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Thoracic Surgery: Answers
289
aggressive malignant
nonencapsulated neuroblastoma. Derived from embryologic origins,
these tumors arise in the adrenal glands or in the sympathetic
ganglia. However,
ganglioneuromas and ganglioneuroblastomas
arise mostly in the sympathetic ganglia of the
posterior mediastinum.
Fifty percent of neuroblastomas arise in the adrenal glands
and up to
30% in the mediastinum.
Ganglioneuromas are benign tumors composed of one or more mature
ganglionic cells.
Arising from the nerve ganglion cells, they
are the most benign and differentiated of the
autonomic ganglionic
tumors. Most patients are asymptomatic and receive diagnoses
in the
second or third decade of life. Radiographically,
the tumors are oblong and well-marginated,
occurring along the
anterolateral aspect of the spine and spanning three to five
vertebrae. CT
scanning is not particularly helpful
as the mass can be homogenous or heterogeneous.
Complete surgical
resection is ideal.
Ganglioneuroblastomas have histologic features of both ganglioneuromas
and
neuroblastomas. They are the least common type of neurogenic
tumor. Prognosis depends on
histologic appearance. Both sexes
are equally affected in the first decade of life. Symptoms
may arise due to large tumor size, intraspinal extension, and
metastasis. Staging is similar to
that for neuroblastoma.
Neuroblastoma is a disease of young children, with 95% occurring
in patients < 5 years of
age. Neuroblastomas are highly
aggressive and readily metastasizing tumors that are
composed
of small round cells arranged in sheets or pseudorosettes.
They are nonencapsulated
lesions, often exhibiting hemorrhage,
necrosis, or cystic degeneration. Symptoms include
pain, neurologic
deficits, Horner syndrome, respiratory distress, and ataxia.
Neuroblastomas
have the highest propensity of any tumors in
its class to produce vasoactive substances that
can cause hypertension,
flushing, and diarrhea.
Grossly, these tumors appear as an elongated paraspinous mass,
sometimes impinging on
adjacent structures and causing skeletal
damage. On CT scans, 80% of these tumors have
calcification.
As with all neurogenic tumors, MRI is useful to determine the
extent of
intraspinal involvement. Radionuclide imaging with
123
I metaiodobenzylguanide can also be
used to detect primary
and metastatic disease.
Treatment for neuroblastoma depends primarily on the stage of
disease (Table).
Table. Staging of Neuroblastoma and Ganglioneuroblastomas
Stage
Characteristics
I
Well-circumscribed, noninvasive ipsilateral tumors
II
Local invasion without extension across the midline, ipsilateral regional lymph
node involvement
III
Tumor extension across the midline and involvement of bilateral regional lymph
nodes
IV
Metastatic disease
IVS
Clinical stage I or II and metastatic disease limited to the liver, skin and bone
marrow
Treatment for limited-stage disease is surgical
resection. For patients with stage I disease,
resection is usually
curative. For patients with partially resectable stage II and
III disease,
treatment includes postoperative chemotherapy and
radiation. For patients with stage IV
Shahzad G. Raja
290
disease, there is much
controversy over the role of surgery; however, some studies
have
suggested that delayed surgery after initial treatment
with chemotherapy and radiation results
in a better outcome
than initial surgical intervention. In addition, there are ongoing
studies
looking at the role of radioactive
131
I metaiodobenzylguanide
therapy in combination with
chemotherapy in patients with advanced-stage
disease. Poor prognostic factors in
neuroblastoma include
large tumor size, poorly differentiated cell type, advanced
stage,
extrathoracic origin, and presentation in an elderly
patient.
References
Duwe BV, Sterman DH, Musani AI. Tumors of the mediastinum. Chest. 2005;128:2893-909.
Davis, S, Rogers MA, Pendergrass TW. The incidence and epidemiologic characteristics of
neuroblastoma in the United States. Am J Epidemiol. 1987;126:1063-1074.
Forsythe A, Volpe J, Muller R. Posterior mediastinal ganglioneuroma. Radiographics.
