It has recently been reported that the placement of a transanal drainage tube after rectal cancer surgery reduces the rate of anastomotic leakage. However, transanal drainage tube cannot completely ...prevent anastomotic leakage and the management of transanal drainage tube needs to devise. We investigated the information obtained during transanal drainage tube placement and evaluated the relationship between these factors and anastomotic leakage. Fifty-one patients who underwent anterior resection of rectal cancer was retrospectively reviewed. transanal drainage tube was placed for more than 5 days after surgery. The daily fecal volume from transanal drainage tube was measured on postoperative day 1-5, and the defecation during transanal drainage tube placement was investigated. Anastomotic leakage during transanal drainage tube placement occurred in 4 patients. The anastomotic leakage rate during transanal drainage tube placement in patients whose maximum daily fecal volume or total fecal volume from the transanal drainage tube during postoperative days 1-5 was large was significantly higher than that in patients whose fecal volume was small. The anastomotic leakage rate of the patients with intentional defecation during transanal drainage tube placement was significantly higher than that of the patients without intentional defecation during transanal drainage tube placement. The maximum daily fecal volume and the total fecal volume from the transanal drainage tube during postoperative days 1-5 in patients who experienced intentional defecation during transanal drainage tube placement was significantly higher than that of patients without intentional defecation during transanal drainage tube placement. A large fecal volume from transanal drainage tube after anterior rectal resection or intentional defecation in patients with transanal drainage tube placement were suggested to be risk factors for anastomotic leakage.
Neoadjuvant therapy for locally advanced rectal cancer is becoming increasingly common. However, biomarkers predicting the response to neoadjuvant therapy have not been established. ...Tumor‐infiltrating lymphocytes (TILs) have a crucial effect on tumor progression and survival outcome as the primary host immune response, and an antitumor immune effect has been reported to contribute to the response to radiotherapy and chemotherapy. We investigated the significance of TILs before and after neoadjuvant treatment and the change in the density of those TILs. Sixty‐four patients who underwent radical resection after neoadjuvant treatment for locally advanced rectal cancer were enrolled. The number of TIL subsets was examined using immunohistochemical staining of pretreatment biopsy samples and post‐treatment resected specimens. In both the neoadjuvant chemotherapy cohort and the neoadjuvant chemoradiotherapy cohort, a low density of CD8+ TILs in pretreatment biopsy samples was associated with a poor response, and a low density of CD8+ TILs in post‐treatment resected specimens was similarly associated with a poor response. In the neoadjuvant chemoradiotherapy cohort, the density of CD8+ TILs in post‐treatment resected specimens was significantly increased compared with that in pretreatment biopsy samples. We concluded that T lymphocyte‐mediated immune reactions play an important role in tumor response to neoadjuvant treatment for rectal cancer, and the evaluation of TILs in pretreatment biopsy samples might be a predictor of the clinical effectiveness of neoadjuvant treatment. Furthermore, neoadjuvant therapy, especially chemoradiotherapy, could induce the activation of the local immune status.
The antitumor immune effect has been reported to contribute to the response to radiotherapy and chemotherapy for rectal cancer. Our results showed that the density of CD8+ tumor‐infiltrating lymphocytes (TILs) in pretreatment biopsy samples of rectal cancer was positively correlated with the response to neoadjuvant chemoradiotherapy and chemotherapy. We concluded that the density of CD8+ TILs may be a predictor of the clinical effectiveness of neoadjuvant treatment.
Remnant gastric cancer(RGC) and gastric stump cancer after distal gastrectomy(DG) are recognized as the same clinical entity. In this review, the current knowledges as well as the non-settled issues ...of RGC are presented. Duodenogastric reflux and denervation of the gastric mucosa are considered as the two main factors responsible for the development of RGC after benign disease. On the other hand, some precancerous circumstances which already have existed at the time of initial surgery, such as atrophic gastritis and intestinal metaplasia, are the main factors associated with RGC after gastric cancer. Although eradication of Helicobacter pylori(H. pylori) in remnant stomach is promising, it is still uncertain whether it can reduce the risk of carcinogenesis. Periodic endoscopic surveillance after DG was reported useful in detecting RGC at an early stage, which offers a chance to undergo minimally invasive endoscopic treatment or laparoscopic surgery and leads to an improved prognosis in RGC patients. Future challenges may be expected to elucidate the benefit of eradication of H. pylori in the remnant stomach if it could reduce the risk for RGC, to build an optimal endoscopic surveillance strategy after DG by stratifying the risk for development of RGC, and to develop a specific staging system for RGC for the standardization of the treatment by prospecting the prognosis.
