Hard Palate Metastasis from Rectal Adenocarcinoma.

The most common sites of metastasis from colorectal cancer are liver, lungs, and peritoneum. Oral cavity metastasis is extremely rare, accounting for only 1-2% of all oral cancers. We report the case of a 71-year-old male who presented with hard palate metastasis 20 months after his initial diagnosis for T4N1M1 rectal adenocarcinoma according to the UICC TNM classification. To the best of our knowledge, hard palate metastasis from colorectal cancer has never been previously reported in the literature. The hard palate metastasis deteriorates oral function, resulted in unfavorable prognosis. Early detection of oral cavity metastasis could lead to the opportunities for additional treatment and improve outcomes following treatment.

[A Case of Rectal Cancer and Multiple Lung Metastases That Had Complete Response Treated by XELOX plus Bevacizumab after Primary Lesion Resection].

A 54-year-old woman visited our hospital complaining of abdominal distension. Endoscopic examination revealed type 3 tumor in the rectum located 15 cm from the anal edge. Enhanced computed tomography showed multiple ground glass-like shadows in both lungs that were suspected of multiple metastases. We diagnosed as having rectal cancer with multiple lung metastases. After placing the stent transanally to release the intestinal obstruction, we performed laparoscopic high anterior resection. Then, the patient received chemotherapy with 10 courses of XELOX plus bevacizumab and 9 courses of the regimen without oxaliplatin. A whole-body CT revealed complete response. And while taking capecitabine the patient remains well and without recurrence. We describe the present case with reference to the literature.

Gastric cancer cells alter the immunosuppressive function of neutrophils.

Tumor­associated neutrophils (TANs) have an immunosuppressive function and play an important role in tumor progression. However, the detailed mechanism is largely unknown. The present study investigated the immunosuppressive ability of TANs in gastric cancer. Tumor tissue culture supernatant (TTCS) and non­tumor tissue culture supernatant (NTCS) were purified and added to neutrophils. Expression of programmed cell death ligand­1 (PDL­1), 7­amino­actinomycin D and human leukocyte antigen­DR (HLA­DR), and the levels of hydrogen peroxide (H2O2) were determined. Levels of programmed cell death­1 (PD­1) and CD25 were assessed in T cells co­cultured with neutrophils. Furthermore, CD4+ T cells were co­cultured with dendritic cells and neutrophils to examine their proliferation. CD15 and PD­1 immunohistochemical staining was also performed to explore the positional relationship. The results revealed that the neutrophils incubated with TTCS showed upregulation of PDL­1 expression, as well as a decreases in the ratio of apoptotic cells, expression of HLA­DR, and levels of H2O2. CD4+ T cells co­cultured with neutrophils conditioned with TTCS showed a decrease in proliferation, upregulation of PD­1 expression, and downregulation of CD25 expression. IHC showed that PD­1+ T cells formed clusters and TANs infiltrated around the clusters. In conclusion, neutrophils in gastric cancer tissue inhibit the proliferation of CD4+ T cells and may form a local immunosuppressive environment through the PD­1/PDL­1 pathway.

Impact of tumor-infiltrating LAMP-3 dendritic cells on the prognosis of esophageal squamous cell carcinoma.

BACKGROUND: Dendritic cells (DCs) are the most potent antigen-presenting cells to induce cytotoxic T lymphocytes in the tumor environment. After acquiring antigens, DCs undergo maturation and their expression of MHC and co-stimulation molecules are enhanced, along with lysosome-associated membrane glycoprotein 3 (LAMP-3), which is a specific marker of mature DCs. In general, mature DCs are usually considered to be immunostimulatory in the cancer microenvironment. In addition, it is known that tumor-infiltrating lymphocytes (TILs) are associated with a good prognosis in esophageal squamous cell carcinoma (ESCC). However, few studies have targeted the interaction between DCs and TILs in the local immunity of ESCC. We investigated the localization of mature DCs within ESCC tissue and their relationship to TILs as well as the clinical outcome. METHODS: We evaluated 80 ESCC patients who underwent surgical treatment without preoperative treatment, using immunohistochemistry with LAMP-3 and CD8. RESULTS: The results showed that LAMP-3 DCs were predominantly observed in the peritumoral area. Intratumoral CD8 T cells were found to be associated with a favorable prognosis, and the number of infiltrating LAMP-3 DCs was correlated with the number of intratumoral CD8 T cells. CONCLUSION: At the local tumor site, mature LAMP-3 DCs might be associated with increasing tumor infiltrating CD8 T cells.

