IMPORTANCE Lymph node status is the primary determinant in treatment decision making in early gastric cancer (EGC). Current evaluation methods are not adequate for estimating lymph node metastasis (LNM) in EGC. OBJECTIVE To develop and validate a prediction model based on a fully quantitative collagen signature in the tumor microenvironment to estimate the individual risk of LNM in EGC. DESIGN, SETTING, AND PARTICIPANTS This retrospective study was conducted from August 1, 2016, to May 10, 2018, at 2 medical centers in China (Nanfang Hospital and Fujian Provincial Hospital). Participants included a primary cohort (n = 232) of consecutive patients with histologically confirmed gastric cancer who underwent radical gastrectomy and received a T1 gastric cancer diagnosis from January 1, 2008, to December 31, 2012. Patients with neoadjuvant radiotherapy, chemotherapy, or chemoradiotherapy were excluded. An additional consecutive cohort (n = 143) who received the same diagnosis from January 1, 2011, to December 31, 2013, was enrolled to provide validation. Baseline clinicopathologic data of each patient were collected. Collagen features were extracted in specimens using multiphoton imaging, and the collagen signature was constructed. An LNM prediction model based on the collagen signature was developed and was internally and externally validated. MAIN OUTCOMES AND MEASURES The area under the receiver operating characteristic curve (AUROC) of the prediction model and decision curve were analyzed for estimating LNM. RESULTS In total, 375 patients were included. The primary cohort comprised 232 consecutive patients, in whom the LNM rate was 16.4% (n = 38; 25 men [65.8%] with a mean [SD] age of 57.82 [10.17] years). The validation cohort consisted of 143 consecutive patients, in whom the LNM rate was 20.9% (n = 30; 20 men [66.7%] with a mean [SD] age of 54.10 [13.19] years). The collagen signature was statistically significantly associated with LNM (odds ratio, 5.470; 95% CI, 3.315-9.026; P < .001). Multivariate analysis revealed that the depth of tumor invasion, tumor differentiation, and the collagen signature were independent predictors of LNM. These 3 predictors were incorporated into the new prediction model, and a nomogram was established. The model showed good discrimination in the primary cohort (AUROC, 0.955; 95% CI, 0.919-0.991) and validation cohort (AUROC, 0.938; 95% CI, 0.897-0.981). An optimal cutoff value was selected in the primary cohort, which had a sensitivity of 86.8%, a specificity of 93.3%, an accuracy of 92.2%, a positive predictive value of 71.7%, and a negative predictive value of 97.3%. The validation cohort had a sensitivity of 90.0%, a specificity of 90.3%, an accuracy of 90.2%, a positive predictive value of 71.1%, and a negative predictive value of 97.1%. Among the 375 patients, a sensitivity of 87.3%, a specificity of 92.1%, an accuracy of 91.2%, a positive predictive value of 72.1%, and a negative predictive value of 96.9% were found. CONCLUSIONS AND RELEVANCE This study's findings suggest that the collagen signature in the tumor microenvironment is an independent indicator of LNM in EGC, and the prediction model based on this collagen signature may be useful in treatment decision making for patients with EGC.
