FEASIBILITY OF SENTINEL NODE DETECTION IN ESOPHAGEAL CANCER

In the twentieth century, lymph node dissection based on metastatic
distribution has developed as the standard procedure for surgical management of
gastrointestinal cancer.

The fear that invisible micrometastases might be present has encouraged
aggressive resection with lymphadenectomy to control the disease.

However, the prognostic benefits of extensive surgery are still unknown and the
universal application of radical surgery may affect surgical morbidity,
mortality, and quality of life after surgery, particularly in patients without
lymphatic spread.

In the twenty-first century, a novel technology to detect micrometastases
without extensive surgical resection is required to establish an individualized
surgical management approach to gastrointestinal cancer.

Lymphatic mapping techniques are now used in the control of superficial
malignancies, such as malignant melanoma and breast cancer, providing a novel
tool that may also be of use for gastrointestinal cancers [1]

Although the sentinel node concept has been validated and clinically applied to
breast cancer and malignant melanoma, its clinical significance in other solid
tumors has not been thoroughly investigated.


Esophageal cancer is a particularly aggressive GI malignancy because of the
high incidence and widespread distribution of lymph node metastasis. However,
the SN concept seems to be applicable according to recent reports.[8,9]



There are several specific features of SN mapping in esophageal cancer:

o A dye-guided method is not applicable for esophageal cancer because of its
anatomical situation. It is impossible to trace the flow of blue dye without
destruction of the lymphatic network.

o SNs in esophageal cancer are multiple and distributed widely from the
cervical to the abdominal area. Therefore, the lymphoscintigram is essential to
identify the SNs in esophageal cancer.

o Recently, chemoradiotherapy (CRT) has attracted attention as a
multidisciplinary curative treatment for cT1N0 esophageal cancer. In this
approach, control of micrometastasis is essential. Lymphoscintigrams revealing
the distribution of SNs in each individual case are useful to design the field
of irradiation.

o A complete sampling of multiple and widespread SNs in esophageal cancer is
not a minimally invasive procedure, unlike in breast cancer. At present local
resection of a primary esophageal cancer with negative SNs is not practical.
However, selective and modified lymphadenectomy for clinically N0-stage
esophageal cancer should become feasible and clinically useful.

o Although three-field lymph node dissection is recognized as an extensive and
curative procedure for thoracic esophageal cancer, its prognostic significance
is still controversial. Uniform application of this highly invasive procedure
may increase the morbidity and reduce quality of life after surgery.

o Individualized selective lymphadenectomy for clinically N0-stage esophageal
cancer based on SN status would be a reasonable surgical approach.[10]

o If mediastinal SNs are all negative and no hot spot is detected in the
cervical area by preoperative scintigraphy, cervical lymph node dissection
would not be necessary.


o Approaches for lower thoracic and abdominal esophageal cancer, including
Barrett*s adenocarcinoma, could be individualized by SN status. If abdominal
SNs are all negative and no hot spot is detected in the mediastinal area by
preoperative scintigraphy, transthoracic extensive lymph node dissection is not
required. [2]





With regard to gastrointestinal (GI) cancers in particular, surgeons have been
cautious because of the high frequency of skip metastasis and the complicated
lymphatic system in the GI tract. The so-called skip metastasis has been
defined according to anatomic classification of regional lymph nodes and that
the lymphatic drainage route must be patient or lesion specific.


In a recent study 131 patients with GI cancers (esophagus: 22, stomach: 71,
colorectum: 38), the detection rate of sentinel nodes was 91% and overall
diagnostic accuracy of lymph node metastasis by sentinel node status was 97%.
Initial results suggest further investigation of this procedure as an accurate
staging and a minimally invasive approach to early GI cancers.[4]




In the Tsioulias's study lymphatic mapping (LM) was performed in 65 patients
with GI neoplasms by injecting 0,5 to 1 ml of isosulfan blue dye around the
periphery of the neoplasms [7]. Blue stained SNs were analysed by
hematoxilin-eosin staining, multiple sectioning, and cytokeratin
immunohistochemistry.

The author underlines that the LM can identify aberrant lymphatic drainage,
which may alter the extent of resection. Aberrant drainage patterns are not
uncommon in patients with GI neoplasms, and they are a possible explanation for
inadequate staging and a patient's failure to respond to adjuvant treatment
[7].

Tsioulias concludes that in the meantime LM with focused examination of the SNs
(on serial sectioning and IHC) improves the staging of GI neoplasms and may
affect the selection of the patients for adjuvant therapy. Eventually,
according to the Maruyama opinion, the ability to identify a tumor free SN
might enable the surgeon to avoid the morbidity associated with radical
lymphadenectomy in patients with GI cancer [9].