2004;24:594-597.
Hoefnagel CA. Radionuclide therapy in children with neuroblastoma. Hell J Nucl Med.
2002;2:107-110.
Castel V, Tovar JA, Costa E, et al. The role of surgery in stage IV neruoblastoma. J Pediatr
Surg. 2002;37:1574-1578.
Mastrangelo S, Tornesello A, Diociaiuti L, et al. Treatment of advanced neuroblastoma:
feasibility and therapeutic potential of a novel approach combining 131-I-MIBG and
multiple drug chemotherapy. Br J Cancer. 2001;84:460-464.
3.95 Answer: E
Fibrosing mediastinitis is a rare benign disorder caused by
proliferation of acellular
collagen and fibrous tissue within
the mediastinum. Although many cases are idiopathic,
many (and
perhaps most) cases in the United States are thought to be caused
by an abnormal
immunologic response to Histoplasma capsulatum
infection. Affected patients are typically
young and present
with signs and symptoms of obstruction or compression of the
superior
vena cava, pulmonary veins or arteries, central airways,
or esophagus. There may be two
types of fibrosing mediastinitis:
focal and diffuse. The focal type usually manifests on
computed
tomographic (CT) or magnetic resonance (MR) images as a localized,
calcified
mass in the paratracheal or subcarinal regions of
the mediastinum or in the pulmonary hila.
The diffuse type manifests
on CT or MR images as a diffusely infiltrating, often noncalcified
mass that affects multiple mediastinal compartments.
Airway obstruction may be caused by masses of large granulomatous lymph nodes. Such
nodes may be quite difficult and hazardous to remove because of dense adhesions to adjacent
structures. Incision and curettage of involved lymph nodes is preferable to excision because
of the lower risk of major hemorrhage. If surgical approaches are undertaken for airway or
vena caval decompression, biopsy is mandatory to exclude malignancy.
Presuming that many, perhaps most, cases of fibrosing mediastinitis
in the United States
are related to H capsulatum infection and
an ensuing inflammatory reaction, some
investigators have treated
patients with systemic antifungal agents or corticosteroids.
Most of
the available data in this regard are based on either
case reports or small series; prospective,
randomized controlled
trials have not been performed. The limited data available
suggest that
ketoconazole therapy may result in stabilization
of the disease process or, in some cases,
limited symptomatic
improvement. However, given the unpredictable nature of
the disorder,
Thoracic Surgery: Answers
291
the significance of these uncontrolled data is
not clear. Most studies have shown little or no
beneficial
effect of corticosteroid therapy.
While superior vena caval compression is a classic complication of fibrosing
mediastinitis, it is rare that superior vena caval bypass is required for superior vena caval
decompression. The slow course of the disease usually allows recruitment of adequate venous
collaterals for cerebral and upper extremity drainage. The mere presence of superior vena
caval obstruction does not necessitate extra-anatomic bypass or intravascular stenting unless
persistent symptoms of cerebral congestion are present. The aggressive use of transvenous
stents has dramatically altered the management of this syndrome.
References
Rossi SE, McAdams HP, Rosado-de-Christenson ML, et al. Fibrosing mediastinitis.
Radiographics. 2001;21:737-57.
Doty JR, Flores JH, Doty DB. Superior vena cava obstruction: bypass using spiral vein graft.
Ann Thorac Surg. 1999;67:1111-1116.
Mathisen DJ, Grillo HC. Clinical manifestation of mediastinal fibrosis and histoplasmosis.
Ann Thorac Surg. 1992;54:1053-1057.
Urschel HC Jr, Razzuk MA, Netto GJ, et al. Sclerosing mediastinitis: improved management
with histoplasmosis titer and ketoconazole. Ann Thorac Surg. 1990;50:215-221.
