Long-term survival of patients with stage II and III gastric cancer who underwent gastrectomy with inadequate nodal assessment.

BACKGROUND: Gastric cancer is an aggressive disease with frequent lymph node (LN) involvement. The NCCN recommends a D2 lymphadenectomy and the harvesting of at least 16 LNs. This threshold has been the subject of great debate, not only for the extent of surgery but also for more appropriate staging. The reclassification of stage IIB through IIIC based on N3b nodal staging in the eighth edition of the American Joint Committee on Cancer (AJCC) staging system highlights the efforts to more accurately discriminate survival expectancy based on nodal number. Furthermore, studies have suggested that pathologic assessment of 30 or more LNs improve prognostic accuracy and is required for proper staging of gastric cancer. AIM: To evaluate the long-term survival of advanced gastric cancer patients who deviated from expected survival curves because of inadequate nodal evaluation. METHODS: Eligible patients were identified from the Surveillance, Epidemiology, and End Results database. Those with stage II-III gastric cancer were considered for inclusion. Three groups were compared based on the number of analyzed LNs. They were inadequate LN assessment (ILA, < 16 LNs), adequate LN assessment (ALA, 16-29 LNs), and optimal LN assessment (OLA, ≥ 30 LNs). The main outcomes were overall survival (OS) and cancer-specific survival. Data were analyzed by the Kaplan-Meier product-limit method, log-rank test, hazard risk, and Cox proportional univariate and multivariate models. Propensity score matching (PSM) was used to compare the ALA and OLA groups. RESULTS: The analysis included 11607 patients. Most had advanced T stages (T3 = 48%; T4 = 42%). The pathological AJCC stage distribution was IIA = 22%, IIB = 18%, IIIA = 26%, IIIB = 22%, and IIIC = 12%. The overall sample divided by the study objective included ILA (50%), ALA (35%), and OLA (15%). Median OS was 24 mo for the ILA group, 29 mo for the ALA group, and 34 mo for the OLA group (P < 0.001). Univariate analysis showed that the ALA and OLA groups had better OS than the ILA group [ALA hazard ratio (HR) = 0.84, 95% confidence interval (CI): 0.79-0.88, P < 0.001 and OLA HR = 0.73, 95%CI: 0.68-0.79, P < 0.001]. The OS outcome was confirmed by multivariate analysis (ALA HR = 0.68, 95%CI: 0.64-0.71, P < 0.001 and OLA: HR = 0.48, 95%CI: 0.44-0.52, P < 0.001). A 1:1 PSM analysis in 3428 patients found that the OLA group had better survival than the ALA group (OS: OLA median = 34 mo vs ALA median = 26 mo, P < 0.001, which was confirmed by univariate analysis (HR = 0.81, 95%CI: 0.75-0.89, P < 0.001) and multivariate analysis: (HR = 0.71, 95%CI: 0.65-0.78, P < 0.001). CONCLUSION: Proper nodal staging is a critical issue in gastric cancer. Assessment of an inadequate number of LNs places patients at high risk of adverse long-term survival outcomes.

Laparoscopic Compared with Open D2 Gastrectomy on Perioperative and Long-Term, Stage-Stratified Oncological Outcomes for Gastric Cancer: A Propensity Score-Matched Analysis of the IMIGASTRIC Database.

BACKGROUND: The laparoscopic approach in gastric cancer surgery is being increasingly adopted worldwide. However, studies focusing specifically on laparoscopic gastrectomy with D2 lymphadenectomy are still lacking in the literature. This retrospective study aimed to compare the short-term and long-term outcomes of laparoscopic versus open gastrectomy with D2 lymphadenectomy for gastric cancer. METHODS: The protocol-based, international IMIGASTRIC (International study group on Minimally Invasive surgery for Gastric Cancer) registry was queried to retrieve data on patients undergoing laparoscopic or open gastrectomy with D2 lymphadenectomy for gastric cancer with curative intent from January 2000 to December 2014. Eleven predefined, demographical, clinical, and pathological variables were used to conduct a 1:1 propensity score matching (PSM) analysis to investigate intraoperative and recovery outcomes, complications, pathological findings, and survival data between the two groups. Predictive factors of long-term survival were also assessed. RESULTS: A total of 3033 patients from 14 participating institutions were selected from the IMIGASTRIC database. After 1:1 PSM, a total of 1248 patients, 624 in the laparoscopic group and 624 in the open group, were matched and included in the final analysis. The total operative time (median 180 versus 240 min, p < 0.0001) and the length of the postoperative hospital stay (median 10 versus 14.8 days, p < 0.0001) were longer in the open group than in the laparoscopic group. The conversion to open rate was 1.9%. The proportion of patients with in-hospital complications was higher in the open group (21.3% versus 15.1%, p = 0.004). The median number of harvested lymph nodes was higher in the laparoscopic approach (median 32 versus 28, p < 0.0001), and the proportion of positive resection margins was higher (p = 0.021) in the open group (5.9%) than in the laparoscopic group (3.2%). There was no significant difference between the groups in five-year overall survival rates (77.4% laparoscopic versus 75.2% open, p = 0.229). CONCLUSION: The adoption of the laparoscopic approach for gastric resection with D2 lymphadenectomy shortened the length of hospital stay and reduced postoperative complications with respect to the open approach. The five-year overall survival rate after laparoscopy was comparable to that for patients who underwent open D2 resection. The types of surgical approaches are not independent predictive factors for five-year overall survival.

