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Abstract Background Laparoscopic surgery is reported to be useful in obese or elderly patients with colon cancer, who are at increased risk of postoperative complications because of comorbidities and physical decline. However, its usefulness is less clear in patients who are both elderly and obese and may be at high risk of complications. Methods Data for obese patients (body mass index ≥25) who underwent laparoscopic or open surgery for stage II or III colon cancer between January 2009 and December 2013 were collected by the Japan Society of Laparoscopic Colorectal Surgery. Surgical outcomes, postoperative complications, and relapse‐free survival (RFS) were compared between patients who underwent open surgery and those who underwent laparoscopic surgery according to whether they were elderly (≥70 y) or nonelderly (

Abstract Background Systemic inflammation is recognized as a hallmark of cancer that contributes to tumor development and progression in various malignancies. The Naples prognostic score (NPS) was established as a prognostic indicator for colorectal cancer (CRC). This study aims to examine the predictive value of the NPS for survival in CRC patients undergoing curative resection by a propensity score matching (PSM) analysis. Methods A total of 533 CRC patients were enrolled in this study. Overall survival (OS) and disease-free survival (DFS) were compared between high-NPS and low-NPS groups. A time-dependent receiver operator characteristic (ROC) curve analysis was conducted to calculate the area under curve (AUC) of the NPS for OS. A multivariable Cox-proportional hazards regression analysis and PSM analysis were used to identify independent prognostic factors for OS and DFS. We compared the predictive value of the NPS to that of the neutrophil-to-lymphocyte ratio (NLR), lymphocyte-to-monocyte ratio (LMR), platelet-to-lymphocyte ratio (PLR), Onodera prognostic nutritional index (PNI), and controlling nutritional status score (CONUT) for OS. Results High-NPS was significantly associated with worse OS and DFS. After PSM, 123 patients were included in each group. A multivariate analysis revealed that Age ≥ 68, ASA-PS ≥ 3, high NPS and undifferentiated tumor type were independently associated with OS, while high NPS, advanced T and N stage were independently associated with DFS after PSM. The NPS had the greatest AUC for OS in comparison to the NLR, LMR, PNI and CONUT. Conclusions We successfully validated the prognostic utility of the NPS for CRC patients after curative resection.

Abstract Gastric cancer (GC) with microsatellite instability (MSI) has been reported to be sensitive to immunotherapy, however some of GC cases with MSI remain resistant to immunotherapy. Cancer cell lines showing MSI might be useful for the analysis of mechanisms of immunotherapy, while only a few GC cell lines with MSI are available so far. In this study, we established a unique GC cell line with MSI, OCUM‐13, from a primary GC with abundant tumor‐infiltrating lymphocytes. MSI assay indicated that OCUM‐13 cells as well as the primary tumor showed a band shift in more than 3 of 5 microsatellite loci, suggesting that OCUM‐13 did have high MSI. The subcutaneous inoculation of OCUM‐13 cells into mice performed tumor formation. Insulin‐like growth factor 1 receptor inhibitor decreased the growth of OCUM‐13 cells. The newly established cell line with MSI, OCUM‐13, might be useful for the analysis of cancer therapy for GC with MSI.

Abstract Background Postoperative complications of colorectal cancer mainly include infections (surgical site infection, remote infection, etc.), post-operative ileus (POI), and anastomosis leakage. POI reportedly prolongs the hospital stay and increases medical costs. Therefore, predicting POI is very important. There have been some reports on the relationships between sarcopenia and postoperative complications in colorectal cancer patients, but none have been limited to POI. We therefore conducted a retrospective clinical study with a logistic regression analysis to confirm the risk factors for ileus after colorectal cancer surgery. Methods We retrospectively analyzed 213 patients who underwent elective oncological colorectal surgery for colorectal cancer from November 2017 to July 2021. The skeletal muscle mass (SMM, kg) was estimated using a whole-body bioelectrical impedance analysis (BIA), and the skeletal muscle index (SMI) was calculated as the SMM/height2. We divided all patients into 2 groups based on a low SMI (male

Abstract Background Mediastinal foreign bodies might cause mediastinal organ injury or mediastinal abscess. The prompt removal surgery of mediastinal foreign bodies is needed to prevent those complications. We report a case in which a mediastinal foreign body was removed by video-mediastinoscopy. Case presentation The patient, a 74-year-old man with a chief complaint of hoarseness, was referred to our department for surgical management of a wooden foreign body that had traumatically migrated into the superior mediastinum. During the surgery, the video-mediastinoscopy was introduced under the pneumomediastinal pressure. We could dissect the scar tissue and remove the azalea tree branch safely and carefully, without damaging the other mediastinal organs. He was discharged on postoperative day 5, with no complications. Conclusions Video-mediastinoscopic approach under pneumomediastinal pressure is minimally invasive and could provide wide surgical view. Therefore, we consider it useful and effective for removal of foreign bodies in the mediastinum.