The Effect of Systolic Variation of Mitral Regurgitation on Discordance Between Noninvasive Imaging Modalities.

OBJECTIVES: This study sought to assess the impact of systolic variation of mitral regurgitation (MR) has on discordance between echocardiography and magnetic resonance imaging (MRI). BACKGROUND: Studies have shown discordance between echocardiography and MRI when assessing the severity of MR. Contributing factors to this discordance may include the systolic variation of MR and the use of the color Doppler jet at a single point in time as the basis of many echocardiographic methods. METHODS: This analysis included 117 patients (62 ± 14 years of age; 58% male) with MR who underwent echocardiographic and MRI evaluation. Discordance was defined as the difference between the grades of MR (mild, moderate, or severe) by MRI and echocardiography. For each patient, 2 echocardiographic methods, the continuous wave time index and the color Doppler time index, and 1 MRI method, the systolic variation score (SVS), were measured to quantify systolic variation of MR. RESULTS: There was absolute agreement between echocardiography and MRI in 47 (40%) patients, a 1-grade difference in 54 (46%) patients, and a 2-grade difference in 16 (14%) patients. Only the SVS significantly differed between patients with and without discordance (0.60 ± 0.23 vs. 0.47 ± 0.21; p = 0.003). On receiver-operating characteristic analysis SVS had moderate predictive power of discordance (area under the curve: 0.67; p = 0.003), with an SVS of 53 having a sensitivity of 61% and a specificity of 65% to predict discordance. CONCLUSIONS: Discordance between MRI and echocardiographic assessment of MR severity is associated with systolic variation of MR as quantified by MRI using the SVS. Continuous wave Doppler and the presence of color Doppler were not correlated with discordance. This study highlights an advantage of MRI. Namely, it does not rely on a single point in time to determine MR severity. Because systolic variation had only moderate sensitivity and specificity for predicting discordance, other factors are also responsible for the discordance between the 2 techniques.

[A Case of Spontaneous Rupture of Non-Viral Hepatocellular Carcinoma with Subcapsular Hematoma].

An 86-year-old man visited our hospital complaining of upper abdominal pain. Enhanced computed tomography showed a 37×23mm tumor with subcapsular hematoma in S3. Hepatitis B and C virus markers were negative, and serum tumor markers were elevated. The patient was diagnosed with ruptured non-viral hepatocellular carcinoma with subcapsular hematoma. Because his condition and vital signs remained stable after conservative management of the liver tumor and hematoma, elective hepatectomy was performed. The postoperative course was good, and he was discharged 12 days postoperatively without any complications. We experienced a relatively rare case of ruptured non-viral hepatocellular carcinoma with subcapsular hematoma. We describe this case with reference to the literature.

Neutrophils in primary gastric tumors are correlated with neutrophil infiltration in tumor-draining lymph nodes and the systemic inflammatory response.