3.96 Answer: B
The OEO2 trial aimed to assess the effects of preoperative chemotherapy on survival,
dysphagia, and performance status in this group of patients. 802 previously untreated patients
with resectable esophageal cancer of any cell type were randomly allocated either two 4-day
cycles, 3 weeks apart, of cisplatin 80 mg/m(2) by infusion over 4 h plus fluorouracil 1000
mg/m(2) daily by continuous infusion for 4 days followed by surgical resection (CS group,
n=400), or resection alone (S group, 402). Clinicians could choose to give preoperative
radiotherapy to all their patients irrespective of randomisation. Primary outcome measure was
survival time. Analysis was by intention to treat. No patients dropped out of the study. The
trial showed that resection was microscopically complete in 233 (60%) of 390 assessable CS
patients and 215 (54%) of 397 S patients (p<0.0001). Postoperative complications were
reported in 146 (41%) CS and 161 (42%) S patients. Overall survival was better in the CS
group (hazard ratio 0.79; 95% CI 0.67-0.93; p=0.004). Median survival was 512 days (16.8
months) in the CS group compared with 405 days (13.3 months) in the S group (difference
107 days; 95% CI 30-196), and 2-year survival rates were 43% and 34% (difference 9%; 3-
14). The results of the OEO2 trial suggested that two cycles of preoperative cisplatin and
fluorouracil improve survival without additional serious adverse events in the treatment of
patients with resectable esophageal cancer.
Reference
Medical Research CouncilWorking Group. Surgical resection with or without preoperative
chemotherapy in oesophageal cancer: a randomised controlled trial. Lancet.
2002 ;359:1727-33.
Shahzad G. Raja
292
3.97 Answer: A
Atrial fibrillation (AF) can occur after manipulation of thoracic or mediastinal structures
and it can also be a harbinger of other complications brewing in a postoperative patient.
Murthy and colleagues recently published an article reviewing atrial fibrillation after
esophagectomy. They examined the records of 921 patients who underwent esophagectomy
between 1982 and 2000 and found that postoperative atrial fibrillation occurred in 22% of the
patients. Amar and colleagues reported on the experience at Memorial Sloan-Kettering in 527
patients undergoing noncardiac thoracic surgical procedures. One hundred nine of these
patients underwent esophagectomy with an 11.3% incidence of postoperative AF. The four
variables predictive of AF included age, a history of cardiac disease, increasing intraoperative
blood loss, and more extensive thoracic dissection. Patients who had AF were also more
likely to develop other complications including respiratory failure, anastomotic leaks, and
sepsis.
This association with other complications is not surprising. Often one complication, such
as an anastomotic leak, begets a series of others complications that may ultimately result in
the death of the patient. Murthy and colleagues found that the mortality in their group of
patients was 23% in those who had postoperative AF versus 6.3% in those that did not. When
hospital deaths were excluded, atrial fibrillation was not found to be predictive of a difference
in median survival. The authors concluded that while AF itself is not difficult to treat
postoperatively, it may be a sign that a patient is not doing as well as they appear to be doing.
De Decker and colleagues prepared an evidence-based review on cardiac complications
after noncardiac thoracic surgery. They identified 12 prospective trials that used prophylactic
antiarrhythmia therapy in patients undergoing thoracic procedures. Only one of these studies
was comprised solely of patients undergoing esophageal resection. The results are too
numerous to discuss in detail here but a significant reduction in postoperative arrhythmias
was seen in studies with the use of flecainide, diltiazem, and magnesium sulfate. No benefit
was shown in the studies reviewed that utilized digoxin.
Despite the common practice of epidural pain management in patients undergoing
esophagectomy and other noncardiac thoracic procedures, there is a paucity of information on
the effects on postoperative atrial fibrillation. The potential benefit is from the relative
sympathectomy on the heart created by the epidural which in turn may reduce the incidence
of arrhythmias.
References
Force S. The ―innocent bystander‖ complications following esophagectomy: Atrial
fibrillation, recurrent laryngeal nerve injury, chylothorax, and pulmonary complications.
Semin Thorac Cardiovasc Surg. 2004;16:117-123.
