Hidenori Akaike

CCL17 and CCL22 chemokines within tumor microenvironment are related to accumulation of Foxp3+ regulatory T cells in gastric cancer

It has been reported that an increased population of regulatory T cells (Tregs) is one of the reasons for impaired anti‐tumor immunity. Recently, Foxp3 has been reported as a reliable marker of Tregs. The authors investigated the frequency of Foxp3+ Tregs within CD4+ cells in TILs, regional lymph nodes and PBLs of gastric cancer patients (n = 45). Furthermore, to elucidate the mechanisms behind Treg accumulation within tumors, they evaluated the relationship between CCL17 or CCL22 expression and the frequency of Foxp3+ Tregs in gastric cancer. CD4+CD25+Foxp3+ Tregs as a percentage of CD4+ cells were counted by flow cytometry and evaluated by immunohistochemistry. Moreover, an in vitro migration assay using Tregs derived from gastric cancers was performed in the presence of CCL17 or CCL22. As a result, the frequency of Foxp3+ Tregs in TILs was significantly higher than that in normal gastric mucosa (12.4% ± 7.5% vs. 4.1% ± 5.3%, p < 0.01). Importantly, the increase in Tregs in TILs occurred to the same extent in early and advanced disease. Furthermore, the frequency of CCL17+ or CCL22+ cells among CD14+ cells within tumors was significantly higher than that of normal gastric mucosa, and there was a significant correlation between the frequency of CCL17+ or CCL22+ cells and Foxp3+ Tregs in TILs. In addition, the in vitro migration assay indicated that Tregs were significantly induced to migrate by CCL17 or CCL22. In conclusion, CCL17 and CCL22 within the tumor are related to the increased population of Foxp3+ Tregs, with such an observation occurring in early gastric cancer.

Protein-Bound Polysaccharide K Partially Prevents Apoptosis of Circulating T Cells Induced by Anti-Cancer Drug S-1 in Patients with Gastric Cancer

Background and Methods:It has been shown that T-cell dysfunction, including apoptosis of peripheral blood T cells, commonly occurs in patients receiving chemotherapy. In order to evaluate whether concomitant administration of the oral biological response modifier protein-bound polysaccharide K (PSK) could induce anti-apoptotic effects in patients treated with the anti-cancer drug, S-1, peripheral blood T cells were analyzed for induction of apoptosis, caspase-3 activities and expression of proapoptotic protein Bax and anti-apoptotic protein Bcl-2 in patients with curatively resected stage III gastric cancer, who were randomly assigned to postoperative adjuvant therapy with S-1 alone (n = 10) or S-1 combined with PSK (n = 10). Results: T-cell apoptosis 5 weeks after adjuvant therapy was significantly higher in the S-1 group (24.1 ± 5.0%) than in the S-1 + PSK group (19.1 ± 3.9%). S-1 induced T-cell apoptosis and concomitantly elevated caspase-3 activities and Bax expression in peripheral blood T cells. In addition, PSK partially prevented the T-cell apoptosis induced by S-1. Conclusion:PSK could partially prevent the T-cell apoptosis induced by S-1.

