A Single-Institution Validation Study of Lymph Node Staging By the AJCC 8th Edition for Patients with Pancreatic Head Cancer: A Proposal to Subdivide the N2 Category

Asano, Daisuke; Nara, Satoshi; Kishi, Yoji; Esaki, Minoru; Hiraoka, Nobuyoshi; Tanabe, Minoru; Shimada, Kazuaki

doi:10.1245/s10434-019-07390-z

Cited by 17 publications

(14 citation statements)

References 42 publications

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“…[6][7][8][9][10][11][12] Patients with regional lymph node involvement have a worse outcome than that in patients without node involvement. 6,8,11,15,23 Honselmann et al 24 showed that the time to For the N1 subgroup (1-3 involved nodes), patients who underwent adjuvant chemotherapy had better outcomes than patients without chemotherapy (P < .001 by a log-rank test, A). However, for the N2 subgroup (4 involved nodes), no difference in outcome was observed between patients who underwent chemotherapy and patients who did not undergo chemotherapy (P ¼ .715, B).…”

Section: Discussionmentioning

confidence: 99%

“…2,5 However, for patients who have undergone curative resection, the 5-year survival rate is only *20%. 3,6 Regional and distant recurrences lead to failure of curative operation. 3 Therefore, methods to identify the risk factors of recurrence and to provide therapeutic strategies are urgently needed to improve the outcome of patients with resected pancreatic cancer.…”

Section: Introductionmentioning

confidence: 99%

“…2 Lymphatic metastasis is one of the most important risk determinants for the recurrence of resected pancreatic cancer. [6][7][8][9][10][11][12] The American Joint Committee on Cancer's (AJCC) TNM classification of nodal substage has been modified from the nodal status in the 7th edition (N0, node negative; N1, node positive) to nodal involvement with details on the number of positive nodes in the 8th edition (N0, no regional node involvement; N1, 1-3-regional node involvement; N2, 4-regional node involvement). [13][14][15] This modification implies that the degree of lymph node involvement has an important impact on the patients' prognosis, which has also been validated in previous reports.…”

Section: Introductionmentioning

confidence: 99%

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Resected Pancreatic Cancer With N2 Node Involvement Is Refractory to Gemcitabine-Based Adjuvant Chemotherapy

Liu

Jin

et al. 2020

Cancer Control

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Lymphatic metastasis is a major determinant of the outcome of resected pancreatic cancer. Gemcitabine-based adjuvant chemotherapy can improve the outcome of resected pancreatic cancer. However, the efficacy of gemcitabine against pancreatic cancer stratified by nodal involvement is unclear. In this study, patients who had undergone curative resection of pancreatic adenocarcinoma (612 cases) were included. The efficacy of adjuvant gemcitabine-based regimen, stratified by nodal status (negative, positive) or N substage (N0, no nodal involvement; N1, 1-3-node involvement; N2, ≥4-node involvement), was examined. Both the node-negative (hazard ratio [HR] = 0.62, 95% confidence interval [CI], 0.44-0.87, P = .006) and node-positive subgroups (HR = 0.45, 95% CI, 0.33-0.62, P < .001) benefited from gemcitabine-based adjuvant chemotherapy. Patients with N0 (ie, the node-negative subgroup) or N1 (HR = 0.36, 95% CI, 0.25-0.52, P < .001) disease benefited from gemcitabine-based chemotherapy. However, patients with N2 tumors (HR = 0.95, 95% CI, 0.50-1.78, P = .867) had poor response to gemcitabine-based treatment. Therefore, we postulate that resected pancreatic cancer with N2 node involvement is refractory to gemcitabine-based adjuvant chemotherapy. A more intensive adjuvant regimen may be required for N2 subgroup patients.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Resected Pancreatic Cancer With N2 Node Involvement Is Refractory to Gemcitabine-Based Adjuvant Chemotherapy

Liu

Jin

et al. 2020

Cancer Control

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“…None of the patients received any preoperative treatment, and all of the patients received a postoperative chemotherapeutic regimen of six cycles of standard gemcitabine [14]. Clinicopathologic features were staged according to the 2002 International Union Against Cancer's tumor-node-metastasis (TNM) classification system [15].…”

Section: Immunohistochemical Analysismentioning

confidence: 99%

HEATR1 Deficiency Promotes Chemoresistance via Upregulating ZNF185 and Downregulating SMAD4 in Pancreatic Cancer