IMPORTANCE Late recurrence (more than 2 years) after liver resection for hepatocellular carcinoma (HCC) is generally considered as a multicentric tumor or a de novo cancer. OBJECTIVE To investigate the risk factors, patterns, and outcomes of late recurrence after curative liver resection for HCC. DESIGN, SETTING, AND PARTICIPANTS This study was a multicenter retrospective analysis of patients who underwent curative liver resection for HCC at 6 hospitals in China from January 2001 to December 2015. Among 734 patients who were alive and free of recurrence at 2 years after resection, 303 patients developed late recurrence. Data were analyzed from June 2017 to February 2018. INTERVENTIONS Liver resection for HCC. MAIN OUTCOMES AND MEASURES Risk factors of late recurrence as well as patterns, treatments, and long-term outcomes of patients with late recurrence. Univariate and multivariate Cox regression analyses were performed to identify independent risk factors of late recurrence. RESULTS Of the included 734 patients, 652 (88.8%) were male, and the mean (SD) age was 51.0 (10.3) years. At a median (interquartile range) follow-up of 78.0 (52.8-112.5) months, 303 patients (41.3%) developed late recurrence. Multivariate analysis revealed that male sex, cirrhosis, multiple tumors, satellite nodules, tumor size greater than 5 cm, and macroscopic and microscopic vascular invasion were independent risk factors of late recurrence. Of the 303 patients with late recurrence, 273 (90.1%) had only intrahepatic recurrence, 30 (9.9%) had both intrahepatic and extrahepatic recurrence, and none had only extrahepatic recurrence. Potentially curative treatments were given to 165 of 303 patients (54.5%) with late recurrence, which included reresection, transplant, and local ablation. Multivariate Cox regression analysis showed that regular surveillance for postoperative recurrence (hazard ratio [HR], 0.470; 95% CI, 0.310-0.713; P = .001), cirrhosis (HR, 1.381; 95% CI, 1.049-1.854; P = .02), portal hypertension (HR, 2.424; 95% CI, 1.644-3.574; P < .001), Child-Pugh grade of B or C (HR, 1.376; 95% CI, 1.153-1.674; P < .001), Barcelona Clinic Liver Cancer stage B (HR, 1.304; 95% CI, 1.007-1.708; P = .04) and stage C (HR, 2.037; 95% CI, 1.583-2.842; P < .001), and potentially curative treatment (HR, 0.443; 95% CI, 0.297-0.661; P < .001) were independent predictors of overall survival for patients with late recurrence. CONCLUSIONS AND RELEVANCE Late recurrence after HCC resection was associated with sex, cirrhosis, and several aggressive tumor characteristics of the initial HCC. The patterns of late recurrence suggested surveillance for recurrence after 2 years of surgery should be targeted to the liver. Postoperative surveillance improved the chance of potentially curative treatments, with improved survival outcomes in patients with late recurrence.
IMPORTANCE Localization of small lung nodules are challenging because of the difficulty of nodule recognition during video-assisted thoracoscopic surgery. Using 3-dimensional (3-D) printing technology, a navigational template was recently created to assist percutaneous lung nodule localization; however, the efficacy and safety of this template have not yet been evaluated. OBJECTIVE To assess the noninferiority of the efficacy and safety of a 3-D-printed navigational template guide for localizing small peripheral lung nodules. DESIGN, SETTING, AND PARTICIPANTS This noninferiority randomized clinical trial conducted between October 2016 and October 2017 at Shanghai Pulmonary Hospital, Shanghai, China, compared the safety and precision of lung nodule localization using a template-guided approach vs the conventional computed tomography (CT)-guided approach. In total, 213 surgical candidates with small peripheral lung nodules (<2 cm) were recruited to undergo either CT- or template-guided lung nodule localization. An intention-to-treat analysis was conducted. INTERVENTIONS Percutaneous lung nodule localization. MAIN OUTCOMES AND MEASURES The primary outcome was the accuracy of lung nodule localization (localizer deviation), and secondary outcomes were procedural duration, radiation dosage, and complication rate. RESULTS Of the 200 patients randomized at a ratio of 1:1 to the template- and CT-guided groups, most were women (147 vs 53), body mass index ranged from 15.4 to 37.3, the mean (SD) nodule size was 9.7 (2.9) mm, and the mean distance between the outer edge of target nodule and the pleura was 7.8 (range, 0.0-43.9) mm. In total, 190 patients underwent either CT- or template-guided lung nodule localization and subsequent surgery. Among these patients, localizer deviation did not significantly differ between the template- and CT-guided groups (mean [SD], 8.7 [6.9] vs 9.6 [5.8] mm; P = .36). The mean (SD) procedural durations were 7.4 (3.2) minutes for the template-guided group and 9.5 (3.6) minutes for the CT-guided group (P < .001). The mean (SD) radiation dose was 229 (65) mGy x cm in the template-guided group and 313 (84) mGy x cm in CT-guided group (P < .001). CONCLUSIONS AND RELEVANCE The use of the 3-D-printed navigational template for localization of small peripheral lung nodules showed efficacy and safety that were not substantially worse than those for the CT-guided approach while significantly simplifying the localization procedure and decreasing patient radiation exposure.
