Intraoperative lymphatic mapping and selective lymphadenectomy are revolutionary concepts that, in a short period, have shown the potential to alter dramatically the management of many patients with solid neoplasms. The rapid adaptation of this approach to the staging of solid neoplasms by the surgical oncology community has resulted in an explosion of data. Initially described as a surgical technique in which each surgeon had to climb a learning curve, ILM and selective lymph node dissection (SLND) are now recognized as a multidisciplinary surgical approach to the management of the patient with cutaneous melanoma and breast cancer. The potential values of ILM and SLND are being examined vigorously now in numerous other solid neoplasm resections ( 1 ).
Bilchik et al.( Wayne Cancer Institute, Santa Monica) have conducted several studies of intraoperative lymphatic mapping and sentinel lymphadenectomy for the staging of GI neoplasms. LM is performed following injection of 0,5-1 ml of isosulfan blue dye, and blue stained sentinel lymph nodes are analyzed by hematoxilin and eosin staining, multiple sectioning, and cytokeratin immunohistochemistry.
They believe that lymphatic mapping can identify the sentinel lymph nodes that drains a GI neoplasms without adding significantly to the time, cost, or morbidity of the primary surgical procedure.
Moreover LM can identify aberrant lymphatic drainage, which may alter the extent of resection ( 2 ).
Kosaka et al reports skip metastases in 15% of 51 patients with gastric cancer. Aberrant lymphatic drainage is a possible explanation for inadequate staging and a patient's failure to respond to adjuvant treatment ( 3 ).
The cumulative data indicate that the histological status of SLN accurately reflects the tumor status of the entire regional node basin in 96% of cases, excluding rectal neoplasms. Focused examination of SLN based on serial sectioning and immunohistochemistry further increases staging accuracy. SLN analysis may be particular relevant in identifying micrometastastic spread from T1-T2 neoplasms. In fact the findings suggest an inverse relationship between a GI neoplasm's T stage and the presence of isolated nodal metastases. Among the patients with colorectal cancer the SLN was the only positive node in all T1, 86% of T2, 56% of T3 and 20% of T4 cases.
This 96% success rate in identifying the SLN is higher than the 82% initially reported by Morton et al for LM in primary melanoma or the 66% initially reporetd by Giuliano et al for LM in primary breast cancer.
Eventually the ability to identify a tumor free SLN might enable the surgeon to avoid the morbidity of radical lymphadenectomy in patients with gastric and pancreatic cancer. A prospective phase II trial is underway to determine whether LM with focused examination of the SLNs can improve the staging of GI neoplasms and the selection of patients for adjuvant therapy ( 2 ).
Y Kitagawa et al. ( Keio University, Tokyo ) riaffirm that the application of the sentinel node concept for solid tumors other than melanoma and breast cancer, including GI cancer is still controversial, but it is worthwhile to continue evaluating this procedure to determine its role in an accurate staging, and a minimally invasive approach to early GI cancer. They have demonstrated the feasibility of radioguided SN mapping during laparotomy in patients with esophageal, gastric and colorectal cancers. In 188 patients, the SNs identified by this technique had an overall diagnostic accuracy of 96% for regional lymph node metastasis. Aberrant drainage sites that have been called skip metastases from the primary lesion were detectable using this method.
More recently the authors have undertaken SN mapping during laparoscopic surgery. A combination of radiotracer and blue dye optimize the identification of SNs that drains GI cancers. Their preliminary data indicate that laparoscopic mapping of the SN is a sensitive intraoperative technique for identifying lymph node micrometastasis and they believe that it will become an important component of a minimally invasive approach to early stage GI cancers.
In fact they reported curative laparoscopic wedge resection for mucosal gastric cancer. This curative laparoscopic procedure might be extended to tumors that invade the submucosal area, if the absence of nodal metastases can be confirmed by a similarly noninvasive but highly accurate technique.
Each excised SN is immediately frozen, sectioned, and stained by hematoxilin and eosin and by immunohistochemistry using antibodies to cytokeratin. The mean number of SNs detected by this laparoscopic approach is comparable with the mean number detected during laparotomy. Intraoperative survey using the laparoscopic gamma probe after wedge resection of the primary lesion ( this lesion causes a high level of background activity in the abdominal cavity ) is useful in detecting SNs in unexpected areas and in confirming the complete harvest of SNs ( 4, 5, 6 ).
Takashi Aikou et al. have conducted several studies of sentinel node navigation surgery to determine the extent of lymph node dissection necessary in patients with early gastric cancer.
H&S examination of 2605 lymph nodes from108 consective patients with submucosal gastric cancer revealed a 19% rate of lymph node metastases. Of 87 (81%) patients whose nodes were H&S negative, 20 (23%) had CK-positive MM. These MM were limited to regional area of the lymphatic pathway near the primary tumor. In the 21 (19%) patients whose nodes were H&S positive, the distribution of nodal metastases was beyond one regional lymphatic pathway.
