Gastric Cancer Sentinel Lymph Node Mapping
Gastric Cancer Sentinel Lymph Node Mapping
Gastric cancer has an incidence in North America of over 24,000 new cases annually, of which
 approximately 15% are diagnosed at an early stage. Standard of care for early gastric cancer
 (EGC) treatment has historically included anatomical resection with regional lymphadenectomy.
 However, with the recent emergence of organ-sparing techniques, select patients with a very
 low risk of lymph node metastases are able to avoid anatomical resection and its inherent
 short and long term consequences. Despite this advance, EGC patients with high risk features
 continue to require anatomical resection to achieve adequate lymph node staging, despite the
 fact that 75-95% of these patients ultimately are found to have node negative disease. Due to
 the inadequacy of standard imaging modalities to reliably detect nodal metastases in EGC
 patients, sentinel lymph node sampling for gastric cancer was developed using principals
 similar to those used broadly for breast and melanoma patients. Early reports from Asia
 suggest this technique has very high success rates, accuracy and sensitivity, however it has
 never been verified in a North American context. This study aims to test SLN sampling for
 North American gastric cancer patients at a high volume regional treatment centre, with an
 aim to expand the application of organ sparing resection to EGC patients.

 This project aims to determine the sensitivity and accuracy of sentinel lymph node sampling
 for early gastric cancer patients at a high volume, North American, tertiary care centre.
Gastric cancer incidence in North America is 7.4/100,000 population, with 24,590 new cases
 diagnosed annually in the United States1. Of these, approximately 15% are detected at the
 early gastric cancer stage with no spread to regional lymph nodes2. Recent advances in
 gastric cancer detection, such as endoscopic use of narrow band imaging and magnification
 endoscopy, can help improve the detection rate of early lesions3-5. Gastric cancers detected
 at an early stage have an excellent prognosis, with reported long term overall survival rates
 of 71-92%6-9 due to the low rate of peritoneal and distant metastatic spread which frequently
 occur in patients with more advanced lesions. However, the mainstay of treatment even for
 early gastric cancers (EGC) remains anatomical resection with regional lymphadenectomy. While
 oncologically sound, anatomical resection is often associated with complications and
 unpleasant short and long-term side effects, including post-operative weight loss, dumping
 syndrome, vitamin deficiencies, anastomotic complications, delayed gastric emptying, and bile
 reflux, among others. Given the long life expectancy of patients after resection of EGC,
 curative resection with organ preservation to improve post-operative quality of life should
 be a treatment goal.

 Recently, organ-sparing techniques have emerged which allow select early gastric cancers to
 be treated without anatomical resection. These techniques, including endoscopic mucosal
 resection (EMR) and endoscopic submucosal dissection (ESD), allow for curative resection of
 highly-selected lesions with complete organ preservation. The shortcoming of all organ
 sparing resection techniques presently is that lymphadenectomy is not performed, leading some
 patients to perhaps be under-staged and therefore under-treated.

 According to the Japanese Gastric Cancer Treatment Guidelines10, early lesions are deemed
 appropriate for organ-sparing endoscopic resection if they meet the following criteria:
 confined to the mucosa (T1a), tumour size <2cm, no ulceration, and well-differentiated tumour
 grade. Together, tumours with these features have a very low risk of lymph node metastases
 (<1%). Long-term outcomes of ESD are highly favorable, with local recurrence and overall
 survival rates comparable to anatomical resection7,8. For tumours that do not meet the above
 criteria however, risk of lymph node involvement is drastically increased, with submucosal
 invasion, ulceration, tumour size >3cm, poorly differentiated tumour type, and lymphovascular
 invasion conferring a risk of lymphatic metastases of 4-26%11. For this reason, current best
 practices recommend EGCs with high risk features continue to undergo anatomical resection
 with regional lymphadenectomy. However 75-95% of such patients will ultimately have no
 regional metastases on final pathological analysis, suggesting they could have been spared
 anatomical resection if only their lymph node basins had been definitively staged prior to
 surgery.

 Presently, several imaging modalities are available to characterize lymph node stage for
 gastric cancer, including endoscopic ultrasound (EUS), computed tomography (CT) and positron
 emission tomography (PET). Unfortunately, the sensitivity of these modalities is woefully
 inadequate to accurately predict microscopic lymph node metastases, and therefore they cannot
 be reliably used to differentiate high risk EGCs that require anatomical resection and
 lymphadenectomy from those amenable to organ-sparing resection12-15.

 To address this gap in the ability to accurately detect nodal metastases in early gastric
 cancer, sentinel lymph node (SNL) sampling was pioneered in Asia and has undergone refinement
 and study there since the early 2000s. A recent multi-institutional study of 397 patients
 conducted across 12 centres in Japan reported rates of SLN detection of 97.5% and accuracy of
 SLN stage when compared to post-resection stage of 99%16. These numbers rival those reported
 for SLN biopsy of breast and melanoma cancers in large randomized controlled trials17,18.
 Indeed, for these tumour types, SLN biopsy is now the standard of care globally for staging
 clinically node-negative patients due to its diagnostic superiority over other staging
 modalities. Following the success of SLN sampling in gastric cancer, select Asian
 institutions are now applying this technique to diverting sentinel node-negative (SLN -ve) T1
 and T2 gastric cancer patients away from anatomical resection with extensive lymphadenectomy
 and towards organ-sparing endoscopic or wedge resection.

 The Upper GI Oncology Program at the McGill University Health Centre sees approximately 80
 gastric cancer patients per year, in whom SLN sampling has the potential to inform resection
 decisions ~25-30%. Currently, the program performs 15-20 ESDs annually for both early
 esophageal and gastric lesions, and approximately 30-40 anatomical resections are performed
 in node-negative gastric and esophageal cancer patients per year. Implementation of the
 gastric SNL sampling technique would enable expansion of the ESD program to offer
 organ-sparing curative resections to EGC patients who presently can only be offered
 anatomical resection.

 The purpose of this study is to determine the utility and feasibility of SLN sampling for
 gastric cancer in a North American context.
Inclusion Criteria:

 -  All patients who are deemed healthy enough to withstand laparoscopic or open anatomic
 gastrectomy with extended regional (D2) lymphadenectomy will be eligible. Patients
 much have biopsy-proven, single lesion, <4cm gastric adenocarcinoma, of stage
 cT1/T2/T3 N0 M0.

 Exclusion Criteria:

 -  Not able to withstand anatomical gastric resection with D2 lymphadenectomy, patient
 refusal, N+ve disease on pre-op work up, disease progression before surgery