Patients with metastases to more than regional lymph nodes
Patients with metastases to more than 15 regional Concanamycin A nodes such condition were categorized to have stage IV disease in the 6th edition of the AJCC staging system, implying an extremely poor prognosis of this disease similar to distant metastases.6,7 In the 7th AJCC staging system, patients with metastases to more than 15 regional lymph nodes were classified as N3b and categorized as stage III.8 Finally, the prognostic value of metastases to more than 15 regional lymph nodes was modified to stage IIIB or IIIC and was separated from those with 7e15 regional lymph node metastases in the latest version of AJCC (8th edition).9
Determining the survival outcome for patients with metastases to more than 15 regional lymph nodes is difficult due to the following reasons. First, although removing more than 30 regional lymph nodes is desirable,10 the optimal number of regional lymph nodes that should be retrieved is still debated.11 The inevitable increase in the number of dissected lymph nodes dissected results in a high incidence of postoperative morbidities and mortalities.5 Although the high number of metastatic regional lymph nodes implied poor outcome, the prognostic value of more than 15 met-astatic regional lymph nodes is yet to be completely established. Therefore, the numbers of metastatic regional lymph nodes alone have no further clinical value in patients classified as N3b. Recently, a high lymph node metastatic ratio (LNR) had been described as a poor prognostic factor in several gastric cancer studies.12e16 In line with previous reports, the present study aimed to identify the prognostic value of LNR and to develop an LNR-based prognostic model for predicting the survival outcome after D2 surgery in pa-tients with gastric cancer and metastases to more than 15 regional lymph nodes.
2. Material and methods
2.1. Patients and treatment
The present study included 139 gastric cancer patients with metastasis to more than 15 regional lymph nodes who
underwent radical gastrectomy and D2 lymph node dissec-tions between 2007 and 2014 at the Chang Gung Memorial Hospital Linkou Branch. All patients received curative sur-gery with no residual tumor resection (R0) or microscopic residual tumor resection (R1). Patients who had recurrent tumors, metastatic tumors, grossly residual tumor (R2 resection), or prior chemotherapy or radiotherapy were excluded. All patients were advised to receive adjuvant chemotherapy within 6 weeks after the radical surgery. However, the final decision to receive or decline such therapy was made by the patient. Adjuvant chemotherapy was a 5-fluorouracil-based regimen, which included 5-fluorouracil administered intravenously,17 uracil-tegafur (UFT),18 titanium silicate (TS)-1,19 or capecitabine plus oxaliplatin (XELOX),20 and was determined according to the physician’s discretion. The 5-fluorouracil or XELOX regimen was administered for 6 months, whereas the UFT or TS-1 regimen was administered for up to 1 year. Patient char-acteristics were analyzed to identify the variables associ-ated with survival outcome. The study complied with the 1996 Helsinki Declaration and was approved by the insti-tutional review board of the hospital.
2.2. Data collection and follow-up
Administrative and clinical data consisted of patient de-mographics collected retrospectively, including clinical features with age, sex, and Eastern Cooperative Oncology Group performance status (ECOG PS); American Society of Anesthesiologists (ASA) score; history of previous cancer; pre-existing comorbidities; stump cancer or not; family history of gastric cancer; preoperative body mass index (BMI); preoperative carcinoembryonic antigen (CEA) level; preoperative cancer antigen 19-9 (CA19-9) level; and pathological results, including Helicobacter pylori infec-tion; surgical margin; perineural, lymphatic, or vascular invasion; Lauren classification21; lymph node retrieval ratio; LNR; and tumor (T) classification. Data were recor-ded by the primary care clinicians using an electronic pa-tient record form at the time of cancer diagnosis. Comorbidities were represented by modified Charlson Comorbidity Index (CCI),22 excluding patient age and cancer diagnosis. The overall survival (OS) and disease-free survival (DFS) rates were calculated from the time of surgery to the time of death and tumor recurrence, respectively. Data on the dates of the surgery, tumor recurrence, and the death of each patient were obtained from the institutional cancer center registry or the Na-tional Register of Death Database in Taiwan. All of the included patients were followed-up until the date of death or June 30, 2016.