Abstract Accumulating evidence indicates that alterations of gut microbiota are associated with colorectal cancer (CRC). Therefore, the use of gut microbiota for the diagnosis of CRC has received attention. Recently, several studies have been conducted to detect the differences in the gut microbiota between healthy individuals and CRC patients using machine learning‐based gut bacterial DNA meta‐sequencing analysis, and to use this information for the development of CRC diagnostic model. However, to date, most studies had small sample sizes and/or only cross‐validated using the training dataset that was used to create the diagnostic model, rather than validated using an independent test dataset. Since machine learning‐based diagnostic models cause overfitting if the sample size is small and/or an independent test dataset is not used for validation, the reliability of these diagnostic models needs to be interpreted with caution. To circumvent these problems, here we have established a new machine learning‐based CRC diagnostic model using the gut microbiota as an indicator. Validation using independent test datasets showed that the true positive rate of our CRC diagnostic model increased substantially as CRC progressed from Stage I to more than 60% for CRC patients more advanced than Stage II when the false positive rate was set around 8%. Moreover, there was no statistically significant difference in the true positive rate between samples collected in different cities or in any part of the colorectum. These results reveal the possibility of the practical application of gut microbiota‐based CRC screening tests.

Abstract Background Cancer-associated fibroblasts (CAFs) play an important role in cancer growth by interacting with cancer cells, but their effects differ depending on the type of cancer. This study investigated the role of CAFs in biliary tract cancers (BTCs), compared with pancreatic ductal adenocarcinoma (PDAC) as a comparison cohort. Methods We retrospectively evaluated alpha-smooth muscle actin (αSMA) expression in CAFs from 114 cases of PDAC and 154 cases of BTCs who underwent surgical treatment at our institution from 1996 to 2017. CAFs were isolated from resected specimens of BTC and PDAC, and tested for the effects of their supernatants and cytokines on cancer cell proliferation. Results PDAC patients with positive αSMA expression showed significantly shorter overall survival and recurrence-free survival than αSMA-negative patients (p = 0.003, p = 0.009, respectively). BTC patients with positive αSMA expression showed better recurrence-free survival than αSMA-negative patients (p = 0.03). CAF-conditioned medium suppressed the proliferation of cancer cells for only OCUCh-LM1 cells and not PDAC cells. Blockage of Interleukin-8 (IL-8) or its receptor C-X-C motif chemokine receptor 2 (CXCR2) by antibodies canceled the suppressive effect of the IL-8. Conclusions CAFs are a good prognostic factor in BTC, but not for PDAC. Moreover, CAF-produced Interleukin-8 suppresses the proliferation of OCUCh-LM1 cell lines.

Abstract Background Tertiary lymphoid structures (TLSs) have been reported to be involved in immune responses in many carcinomas. This study investigated the significance of TLSs in esophageal squamous cell carcinoma, focusing on TLS maturation. Methods The relationships of TLSs with clinicopathological features of 236 patients who underwent curative surgery for stage 0-IV esophageal squamous cell carcinoma were investigated. Mature TLSs, in which the germinal center formation was rich in CD23+ cells, were classified as TLSs containing a germinal center (GC-TLSs). GC-TLS densities were measured, and CD8+ cells were counted. The prognostic impact of GC-TLSs was assessed by Kaplan–Meier plots using the log-rank test for the relapse-free survival. A comparative study of GC-TLSs was performed using the Wilcoxon rank sum test. The relationship between GC-TLSs and CD8+ cells was examined by Spearman’s rank correlation coefficient test. Results TLSs were located mainly at the invasive margin of the tumor in cases with esophageal squamous cell carcinoma. Among the patients treated with neoadjuvant chemotherapy, those with advanced disease had a better prognosis in the GC-TLS high-density group than did those in the GC-TLS low-density group. Patients in whom neoadjuvant chemotherapy was effective had more GC-TLSs than those in whom it was less effective. The density of GC-TLSs and the number of tumor-infiltrating CD8+ cells were higher in patients treated with neoadjuvant chemotherapy than in those without chemotherapy, and a weak correlation between the density of GC-TLSs and the number of tumor-infiltrating CD8+ cells was observed. Moreover, co-culturing of PBMCs with an anticancer drug-treated esophageal squamous cell carcinoma cell line increased the CD20 and CD23 expression in PBMCs in vitro. Conclusion TLS maturation may be important for evaluating the local tumor immune response in patients treated with neoadjuvant chemotherapy for esophageal squamous cell carcinoma. The present results suggest that TLS maturation may be a useful target for predicting the efficacy of immunotherapy, including immune checkpoint inhibitor treatment for esophageal squamous cell carcinoma.

Abstract Background Tumor heterogeneity has frequently been observed in gastric cancer (GC), but the correlation between patients’ clinico-pathologic features and the tumoral heterogeneity of GC-associated molecules is unclear. We investigated the correlation between lymph node metastasis and the intra-tumoral heterogeneity of driver molecules in GC. Materials and methods We retrospectively analyzed the cases of 504 patients who underwent a gastrectomy at the Department of Gastroenterological Surgery, Osaka Metropolitan University and 389 cases drawn from The Cancer Genome Atlas (TCGA) data. We performed a clustering analysis based on eight cancer-associated molecules including HER2, c-Met, and p-Smad2 using the protein expression revealed by our immunohistochemical study of the patients’ and TCGA cases. We determined the correlations between HER2 expression and the other molecules based on the degree of lymph node metastasis. Results Immunohistochemical staining data showed that a 43 of the 504 patients with GC (8.5%) were HER2-positive. In the HER2-positive cases, the expressions of c-Met and p-Smad2 were increased in accord with the lymph-node metastatic level. The overall survival of the HER2-positive GC patients with both p-Smad2 and c-Met expression was significantly (p = 0.030) poorer than that of the patients with p-Smad2-negative and/or c-Met-negative expression. The results of the TCGA data analysis revealed that 58 of the 389 GC cases (14.9%) were ERBB2-positive. MET expression was more frequent in the N1 metastasis group than the N0 group. In the high lymph-node metastasis (N2 and N3) group, SMAD2 expression was more frequent, as was ERBB2 and MET expression. Conclusion p-Smad2 and c-Met signaling might play important roles in lymph node metastasis in HER2-positive GC.

