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PurposeRisk stratification to select appropriate candidates for adjuvant therapy is required for esophageal cancer patients based on adjuvant therapy advancement including immunotherapy. The current study aims to develop a novel staging system using pathological stage (pStage) and response to neoadjuvant chemotherapy (NAC) for esophageal squamous cell carcinoma (ESCC).MethodsESCC patients who received NAC and underwent transthoracic esophagectomy at two Japanese high-volume esophageal centers were retrospectively reviewed. The prognostic value of NAC response was evaluated within the same pStage, and a novel risk stratification to predict cancer-specific survival (CSS) was developed.ResultsThe HR (95% CI) of pathological responders in pStage 0–I, II, III, and IV was 0.29 (0.07–1.17), 0.37 (0.12–1.10), 0.37 (0.15–0.92), and 0.24 (0.06–0.98), respectively. Responders in pStage 0–II were classified to be in the same class and those in pStage III/IV in another group, because the 5-year CSS (5y-CSS) rate of responders in pStage 0–I, II, III, and IV was 94%, 92%, 76%, and 71%, respectively. Combining nonresponders in pStage 0–II as the same group, all patients were subdivided into five groups. Intriguingly, the 5y-CSS in pStage III–IV responders was 75%, almost identical to that of nonresponders in pStage 0–II (78%).ConclusionsThe histological response influenced the long-term outcomes of patients who underwent esophagectomy after NAC, even within groups stratified by pathologic stage. The current risk stratification system will contribute to selecting appropriate candidates for adjuvant therapy.

PurposeTo appropriately adopt the organ preservation approach, including subsequent chemoradiotherapy (CRT) in patients who respond to neoadjuvant chemotherapy (NAC), the distribution of residual disease, including pathological lymph nodes (LNs) and recurrence site, needs to be recognized preoperatively. This study was designed to evaluate whether endoscopic response evaluation can predict residual tumor distribution.MethodsPatients with esophageal squamous cell carcinoma who underwent transthoracic esophagectomy (TTE) were retrospectively reviewed. Endoscopic responder (ER) to NAC was defined according to primary tumor endoscopic findings. Recurrence-free survival (RFS), overall survival (OS), and residual tumor patterns were compared between groups.ResultsOf 193 patients, 40 (20%) were classified as ER. ERs showed significantly better RFS and OS. The pN location was found within the primary tumor and cN field in 88% of ERs, which was significantly higher than non-ERs at 63% (p = 0.004). Furthermore, the postoperative recurrence incidence in the distant organ was significantly lower in the ERs than the non-ERs (8%, 32%, respectively, p = 0.002). Residual disease, including postoperative initial recurrence, existed within the same field as the primary tumor and cN in 88% of ERs, significantly higher than 42% in the non-ERs (p < 0.001).ConclusionsEndoscopic response evaluation can preoperatively predict distribution of residual tumors after NAC, which could help radiation field selection in subsequent definitive CRT when patients prefer to omit TTE. Along with improvements in NAC response rate, this could facilitate organ preservation in patients who respond to NAC.

BackgroundAlthough squamous cell carcinoma antigen (SCC-Ag) is a tumor marker widely used to estimate the progression of esophageal SCC (ESCC), only a few studies have focused on the relationship between serum SCC-Ag levels and the therapeutic effect of neoadjuvant chemotherapy (NAC).ObjectiveThis study aimed to elucidate the clinical significance of pretherapeutic serum SCC-Ag levels in patients who underwent NAC followed by esophagectomy.MethodsData of 453 patients who underwent NAC followed by esophagectomy were collected from the esophageal cancer database of two high-volume Japanese centers. Serum SCC-Ag levels were measured prior to NAC, and the pathological therapeutic effect of NAC and patient survival were evaluated. Patients were classified according to the tertiles of the serum SCC-Ag value (low, middle, and high groups), and the outcomes among the groups were compared.ResultsThe levels of serum SCC-Ag were significantly associated with tumor stage (p < 0.01). With regard to the pathological therapeutic effect, the levels of serum SCC-Ag were negatively correlated with the therapeutic effect (p = 0.02). Moreover, increased levels of serum SCC-Ag negatively influenced relapse-free survival (p < 0.01). Multivariate analyses revealed the ‘high’ group as the independent factor for both the unfavorable therapeutic effect (p = 0.01) and the increased risk of disease recurrence (p < 0.01) when compared with the ‘low’ group.ConclusionElevated levels of pretherapeutic serum SCC-Ag are significantly associated with advanced tumor stage, poor response to NAC, and increased risk of disease recurrence.

