Save or sacrifice the internal mammary pedicle during anterior mediastinotomy?

Abstract

Ligation and dissection of internal mammary vessels is the most under-estimated complication of anterior mediastinotomy. However, patients requiring anterior mediastinotomy may experience long survival that makes the development of ischemic heart disease throughout their life possible. Therefore, the un-judicial sacrifice of the internal mammary pedicle may deprive them from the benefit to have their internal mammary artery used as a graft in order to successfully bypass severe left anterior descending artery stenoses. We recommend the preservation of the internal mammary pedicle during anterior mediastinotomy, which should be a common message among our colleagues from the beginning of their training.

Full text

138 Annals of Thoracic Medicine - Vol 9, Issue 3, July-September 2014
Save or sacrice the internal
mammary pedicle during anterior
mediastinotomy?
Efstratios Apostolakis, Nikolaos A. Papakonstantinou1, Serafeim Chlapoutakis,
Christos Prokakis
Abstract:
Ligation and dissection of internal mammary vessels is the most under-estimated complication of anterior
mediastinotomy. However, patients requiring anterior mediastinotomy may experience long survival that makes
the development of ischemic heart disease throughout their life possible. Therefore, the un-judicial sacrice of
the internal mammary pedicle may deprive them from the benet to have their internal mammary artery used
as a graft in order to successfully bypass severe left anterior descending artery stenoses. We recommend the
preservation of the internal mammary pedicle during anterior mediastinotomy, which should be a common
message among our colleagues from the beginning of their training.
Key words:
Anterior mediastinotomy, coronary artery disease, internal mammary artery graft, lung cancer, mediastinal tumors
The anterior mediastinotomy proposed by
McNeil and Chamberlain[1] is a reliable
and well established diagnostic tool for the
histological identication of anterior and superior
mediastinal tumors and lymph nodes (LNs).
Ligation of internal mammary vessels is the most
underestimated complication among its potential
complications since the primary end point of the
procedure is the acquisition of sufcient tissue
samples for histological identification of the
mediastinal lesion. In most textbooks, the sacrice
of these vessels is considered an acceptable,
meaningless maneuver that will provide a wider
operative field facilitating the acquisition of
adequate tissue samples. It is reported that “the
internal mammary artery and vein are retracted
or-rarely-divided and ligated.”[2,3] It has also
been stated that “occasionally it is necessary
to ligate and divide these vessels to provide
adequate exposure”[4] or “sometimes they
must be divided to gain sufcient exposure”[5]
or “the internal mammary artery and vein are
usually ligated,”[6] or “if additional exposure is
necessary, the internal mammary pedicle can be
divided anteriorly.”[7] In Thoracic Surgery Atlas
by Mark Ferguson, on pages 142-143, the internal
mammary vessels are shown ligated and divided
by surgical clips.[4] However, some patients may
have diseases associated with long survival and
may be deprived from the benet to have their left
internal mammary artery (LIMA) used as a graft
to bypass anterior descending artery stenoses
provided that the aforementioned vessel has
injudiciously been sacriced during a previous
anterior mediastinotomy procedure. In addition,
adjuvant radiotherapy of the mediastinum will
be required at a group of patients previously
experienced anterior mediastinotomy. However,
patients receiving adjuvant radiotherapy are at
a greater risk of coronary artery disease (CAD)
induction or aggravation. In the absence of data
on this issue, we will try to evaluate its potential
consequences based on the impact of LIMA graft
on the outcome of patients with ischemic heart
disease and on the background of the diseases
requiring anterior mediastinotomy for tissue
biopsy. Finally, alternative procedures for tissue
biopsy will be provided.
Lima Graft and its Impact on Prognosis
Of Patients Undergoing Coronary Artery
Bypass Grafting (CABG)
Now-a-days, the LIMA to the left anterior
descending (LAD) coronary artery graft is
unanimously considered the method of choice
during CABG.[8] A patent LAD is associated
with signicantly improved survival in patients
suffering from ischemic heart disease. A study
by Holzhey et al.[9] reported 90.2% 5-year survival
and 85.5% 5-year freedom from major adverse
cardiac events when a LIMA to LAD graft is used
to bypass a completely stenotic coronary vessel.
This study claims that a LIMA to LAD bypass is
the treatment of choice for the management of
patients with chronically completely occluded
anterior descending arteries. When an in situ
LIMA graft is used to bypass stenotic lesions of
the LAD, the graft patency may reach up to 95%
at 10 years, whereas right internal mammary
Address for
correspondence:
Mr. Nikolaos A.