IMPORTANCE Peritoneal metastasis is the most frequent pattern of postoperative recurrence in patients with gastric cancer. Extensive intraoperative peritoneal lavage (EIPL) is a new prophylactic strategy for treatment of peritoneal metastasis of locally advanced gastric cancer; however, the safety and efficacy of EIPL is currently unknown. OBJECTIVE To evaluate short-term outcomes of patients with advanced gastric cancer who received combined surgery and EIPL or surgery alone. DESIGN, SETTING, AND PARTICIPANTS From March 2016 to November 2017, 662 patients with advanced gastric cancer receiving D2 gastrectomy were enrolled in a large, multicenter, randomized clinical trial from 11 centers across China. In total, 329 patients were randomly assigned to receive surgery alone, and 333 patients were randomly assigned to receive surgery plus EIPL. Clinical characteristics, operative findings, and postoperative short-term outcomes were compared between the 2 groups in the intent-to-treat population. MAIN OUTCOMES AND MEASURES Short-term postoperative complications and mortality. RESULTS The present analysis included data from 550 patients, 390 men and 160 women, with a mean (SD) age of 60.8 (10.7) years in the surgery alone group and 60.6 (10.8) in the surgery plus EIPL group. Patients assigned to the surgery plus EIPL group exhibited reduced mortality (0 of 279 patients) compared with those assigned to surgery alone (5 of 271 patients [1.9%]) (difference, 1.9%; 95% CI, 0.3%-3.4%; P=.02). A significant difference in the overall postoperative complication rate was observed between patients receiving surgery alone (46 patients [17.0%]) and those receiving surgery plus EIPL (31 patients [11.1%]) (difference, 5.9%; 95% CI, 0.1%-11.6%; P=.04). Postoperative pain occurred more often following surgery alone (48 patients [17.7%]) than following surgery plus EIPL (30 patients [10.8%]) (difference, 7.0%; 95% CI, 0.8%-13.1%; P=.02). CONCLUSIONS AND RELEVANCE Inclusion of EIPL can increase the safety of D2 gastrectomy and decrease postoperative short-term complications and wound pain. As a new, safe, and simple procedure, EIPL therapy is easily performed anywhere and does not require any special devices or techniques. Our study suggests that patients with advanced gastric cancer appear to be candidates for the EIPL approach.
Importance Laparoscopic distal gastrectomy and neoadjuvant chemotherapy are increasingly used to treat locally advanced gastric cancer. However, the safety and efficacy of the laparoscopic procedure after neoadjuvant chemotherapy remain unclear. Objective To evaluate the short-term outcomes of patients with locally advanced gastric cancer who received either laparoscopic distal gastrectomy or open distal gastrectomy. Design, Setting, and Participants Between April 23, 2015, and November 16, 2017, a phase 2, open-label, noninferiority randomized clinical trial was conducted at the Gastrointestinal Cancer Center of Peking University Cancer Hospital and Institute in Beijing, China. Patients (n = 96) between 18 and 80 years of age with locally advanced gastric cancer (cT2-4aN+M0) who were receiving neoadjuvant chemotherapy were enrolled and randomized. An as-treated population and a modified intention-to-treat (mITT) population were defined for the data analysis. Interventions Patients were randomized to undergo either laparoscopy-assisted distal gastrectomy (LADG) with D2 lymphadenectomy or open distal gastrectomy (ODG) with D2 lymphadenectomy. Main Outcomes and Measures The primary end point was 3-year recurrence-free survival rate. Secondary end points were surgical radicality, 30-day postoperative morbidity and mortality, 2-week postoperative recovery indexes, and adjuvant chemotherapy completion status. Results In total, 95 patients were eligible for as-treated analyses (LADG: 45, of whom 13 were female [29%], with a median [interquartile range (IQR)] age of 59 [52-65] years; ODG: 50, of whom 16 were female [32%], with a median [IQR] age of 61 [55-64] years) and mITT analyses (LADG: 47, of whom 14 were female [30%], with a median [IQR] age of 59 [52-65] years; ODG: 48, of whom 15 were female [31%], with a median [IQR] age of 61 [55-64] years). In the as-treated analyses, the LADG group had a significantly lower postoperative complication rate than the ODG group (20% vs 46%; P = .007). The postoperative visual analog scale score for pain was 1.2 units lower on postoperative day 2 only in the LADG group (95% CI, -2.1 to -0.3; P = .008). Patients in the LADG group had better adjuvant chemotherapy completion (adjusted odds ratio, 4.39; 95% CI, 1.63-11.80; P = .003) and were less likely to terminate adjuvant chemotherapy because of adverse effects (10 [22%] vs 21 [42%]; P = .04). The mITT analyses showed similar results to as-treated analyses. Conclusions and Relevance This trial found that LADG appears to offer the benefits of better postoperative safety and adjuvant chemotherapy tolerance compared with ODG for patients with locally advanced gastric cancer who received neoadjuvant chemotherapy.