BACKGROUND: Tumor-Associated Neutrophils (TANs) may be able to induce lymphangiogenesis and angiogenesis, although the detailed roles of TANs remain unclear. The Neutrophil-Lymphocyte Ratio (NLR) is an inflammation-based prognostic factor for gastric cancer. This study aimed to investigate the distribution of CD15+neutrophils in the primary tumor and Tumor-Draining Lymph Nodes (TDLNs), and to examine the association of TANs with the clinicopathological features (including NLR) of patients with gastric cancer. RESULTS: Immunohistochemical staining showed that the median number of CD15+TANs was 18 and 24 per high-power field (HPF) in primary tumors and TDLNs, respectively. Patients were divided into high and low infiltration groups based on the median number. A high number of infiltrating CD15+TANs in the primary tumors and in the TDLNs were associated with depth of invasion and lymph node metastasis. Kaplan-Meier analysis revealed that a poor overall survival was associated with high numbers of CD15+TANs, and the multivariate analyses revealed that a high number of CD15+TANs in the TDLNs was an independent prognostic factor. The numbers of CD15+TANs in the primary tumors and TDLNs showed weak positive correlation. The number of CD15+TANs in the primary tumors was positively correlated with the preoperative NLR, (P = 0.001, R = 0.327) and immunohistochemical staining revealed that C-X-C motif chemokine receptor 2 (CXCR2) +neutrophils might be the origin of the CD15+TANs. Flow cytometry analysis indicated that infiltrating neutrophils increased in the tumor and TDLN compared to non-cancerous tissue. Neutrophils treated with cancer supernatant upregulated TWIST and IL-6 genes in vitro. CONCLUSION: Our findings suggested that local infiltration of CD15+TANs may be correlated with inflammation in TDLNs and systemic response to cause metastasis in gastric carcinoma.

[Significance of Immune-Cell Infiltration in Gastric].

There are many reports on the association between infiltrating immune cells andcancer prognosis. It is generally thought that cancer cells escape from the immune surveillance system in vivo. Cells associatedwith tumor immunosuppressive mechanisms include macrophages, regulatory T cells, bone marrow-derived immunosuppressive cells(MDSC), andneutrophils. These immunosuppressive cells enhance the production of TGF-b andIL -10 andthe expression of PDL-1 by cytokines producedby stromal cells such as cancer cells andfibroblasts, thereby inducing cytotoxic T cells lymphocytes(CTL). On the other hand, it has been proved that CD8+ T cells react in an antigen-specific manner even in advanced gastric cancer, suggesting the possibility that memory T cells, NK cells andNKT cells in gastric cancer tissues correlate with goodprognosis. Recently, it has been reportedthat the presence of follicular lymphoidstructure calledtertiary lymphoidstructure(TLS)in gastric cancer tissue is associatedwith favorable prognosis. Although immune responses are suppressedin gastric cancer tissues, the effectiveness of an immune checkpoint inhibitor(anti-PD-1 antibody)has been provedin 2017. The tumor-infiltrating immune cells is known as a predictive effect biomarker. As cancer genome research progresses, which type of immune response is induced is gradually being elucidated in near future. Thus, assessing the invasive morphology and function of various tumorinfiltrating immune cells is considered to be extremely important in Precision Medicine for gastric cancer.

B cells in tertiary lymphoid structures are associated with favorable prognosis in gastric cancer.

BACKGROUND: The role of tumor-infiltrating B cells in the tumor microenvironment is still unclear. Recent studies have reported that B cells and tertiary lymphoid structures (TLSs) that contain B cell follicles correlate with the favorable prognosis of cancer patients. The aim of this study was to investigate the association between tumor-infiltrating B cells and clinicopathological features in gastric cancer. METHODS: Tumor blocks were obtained from 226 patients with stage Ib to stage IV gastric cancer. The density of CD20+ B cells within the tumor and in the invasive margin area was assessed using immunohistochemistry. We also evaluated CD3+ T cells, CD21+ follicular dendritic cells, Bcl6+ germinal center B cells, and PNAd+ high endothelial venules to show the presence of TLSs. RESULTS: Tumor-infiltrating B cells were mostly organized as clusters that were surrounded by CD3+ T cells. The B cell area contained follicular dendritic cells and some clusters contained Bcl6+ B cells. High endothelial venules were present around follicles. We identified these follicles as TLSs. A high number of CD20+ B cells were associated with significantly better overall survival, and multivariate analysis also showed that CD20 high was one of the independent predictors of prognosis. In addition, there was a significant correlation between CD20+ B cell and CD8+ T cell infiltration. CONCLUSIONS: B cells mostly infiltrated tumors as TLSs and were associated with better prognosis in patients with gastric cancer.

[Effectiveness of Intraoperative Histologic Assessment of Surgical Margins for Breast-Conserving Surgery].