Abstract Background The surgical Apgar score (SAS) predicts postoperative complications (POCs) following gastrointestinal surgery. Recently, the SAS was reported to be a predictor of not only POCs but also prognosis. However, the impact of the SAS on oncological outcomes in patients with colorectal cancer (CRC) has not been fully examined. The present study therefore explored the oncological significance of the SAS in patients with CRC, using a propensity score matching (PSM) method. Methods We retrospectively analyzed 639 patients who underwent radical surgery for CRC. The SAS was calculated based on three intraoperative parameters: estimated blood loss, lowest mean arterial pressure, and lowest heart rate. All patients were classified into 2 groups based on the SAS (≤6 and >6). The association of the SAS with the recurrence-free survival (RFS), overall survival (OS), and cancer-specific survival (CSS) was analyzed. Results After PSM, each group included 156 patients. Univariate analyses revealed that a lower SAS (≤6) was significantly associated with a worse OS and CSS. A multivariate analysis revealed that the age ≥75 years old, ASA-Physical Status ≥3, SAS ≤6, histologically undifferentiated tumor type, and an advanced pStage were independent factors for the OS, and open surgery, a SAS ≤6, histologically undifferentiated tumor type and advanced pStage were independent factors for the CSS. Conclusions A lower SAS (≤6) was an independent prognostic factor for not only the OS but also the CSS in patients with CRC, suggesting that the SAS might be a useful biomarker predicting oncological outcomes in patients with CRC.

Abstract Background Therapeutic agents for dyslipidaemia, in particular statins, have been recently reported to suppress growth and metastasis of breast cancer. However, the predictive value of lipid control in breast cancer patients has not been discussed sufficiently. In addition, though immunometabolism is a relatively novel approach for tumour immunotherapy, the relationship between lipid metabolism and immune status has not been well documented. We therefore investigated the effects of lipid metabolism on antitumour immune response and cancer prognosis. Methods Except for patients with ductal carcinoma in situ, 938 patients treated with curative surgery were examined. The correlation between treatment for dyslipidaemia or serum lipid levels and clinicopathological features, including the prognosis, was evaluated retrospectively. Also, we stratified these results by intrinsic subtype of breast cancer, menopause, and type of therapeutic agents for dyslipidaemia. Moreover, neutrophil- to-lymphocyte ratio (NLR) and tumour-infiltrating lymphocytes (TILs) were used as indicators of systemic and local immune status, respectively. Results Of 194 patients treated for dyslipidaemia, recurrence-free survival (RFS) and overall survival (OS) did not differ significantly between users of drugs for dyslipidaemia and non-users (p = 0.775 and p = 0.304, log-rank, respectively). Among postmenopausal, hormone receptor (HR)-positive/human epidermal growth factor receptor 2 (HER2)-negative breast cancer patients treated for dyslipidaemia, the good serum lipid control group had significantly better RFS (p = 0.014, log-rank), lower postoperative NLR (p = 0.012), and higher TILs in resected tissues (p = 0.024) than the poor control group. Multivariate analysis showed that postoperative serum lipid levels were a risk factor for recurrence (hazard ratio = 4.722, 95% confidence interval 1.006–22.161, p = 0.049). Conclusions Good control of serum lipid metabolism may improve the tumour immune microenvironment and prognosis in postmenopausal HR-positive/HER2-negative breast cancer patients.

Abstract Background Lymphocytes that surround cancer participate in tumor-related immune responses and are called tumor-infiltrating lymphocytes (TILs). Several recent reports suggest TILs index the tumor microenvironment and predict the therapeutic effect of chemotherapy. However, only few studies have studied the relationship between age and TILs. Aging reduces host immunity, and we predict that it may also affect TILs. Thus, we hypothesized that older breast cancer (BC) patients may have low TIL density than younger BC patients. Here, we retrospectively analyzed the differences in TILs by age and the therapeutic effects of preoperative chemotherapy (POC) in BC patients who were aged either less than 45 years or more than 60 years. Methods We retrospectively examined the data of 356 breast cancer patients who underwent POC, including 75 patients aged ≤ 45 years and 116 patients aged > 60 years. Using pre-treatment needle biopsy specimens, TIL density was compared for each age group by Student’s t-test. After analyzing different factors that affect TIL density, prognostic factors were also examined. Results Older patients with triple-negative BC had significantly lower TIL density than younger patients, while in human epidermal growth factor receptor 2 (HER2)-enriched BC, TIL density was significantly higher in the younger age group than that in the older age group. In addition, younger patients with HER2-rich breast cancer showed significantly higher complete pathological response rates than older patients with HER2-rich BC. In addition, significant differences in overall survival were observed among these patients with triple-negative BC. Conclusions Our study suggests that younger BC patients possess significantly higher TIL density than older patients. These differences may influence the therapeutic efficacy in highly immunogenic subtypes.