Until the late 1990s, the application of the sentinel node (SN) concept to
gastrointestinal (GI) malignancies was not recognized because of the
multidirectional and complicated lymphatic flow from the GI tract. However,
several studies supporting the validity of the SN concept for GI cancers have
been reported in the past 5 years.

Because of its anatomical location, gastric cancer is one of the most suitable
targets for minimally invasive surgery based on SN status. Laparoscopic local
resection is theoretically feasible for curative treatment of SN-negative early
gastric cancer.

Although SNs in esophageal cancer are multiple and are distributed widely from
the cervical to the abdominal area, selective and modified lymphadenectomy for
clinically N0-stage esophageal cancer is likely to become feasible and
clinically viable. Total mesorectal excision (TME) is accepted as a standard
surgical procedure for rectal cancer. However, there is a risk of aberrant
distribution of SNs beyond the extent of TME; for example, SNs may be lateral
to the lower rectum. SN mapping with scintigraphy is useful for effective
sampling of SNs in unexpected areas and accurate staging without extensive
lymph node dissection.

There are several practical issues to be overcome. The techniques and
feasibility of laparoscopic SN sampling are still under investigation.
Large-scale multicenter prospective validation studies for SN mapping in GI
cancer are essential. If these remaining issues can be solved, SN mapping for
GI cancer will have great clinical impact [2].

To test the validity and feasibility of this concept in GI cancers, we propose
a radio-guided intraoperative sentinel node procedure using preoperative
endoscopic submucosal injection of radioactive tracer followed by
intra-operative gamma-probing.

prospective study

LYMPHOSCINTIGRAPHY


Tracer injection

The patient is seen in the Department of Gastoenterology on the afternoon
before the day of the surgery, or in the morning of the day of surgery.
Before surgery, 0.5 ml 40 MBq of Tc-99m colloid albumine (Nanocoll) will be
injected endoscopically into four submucosal sites surrounding the tumor.
Injections will be performed with 23-gauge endoscopic injection sclerotherapy
needles.
The total dose injected into each patient will be 160 MBq (4,5 mCi) [13].
The time interval between injection of the tracer and surgery should be al
least two hours to allow the tracer to reach the drainings lymph nodes.


Imaging and reporting


Dynamic images starting shortly after injection during 30 minutes are helpful
to depict the SN.

Static lymphoscintigraphy (128x128 matrix) is performed 2 hours after injection
of the tracer and may be repetead 1-2 hours before operation.

The following thorax and abdomen views are advised: anterior, left and right
lateral.

The use of a flood source to delinate the body contour are helpful.

The images should be discussed with the surgeon pre-operatively and should be
available during surgery.




6. SURGICAL APPROACH

Surgery should be performed within 24 hours after injection of the tracer.

The standard surgical approach will be an abdomino-right-transthoracic en bloc
esophagectomy with 2-field lymphadenectomy for squamous cell cancer and a
radical transhiatal tumor resection with extensive lymphadenectomy in the lower
posterior mediastinum in patients with adenocarcinoma of the distal esophagus.

The extent of lymphadenectomy in the upper abdominal compartment and lower
posterior mediastinum will be identical for all surgical approaches and
comprised a suprapancreatic lymphadenectomy, including all lymph nodes along
the common hepatic artery, celiac axis, and splenic artery toward the splenic
hilum. Also will be included all lymph nodes along the proximal two thirds of
the lesser gastric curvature and the gastric fundus, left and right paracardiac
nodes, distal paraesophageal nodes, and nodes in the lower posterior
mediastinum up to the tracheal bifurcation.

With the transhiatal approach, this will be achieved after a wide anterior
splitting of the diaphragmatic hiatus and transhiatal exposure of the lower
posterior mediastinum.

Patients with an abdomino-right-thoracic approach will have an additional
formal extended mediastinal lymphadenectomy comprising all nodes at the
tracheal bifurcation along the left and right main stem bronchi, the upper
mediastinal compartment, and along the left recurrent nerve.

Based on a standard tracer dose of 160 MBq the maximum total body amount of
radiation absorbed by the surgeon will be 15 microSv/hr. The maximum amount of
radiation allowd per year for the hands, that are the most exposed during the
procedure, is 15 milliSv. Most of the radiation dose is coming from the
injection site, only a few percent originates from the sentinel node.

Exposure of the other operating staff and pathology staff will be lower as the
distance to the radiation source is further and the exposure time is shorter.

For transportation within the hospital a leakproof bag or box will be suffice.