Background Microsatellite instability (MSI) and programmed death-ligand 1 (PD-L1) are candidate predictors for the response to immune checkpoint inhibitors, and may predict chemotherapy sensitivity. We investigated the simultaneous expression of mutL homolog 1 (MLH1), a mismatch repair gene, and PD-L1 in gastric cancers. Methods We examined MLH1 and PD-L1 expression in surgical specimens from 285 gastric cancer patients treated with or without preoperative chemotherapy, and assessed the relation between expression results and both histological response and recurrence-free survival (RFS). Results Of 285 patients, 28 (9.8%) and 70 (24.6%) exhibited negative MLH1 and high PD-L1 expression, respectively. Most MLH1-negative tumors (85.7%) showed high MSI, and these tumors exhibited high PD-L1 expression more frequently than MLH1-positive tumors (57.1% vs. 21.0%, P < 0.001). MLH1-negative patients were significantly less likely to respond to preoperative chemotherapy than MLH1-positive patients (16.7% vs. 61.2%, P = 0.005), whereas there was no significant difference between high-and low-PD-L1 expression patients (55.9% vs. 56.6%, P = 0.95). RFS in patients without preoperative chemotherapy was significantly longer in the MLH1-negative group than in the MLH1-positive group (HR 0.30; 95% CI 0.09-0.95; P = 0.030), whereas in patients with preoperative chemotherapy there was no significant difference in RFS between the two groups (HR 0.70; 95% CI 0.30-1.63; P = 0.41). PD-L1 expression was not associated with RFS in patients with or without chemotherapy. Conclusions Loss of MLH1 was associated with chemoresistance and did not prolong survival following neoadjuvant chemotherapy. The strong association between MLH1 and MSI status suggests that immune checkpoint inhibitors may be preferable to conventional chemotherapy for MLH1-negative gastric cancer.

Background Elderly patients with gastric cancer are frequently treated surgically in current clinical practice. Although several studies have investigated short‐term outcomes after gastrectomy in elderly patients, most did not evaluate long‐term outcomes. Methods We analyzed 1154 consecutive patients who underwent curative gastrectomy for gastric cancer between 2001 and 2013. We classified them into two groups: the elderly group (n = 241), consisting of patients aged ≥75 years, and the non‐elderly group (n = 913), consisting of patients aged <75 years, and compared the short‐ and long‐term outcomes between the two groups. The risk factors for death from other diseases in elderly patients were also examined. Results Although the incidence of postoperative pneumonia was significantly higher in the elderly group (P < 0.001), the proportion of overall postoperative complications did not differ significantly between the two groups (P = 0.097). The disease‐specific survival was similar between the two groups (P = 0.743), whereas the overall survival in the elderly group was significantly shorter than that in the non‐elderly group (P < 0.001) because of a higher incidence of death from other diseases throughout all gastric cancer stages. Multivariate analysis revealed that a low preoperative prognostic nutrition index (PNI) and multiple comorbidities were significant risk factors for death from other diseases within 5 years in the elderly group. Conclusions Despite acceptable short‐term outcomes, long‐term outcomes in elderly patients with gastric cancer were poor due to the high incidence of death from other diseases. Indications for surgery in elderly patients with a low PNI or multiple comorbidities should be considered carefully.

Although the incidence of gastroesophageal junction (GEJ) adenocarcinoma has been increasing worldwide, no standardized surgical strategy for its treatment has been established. This study aimed to provide an update on the surgical treatment of GEJ adenocarcinoma by reviewing previous reports and propose recommended surgical approaches. The Siewert classification is widely used for determining which surgical procedure is used, because previous studies have shown that the pattern of lymph node (LN) metastasis depends on tumor location. In terms of surgical approaches for GEJ adenocarcinoma, a consensus was reached based on two randomized controlled trials. Siewert types I and III are treated as esophageal cancer and gastric cancer, respectively. Although no consensus has been reached regarding the treatment of Siewert type II, several retrospective studies suggested that the optimal treatment strategy includes paraaortic LN dissection. Against this background, a Japanese nationwide prospective trial is being conducted to determine the proportion of LN metastasis in GEJ cancers and to identify the optimal extent of LN dissection in each type.

Objectives: To investigate the residual pattern of esophageal cancer in the esophageal wall after neoadjuvant chemotherapy (NAC) and its clinical significance. Background: NAC is a standard treatment for locally advanced esophageal cancer; however, residual tumor patterns in resected specimens after NAC and their clinico-pathological characteristics remain unknown. Methods: One hundred twenty consecutive patients with cT3 or deeper esophageal cancer underwent curative esophagectomy after NAC and achieved grade 2 histological responses between 2000 and 2016. Hematoxylin-eosin staining of residual tumor sections revealed 4 remnant categories: Type 1: shallow, Type 2: central, Type 3: deep, and Type 4: diffuse. We examined associations between these Types and clinico-pathological factors, including prognosis. Results: Forty-five (38%) specimens had no residual tumor cells in the mucosal layer. The adventitia layer displayed the lowest residual tumor cell frequency (18%) among all layers. Types 1, 2, 3, and 4 residual tumor patterns were found in 49 (41%), 33 (28%), 9 (8%), and 29 (24%) patients, respectively. Type 4 showed the maximum standard uptake value after NAC; Types 3 and 4 had higher ratios of venous invasion than Type 1 or 2. Patients with Type 3 or 4 more frequently developed pleural dissemination or distant metastasis than patients with Type 1 or 2. Survival was similar among the 4 Types. Conclusions: After NAC for locally advanced esophageal cancer, the shallow residual tumor pattern was most common, but approximately 40% of specimens showed no tumor cells in the mucosal layer. Deep and diffuse remnant patterns were associated with high risks of pleural dissemination and distant metastasis.

Primary malignant melanoma of the esophagus (PMME) has been reported to be a rare and highly malignant disease, and to date a standard treatment strategy has not been established due to limited evidence. The aim of the present study was to investigate the clinicopathological characteristics of this extremely rare disease. A total of 6 out of 2,093 patients with PMME treated in our institution between 1995 and 2016 were retrospectively analyzed and their clinicopathological parameters including treatment course and long-term survival were investigated. The major clinicopathological characteristics of patients were that they were >70 years of age, male sex, dysphagia at first diagnosis, and macroscopic black protruding tumors located in the lower third of the thoracic esophagus. Four of the five patients receiving pretherapeutic endoscopic biopsy were correctly diagnosed with PMME, and two patients received preoperative treatment with ineffective histopathological responses. There were two unresectable cases, one was treated with an immune-checkpoint inhibitor and the other received palliative care. Three of the four patients receiving curative surgery developed hematogenous recurrence within two years of surgery and only one patient with pT1aN0M0 achieved long-term survival. The median overall survival of all six patients was 19.6 (6.4–40.5) months. Patients with stage I disease exhibited significantly more favorable prognoses than those with stage II–IV (P=0.025) and surgically-treated patients had significantly better prognoses than those who did not receive surgery (P=0.018). In conclusion, PMME was associated with highly malignant features and tended to develop hematogenous metastases even after radical resection. Early diagnosis appears to be important to cure this refractory disease.