Abstract 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 (CRPmax) and white blood cell count (WBCmax), 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, CRPmax, WBCmax and infectious complications were significantly associated with both overall survival (OS) (p 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 WBCmax and infectious complications were not. CRPmax, 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.

BackgroundThe 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).MethodsA 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.ResultsWith 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).ConclusionsHigh Immunoscore group had significantly superior OS and RFS and was an independent good prognostic factor for OS and RFS.

Abstract Background In the Response Evaluation Criteria for Solid Tumors (RECIST) diagnostic criteria, the concepts of progression by preexisting disease (PPL) and progression by new metastases (PNM) have been proposed to distinguish between the progression types of cancer refractory to treatment. According to the tumor biology of cancer progression forms, the “PPL” form indicates invasion, and the “PNM” form indicates metastasis. On the other hand, recent studies have focused on the clinical importance of inflammatory markers as indicators of the systemic tumor immune response. In particular, absolute lymphocyte count (ALC) is an indicator of the host’s immune response. Thus, we developed a new measure that combined progression form with ALC. In this study, we clinically validated the combined assessment of progression form and ALC in eribulin chemotherapy. Methods From August 2011 to April 2019, a total of 486 patients with locally advanced or metastatic breast cancer (MBC) underwent treatment. In this study, only 88 patients who underwent chemotherapy using eribulin were included. The antitumor effect was evaluated based on the RECIST criteria, version 1.1. To measure ALC, peripheral blood samples collected before eribulin treatment were used. The cut-off value for ALC in this study was 1500/μl, based on previous studies. Results The PPL group (71 patients, 80.7%) had significantly longer progression-free survival (PFS) (p = 0.022, log-rank) and overall survival (OS) (p < 0.001, log-rank) than the PNM group (17 patients, 19.3%). In the 51 patients with ALC < 1500/μl, the PPL group had a significantly better prognosis than the PNM group (PFS: p = 0.035, OS: p < 0.001, log-rank, respectively). On the other hand, in the 37 patients with ALC ≥ 1500/μl, the PPL group had a better OS compared with the PNM group (p = 0.055, log-rank), but there was no significant difference in PFS between the two groups (p = 0.541, log-rank). Furthermore, multivariate analysis that validated the effect of OS showed that high ORR and “high-ALC and PPL” were factors for a good prognosis (p < 0.001, HR = 0.321; p = 0.036, HR = 0.290). Conclusions The progression form of PNM had a worse prognosis than PPL in patients treated with eribulin. In breast cancer patients with eribulin chemotherapy, good systemic immune status, such as ALC ≥ 1500/μl, was associated with less progression, particularly metastasis, and better prognosis. Furthermore, the biomarker “high-ALC (ALC ≥ 1500/μl) and PPL” was particularly useful as a prognostic marker following eribulin chemotherapy.

Abstract Cancer stem cells (CSCs) play an important role in the progression of carcinoma and have a high potential for survival in stress environments. However, the mechanisms of survival potential of CSCs have been unclear. The aim of this study was to clarify the significance of autophagy systems of CSCs under stress environments. Four gastric cancer cell line were used. Side population (SP) cells were sorted from the parent cells, as CSC rich cells. The expression of stem cell markers was examined by RT-PCR. The viability of cancer cells under starvation and hypoxia was evaluated. The expression level of the autophagy molecule LC3B-II was examined by western blot. The numbers of autophagosomes and autolysosomes were counted by electron microscope. SP cells of OCUM-12 showed a higher expression of stem cell markers and higher viability in starvation and hypoxia. Western blot and electron microscope examinations indicated that the autophagy was more induced in SP cells than in parent cells. The autophagy inhibitor significantly decreased the viability under the stress environments. These findings suggested that Cancer stem cells of gastric cancer might maintain their viability via the autophagy system. Autophagy inhibitors might be a promising therapeutic agent for gastric cancer.

Abstract Purpose The body mass index (BMI) is commonly used as a simple indicator of obesity; patients with early-stage breast cancer who are obese (OB) per BMI measurements have been shown to have high postoperative recurrence and low survival rates. On the other hand, it has been shown that lymphocytes present in the vicinity of malignant growths that are involved in the tumors’ immune responses influence the efficacy chemotherapy. Therefore, we hypothesized that OB patients with breast cancer have a lower density of tumor-infiltrating lymphocytes (TILs), which may influence the therapeutic effect of preoperative chemotherapy (POC). In this study, we measured pretreatment BMI and TILs in patients with breast cancer who underwent POC, examined the correlations between these two factors, and retrospectively analyzed their therapeutic outcomes and prognoses. Methods The participants in this study were 421 patients with breast cancer who underwent surgical treatment after POC between February 2007 and January 2019. The patient’s height and weight were measured before POC to calculate the BMI (weight [kg] divided by the square of the height [m2]). According to the World Health Organization categorization, patients who weighed under 18.5 kg/m2 were classified as underweight (UW), those ≥18.5 kg/m2 and > 25 kg/m2 were considered normal weight (NW), those ≥25 kg/m2 and