Murthy SC, Law S, Whooley BP, et al. Atrial fibrillation after esophagectomy is a marker for
postoperative morbidity and mortality. J Thorac Cardiovasc Surg. 2003;126:1162-1167.
Amar D, Zhang H, Leung DH, et al. Older age is the strongest predictor of postoperative
atrial fibrillation. Anesthesiology. 2002;96:352-356.
De Decker K, Jorens PG, Van Schil P. Cardiac complications after noncardiac thoracic
surgery: An evidence-based current review. Ann Thorac Surg. 2003;75:1340-1348.
Thoracic Surgery: Answers
293
3.98 Answer: D
Injury to the recurrent laryngeal nerve (RLN) has been reported at varying rates after
transhiatal and transthoracic esophagectomy. Orringer reported a 7% rate of nerve injury in
1085 patients after transhiatal esophagectomy. Two-thirds of these patients had transient
symptoms while one-third had persistent hoarseness requiring vocal cord medialization.
Orringer commented that rate of injury did decline as they gained more experience with the
procedure (32% 1978–82, 5% 1983–1992, 2% 1993–1997). The rate of nerve injury seems to
be related, in part, to how hard one looks for abnormal cord movement. Johnson and
colleagues performed indirect laryngoscopy in 47 patients before and after transhiatal
esophagectomy. They found ―unilateral vocal cord palsy‖ in 34% of the patients and in all but
one patient the injury was on the same side as the neck incision. Hulscher and colleagues
reported a 22% incidence of RLN injury in 241 patients who underwent transhiatal
esophagectomy with a left cervical anastomosis. In the majority of patients, the nerve injury
was ipsilateral to the cervical incision but, in three patients, the nerve injury was bilateral. The
thoracic group at the Brigham and Women‘s Hospital reported on 342 patients who received
radical mediastinal lymph node dissection and cervical esophagogastrostomy following
thoracotomy or transhiatal resection. Recurrent nerve injuries occurred in 14% of the patients.
Recurrent laryngeal nerve injury appears to be less common after an Ivor-Lewis
esophagectomy, most likely due to the absence of a neck dissection. Visbal and colleagues
reported a 0.9% RLN rate after 220 consecutive Ivor Lewis esophagectomies at the Mayo
Clinic. Rindani and colleagues reviewed the results of 44 papers, comprising over 5000
patients that reported on either transhiatal or transthoracic esophagectomy. The authors found
a higher reported rate of RLN injury after transhiatal esophageal resection (11.2% vs. 4.8%).
Doty and colleagues examined their data and found that neoadjuvant therapy does not seem to
increase the rate of RLN injury. They reported a 3.3% rate of hoarseness following
neoadjuvant chemoradiation therapy followed by esophagectomy. In that study, the operative
approach included transhiatal, Ivor-Lewis, thoracoabdominal and three-hole incisional
approaches.
Recurrent nerve injury appears to play a significant role in the overall postoperative well
being of the patient. Hulscher found a significant association between pulmonary
complications and the presence or absence of a RLN palsy. The rate of pulmonary
complication was 24% in those with a RLN injury and 2.4% in patients without.
References
Force S. The ―innocent bystander‖ complications following esophagectomy: Atrial
fibrillation, recurrent laryngeal nerve injury, chylothorax, and pulmonary complications.
Semin Thorac Cardiovasc Surg. 2004;16:117-123.
Orringer MB, Marshall B, Iannettoni MD. Transhiatal esophagectomy: Clinical experience
and refinement. Annals of Surgery. 1999;230:392-400.
Johnson PR, Kanegoanker GS, Bates T. Indirect laryngoscopic evaluation of vocal cord
function in patients undergoing transhiatal esophagectomy. Journal of the American
College of Surgeons. 1994;178:605-608.
Hulscher JB, van Sandick JW, Devriese PP, et al. Vocal cord paralysis after subtotal
oesophagectomy. Br J Surg. 1999;86:1583-1587.