BackgroundDetecting pathological complete response (pCR) before surgery would facilitate nonsurgical approach after neoadjuvant chemotherapy (NAC). We developed an artificial intelligence (AI)-guided pCR evaluation using a deep neural network to identify pCR before surgery.MethodsThis study examined resectable esophageal squamous cell carcinoma (ESCC) patients who underwent esophagectomy after NAC. The same number of histological responders without pCR and non-responders were randomly selected based on the number of pCR patients. Endoscopic images were analyzed using a deep neural network. A test dataset consisting of 20 photos was used for validation. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of AI and four experienced endoscopists' pCR evaluations were calculated. For pathological response evaluation, Japanese Classification of Esophageal Cancer was used.ResultsThe study enrolled 123 patients, including 41 patients with pCR, the same number of histological responders without pCR, and non-responders [grade 0, 5 (4%); grade 1a, 36 (30%); grade 1b, 21 (17%); grade 2, 20 (16%); grade 3, 41 (33%)]. In 20 models, the median values of sensitivity, specificity, PPV, NPV, and accuracy for endoscopic response (ER) detection were 60%, 81%, 77%, 67%, and 70%, respectively. Similarly, the endoscopists’ median of these was 43%, 90%, 85%, 65%, and 66%, respectively.ConclusionsThis proof-of-concept study demonstrated that the AI-guided endoscopic response evaluation after NAC could identify pCR with moderate accuracy. The current AI algorithm might guide an individualized treatment strategy including nonsurgical approach in ESCC patients through prospective studies with careful external validation to demonstrate the clinical value of this diagnostic approach including primary tumor and lymph node.

AimWe investigated whether or not postoperative complications (POCs) themselves have a negative survival impact or indirectly worsen the survival due to insufficient adjuvant chemotherapy in a pooled analysis of two large phase III studies performed in JapanPatients and methodsThe study examined the patients who enrolled in 1304, phase III study comparing the efficacy of 6 and 12 months of capecitabine as adjuvant chemotherapy for stage III colon cancer patients and in 882, a phase III study to confirm the tolerability of oxaliplatin, fluorouracil, and l-leucovorin in Japanese stage II/III colon cancer patients. In our study, POCs were defined as the following major surgical complications: anastomotic leakage, pneumonia, bowel obstruction/ileus, surgical site infection, postoperative bleeding, urinary tract infection, and fistula. Patients were classified as those with POCs (C group) and those without POCs (NC group).ResultsA total of 2095 patients were examined in the present study. POCs were observed in 169 patients (8.1%). The overall survival (OS) rates at 5 years after surgery were 75.3% in the C group and 86.5% in the NC group (p = 0.0017). The hazard ratio of POCs for the OS in multivariate analysis was 1.70 (95% confidence interval, 1.19 to 2.45; p = 0.0040). The time to adjuvant treatment failure (TTF) of adjuvant chemotherapy was similar between the groups, being 68.6% in the C group and 67.1% in the NC group for the 6-month continuation rate of adjuvant chemotherapy. The dose reduction rate of adjuvant chemotherapy and adjuvant treatment suspension rate were also similar between the groups (C vs. NC groups: 45.0% vs. 48.7%, p = 0.3520; and 52.7% vs. 55.0%, p = 0.5522, respectively).ConclusionPOCs were associated with a poor prognosis but did not affect the intensity of adjuvant chemotherapy. These results suggested that POCs themselves negatively influence the survival.