BACKGROUND: The effectiveness of intraoperative histologic assessment of surgical margins for breast-conserving surgery is unclear. In this study, we investigated the effectiveness of intraoperative histologic assessment of surgical margins for breast-conserving surgery. METHODS: Sixty-six patients who underwent breast-conserving surgery for breast cancer at our hospital between January 2007 and December 2013 were retrospectively examined for an association between the surgical margin status and locoregional recurrence. The surgical margins were then evaluated by intraoperative histologic assessment. RESULTS: The median observation period was 52 months. Positive margins were found in 14 patients (21%). A total mastectomy was performed in 9 patients, and additional resection in 5 patients. In the permanent tissue sample, the intraoperative assessment was found to be false negative in 2 patients (3.8%), who received boost irradiation postoperatively. No locoregional recurrence was observed in all patients who underwent additional resection or total mastectomy due to positive margins. The rate of margin positivity was significantly higher in invasive lobular carcinomas and in cancers with intraductal extension. CONCLUSIONS: Intraoperative histologic assessment of the surgical margin was useful for reducing the rate of local recurrence.

[A Case of Locally Advanced Breast Cancer Treated with Modified Radical Mastectomy with Immediate Reconstruction Using a Tissue Expander after Endocrine Therapy].

We experienced a case of locally advanced breast cancer treated with modified radical mastectomy with immediate reconstruction using a tissue expander after endocrine therapy. A 64-year-old postmenopausal woman had a 50 mm tumor in her right breast with extensive reddening of the skin. She had axillary lymph node metastasis. Core needle biopsy showed invasive ductal carcinoma with positive hormone receptor (ER+, PgR+) and negative HER2 status. The patient was diagnosed with locally-advanced breast cancer (cT4bN1M0, stage ⅢB). She was treated with anastrozole at a dose of 1 mg per day. The tumor decreased in size gradually and became operable after 7 months of anastrozole monotherapy. She underwent modified radical mastectomy with immediate reconstruction using a tissue expander. The resected specimen was a 30 mm tumor; adverse effects due to endocrine therapy were of Grade 1a severity. Seven months after adjuvant chemotherapy (FEC→DTX), the tissue expander was removed, and the right breast was reconstructed using an implant. No complications were noted, and the patient was treated with radiation therapy. Ten months have passed since surgery, and no local recurrence or distant metastasis has been noted.

Retrospective analysis of capecitabine and oxaliplatin (XELOX) plus bevacizumab as a first-line treatment for Japanese patients with metastatic colorectal cancer.

XELOX plus bevacizumab is an effective treatment strategy and has a manageable tolerability profile when administered to Japanese patients with metastatic colorectal cancer (mCRC). In this study, we retrospectively reviewed cases in which XELOX plus bevacizumab were administered in order to evaluate its efficacy and safety in clinical practice. In total, 40 patients with mCRC who presented at Fuchu Hospital received XELOX plus bevacizumab as a first-line treatment between September, 2009 and April, 2012. Eligible patients had histologically confirmed mCRC. XELOX consisted of a 2-h intravenous infusion of oxaliplatin 130 mg/m2 on day 1 plus oral capecitabine 1,000 mg/m2 twice daily for 2 weeks of a 3-week cycle. Overall survival (OS) and survival benefit were analyzed when patients continued with XELOX plus bevacizumab beyond disease progression. The median progression-free survival (PFS) was 290 days [95% confidence interval (CI): 222-409 days] and the median OS was 816 days (95% CI: 490 days-not calculated). The response rate (RR; complete plus partial response) was 67.5%, and the disease control rate (RR plus stable disease) was 90%. The most common adverse events observed following administration of XELOX plus bevacizumab were neurosensory toxicity (82.5%), anorexia (50%), hypertension (45%) and a decrease in the platelet count (40%). The most common grade 3/4 adverse events were neurosensory toxicity (15%) and fatigue (15%). In conclusion, XELOX plus bevacizumab may be considered a routine first-line treatment option for patients with mCRC. Notably, the combination of capecitabine and bevacizumab was safe with an acceptable toxicity profile and induced a significant rate of disease control.