Shahzad G. Raja
294
Swanson SJ, Batirel HF, Bueno R, et al. Transthoracic esophagectomy with radical
mediastinal and abdominal lymph node dissection and cervical esophagogastrostomy for
esophageal carcinoma. Ann Thorac Surg. 2001;72:1918-1925.
Visbal AL, Allen M, Miller DL. Ivor Lewis esophagectomy for esophageal cancer. Ann
Thorac Surg. 2001;71:1803-1808.
Rindani R, Martin CJ, Cox MR.. Transhiatal versus Ivor-Lewis oesophagectomy: Is there a
difference? Aust NZ J Surg. 1999;69:187-194.
Doty JR, Salazar JD, Forastiere AA, et al. Postesopha-gectomy morbidity, mortality, and
length of hospital stay after preoperative chemoradiation therapy. Ann Thorac Surg.
2002;74:227-231.
3.99 Answer: E
The incidence of chylothorax appears to be higher after Ivor-Lewis esophagectomy when
compared with transhiatal esophagectomy. Orringer reported a <1% incidence of
postoperative chlylothorax in 1085 patients after transhiatal esophagectomy. Bousamra also
experienced a smaller than 1% incidence of thoracic duct leaks in 115 patients undergoing
esophagectomy over a ten year period. The thoracic group at the Mayo Clinic reported a
relatively larger number of postoperative chylothoraces following Ivor-Lewis
esophagectomies, although the absolute rate of this complication was only 1.8% of cases.
A low output chylothorax often will resolve with conservative management, but high
output leaks, if not treated, can result in substantial fluid loss, malnutrition and immune
compromise. Dugue and colleagues treated 23 patients for chylothoraces after performing 850
Ivor-Lewis esophagectomies. Fourteen patients were treated successfully with conservative
management consisting of chest tube drainage and parenteral nutrition while the rest required
thoracic duct ligation. The only significant difference between the two groups of patients was
a smaller volume of chylous drainage on the fifth postoperative day in the patients treated
nonsurgically (6.7 mL/kg vs. 23.5 mL/kg).
Many surgeons, such as Merigliano and Orringer have called for early and aggressive
treatment of all chylothoraces following esophagectomy to avoid any associated
complications. Once nonoperative management of a chylothorax has failed or has been
deemed not to be an option, the question becomes how best to stop the leak. Right
thoracotomy with mass ligation of the tissue between the aorta and the spine has been the
standard method, while some prefer to administer preoperative cream to aid in location of the
leak and a more accurate thoracic duct ligation. The advent of thoracoscopy has lead to an
argument for a minimally invasive approach to duct ligation. Fahimi and colleagues reported
successful thoracoscopic management of chylothoraces in six patients, following various
thoracic procedures, with the use of duct ligation, application of fibrin glue, and talc
pleurodesis.
Occasionally a postoperative chylothorax will be resistant to all treatment strategies,
failing conservative therapy, duct ligation, and repeated pleurodesis. These patients may be
candidates for thoracic duct embolization.
References
Force S. The ―innocent bystander‖ complications following esophagectomy: Atrial
fibrillation, recurrent laryngeal nerve injury, chylothorax, and pulmonary complications.
Semin Thorac Cardiovasc Surg. 2004;16:117-123.
Thoracic Surgery: Answers
295
Orringer MB, Marshall B, Iannettoni MD. Transhiatal esophagectomy: Clinical experience
and refinements. Ann Surg. 1999;230:392-415.
Bousamra M, Haasler GB, Parviz M. A decade of experience with transthoracic and
transhiatal esophagectomy. Am J Surg. 2002;183:162-167.
Dugue L, Sauvanet A, Farges O, et al. Output of chyle as an indicator of treatment for
chylothorax complicating oesophagectomy. Br J Surg. 1998;85:1147-1149.
Orringer MB, Bluett M, Deeb GM. Aggressive treatment of chylothorax complicating
transhiatal esophagectomy without thoracotomy. Surgery. 1988;104:720-726.
Merigliano S, Molena D, Ruol A, et al. Chylothorax complicating esophagectomy for cancer:
A Plea for early thoracic duct ligation. J Thorac Cardiovasc Surg. 2000;119:453-457.