Papakonstantinou,
12 Zilon Street, Rizoupoli,
11142 Athens, Greece.
E-mail: nikppk@yahoo.gr
Submission: 29-08-2013
Accepted: 17-11-2013
Departments of
Cardiothoracic Surgery,
School of Medicine,
University Hospital
of Ioannina, 45500
Ioannina, 1General
Surgery, General
Oncology Hospital
of Kifi ssia "Agioi
Anargyroi", 41 Kaliftaki
Street, P.C. 14564,
Kifissia, Athens, Greece
Review Article
Access this article online
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Website:
www.thoracicmedicine.org
DOI:
10.4103/1817-1737.134067
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Apostolakis, et al.: Saving internal mammary pedicle
Annals of Thoracic Medicine - Vol 9, Issue 3, July-September 2014 139
artery graft 10-year patency ranges between 80% and 95%
respectively.[10] As much as 80% of internal thoracic artery
conduits have been proved to be free from failure in the third
decade after CABG.[11] On the contrary, patency of a radial
artery graft is signicantly reduced ranging between 83% and
96% at 4-5 years.[12,13] Prognosis is further deteriorated in those
patients receiving a saphenous vein graft since patency of vein
grafts is dramatically reduced over time. It has been shown that,
whereas 10-year LIMA graft patency is approximately 90%,
that one of a vein graft is reduced to 70%.[14] Another study has
documented 10-year patency rates of 85% for in situ LIMA grafts
and of 61% for saphenous vein grafts.[15] This difference has a
signicant inuence on both the patients’ survival and their
quality of life. Several studies have shown that the use of in situ
LIMA grafts to bypass stenotic LAD lesions is associated with
better long-term graft patency, less late myocardial infarctions,
improved quality of life and longer survival.[16-19] Moreover,
among patients with low ejection fraction (EF < 30%), the use
of LIMA may signicantly improve their survival. In a report
by McCarron et al.,[20] 4-year freedom from death rate reached
up to 77.1% of patients receiving a LIMA graft and 60.7% of
those receiving other vessel grafts. This difference was found
to be statistically signicant (P = 0.026). The aforementioned
results clearly demonstrate that the use of a normal LIMA graft
bypassing the LAD during CABG determines in advance the
patient’s long-term prognosis.
Mediastinal Tumors and Diseases that May Require
Anterior Mediastinotomy for their Histological
Conrmation: Age at Presentation and Survival
• The diagnosis and staging of non-small cell lung
cancer (NSCLC) requires an accurate histopathological
diagnosis.[21] Anterior mediastinotomy is mainly performed
for staging of lung cancer especially that one involving left
upper lobe.[22] This approach indeed provides access to
subaortic and aortopulmonary window areas (LN stations
5 and 6), superior left hilar elements, left upper pulmonary
lobe and parietal pleura.[2,22,23] It may dene whether a
patient with a left upper lobe tumor should be referred to
surgery or not, giving rise to minimal risk.[22] NSCLC is a
disease of the elderly.[24] More than 50% of the patients is
over 65-year-old and one-third of them is even more than
70-year-old on the time the diagnosis is made.[24,25] Whether
a surgical or a multimodality treatment is performed,
prognosis is poor. The study done by Wigle et al.[26] reported
the following 5-year survival rates depending on the stage
of the disease: stage I (2648 patients): 60-70%, Stage II (1097
patients): 40-50%, Stage IIIA (1241 patients): 25-40%, Stage
IIIB (1327 patients): 2-15% and Stage IV (1427 patients):
1-10%. In another study including 2378 patients suffering
from NSCLC, the 5-year survival rate after complete tumor
resection was 50.2%; and the 5-year survival rate depending
on stage was 72% for Stage IA, 59.8% for Stage IB, 47.8%
for Stage II, 45% for Stage IIIA and 38.7% for Stage IIIB.[27]
These differences show that various parameters such as
sex, age, histological type, tumor differentiation, number
of positive nodes, stage of the disease and complete tumor
resection have an impact on patient’s survival.