If nodal metastases is detected preoperatively or during surgery, the patient should undergo lymphadenectomy ( D2 nodal dissection), because the possibility of micrometastases in another region is high. If nodal metastasis cannot be detected by preoperative diagnostic means or by intraoperative IHC frozen-section examination of the nodal specimen identified during SNNS, less extensive lymphadenectomy may be appropriate.
The wide and complicated lymphatic stream from a gastric tumor contributed to the relatively high (23%) incidence of micrometastases and the frequent occurrence of skip metastases (10%).
The success of SNNS in gastric cancer depends largely on the accuracy of frozen section examination during surgery. The IHC technique for rapid detection of MM requires only 40 minutes. Each node is frozen and bisected longitudinally. Five sections are cut from each face. Each section is incubated with anticytokeratin antibody for 15 minutes, followed by alkaline phosphatase for 10 minutes, and then with chromogen substrate for 2 minutes. The section is then placed in hematoxylin under a glycerin gelatin coverslip. The two remaining portions of each SN are examined by routine H&E staining and by RT-PCR.When compared with routine H&E examination, the rapid IHC-CK technique has increased the intraoperative detection of metastases in frozen sections from 24% to 32% of cases and from 13% to 20% of lymph nodes.
Although the authors are now using RT-PCR routinely for SN examination, they do not have enough data to determine the relatively efficacy of molecular assessment .
Probe directed SNNS may find a role in the management of patients whose gastric mucosal cancer has no clinical evidence of nodal involvement. If lymph node metastases cannot be detected by preoperative diagnostic means or by frozen section IHC examination of the SN identified during SNNS, less extensive lymphadenectomy may be appropriate.
Technical issues affecting the success of SNNS in early gastric cancer include the discrepancy between SNs detected by blue dye and radiopharmaceutical, different rates of radiopharmaceutical uptake in different organs and tissues, size of particles, injection methods, accuracy of frozen section, and criteria used to define SNs ( 7 ).
Takashi Ichikura et al. riaffirm that it remains difficult to precisely predict lymph node metastasis in the majority of patients with a tumor invading the submucosal layer, although risk factors for lymph node metastasis have been determined.
The sentinel node concept is that lymph node metastases spread in an orderly fashion in relation to the lymphatic streams, and that the negative tumor-bearing status of the first lymph node into which the primary tumor drains indicates the negative tumor status of the entire region of lymph nodes beyond.
To assess the applicability of the sentinel node concept to gastric carcinoma, the authors retrospectively analyzed the location of metastatic lymph nodes in patients with metastatic involvement in one or two regional lymph nodes, then attempted intraoperative lymphatic mapping by using a dye.
Their results show the complexity of lymphatic streams within and from the stomach. Lymphatic mapping using indocyanine green can be a tool for identifying sentinel nodes in gastric carcinoma although lymph nodes occupied by cancer tissue may not be detected by this technique ( 9 ).
References
1) Jan H Wong. A historical perspective on the developlment of intraoperative lymphatic mapping and selective lymhadenectomy. Surgical Clinics of North America, 2000, volume 80, n 6, 1675-1682.
2) A J Bilchik et al. Aberrant drainage and missed micrometastases: the value of lymphatic mapping and focused analysis of sentinel lymph nodes in gastrointestinal neoplasms. Annals of Surgical Oncology 2001, 8 (9S): 82-85.
3) Kosaka T et al. Lymphatic routes of the stomach demonstrated by gastric carcinomas with solitary lymph node metastases. Surg Today 1999; 29: 695-700.
4) Y Kitagawa et al. Laparoscopic detection of sentinel lymph nodes in gastrointestinal cancer: a novel and minimally invasive approach. Annals of Surgical Oncology 2001, 8 (9S): 86-89.
5) Y Kitagawa et al. The role of the sentinel lymph node in gastrointestinal cancer. Surgical Clinics of North America, 2000, volume 80, n 6, 1799-1809.
6) Ohgami M et al. Curative laparoscopic surgery for early gastric cancer : five year experience. World Journal Surgery. 1999; 23: 187-93.
7) Takashi Aikou et al. Can sentinel node navigation surgery reduce the extent of lymph node dissection in gastric cancer? Annals of Surgical Oncology 2001, 8 (9s): 90-93.
8) Natsugoe S, Aikou T, et al. The concept of lymph node micrometastasis for sentinel node navigation surgery. J Clin Surg 2000; 55: 317-21.
9) Takashi Ichikura, M.D., Daisaku Morita, M.D., et al. Sentinel Node Concept in Gastric Carcinoma. World Journal of Surgery 2002, volume 26, n3.
10) Palaia R., Cremona F., Delria P., et al. (1999) Sentinel node biopsy in gastric cancer. J. Chemother. 11:230-231.