Fahimi H, Casselman FP, Mariani MA, et al. Current management of postoperative
chylothorax. Ann Thorac Surg. 2001;71:448-451.
Cope C, Salem R, Kaiser LR. Management of chylothorax by percutaneous catheterization
and embolization of the thoracic duct: Prospective trial. J Vasc Intervent Radiol.
1999;10:1248-1254.
3.100 Answer: C
Pulmonary complications remain a major source of morbidity and mortality following
esophagectomy and the incidence may be slightly greater following Ivor-Lewis
esophagectomy compared with transhiatal resection. There have been no definitive
preoperative risk factors shown to significantly increase pulmonary complications after
resection. Pulmonary complications result from a multiple preoperative, intraoperative and
postoperative factors. Smoking at the time of surgery, significant lung disease, older age,
large intraoperative blood loss, significant fluid shifts, postoperative pain, and aspiration all
play a role in the patient‘s pulmonary function.
Orringer reported a 2% incidence of pneumonia following 1085 transhiatal
esophagectomies which resulted in death in 3 out of the 17 patients identified with clinically
significant infiltrates on chest radiographs. The results of the Mayo Clinic experience
revealed a higher incidence of pneumonia following Ivor-Lewis esophagectomy with an
incidence of 12.3%. However, none of their operative deaths were attributed to pneumonia in
this series. Others authors have found a significant increase in operative mortality associated
with pulmonary complications. Ferguson found prolonged ventilation, respiratory failure and
pneumonia to be significant predictors of mortality in 269 patients who underwent
esophagectomy.
Several papers had tried to identify preoperative conditions that would place patients at a
higher risk for pulmonary complications following esophagectomy. A preoperative FEV
1
<
65% of predicted was associated with increased risk of ventilatory support for more than 48
hours after surgery. Other preoperative characteristics that correlated with duration of
mechanical ventilation included preoperative FVC and the use of neoadjuvant
chemoradiation. However, in Ferguson‘s review, FEV
1
was not found to be a significantly
associated with mortality by logistic regression. A retrospective review of 149 patients who
underwent Ivor-Lewis esophagectomy failed to show a correlation between preoperative
FEV
1
and postoperative pulmonary complications. Tsutsui and colleagues, likewise, could not
demonstrate a correlation between preoperative spirometric results and postoperative
pulmonary complications.
Shahzad G. Raja
296
Other studies have reviewed specific risk factors with respect to postoperative pulmonary
complications. Kyriaazanos and colleagues found that patients who required a splenectomy at
the time of esophageal resection experienced a significant increase in pulmonary
complications as well as sepsis, anastomotic leaks and operative mortality. Improved
postoperative pain control is also thought to play a role in reducing pulmonary complications.
Unfortunately, there have been no randomized trials to confirm this idea. Flisberg compared
postoperative epidural analgesia to intravenous analgesia and found decreased pain with
movement in the epidural group but no difference pulmonary function as measured by peak
expiratory flow, first second expired volume and vital capacity.
Neoadjuvant therapy has also been under considerable scrutiny with regard to
postoperative morbidity and mortality. Urschel performed a meta-analysis of randomized
controlled trials comparing neoadjuvant chemotherapy and surgery to surgery alone and
found no significant increase in pulmonary complications in patients undergoing preoperative
therapy. Doty and colleagues also reported a low incidence of pneumonia (2.5%) and
respiratory insufficiency (2.5%) in patients undergoing preoperative chemoradiation therapy
followed by esophagectomy.
References
Force S. The ―innocent bystander‖ complications following esophagectomy: Atrial
fibrillation, recurrent laryngeal nerve injury, chylothorax, and pulmonary complications.
Semin Thorac Cardiovasc Surg. 2004;16:117-123.
Orringer MB, et al. Transhiatal esophagectomy: Clinical experience and refinements. Ann
Surg. 1999;230:392-415.