• Hodgkin lymphoma is the most frequent type of lymphoma
affecting the mediastinum. It is more frequent in women
presenting two peaks of incidence, the rst one between
15 and 35 years of age and the second one after the age
of 55.[28] Most of the cases are diagnosed between the 2nd
and 4th decade of life and the mean age at presentation is
37-year-old.[29] Patients’ survival after treatment is excellent;
in a multicenter randomized trial including 202 patients,
10-year survival was 92.9%.[30]
• Non Hodgkin lymphomas are less frequent. The mean age
at presentation is 37-year-old[31] while T and B lymphoblastic
lymphomas are mainly found in children.[29] Non Hodgkin
lymphomas have significantly poorer survival than
Hodgkin lymphomas; in a 141-patients study, the diagnosis
was made at a mean age of 37-year-old and 3-year survival
rate was 65%.[31]
• Thymomas are thymic epithelial tumors located primarily
in the superior, anterior mediastinum. The mean age at
diagnosis is between 49 and 51-year-old with no statistically
signicant impact of sex on the peak of incidence.[29,32,33]
Patients’ survival is excellent if the disease is diagnosed
early. 5- and 10-year survival rates vary between 89.9-97%
and 84.1-89% respectively.[32,33] In a recent report including
39 patients operated over a period of 16 years, 5-, 10-
and 15-year survival rates were 91.6%, 75.1% and 60%
respectively; patients with advanced disease (Stage III
and IV) experienced 5- and 10-year survival rates of 70%
and 35% respectively.[34]
• The group of mediastinal germ cell tumors includes several
types of tumors that are primarily diagnosed through
anterior mediastinotomy. They are mostly found in young
adults; in a retrospective analysis of 129 patients treated for
mediastinal germ cell tumors the mean age at presentation
was 26 years.[35] Teratomas represent the most frequent
entity of these tumors with a predilection for males and
a peak incidence between the 2nd and the 4th decade of
life.[29] Similarly, in a review including 530 patients with
primary or metastatic testicular seminomas the mean
age was 27 ± 8 years.[36] Both teratomas and seminomas
are associated to good prognosis having 10-year survival
rates of 90% and 70% respectively. On the contrary, non
seminomatous germ cell tumors have a signicantly worse
outcome. At 5-year survival reaches up to 30-40%, whereas
8-year survival is 15%.[35]
• Sarcoidosis is a systemic inammatory granulomatous
disease affecting people of all ages and races characterized
by hilar and mediastinal LN masses. Thoracic
lymphadenopathy detected in up to 85% of cases.[37]
Invasive exploration of the mediastinum is necessary
for histological confirmation and exclusion of other
malignant diseases. In a multicenter ACCESS trial including
736 patients from 10 US medical centers, the mean age at
presentation ranged from 35 to 39 years.[38] Prognosis is
good and 5-year mortality depends on the stage of the
disease at the time the diagnosis is made: 0% for Stage I,
11% for Stage II, 18% for Stage III and 50% for Stage IV.[39]
• Anterior mediastinotomy after pre-operative imaging
may also be used for parathyroidectomy. Approximately
2% of ectopic parathyroid glands causing primary
hyperparathyroidism require a thoracic approach due
to their mediastinal location. If the abnormal gland is
successfully removed, the patients’ calcium levels are
normalized and patients have same survival rates as the
general population.[40]
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Apostolakis, et al.: Saving internal mammary pedicle
140 Annals of Thoracic Medicine - Vol 9, Issue 3, July-September 2014
In overall, the majority of mediastinal tumors referred
for anterior mediastinotomy, excluding NSCLC, occur in
younger ages. According to de Montpréville’s et al. study,[41]
the frequency of these tumors and the mean age at the time
of presentation were as following: 169/420 patients had
NSCLC with a mean age of 59-year-old, 36/420 patients had
small cell lung carcinoma with a mean age of 60-year-old,
62/420 patients had sarcoidosis with a mean age of 39-year-old,
18/420 patients had tuberculosis with a mean age of
46-year-old, 45/420 patients had lymphoma with a mean age
of 39-year-old, 5/420 patients had thymoma with a mean age
of 51-year-old and 12/420 patients had other diagnoses with
a mean age of 45-year-old. Moreover, it is clear that some of
the mediastinal tumors are associated with good to excellent
prognosis. Therefore, some of these patients will have long
enough survival to be candidates to experience ischemic heart
disease requiring coronary revascularization in the future.
Impact of Adjuvant Radiotherapy on the
Development of CAD
Radiotherapy of the mediastinum is applied in patients
suffering from NSCLC with N2 disease or other primary
mediastinal or breast malignancies. However, mediastinal
irradiation also affects coronary arteries resulting in CAD.