Gastrectomy for stage IV gastric cancer: a comparison of different treatment strategies from the SEER database.

In the West, more than one third of newly diagnosed subjects show metastatic disease in gastric cancer (mGC) with few care options available. Gastrectomy has recently become a subject of debate, with some evidence showing advantages in survival beyond the sole purpose of treatment tumor-related complications. We investigated the survival benefit of different strategies in mGC patients, focusing on the role and timing of gastrectomy. Data were extracted from the SEER database. Groups were determined according to whether patients received gastrectomy, chemotherapy, supportive care. Patients receiving a multimodality treatment were further divided according to timing of surgery, whether performed before (primary gastrectomy, PG) or after chemotherapy (secondary gastrectomy, SG). 16,596 patients were included. Median OS was significantly higher (p < 0.001) in the SG (15 months) than in the PG (13 months), gastrectomy alone (6 months), and chemotherapy (7 months) groups. In the multivariate analysis, SG showed better OS (HR = 0.22, 95%CI = 0.18-0.26, p < 0.001) than PG (HR = 0.25, 95%CI = 0.23-0.28, p < 0.001), gastrectomy (HR = 0.40, 95%CI = 0.36-0.44, p < 0.001), and chemotherapy (HR = 0.42, 95%CI = 0.4-0.44, p < 0.001). The survival benefits persisted even after the PSM analysis. This study shows survival advantages of gastrectomy as multimodality strategy after chemotherapy. In selected patients, SG can be proposed to improve the management of stage IV disease.

Sunitinib-induced hyperparathyroidism: a possible mechanism to altered bone homeostasis.

BACKGROUND: Sunitinib malate is an orally bioavailable tyrosine kinase inhibitor that is active against many tyrosine kinase receptors involving crucial pathways in both healthy tissues and malignant tissues. Because its use in clinical practice is quite recent, many of its possible side effects remain unknown. In this report, the authors describe the incidence of new-onset hyperparathyroidism in a cohort of patients with metastatic renal cell carcinoma who received treatment with sunitinib. METHODS: Twenty-six patients who received first-line sunitinib for metastatic renal cell carcinoma were enrolled in this study for a mineral and parathyroid function assessment. Plasma levels of intact parathyroid hormone; serum levels of calcium, phosphorus, 25-hydroxyvitamin D(3), and 1,25-dihydrovitamin D(3); and urinary 24-hour calcium and phosphorus excretion all were measured in each patient. Biochemical evaluations were performed before the beginning of treatment and at the end of each sunitinib treatment period. RESULTS: Eighteen of 26 patients (69.2%) developed hyperparathyroidism with normal serum calcium levels, and 6 of them developed hypophosphatemia. Patients presented with a mean elevation of parathyroid hormone after 2.2 cycles of sunitinib. The levels of 25-OH vitamin D(3) were stable over the course of treatment, whereas 1,25-OH vitamin D(3) levels were increased in 5 hyperparathyroid patients. Those who presenting with elevated parathyroid hormone levels had low or undetectable urinary calcium levels. Parathyroid hormone elevation usually persisted but did not progress during long-term therapy with sunitinib. Permanent treatment interruption resulted in a resolution of hyperparathyroidism. CONCLUSIONS: Hyperparathyroidism developed in an high percentage of patients on sunitinib. Therefore, the authors concluded that sunitinib may affect parathyroid function and bone mineral homeostasis, possibly resulting in abnormal bone remodeling.