Visbal AL, Allen M, Miller DL. Ivor Lewis esophagectomy for esophageal cancer. Ann
Thorac Surg. 2001;71:1803-1808.
Kyriazanos ID, Tachibana M, Yoshimura H, et al. Impact of splenectomy on the early
outcome after oesophagectomy for squamous cell carcinoma of the oesophagus. Eur J
Surg Oncol. 2002;28:113-9.
Ferguson MK, Martin TR, Reeder LB, et al. Mortality after esophagectomy: Risk factor
analysis. World J Surg. 1997;21:599-604.
Avendano CE, Flume PA, Silvestri GA, et al. Pulmonary complications after esophagectomy.
Ann Thorac Surg. 2002;73:922-926.
Tsutsui S, Moriguchi S, Morita M, et al. Multivariate analysis of postoperative complications
after esophageal resection. Ann Thorac Surg. 1992;53:1052-1056.
Doty JR, Salazar JD, Forastiere AA, et al. Postesophagectomy morbidity, mortality, and
length of hospital stay after preoperative chemoradiation therapy. Ann Thorac Surg.
2002;74:227-31.
3.101 Answer: C
The majority of studies have shown that the incidence of hoarseness is higher with a
transhiatal resection or a procedure that utilizes a left neck incision while chylothorax and
pulmonary complications may occur more commonly after transthoracic resections. Atrial
arrhythmias may be seen commonly after either approach.
Rentz reported a larger study on data collected on 945 patients in the National Veterans
Administration System and found a significant increase in the incidence of pneumonia
following transthoracic resection when compared with transhiatal resection (26% vs. 18%, P
Thoracic Surgery: Answers
297
= 0.007). One criticism with this study is the relatively high incidence of pneumonia reported
following esophagectomy. Hulscher performed a meta-analysis that included 24 papers
comparing transhiatal to transthoracic esophagectomy. Three of the studies were randomized,
3 were labeled as prospective but not randomized and 18 were retrospective reviews. Relative
risks (RR) were calculated so that an RR of less than 1 showed a benefit for the transthoracic
group. When all 24 studies were analyzed, transthoracic resections had a higher risk of
pulmonary complications (RR = 1.47) and chylothoraces (RR = 1.7) while the risk of vocal
cord paralysis was greater after transhiatal resection (RR = 0.36). Atrial fibrillation alone was
not addressed but the patients who underwent transhiatal resection had a greater risk of
cardiac complications (RR = 0.34). Hulscher and coworkers also performed a randomized
trial comparing extended transthoracic resection to transhiatal resection. The results were
similar to those found in the meta-analysis with a higher incidence of chylothoraces and
pulmonary complications seen in patients who underwent transthoracic resection. There was
no difference in the incidence of vocal cord paralysis but both surgical groups underwent a
cervical dissection. The transhiatal group experienced a lower postoperative morbidity and
lower ICU and hospital stays.
References
Force S. The ―innocent bystander‖ complications following esophagectomy: Atrial
fibrillation, recurrent laryngeal nerve injury, chylothorax, and pulmonary complications.
Semin Thorac Cardiovasc Surg. 2004;16:117-123.
Rentz J, Bull D, Harpole D, et al. Transthoracic versus transhiatal esophagectomy: A
prospective study of 945 patients. J Thorac Cardiovasc Surg. 2003;125:1114-1120.
Hulscher JB, Tijssen JG, Obertop H, van Lanschot JJ. Transthoracic versus transhiatal
resection for carcinoma of the esophagus: A meta-analysis. Ann Thorac Surg.
2001;72:306-313.
Hulscher JB, van Sandick JW, de Boer AG, et al. Extended transthoracic resection compared
with limited transhiatal resection for advanced adenocarcinoma of the esophagus. N Engl
J Med. 2002;347:1662-1669.