CAD development, the incidence of which ranges from 5.5%
to 12%, requires 3-29 years. The coronary ostia are affected
due to their relatively central location within the radiation
eld. Atherosclerosis progression of the coronary vessels is
accelerated by radiotherapy.[42] Patients receiving radiotherapy
of the mediastinum during their treatment for Hodgkin
lymphoma are expected to have long survival, so they may
develop ischemic heart disease due to both aging and the effects
of radiation on their native coronary vessels. Increased cardiac
related mortality and morbidity rates should be expected,
especially if the dose of delivered radiation exceeds 30 Gy.[43,44]
Several long-term series of patients undergoing radiotherapy
reported more deaths because of second malignancies and
CAD than because of their Hodgkin lymphoma.[42] Heidenreich
et al.[45] reported abnormal stress echo and/or nuclear
scintigraphy ndings in 21% of the 294 patients irradiated in
the mediastinum for Hodgkin lymphoma whose disease was in
complete remission at the time of cardiac evaluation. Coronary
angiograms revealed signicant coronary vessels stenosis in
1/3 of the patients. Thus, the authors concluded that patients
with history of mediastinal radiotherapy for Hodgkin disease
should be under strict cardiac surveillance. According to
Rademaker et al.,[28] 8 out of 9 patients receiving radiotherapy
for Hodgkin lymphoma developed signicant coronary lesions
and most of them were completely asymptomatic. It should
be noted that 5 of these patients presented other risk factors
for atherosclerosis as well, such as hypertension, diabetes
and high blood cholesterol levels. The presence of signicant
lesions and silent ischemia may lead to myocardial infarction
and is associated with increased cardiac related mortality.
In a report of 7033 patients successfully treated for Hodgkin
disease and a mean follow-up of 11.2 years, the standardized
mortality ratio secondary to myocardial infarction was 3.2 for
those who were treated with mediastinal irradiation.[46] We
may conclude that the adjunction of mediastinal irradiation
in the treatment protocols of these patients may accelerate the
development of CAD. The same could happen in those few
patients with NSCLC irradiated in the mediastinum that may
achieve a relatively prolonged survival. Cardiac complications
can be prevented both by managing cardiovascular risk factors
and also by lowering the total radiotherapy dosage.[42]
On the other hand, internal mammary arteries affection by
radiotherapy also raises our concern. Although isolated case
reports demonstrate increased fragility and early failure of
the graft under these circumstances, most of the studies on
this issue support the use of internal mammary arteries in
patients who had their mediastinum irradiated in the past.[47]
Therefore, the internal mammary artery graft is still valid
after radiotherapy and maintains its advantages with regard
to long survival.
Alternative Methods of Biopsy of Mediastinal
Tumors and LNs with Internal Mammary Artery
Preservation
Several, more or less invasive, approaches other than anterior
mediastinotomy are available in order to obtain the necessary
tissue samples. The extended cervical mediastinoscopy, which
is an extension of the classic one, offers the possibility to
evaluate both the anterior and the middle mediastinum taking
samples even at the level of the pulmonary hilum. Not only
LNs stations 2, 3, 4 and 7 but also LNs stations 5, 6, 8 and 10 are
accessible when this procedure is performed.[48,49] A procedure
called Transcervical Extended Mediastinal Lymphadenectomy
is a modication of the aforementioned procedure allowing the
performance of complete mediastinal lymphadenectomy.[48-51]
Its sensitivity of 95.7% and its negative predictive value of
97.6% make some authors to consider this approach as the
“gold standard” for mediastinal restaging of patients with
NSCLC receiving neoadjuvant treatment.[48-51] The anterior
and middle mediastinum is accessed through a 5-8 cm collar
incision and resection of all nodal tissue down to the level of
paraesophageal nodes follows (station 8).[49,51] Although the
operation is technically demanding and long lasting (mean time
161 min), there is no mortality in large series of patients and
morbidity is of the order of 11.3%. Major complications include
temporary (2.3%) or permanent (0.8%) recurrent laryngeal
nerve palsy.[50]
The anterior mediastinoscopy constitutes another alternative
procedure, which is a modification of the anterior
mediastinotomy where the costal cartilage is not removed.[7]
The mediastinoscope is inserted through the selected intercostal
space (2nd, 3rd or 4th) in an oblique direction either laterally[52]
or medially[41] to the internal mammary vessels. In the last
case, the incision is very small approximating 1.5-2 cm and
both the intercostal muscles and the endothoracic fascia are
vertically divided at the border of the sternum. The operation
can be carried out even under local anesthesia. A recent
study Rendina et al.[53] reported that this procedure provided
histological identification in all of the 46 patients with
mediastinal tumors or enlarged LNs in wom it was performed.
Moreover, their hospital recovery lasted only up to 24 h.
The anterolateral mediastinotomy, which is in our opinion
one of the most valid alternative methods, can be performed
via an incision made along the selected intercostal space.
