Pathological response measured using virtual microscopic slides for gastric cancer patients who underwent neoadjuvant chemotherapy

BACKGROUND Although pathological response is a common endpoint used to assess the efficacy of neoadjuvant chemotherapy (NAC) for gastric cancer, the problem of a low rate of concordance from evaluations among pathologists remains unresolved. Moreover, there is no globally accepted consensus regarding the optimal evaluation. A previous study based on a clinical trial suggested that pathological response measured using digitally captured virtual microscopic slides predicted patients’ survival well. However, the pathological concordance rate of this approach and its usefulness in clinical practice were unknown. AIM To investigate the prognostic utility of pathological response measured using digital microscopic slides in clinical practice. METHODS We retrospectively evaluated pathological specimens of gastric cancer patients who underwent NAC followed by surgery and achieved R0 resection between March 2009 and May 2015. Residual tumor area and primary tumor beds were measured in one captured image slide, which contained the largest diameter of the resected specimens. We classified patients with < 10% residual tumor relative to the primary tumorous area as responders, and the rest as non-responders;we then compared overall survival (OS) and relapse-free survival (RFS) between these two groups. Next, we compared the prognostic utility of this method using conventional Japanese criteria. RESULTS Fifty-four patients were evaluated. The concordance rate between two evaluators was 96.2%. Median RFS of 25 responders and 29 non-responders was not reached (NR) vs 18.2 mo [hazard ratio (HR)= 0.35, P = 0.023], and median OS was NR vs 40.7 mo (HR = 0.3, P = 0.016), respectively. This prognostic value was statistically significant even after adjustment for age, eastern cooperative oncology group performance status, macroscopic type, reason for NAC, and T- and Nclassification (HR = 0.23, P = 0.018). This result was also observed even in subgroup analyses for different macroscopic types (Borrmann type 4/non-type 4) and histological types (differentiated/undifferentiated). Moreover, the adjusted HR for OS between responders and non-responders was lower in this method than that in the conventional histological evaluation of Japanese Classification of Gastric Carcinoma criteria (0.23 vs 0.39, respectively). CONCLUSION The measurement of pathological response using digitally captured virtual microscopic slides may be useful in clinical practice.

Feasibility of gastric endoscopic submucosal dissection in elderly patients aged≥80 years

BACKGROUND Endoscopic resection,especially endoscopic submucosal dissection(ESD),is increasingly performed in elderly patients with early gastric cancer,and lesions beyond the expanded indications are also resected endoscopically in some patients.It is essential to assess whether gastric ESD is safe and suitable for elderly patients and investigate what type of lesions carry an increased risk of ESD-related complications.AIM To assess the efficacy and feasibility of gastric ESD for elderly patients,and define high-risk lesions and prognostic indicators.METHODS Among a total of 1169 sessions of gastric ESD performed in Kanagawa Cancer Center Hospital from 2006 to 2014,179 sessions(15.3%)were performed in patients aged≥80 years,and 172 of these sessions were done in patients with a final diagnosis of gastric cancer.These patients were studied retrospectively to evaluate short-term outcomes and survival.The short-term outcomes included the rates of en bloc resection and curative resection,complications,and procedurerelated mortality.Curability was assessed according to the Japanese Gastric Cancer Treatment Guidelines 2010.Fisher’s exact test was used to statistically analyze risk factors.Clinical characteristics of each group were compared using Fisher’s exact test and Mann-Whitney U test.Survival rates at each time point were based on Kaplan-Meier estimation.Overall survival rates were compared between patients with gastric cancer in each group with use of the log-rank test.To identify prognostic factors that jointly predict the hazard of death while controlling for model overfitting,we used the least absolute shrinkage and selection operator(LASSO)Cox regression model including factors curative/noncurative,age,gender,body mass index,prognostic nutritional index,Charlson comorbidity index(CCI),Glasgow prognostic score,neutrophil-to-lymphocyte ratio,and antithrombotic agent use.We selected the LASSO Cox regression model that resulted in minimal prediction error in 10-fold cross-validation.P<0.05 was considered statistically significant.RESULTS The en bloc dissection rate was 97.1%,indicating that a high quality of treatment was achieved even in elderly patients.As for complications,the rates of bleeding,perforation and aspiration pneumonitis were 3.4%,1.1%and 0.6%,respectively.These complication rates indicated that ESD was not associated with a particularly higher risk in elderly patients than in nonelderly patients.A dissection incision>40 mm,lesions associated with depressions,and lesions with ulcers were risk factors for post-ESD bleeding,and location of the lesion in the upper third of the stomach was a risk factor for perforation in elderly patients(P<0.05).Location of the lesion in the lower third of the stomach tended to be associated with a higher risk of bleeding.The overall survival(OS)did not differ significantly between curative and noncurative ESD(P=0.69).In patients without additional surgery,OS rate was significantly lower in patients with a high CCI(≥2)than in those with a low CCI(≤1)(P<0.001).CONCLUSION Gastric ESD is feasible even in patients aged≥80 years.Observation without additional surgery after noncurative ESD is reasonable,especially in elderly patients with CCI≥2.