Abstract Background Postoperative anastomotic leakage (AL) is associated with not only prolonged hospital stay and increased medical costs, but also poor prognosis in esophageal cancer. Several studies have addressed the utility of various inflammation-based and/or nutritional markers as predictors for postoperative complications. However, none have been documented as specific predictors for AL in esophageal cancer. We aimed to identify predictors of AL after esophagectomy for thoracic esophageal cancer, focusing on preoperative inflammation-based and/or nutritional markers. Methods We retrospectively analyzed 295 patients who underwent radical esophagectomy for thoracic esophageal squamous cell carcinoma between June 2007 and July 2020. As inflammation-based and/or nutritional markers, Onodera prognostic nutritional index, C-reactive protein (CRP)-to-albumin ratio (CAR) and modified Glasgow prognostic score were investigated. Optimal cut-off values of inflammation-based and/or nutritional markers for AL were determined by receiver operating characteristic curves. Predictors for AL were analyzed by logistic regression modeling. Results AL was observed in 34 patients (11.5%). In univariate analyses, preoperative body mass index (≥ 22.1 kg/m2), serum albumin level (≤ 3.8 g/dL), serum CRP level (≥ 0.06 mg/dL), CAR (≥ 0.0139), operation time (> 565 min) and blood loss (≥ 480 mL) were identified as predictors of AL. Multivariate analyses revealed higher preoperative CAR (≥ 0.0139) as an independent predictor of AL (p = 0.048, odds ratio = 3.02, 95% confidence interval 1.01–9.06). Conclusion Preoperative CAR may provide a useful predictor of AL after esophagectomy for thoracic esophageal squamous cell carcinoma.

Mammary Paget’s disease is a rare malignancy. Mastectomy or breast-conserving surgery has been considered as the standard treatment, while there have been few reports of neoadjuvant chemotherapy (NAC). A 53-year-old woman with erythema and skin ulceration of the left breast was admitted to our institution. Breast examinations revealed left invasive ductal carcinoma (cT1bN0M0, cStage I), and a punch biopsy of the left mammary erythema indicated Paget’s disease (cTisN0M0, cStage0). The patient received NAC because of multiple lesions. Consequently, the breast tumor clinically disappeared, and the erythema improved. These outcomes made it easier to perform surgery (left mastectomy and sentinel node biopsy). Histopathological examination revealed no residual cancer cells in either the mammary gland or breast skin, and no metastasis was found in the sentinel lymph node. Therefore, NAC may be a useful treatment for mammary Paget’s disease.

Abstract Background Port site metastasis (PSM) after curative gastrectomy for gastric cancer and muscular metastasis from gastric cancer are rare manifestations. Similarly, subcutaneous metastasis from gastric cancer is rare, and muscular and subcutaneous metastases are associated with poor prognosis. We report a case of long-term survival in a patient who underwent curative resection of gastric cancer and repeated recurrence of port site, muscular and subcutaneous metastases from gastric cancer, treated by resection. Case presentation A 75-year-old man was diagnosed with gastric cancer and referred to our department. Upper endoscopy demonstrated a 5-cm circumferential ulcerated lesion at the cardia. Biopsy findings showed a poorly differentiated tubular adenocarcinoma. He underwent laparoscopic total gastrectomy with lymph node dissection, and pathologic examination revealed a moderately differentiated tubular adenocarcinoma stage T4aN1M0 and IIIA according to the UICC (Union for International Cancer Control) classification. He refused adjuvant chemotherapy and was only carefully observed. Twenty-three months after the primary gastrectomy, computed tomography (CT) revealed an irregular mass near the port site wounds. Then the patient underwent mass resection, and the pathological diagnosis was consistent with metastatic adenocarcinoma, located in the subcutaneous tissue at the port site wounds. Thirteen months after the second surgery, CT revealed an enhanced mass in the abdominal wall. Positron emission tomography (PET) CT showed an elevated uptake in the rectus abdominis muscle and a standardized uptake value (SUV) of 3.1. The patient underwent another mass resection, and the pathological diagnosis was consistent with metastatic adenocarcinoma in the rectus abdominis muscle. Thirty-five months after the third surgery, CT revealed a mass in the left gluteal subcutaneous region. Furthermore, PET-CT revealed a 35-mm mass with an elevated SUV of 9.6. Another mass resection procedure was performed, and the pathological diagnosis was consistent with metastatic adenocarcinoma in the subcutaneous tissue. Since tumor cells were present at the resection margin, additional radiation therapy was performed. The patient has survived 78 months after primary gastrectomy. Conclusion The prognosis of muscular and subcutaneous metastases from gastric cancer is poor. However, if the metastatic tumor is solitary, surgical excision could be a feasible treatment option and might prolong survival.

Abstract Background Breast cancer subtypes are known to have different metastatic recurrence sites. Distant metastases are often observed during the post-operative course in patients with human epidermal growth factor receptor 2 (HER2)-enriched breast cancer and triple-negative breast cancer, but are relatively rare in those with hormone receptor-positive and HER2-negative (HR+/HER2−) breast cancer. Tumor-infiltrating lymphocytes (TILs) serve as an index to monitor tumor immune microenvironment and may possibly predict the prognosis and therapeutic effect in breast cancer. This study aimed to investigate the correlation between TIL density and recurrence site in HR+/HER2− breast cancer. Methods In stages I–II of HR+/HER2− breast cancer patients who underwent surgery as the first treatment and received adjuvant endocrine therapy (except adjuvant chemotherapy), forty-two patients relapsed after surgery. TILs were evaluated using needle biopsy specimens for the diagnosis of breast cancer. Morphological assessment was conducted using conventional hematoxylin and eosin staining. Results Six patients had no TILs density. In them, local recurrence was significantly less (p = 0.022), while distant metastases were significantly more (p = 0.015) compared to those in patients with TIL density. Therefore, for the prediction of distant metastases in HR+/HER2− breast cancer without chemotherapy, TILs could be used as predictors in univariate analysis (p = 0.015, odds ratio [OR] = 0.127), although not as independent factors (p = 0.285, OR = 0.144). Conclusions Our findings indicate that TILs may predict distant metastatic recurrence in stages I–II of HR+/HER2− breast cancer in patients who do not undergo chemotherapy.