The mediastinum is accessed through an intercostal space
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Apostolakis, et al.: Saving internal mammary pedicle
Annals of Thoracic Medicine - Vol 9, Issue 3, July-September 2014 141
without costal resection. The internal mammary vessel bundle
is identied and preserved. Its major disadvantages lie in the
extensive muscle dissection required and in the opening of the
pleural cavity which requires chest tube drainage.
In recent years, video assisted techniques for biopsy of
mediastinal tumors and LNs have become popular. These
include both video-assisted mediastinoscopy (VAM) and
video assisted thoracoscopy (VATS) assisted mediastinotomy.
The first one is carried out through a standard cervical
mediastinoscopy approach.[54] LNs of stations 2, 4 and
7 can be easily accessed and resected. Right hilar LNs can
also be accessed.[48] Among 126 patients undergoing VAM,
Jedlicka et al.[55] reported histological conrmation rate of
75% with no mortality. On the contrary, Venissac et al.[56]
documented positive histological ndings in 238/240 patients
undergoing VAM. Among patients with lung cancer, post-
thoracotomy denition of the disease stage conrmed the
results of VAM approach in 93.6% of the cases. Morbidity is
low (0.85-4%) and includes vascular injuries, hemothorax,
air embolism and injury of lung parenchyma or pulmonary
hilum.[56,57] Hunt et al.[58] has proposed a VATS assisted
mediastinotomy approach. In those patients, who suffer from
lung cancer with involvement of different structures that may
not be accessible by a single procedure, a combination of VAM
and VATS may be extremely useful for the evaluation of the
resectability of the tumor.[59]
Transbronchial ne-needle aspiration (FNA) and computed
tomography (CT) guided FNA or core biopsy is other
alternatives. The rst one has sensitivity ranging between 60%
and 90% provided that the diameter of the LN detected on CT
images is over 1 cm.[60] Bleeding and pneumothorax are the
most frequent complications occurring in 2-5% of patients.[61] If
it is guided by endoscopic or endobronchial ultrasonography-
guided transbronchial needle aspiration (EBUS-TBNA), its
utility increases. The sensitivity of EBUS-TBNA for benign
or malignant mediastinal lesions ranges from 88% to 95%, its
specicity is 100%, its negative predictive value ranges from
85% to 93% and its accuracy ranges from 93% to 97%. Hence,
EBUS-TBNA is a safe, minimally invasive technique to access
mediastinal and hilar LNs and set a diagnosis. However,
surgical evaluation such as mediastinoscopy is required in
case of negative ndings.[62] Rarely, apart from pneumothorax
EBUS-TBNA may be complicated with mediastinal infectious
complications which is a severe one.[63,64] CT guided biopsy of
LNs is primarily applied for the determination of the disease
stage in lung cancer patients. It is less frequently used for the
histological conrmation of tumors of the mediastinum due
to their proximity to major mediastinal vascular structures. Its
sensitivity may reach up to 98%.[65] However, it is associated
with iatrogenic pneumothorax in 14-34% of cases.[66,67]
Contraindications to the performance of CT guided biopsy
include chronic obstructive pulmonary disease, diffuse lung
parenchyma disease, limited pulmonary reserves, arterio-
venous malformations and previous pneumonectomy.[23,67]
Conclusions
Ligation and dissection of the internal mammary artery
during anterior mediastinotomy is surprisingly considered
a meaningless event having no further impact on patients’
survival in most textbooks. In this review, we reported that
the majority of the diseases of the mediastinum requiring
histological identification via anterior mediastinotomy
mostly affects young and middle-aged adults but for those
suffering from lung cancer. Moreover, apart from patients
with lung cancer and rare mediastinal tumors related to
unfavorable outcomes (non-Hodgkin lymphomas, non
seminomatous germ cell tumors), all the others may
achieve a long survival after treatment. This fact will
allow the development of ischemic heart disease in some
of them. The effects of radiotherapy used in the treatment
protocols for patients presenting with malignant diseases
may further enhance this possibility. Hence, sacricing the
internal mammary artery during anterior mediastinotomy,
may deprive some patients from the advantages of the
aforementioned vessel regarding the treatment of their
ischemic heart disease. Therefore, preservation of the
internal mammary pedicle via the application of alternative
approaches to diagnose tumors and LNs of the mediastinum
should become common sense to all the thoracic surgeons
from the beginning of their training.
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How to cite this article: Apostolakis E, Papakonstantinou NA,
Chlapoutakis S, Prokakis C. Save or sacrice the internal mammary
pedicle during anterior mediastinotomy?. Ann Thorac Med
2014;9:138-43.
Source of Support: Nil, Conict of Interest: None declared.
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