3.102 Answer: D
A total of 1218 patients with severe emphysema underwent pulmonary rehabilitation and
were randomly assigned to undergo lung-volume-reduction surgery or to receive continued
medical treatment in the National Emphysema Treatment Trial. The primary outcomes for the
trial were mortality and maximal exercise capacity two years after randomization. Secondary
outcomes included the distance walked in six minutes, pulmonary function, quality of life,
and degree of dyspnea. An important goal of the trial was to identify patient-selection criteria
for lung-volume–reduction surgery. Criteria for inclusion were crafted to include all patients
who might benefit from lung-volume–reduction surgery.
Overall mortality was 0.11 death per person-year in both treatment groups (risk ratio for
death in the surgery group, 1.01; P=0.90). After 24 months, exercise capacity had improved
by more than 10 W in 15 percent of the patients in the surgery group, as compared with 3
percent of patients in the medical-therapy group (P<0.001). With the exclusion of a subgroup
of 140 patients at high risk for death from surgery according to an interim analysis, overall
mortality in the surgery group was 0.09 death per person-year, as compared with 0.10 death
per person-year in the medical-therapy group (risk ratio, 0.89; P=0.31); exercise capacity after
Shahzad G. Raja
298
24 months had improved by more than 10 W in 16 percent of patients in the surgery group, as
compared with 3 percent of patients in the medical-therapy group (P<0.001). Among patients
with predominantly upper-lobe emphysema and low exercise capacity, mortality was lower in
the surgery group than in the medical-therapy group (risk ratio for death, 0.47; P=0.005).
Among patients with non-upper-lobe emphysema and high exercise capacity, mortality was
higher in the surgery group than in the medical-therapy group (risk ratio, 2.06; P=0.02).
The trialists concluded that overall, lung-volume-reduction surgery increases the chance
of improved exercise capacity but does not confer a survival advantage over medical therapy.
It does yield a survival advantage for patients with both predominantly upper-lobe
emphysema and low base-line exercise capacity. Patients previously reported to be at high
risk and those with non-upper-lobe emphysema and high base-line exercise capacity are poor
candidates for lung-volume-reduction surgery, because of increased mortality and negligible
functional gain.
References
Fishman A, Martinez F, et al; National Emphysema Treatment Trial Research Group. A
randomized trial comparing lung-volume-reduction surgery with medical therapy for
severe emphysema. N Engl J Med. 2003;348:2059-73.
3.103 Answer: C
The International Staging Committee (ISC) of the International Association for the Study
of Lung Cancer (IASLC) collected 68,463 patients with nonsmall cell lung cancer and 13,032
patients with small cell lung cancer, registered or diagnosed from 1990 to 2000, whose
records had adequate information for analyzing the tumor, node, metastasis (TNM)
classification. The T, N, and M descriptors were analyzed, and recommendations for changes
in the seventh edition of the TNM classification were proposed based on differences in
survival. For the T component, tumor size was found to have prognostic relevance, and its
analysis led to recommendations to subclassify T1 tumors into T1a (< or = 2 cm) and T1b (>2
- < or = 3 cm) and T2 tumors into T2a (>3 - < or = 5 cm) and T2b (>5 - < or = 7 cm), and to
reclassify T2 tumors > 7 cm into T3. Furthermore, with additional nodules in the same lobe as
the primary tumors, T4 tumors would be reclassified as T3; with additional nodules in another
ipsilateral lobe, M1 as T4; and with pleural dissemination, T4 as M1. There were no changes
in the N category. In the M category, M1 was recommended to be subclassified into M1a
(contralateral lung nodules and pleural dissemination) and M1b (distant metastasis). The
proposed changes for the new stage grouping were to upstage T2bN0M0 from stage IB to
stage IIA, and to downstage T2aN1M0 from stage IIB to stage IIA and T4N0-N1M0 from
stage IIIB to stage IIIA. The proposed changes better differentiate tumors of different
prognoses.
Descriptors
Definitions
T
Primary tumor
T0
No primary tumor
T1
Tumor ≤ 3 cm, surrounded by lung or visceral pleura, not more proximal than
the lobar bronchus
T1a
Tumor ≤ 2 cm
T1b
Tumor > 2 but ≤ 3 cm