Angiosarcoma is a malignant mesenchymal tumor characterized by the presence of vascular endothelial cells. Although rare, angiosarcoma developing in the mammary glands has a poor prognosis. We report a case of breast angiosarcoma with a preoperative diagnosis of late recurrence of breast cancer. A 78-year-old woman noticed a tumor in her right breast and visited our hospital. The patient had undergone breast-conserving surgery and axillary lymph node dissection from the right breast 12 years before the visit. The tumor was diagnosed as T4bN0M0, stage IIIB. Anastrozole was administered as postoperative adjuvant therapy for 5 years; the patient also received 50-Gy whole-breast radiation therapy after surgery. Physical examination during her visit revealed an elevated lesion with blue purpura around the nipple in the right breast. We performed breast ultrasound and detected a well-defined 19.6 × 16.4 × 10.7 mm hypoechoic tumor in the left subareolar area. The patient underwent core needle biopsy (CNB). Based on the CNB specimen findings, she was suspected to experience late local recurrence after surgery. Therefore, she underwent total mastectomy after breast-conserving surgery. A dark-red tumor sized 18 × 12 mm was found in a specimen from the nipple. The pathological diagnosis of the specimen revealed short spindle-shaped tumor cells with strong nuclear pleomorphism and a significant interstitial fibrosis. Immunohistochemistry using D2-40 and CD31 antibodies showed irregular luminal proliferation at the anastomosis, infiltration into the surrounding tissue, and massive necrosis, thereby leading to the diagnosis of breast angiosarcoma. We have reported a case of breast angiosarcoma with a preoperative diagnosis of late recurrence of breast cancer.

Abstract Fibroblast growth factor receptor 2 (FGFR2) has two isoforms: IIIb type and IIIc type. Clinicopathologic significance of these two FGFR2 subtypes in gastric cancer remains to be known. This study aimed to clarify the clinicopathologic difference of FGFR2IIIb and/or FGFR2IIIc overexpression. A total of 562 patients who underwent gastrectomy was enrolled. The expressions of FGFR2IIIb and FGFR2IIIc were retrospectively examined by immunohistochemistry or fluorescence in situ hybridization (FISH) using the 562 gastric tumors. We evaluated the correlation between clinicopathologic features and FGFR2IIIb overexpression and/or FGFR2IIIc overexpression in gastric cancer. FGFR2IIIb overexpression was observed in 28 cases (4.9%), and FGFR2IIIc overexpression was observed in four cases (0.7%). All four FGFR2IIIc cases were also positive for FGFR2IIIb, but not in the same cancer cells. FGFR2IIIb and/or FGFR2IIIc overexpression was significantly correlated with lymph node metastasis and clinical stage. Both FGFR2IIIb and FGFR2IIIc were significantly associated with poor overall survival. A multivariate analysis showed that FGFR2IIIc expression was significantly correlated with overall survival. FISH analysis indicated that FGFR2 amplification was correlated with FGFR2IIIb and/or FGFR2IIIc overexpression. These findings suggested that gastric tumor overexpressed FGFR2IIIc and/or FGFR2IIIb at the frequency of 4.9%. FGFR2IIIc overexpression might be independent prognostic factor for patients with gastric cancer.

Abstract It has been reported that circulating tumor cells (CTCs) are beneficial for predicting tumor stage or treatment response. Although epithelial cell adhesion molecules (EpCAMs) and cytokeratin (CK) have been often used for the identification of CTCs, other tumor markers have not been fully investigated as detecting tools for CTCs. Thus, this study aims to clarify the significance of carcinoembryonic antigen (CEA, CD66e)‐positive CTCs in patients with gastric cancer. A total of 150 patients with gastric cancer were enrolled in this study. The mononuclear fraction of peripheral blood was enriched by Ficoll. The number of cells was enumerated depending on the positivity of EpCAM and CEA or CK by flow cytometry. The association of these cells with clinicopathologic characteristics was investigated. The mean age was 70 (range 28–92). The macroscopic type of gastric cancer was classified as 0/1/2/3/4/5 in 59/11/22/38/16/4 patients, respectively. Seventy‐one patients (47.3%) were diagnosed with intestinal‐type cancer, while 76 patients (50.7%) were diagnosed with the diffuse type. The mean numbers of cells with EpCAM−CK+, EpCAM+CK−, EpCAM+CK+, EpCAM−CEA+, EpCAM+CEA−, and EpCAM+CEA+ were 618, 237, 19.9, 1147, 291, and 7.41, respectively. The number of EpCAM−CEA+cells was significantly higher in patients with stage II–III and IV than in patients with stage I. The 3‐year RFS rate in patients with a high number of EpCAM−CEA+cells (>=622) was 57.5%, while it was 79.3% in patients with a low number of EpCAM−CEA+cells (