New laparoscopic sentinel lymph node navigation using a dedicated magnetic probe and magnetic nanoparticle tracer for gastric cancer patients allows minimally invasive surgeries. By identifying the sentinel lymph nodes containing magnetic nanoparticles, patients can avoid excessive lymph node extraction without nuclear facilities and radiation exposure. This paper describes the development of the laparoscopic magnetic probe, ACDC-probe , for laparoscopic sentinel lymph node identification utilizing the nonlinear response of the magnetic nanoparticles magnetized by an alternating magnetic field with a static magnetic field. For highly sensitive detection, the ratio of static to alternating magnetic fields was optimized to approximately 5. The longitudinal detection length was approximately 10 mm for 140 μg of iron, and the detectable amount of iron was approximately 280 ng at a distance of 1 mm. To demonstrate the feasibility of laparoscopic detection using the ACDC-probe and magnetic tracers, an experiment was performed on a wild swine. The gastric sentinel lymph node was clearly identified during laparoscopic navigation. These results suggest that the newly developed ACDC-probe is useful for laparoscopic sentinel lymph node detection and this magnetic technique appears to be a promising method for future sentinel lymph node navigation of gastric cancer patients.

PurposeTo arrange multidisciplinary treatment for esophageal cancer, a simple and accurate predictive marker for prognosis is required. The current multicenter prospective study aims to validate the prognostic significance of fibrinogen and albumin score (FA score) for esophageal cancer patients.Patients and MethodsPatients who were planned to undergo surgical resection for esophageal cancer at four participating institutions were enrolled in this study. Patient background, clinicopathological factors, and blood concentration of plasma fibrinogen and albumin were collected. Patients with elevated fibrinogen and decreased albumin levels were allocated a score of 2; those with only one of these abnormalities were allocated a score of 1; and those with neither of these abnormalities were allocated a score of 0. Recurrence-free survival (RFS) and overall survival (OS) were evaluated as a primary endpoint.ResultsFrom four participating institutions, 133 patients were registered for the current analysis. The distribution of FA score of 0/1/2 was 84 (63%)/34 (26%)/15 (11%), respectively. In the analysis of primary endpoint, the preoperative FA score significantly classified RFS (FA score 1/2: HR 2.546, p = 0.013/6.989, p < 0.001) and OS (FA score 1/2: HR 2.756, p = 0.010/6.970, p < 0.001). We further evaluated the prognostic significance of FA score under stratification by pStage. As a result, with increasing FA score, RFS and OS were significantly worse in both pStage 0–I and II–IV groups.ConclusionsThe prognostic impact of preoperative FA score was confirmed for esophageal cancer patients in the current multicenter prospective trial. FA score can be considered to predict postoperative survival and rearrange the treatment strategy before esophagectomy.

BackgroundAlthough radical esophagectomy with multifield lymph node dissection is a promising treatment to achieve long-term survival for resectable esophageal cancer, survival after postoperative recurrence remains poor. To select the optimal treatment for patients with recurrent esophageal cancer, simple, objective indicators for predicting of long-term outcomes are needed.Patients and MethodsWe conducted a single-institution, retrospective cohort study between 2004 and 2019, wherein 586 patients underwent transthoracic esophagectomy for primary esophageal squamous cell carcinoma. Of these, 133 patients with postoperative recurrence were included in this analysis. Several predictors of survival after recurrence were investigated.ResultsAmong all patients, the 1- and 3-year survival rates after recurrence were 48.0% and 23.1%, respectively. On multivariate analysis, the neutrophil to lymphocyte ratio (NLR) at recurrence was identified as a significant predictor of death after recurrence (hazard ratio 1.061; 95% confidence interval 1.002–1.125; p = 0.043). Time-dependent receiver operating characteristics curves showed that the area under the curve value of the NLR at recurrence was superior to the modified Glasgow Prognostic Score at recurrence in all terms. To simulate the clinical decision process, we set the cut-off NLR at recurrence for survival using survival classification and regression tree (CART) and defined the optimal cut-off value as 3.374.ConclusionsNLR at recurrence was a significant indicator of survival after recurrence in patients with recurrent esophageal cancer. CART analysis was used to determine the optimal cut-off value for the prediction of survival, allowing the NLR to be used clinically to facilitate decision making.