Fang

Kuang

et al. 2020

Journal of Oncology

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Objective. To discover the correlated gene with HEATR1 in regulating chemoresistance of gemcitabine. Methods. Gene chip analysis was performed to find out differential genes between HEATR1-KD and control groups. The top 20 genes were subjected to high-content screening, and functional assay was implemented. Gene expression profiling was carried out to find the downstream target. Immunohistochemistry and survival analysis were performed. Results. ZNF185 fold change (4.5285) was the most significant between the HEATR1-KD and control groups. Knocking down ZNF185 could promote the chemosensitivity, apoptosis, and proliferative inhibition, with SMAD4 significantly upregulated. Patients with high HEATR1 and SMAD4 or low ZNF185 exhibited better survival. Conclusion. HEATR1, ZNF185, and SMAD4 could affect the chemosensitivity of gemcitabine and may be the indicators of gemcitabine selection in the chemotherapy of pancreatic cancer.

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“…PDAC patients with LN metastasis are known to have higher risk of recurrence and shorter survival [4,[10][11][12]. In general, examined LN (ELN) number and LN ratio (LNR) are considered to be fundamental metrics for quality assessment and prognostic strati cation in cancer care [10,13]. Given the crucial nature of N staging in PDAC, the College of American Pathologists recommends that a minimum of 12 LNs should be examined at the time of pancreaticoduodenectomy.…”

Section: Introductionmentioning

confidence: 99%

Lymph Node Metastatic Patterns and Survival Predictors Based on Tumor Size in Pancreatic Ductal Adenocarcinoma

Chen

Gan

et al. 2020

Preprint

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BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal malignancies. Its larger mass size is widely acknowledged to be associated with increased lymph node (LN) metastatic potential. However, the quantitative relationships between tumor size and LN metastasis or survival remain unclear. Thus, this study aims to quantitatively identify the objective relationship between tumor size and prevalence of LN metastases across primary tumor size spectrums.METHODS: 9,958 resected PDAC patients without distant metastasis were retrieved from the Surveillance, Epidemiology, and End Results (SEER) database. The prevalence of LN metastases, LN ratio (LNR) and N2/N1 ratio were assessed amongst different tumor sizes, and the relationships were depicted by matched curves. RESULTS: In the enrolled cohort, age, tumor site, grade, American Joint Committee on Cancer (AJCC) 8th node staging, tumor size, chemotherapy and radiotherapy were identified as significant independent predictors for overall survival (OS) and cancer-specific survival (CSS). For tumors within 1-40 mm in size, the prevalence of node positive disease is closely modelled using a logarithmic formula [0.249×ln (size) + 0.452] × 100%, and then fluctuated between 70.0% and 80.0% when beyond 40 mm. The mean LNR increased in a stepwise manner as tumor size increased from 1-5 mm (LNR=0.024) to 41-45 mm (LNR=0.177); then, beyond 45 mm, it plateaued near 0.170. N2/N1 ratio gradually increased along with tumor size from 1-5 mm (N2/N1=0.286) to 41-45 mm (N2/N1=1.016), and when tumor size reached to 41-45 mm or more, the ratio stabilized around 1.000. CONCLUSION: Regional LN involvement demonstrated a logarithmic growth with increasing tumor sizes in resectable PDAC patients. The probability of metastasis in each regional LN for resectable PDAC patients with tumors greater than 40 mm in size was near 17.0% and their overall prevalence of LN metastasis was 70%-80%. Among which, 50% of patients had an N2 stage.

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A Single-Institution Validation Study of Lymph Node Staging By the AJCC 8th Edition for Patients with Pancreatic Head Cancer: A Proposal to Subdivide the N2 Category

Cited by 17 publications

References 42 publications

Resected Pancreatic Cancer With N2 Node Involvement Is Refractory to Gemcitabine-Based Adjuvant Chemotherapy

Resected Pancreatic Cancer With N2 Node Involvement Is Refractory to Gemcitabine-Based Adjuvant Chemotherapy

HEATR1 Deficiency Promotes Chemoresistance via Upregulating ZNF185 and Downregulating SMAD4 in Pancreatic Cancer

Lymph Node Metastatic Patterns and Survival Predictors Based on Tumor Size in Pancreatic Ductal Adenocarcinoma

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