The impact of tumor-infiltrating lymphocytes (TILs) and tumor-associated macrophages (TAMs) on the prognosis of biliary tract cancer (BTC) is not completely understood. Therefore, in our study, we ...investigated the effects of the various immune cells infiltration in tumor microenvironment (TME).
A total of 130 patients with BTC who underwent surgical treatment at our institution were enrolled in this study. We retrospectively evaluated TILs and TAMs with immunohistochemical staining.
With CD8-high, CD4-high, FOXP3-high, and CD68-low in TME as one factor, we calculated Immunoscore according to the number of factors. The high Immunoscore group showed significantly superior overall survival (OS) and recurrence-free survival (RFS) than the low Immunoscore group (median OS, 60.8 vs. 26.4 months, p = 0.001; median RFS not reached vs. 17.2 months, p < 0.001). Also, high Immunoscore was an independent good prognostic factor for OS and RFS (hazards ratio 2.05 and 2.41 and p = 0.01 and p = 0.001, respectively).
High Immunoscore group had significantly superior OS and RFS and was an independent good prognostic factor for OS and RFS.
Tertiary lymphoid structures (TLSs), which consist of B cells, T cells, follicular dendritic cells and high endothelial venules, have recently been found to be associated with effective antitumor ...immune responses in patients with cancer. Tumor‑infiltrating T cells and B cells have each been demonstrated to be associated with survival in patients with cancer. We hypothesized that TLSs, an assembly of immune cells, may be important for the initiation and/or maintenance of T cell and B cell responses against tumors. The aim of the present study was to examine the cellular mechanism of B cells in TLSs within gastric cancer and to understand the antitumor immune response of TLSs. Each B cell subset in a tumor was examined using flow cytometry to evaluate B cell differentiation and the functional status of B cells. In addition, B cell clonality was investigated by analyzing the B cell antigen receptor gene using PCR, and the function and formation/maintenance of TLSs were evaluated using reverse transcription‑quantitative PCR. Tumor‑infiltrating B cells were more differentiated compared with that in distant non‑tumor tissues and tumor‑draining lymph nodes. The PCR results revealed specific BCR gene expression in tumor‑infiltrating B cells. The expression of co‑stimulatory factors, CD80 and CD86, was observed, in addition to the constantly expressed major histocompatibility complex molecules (HLA‑ABC and HLA‑DR). CD70 was expressed in addition to CD27 in both CD20+ B cells and CD8+ T cells, indicating that these factors are activated together through their interaction. The mRNA expression levels of CCL21, CXCL13, PD‑L1, perforin and granzyme B in TLSs was significantly higher compared with that in non‑TLSs. The majority of tumor‑infiltrating B cells in gastric cancer exist in the form of TLSs around the tumor and have been antigen‑sensitized and differentiated, and proliferated in TLSs but not in the lymph nodes. In addition, B cells in TLSs might primarily function as antigen‑presenting cells and be associated with the induction of cytotoxic T cells.
Background
Although the role of Lipocalin-2 (LCN2) in cancer development has been focused on recent studies, the molecular mechanisms and clinical relevance of LCN2 in gastric cancer (GC) still ...remain unclear.
Methods
Transcriptome analysis of GC samples from public human data was performed according to Lauren’s classification and molecular classification. In vitro, Western blotting, RT-PCR, wound healing assay and invasion assay were performed to reveal the function and mechanisms of LCN2 in cell proliferation, migration and invasion using LCN2 knockdown cells. Gene set enrichment analysis (GSEA) of GC samples from public human data was analyzed according to LCN2 expression. The clinical significance of LCN2 expression was investigated in GC patients from public data and our hospital.
Results
LCN2 was downregulated in diffuse-type GC, as well as in Epithelial–Mesenchymal Transition (EMT) type GC. LCN2 downregulation significantly promoted proliferation, invasion and migration of GC cells. The molecular mechanisms of LCN2 downregulation contribute to Matrix Metalloproteinases-2 (MMP2) stimulation which enhances EMT signaling in GC cells. GSEA revealed that LCN2 downregulation in human samples was involved in EMT signaling. Low LCN2 protein and mRNA levels were significantly associated with poor prognosis in patients with GC. LCN2 mRNA level was an independent prognostic factor for overall survival in GC patients.
Conclusions
LCN2 has a critical role in EMT signaling via MMP2 activity during GC progression. Thus, LCN2 might be a promising therapeutic target to revert EMT signaling in GC patients with poor outcomes.
