial cells of Cajal in wall of gut; incidence has increased because
frequently found during upper endoscopy; GIST vary from malignant to benign, TNM system for GIST under development;
resection only cure
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| Evaluating tumor: immunohistochemistry—request c-Kit (CD117) and CD34 stains from pathologist; mitotic count—
important for differentiating benign from malignant (range of 3-5 per 50x high-power field)
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| Laparoscopic resection: reliable endoscopic stapler available; tumors located mostly in foregut and reachable by upper endoscopy;
previously 2-cm margin considered sufficient, but now negative (R0) margin recommended; LN involvement
rare; studies show equal operating room times, and reduced blood loss and hospital stay using MIS vs open approach; no
long-term studies showing efficacy of laparoscopic resection; initial recommendation to use for tumors ≤2 cm now expanded
to include larger tumors
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| Prospective database: patients—50 consecutive patients (equal numbers of men and women), most had stomach tumors,
60 yr of age on average; techniques—wedge resection using typical resective techniques, enterectomy, and one
total laparoscopic gastrectomy; use split-leg table, flexible endoscopy, laparoscopy, and US; need ability to cut frozen
sections to evaluate margin
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| Case examples: first example—for surgery of upper foregut, used 2-mm and 3-mm trocars for access to stomach and
flexible endoscopy (sutures used but not absolutely necessary if removed submucosally); second example—for lesion
of anterior gastric wall, put holding suture on lesion to lift and remove with good margin using gastric stapler; third
example—for lesion on posterior gastric wall (more difficult approach), make gastrotomy with UltraCision or LigaSure
device; for posterior wall, must suture to pick up, do full-thickness excision (use stapler), and test back wall
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| Postoperative care: clear liquid diet through nasogastric tube for 24 to 36 hr; regular diet by second to third day
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| Outcomes: no ruptures of tumors or intra-abdominal complications; no conversions to open procedures; no gastric leaks
because conventional methods used to close; complications minor; no mortalities; average tumor size—4.4 cm; all margins
R0; average mitotic count 5 to 50 per high power field (low malignant potential); 2 early patients died from disease
during 36 mo follow-up, but now CT performed on all patients, and imatinib used for patients with evidence of advanced
disease; no port-site recurrences observed; lesions from patients with recurrence showed positive staining by CD117 or
CD34; American College of Surgeons Oncology Group (ACOSOG) trial used imatinib and found role for large tumors in
adjuvant setting; trial stopped early because of clear advantage for patients with large (3-cm) GIST with high mitotic index
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Suggested Reading
Ahn JE et al: Diagnostic accuracy of CT and Ultrasonography for evaluating metastatic cervical lymph nodes in patients
with thyroid cancer. World J Surg 32:1552, 2008; Aksnes LH et al: Limb-sparing surgery preserves more function than
amputation: a scandinavian sarcoma group study of 118 patients. J Bone Joint Surg Br 90:786, 2008; Alam I et al: Laparoscopic
management of acutely presenting gastrointestinal stromal tumors: a study of 9 cases and review of literature. J
Laparoendosc Adv Surg Tech A 17:626, 2007; Cognetti DM et al: Management of the neck in differentiated thyroid
cancer. Surg Oncol Clin N Am 17:157, 2008; De Giorgi U et al: Critical update and emerging trends in imatinib treatment
for gastrointestinal stromal tumor. Rev Recent Clin Trials 2:43, 2007; Dionigi G et al: Medullary thyroid carcinoma:
surgical treatment advances. Curr Opin Otolaryngol Head Neck Surg 16:158, 2008; Eilber FC, Dry SM:
Diagnosis and management of synovial sarcoma. J Surg Oncol 37:314, 2008; Elaraj DM, Clark OH: Changing management
of patients with papillary thyroid cancer. Cur Treat Options Oncol 8:305, 2007; Fitzgibbons SC et al: The
treatment of thyroid cancer. Am Surg 74:389, 2008; Gerrard G, Gill V: Thyroid cancer guidelines—what’s new? Clin
Oncol (R Coll Radiol) 20:264, 2008; Gosnell JE, Clark OH: Surgical approaches to thyroid tumors. Endocrinol
Metab Clin North Am 37:437, 2008; Gronchi A et al: Combined modalities approach for localized adult extremity soft-
tissue sarcoma. Expert Rev Anticancer Ther 8:1135, 2007; Grubbs EG, Evans DB: Role of lymph node dissection in
primary surgery for thyroid cancer. J Natl Compr Canc Netw 5:623, 2007; Hohenberger P, Wysocki WM: Neoadjuvant
treatment of locally advanced soft tissue sarcoma of the limbs: which treatment to choose? Oncologist 13:175, 2008;
James SL, Avies AM: Post-operative imaging of soft tissue sarcomas. Cancer Imaging 8:8, 2008; Muhic A et al:
Local control and survival in patients with soft tissue sarcomas treated with limb sparing surgery in combination with interstitial
brachytherapy and external radiation. Radiation Oncol, 2008 Jun 25 [Epub ahead of print]; Pacini F et al: Differentiated
thyroid cancer: ESMO clinical recommendations for diagnosis, treatment and follow-up. Ann Oncol 19Suppl2:ii99,
2008; Son YI et al: Extent of prophylactic lymph node dissection in the central neck area of patients with papillary thyroid
carcinoma: comparison of limited versus comprehensive lymph node dissection in a 2-year safety study. Ann Surg Oncol
15:2020, 2008; Thway K: Angiomatoid fibrous histiocytoma: a review with recent genetic findings. Arch Pathol Lab Med
132:273, 2008.
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