Abstract Background Iron is required for the proliferation of cancer cells, and its depletion suppresses tumor growth. Eribulin mesylate (eribulin), a non-taxane microtubule inhibitor, disrupts the tumor microenvironment via vascular remodeling and obstruction of the epithelial-mesenchymal transition (EMT). Herein, we investigated the effects of the iron chelator on tumor-related properties of breast cancer cells and the effects of iron chelator plus eribulin on tumor growth in vivo. Methods Two triple-negative breast cancer (TNBC) cell lines, MDA-MB-231 and BT-549, and one hormone-receptor positive breast cancer cell line, MCF-7, were used in our study. Cell proliferation, cell migration, cell cycle position, and gene expression were analyzed via MTT assays, wound-healing assays, flow cytometry, and quantitative real-time-polymerase chain reaction, respectively. For the in vivo experiments, mice with breast cancer xenografts were treated with the inhibitors, alone or together, and tumor volume was determined. Results Iron chelator inhibited breast cancer cell proliferation and decreased the proportion of S-phase cells. Conversely, it induced hypoxia, angiogenesis, EMT, and immune checkpoints, as determined by quantifying the expression of marker mRNAs in MDA-MB-231 and MCF-7 cells. Eribulin suppressed the expression of the hypoxia and EMT related marker mRNAs in the presence of iron chelator. Iron chelator plus eribulin inhibited tumor growth in vivo to a greater extent than did either inhibitor alone. Conclusions Although iron chelator induces oncogenic events (hypoxia, angiogenesis, EMT, and immune checkpoints), it may be an effective treatment for breast cancer when administered in combination with eribulin.

Abstract Although the incidence of hematological toxicity due to Trifluridine/tipiracil (FTD/TPI) treatment is high, the incidence of severe adverse events has been reported to be relatively low. However, it should be noted that patients with renal impairment are prone to severe hematological adverse events.

Abstract Background Invasion is often found during postoperative pathological examination of cases diagnosed as ductal carcinoma in situ (DCIS) by histological examinations such as core needle biopsy (CNB) or vacuum-assisted biopsy (VAB). A meta-analysis reported that 25.9% of invasive ductal carcinoma (IDC) cases are preoperatively diagnosed by CNB as DCIS. Risk factors for invasion have been studied by postoperative examination, but no factors have been found that could be obtained preoperatively from blood tests. In this study, we investigated factors predictive of invasion based on preoperative blood tests in patients diagnosed with DCIS by preoperative biopsy. Methods In this study, 118 patients who were diagnosed with DCIS by preoperative biopsy were included. Biopsies were performed with 16-gauge CNB or VAB. Peripheral blood was obtained at the time of diagnosis. This study evaluated absolute platelet count, absolute lymphocyte count, lactate dehydrogenase, carcinoembryonic antigen, and cancer antigen 15–3 (CA15–3). The platelet–lymphocyte ratio (PLR) was calculated by dividing the absolute platelet count by the absolute lymphocyte count, and patients were grouped into high PLR (≥160.0) and low PLR (

Abstract Background Liver abscess due to gastrointestinal perforation by foreign bodies is rare. Furthermore, there are few case reports of liver abscess via the portal vein caused by perforation of the lower gastrointestinal tract by a foreign body. Case presentation A 54-year-old man visited our hospital because of a fever that had lasted for 1 month. There were no physical findings except for the fever. Laboratory tests showed only elevated inflammatory markers. Abdominal contrast-enhanced computed tomography revealed an abscess in the right lobe of the liver and a high-density object in the small intestine. We diagnosed him with liver abscess secondary to intestinal perforation by a foreign body. The patient underwent drainage of the liver abscess and laparoscopic surgery for perforation of the small intestine. A fish bone had perforated the top of Meckel’s diverticulum, which had been covered by the ileal mesentery. We successfully performed diverticulectomy and removed the fish bone. The patient was discharged without complications on the 13th postoperative day. Conclusions Liver abscess caused by foreign bodies requires multidisciplinary treatment, so we must detect and remove the cause of the abscess earlier. Liver abscess can form via the portal vein secondary to lower gastrointestinal perforation, as in this case. When exploring the cause of liver abscess, we should investigate the whole body, including the lower gastrointestinal tract.

Abstract Background Lymph node metastasis is more likely in early-stage breast cancer with lower tumor-infiltrating lymphocyte (TIL) density. Therefore, we investigated the correlation between TILs and lymph node metastasis in cT1 breast cancer patients undergoing surgery and the usefulness of TILs in predicting sentinel lymph node metastasis (SLNM) in cT1N0M0 breast cancer. Methods We investigated 332 breast cancer patients who underwent surgery as the first-line treatment after preoperative diagnosis of cT1. A positive diagnosis of SLNM as an indication for axillary clearance was defined as macrometastasis in the sentinel lymph node (SLN) (macrometastasis: tumor diameter > 2 mm). Semi-quantitative evaluation of lymphocytes infiltrating the peritumoral stroma as TILs in primary tumor biopsy specimens prior to treatment was conducted. Results For SLN biopsy (SLNB), a median of 2 (range, 1–8) SLNs were pathologically evaluated. Sixty cases (19.4%) of SLNM (macrometastasis: 46, micrometastasis: 16) were observed. Metastasis was significantly greater in breast cancers with tumor diameter > 10 mm than in those with diameter ≤ 10 mm (p = 0.016). Metastasis was significantly associated with lymphatic invasion (p