It has been reported that CD63, an exosome marker, is expressed in solid cancer tissues. However, its significance in patients with gastric cancer has not been clarified. Exosomes derived from cancer ...cells and stromal cells might play an important role in the intracellular communications involved in the development of carcinoma. This study aimed to clarify the relationship between CD63 expression in cancer cells and stromal cells and clinical-pathologic factors.
A total of 595 gastric cancer patients were enrolled in this study. CD63 expression in cancer cells and stromal cells was analyzed by immunohistochemistry. The correlations between CD63 expression and several clinicopathological factors were investigated.
CD63 expression was mainly observed on the cell membranes of cancer cells, and in the cytoplasm of stromal cells. Of 595 patients, 247 cases had CD63-positive cancer cells, and 107 cases had CD63-positive stromal cells. Cases with CD63-positive cancer cells were significantly correlated with scirrhous-type gastric cancer, tumor depth, lymph node metastasis, lymphatic invasion, and tumor size. Cases with CD63-positive stromal cells were significantly correlated with age (≥65), tumor depth (T3-4), lymphatic invasion, and tumor size (≥ 5 cm). The 5-year survival rate was significantly lower (p<0.001) in patients with CD63-positive than CD63-negative tumors. Multivariate analysis showed that CD63 expression in cancer cells was a significant independent prognostic factor in patients with gastric cancer.
CD63 might be a prognostic marker for patients with gastric cancer. CD63-positive exosomes might be associated with the interaction between stromal cells and cancer cells.
This study examined whether the systemic inflammatory response present in the early phase of the postoperative state correlates with long-term outcomes and to identify markers in patients with stage ...II/III gastric cancer. 444 consecutive patients who underwent radical gastrectomy for stage II/III gastric cancer were retrospectively reviewed. We evaluated maximum serum C-reactive protein (CRP
) and white blood cell count (WBC
), defined as the maximum serum CRP level and maximum WBC count during the interval from surgery until discharge, as systemic inflammation markers. In univariate analyses, CRP
, WBC
and infectious complications were significantly associated with both overall survival (OS) (p < 0.001, p < 0.001 and p = 0.011, respectively) and relapse-free survival (RFS) (p < 0.001, p = 0.001 and p < 0.001, respectively). Multivariate analysis revealed that high-CRP
(> 9.2 mg/dL) was an independent prognostic factor for OS (hazard ratio (HR) 1.68, 95% confidence interval (CI) 1.19-2.36, p = 0.003) and RFS (HR 1.56, 95% CI 1.12-2.18, p = 0.009), while WBC
and infectious complications were not. CRP
, which reflects the magnitude of systemic inflammation induced by surgical stress and postoperative complications in the early phase after surgery, may be a promising prognostic indicator in patients with stage II/III gastric cancer who undergo curative resection.
Background
It is known that the area under the plasma concentration curve of nedaplatin (AUC
NDP
) is associated with the relative reduction ratio of platelets and that the AUC
NDP
is based on ...nedaplatin dose normalized by creatinine clearance (CrCL) (AUC
dose/CrCL
). Based on these relationships, in this retrospective study, we aimed to determine the unestablished dose
NDP
safe for patients with impaired renal function who received an initial combination chemotherapy with nedaplatin and 5-fluorouracil.
Methods
We performed a retrospective cohort analysis of consecutive patients with esophageal cancer who received an initial combination chemotherapy with ≤ 90 mg m
−2
day
−1
of nedaplatin on day 1 and 800 mg m
−2
day
−1
of 5-fluorouracil on days 1–5. AUC
dose/CrCL
was estimated using the formula, 3.2134 × dose
NDP
/CrCL + 4.4185. Data obtained during the first 28 days following nedaplatin administration were analyzed to compare AUC
dose/CrCL
between the patients with and without grade ≥ 3 thrombocytopenia. Receiver-operating characteristic (ROC) curve analysis was performed to determine the optimal AUC
dose/CrCL
cutoff value.
Results
Of the 136 patients included in this study, 8 (5.9%) presented with grade ≥ 3 thrombocytopenia. There were statistically significant differences in the AUC
dose/CrCL
between the patients with and those without grade ≥ 3 thrombocytopenia (11.79 vs. 10.09 µg h
−1
mL
−1
;
P
= 0.00828). We found that the appropriate cutoff value for the AUC
dose/CrCL
using the ROC curve was 10.945 µg h
−1
mL
−1
.
Conclusions
Our results indicate that safe dose
NDP
should be estimated to satisfy the following formula: Dose
NDP
(mg) < CrCL × 2.031.
PDF