miR-122-5p as a novel biomarker for alpha-fetoprotein-producing gastric cancer

AIM To investigate the clinical utility of alpha-fetoprotein (AFP)-producing gastric cancer (AFPGC)-specific microRNA (miRNA) for monitoring and prognostic prediction of patients. METHODS We performed a comprehensive miRNA array-based approach to compare miRNA expression levels between AFP-positive and AFP-negative cells in three patients with primary AFPGC. We next examined the expression levels of the selected miRNAs in five AFPGC and ten non-AFPGC tissue samples by quantitative reverse transcription-polymerase chain reaction to validate their utility. We also investigated the expression levels of the selected miRNA not only in tissue but also in plasma samples. Moreover, we investigated the relationship between plasma AFP levels and plasma selected miRNA expression levels, and also investigated the correlation of the selected miRNA expression levels and malignant potential. RESULTS Among the five miRNAs selected from the miRNA array results, the expression levels of miR-122-5p were significantly higher in the AFPGC patients than in the non-AFPGC patients (P < 0.05). In tissue samples, miR-122-5p expression level tended to be lower in the non-AFPGC tissue than the normal gastric mucosa. Conversely, in the AFPGC tissue, miR-122-5p expression level was significantly higher in the AFPGC tissue than both the normal gastric mucosa and the non-AFPGC tissue samples (P < 0.05). Plasma miR-122-5p expression levels were also significantly higher in the AFPGC patients than the health volunteers and the non-AFPGC patients (P < 0.05) and were strongly correlated with plasma AFP levels (r = 0.7975, P < 0.0001). Moreover, the correlation of miR-122-5p expression in tissue samples with malignant potential was stronger than that of plasma AFP level in the AFPGC patients. In contrast, no correlation was found between miR-122-5p expression levels and liver metastasis in the non-AFPGC patients. CONCLUSION miR-122-5p might be a useful biomarker for early detection and disease monitoring in AFPGC.

Successful laparoscopic partial gastrectomy and spleen-preserving distal pancreatectomy for gastric duplication cyst connecting with the pancreatic tail

Highlights • Gastric duplication cyst(GDC) contiguous with the stomach and pancreatic tail is extremely rare.• GDCs are usually diagnosed at a younger age. In adults, they are very rare disease and the diagnosis may be difficult.• Surgical resection is considered to be the best treatment due to the difficulty of diagnosis.• Laparoscopic surgery is less invasive and should be selected whenever possible.

Clinical Impact of Histological Heterogeneity in the Metastatic Lymph Nodes of Patients with Colorectal Cancer

Aim: The purpose of this study was to evaluate the clinical impact of histological heterogeneity in patients with node-positive colorectal cancer (CRC). Patients and Methods: One hundred and twenty-nine patients who underwent curative surgical resection for histological node-positive CRC were enrolled. Patients were divided according to the histological heterogeneity in the primary lesion into p-hetero and p-homo groups. The p-hetero group was further divided according to histological heterogeneity in the metastatic lymph nodes into n-hetero and n-homo groups. Results: There were no significant differences between p-homo and p-hetero groups and between n-homo and n-hetero groups in prognosis. However, the recurrence-free survival rate of the n-homo group was significantly lower than that of the n-hetero group in the N2 category. Conclusion: Histological heterogeneity in metastatic lymph nodes may be useful for predicting prognosis, and prognosis in those with histological heterogeneity in a metastatic lymph node is not necessarily poor, even in those of the N2 category.

Current status of laparoscopic total gastrectomy

In this article, the current state of laparoscopic total gastrectomy (LTG) was reviewed, focusing on lymph node dissection and reconstruction. Lymph node dissection in LTG is technically similar to that in laparoscopic distal gastrectomy for early gastric cancer; however, LTG for advanced gastric cancer requires extended lymph node dissections including splenic hilar lymph nodes. Although a recent randomized controlled trial clearly indicated no survival benefit in prophylactic splenectomy for lymph node dissection at the splenic hilum, some patients may receive prognostic benefit from adequate splenic hilar lymph node dissection. Considering reconstruction, there are two major esophagojejunostomy (EJS) techniques, using a circular stapler (CS) or using a linear stapler (LS). A few studies have shown that the LS method has fewer complications; however, almost all studies have reported that morbidity (such as anastomotic leakage and stricture) is not significantly different for the two methods. As for CS, we grouped various studies addressing complications in LTG into categories according to the insertion procedure of the anvil and the insertion site in the abdominal wall for the CS. We compared the rate of complications, particularly for leakage and stricture. The rate of anastomotic leakage and stricture was the lowest when inserting the CS from the upper left abdomen and was significantly the highest when inserting the CS from the midline umbilical. Scrupulous attention to EJS techniques is required by surgeons with a clear understanding of the advantages and disadvantages of each anastomotic device and approach.