Abstract Background Although many studies have identified several inflammation-based and/or nutritional markers with prognostic value for patients with various types of cancer, the optimal markers and cut-off values for these markers remain obscure. Therefore, this retrospective study aimed to identify optimal markers and their cutoffs. Methods We compared prognostic values among established preoperative inflammation-based and/or nutritional markers in 225 patients who underwent R0 resection for stage III gastric cancer. Inflammation-based and/or nutritional markers comprised C-reactive protein to albumin ratio (CAR), neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR), prognostic nutritional index (PNI), Glasgow prognostic score (GPS), and prognostic index (PI). Time-dependent receiver operating characteristic curves were analyzed to assess predictive ability and to determine the optimal cut-off values. Prognostic factors predicting overall survival (OS) and cancer specific survival (CSS) were analyzed using Cox proportional hazards models. Results Multivariate analyses revealed that CAR and PLR cut-off values of 0.47 and 172, respectively, were independent prognostic factors for overall survival (OS) (HR, 2.257; 95% CI, 1.180–4.319; p = 0.014 and HR, 1.478; 95% CI, 1.025–2.133; p = 0.037, respectively) and cancer-specific survival (CSS) (HR, 2.771; 95% CI, 1.398–5.493; p = 0.004 and HR, 1.552; 95% CI, 1.029–2.341; p = 0.036, respectively). These results were different from those we previously reported in patients with stage II. Conclusions Among inflammation-based and/or nutritional markers, CAR and PLR were independent prognostic factors of OS and CSS in patients with stage III gastric cancer. The optimal markers and their cut-off values should be determined in specific populations.

Cowden syndrome is extremely rare and is characterized by multiple hamartomas in various tissues, including the skin, mucous membranes, gastrointestinal tract, breast, thyroid, and brain, and has an increased risk of breast, thyroid, and uterine cancers. Here, we report a case of Cowden syndrome diagnosed following presentation with bilateral breast cancer and provide a discussion of the relevant literature. A 47-year-old woman with a tumor in her right breast was referred to our hospital. She was diagnosed with bilateral breast cancer upon imaging and underwent a bilateral mastectomy and sentinel lymph node biopsy. Previously, she had undergone total thyroidectomy to treat a thyroid tumor. Approximately 3 years later, she was diagnosed with Lhermitte-Duclos disease affecting her left cerebellar hemisphere. As her sister and mother had also been diagnosed with breast cancer, we suspected that she might have an inherited disease. Since 80% of individuals with Cowden syndrome have a mutation in the phosphatase and tension homolog (PTEN) gene, we did not perform any genetic testing. Instead, we used the syndrome’s pathognomonic criteria and major criteria (breast cancer, thyroid tumor, and Lhermitte-Duclos disease) to diagnose our patient with Cowden syndrome. While treatment of Cowden syndrome is currently limited to strategies that can manage the symptoms, patients are at an increased risk of certain cancers and require regular screening to allow for early detection of disease.

Abstract Background The selection of treatment for a patient with breast cancer largely relies on the cancer subtype. However, this process is complicated by changes in tumor biology at relapse. Smoking has been identified as a risk factor for breast cancer. The direct effect of a tobacco component delivered via blood circulation on the mammary gland tissue and subsequent DNA damage have been proposed to explain the association between cigarette smoking and breast cancer carcinogenesis. This postulation is supported by both tissue culture and animal studies demonstrating that the associated DNA damage further alters breast cancer cells, as indicated by an increased proliferative capacity and malignant transformation. In this study, we aimed to explore the relationship between changes in Estrogen receptor (ER), progesterone receptor (PgR), and human epidermal growth factor receptor 2 (HER2) each receptor at recurrence, and smoking and the prognosis after recurrence. Methods This retrospective study included 989 patients with primary breast cancer who developed relapse after surgery and 50 patients who underwent regenerative biopsy or surgery from December 2007 to March 2018. ER, PgR, and HER2 expression in the primary and recurrent lesions was evaluated using immunohistochemistry, and the correlations of these expression patterns with smoking history (pack-years) were examined. Results When ER was evaluated in recurrent tumors, negative and positive conversions were recognized in 3 (6.0%) and 1 patient (2.0%), respectively. When PgR was evaluated, negative conversion was recognized in 15 patients (30.0%). When HER2 was evaluated, positive conversion was recognized in 6 patients (12.0%). Consequently, we observed a change in the intrinsic subtype in in 5 patients with recurrent tumors (10.0%). Although most clinical factors were not correlated with smoking, a positive conversion of HER2 in recurrence was significantly more frequent among smokers than among non-smokers (p = 0.024). Conclusions Biological changes during breast cancer recurrence should be given careful clinical consideration because they affect treatment after recurrence. Our results suggest that smoking may induce increased HER2 expression in recurrent breast tumors.

Abstract Background We report a rare case of giant esophageal lipoma treated with thoracoscopic enucleation successfully. Case presentation A 69-year-old woman was referred to our department with dysphagia. Computed tomography examination revealed a large hypoattenuating submucosal mass with dense fat in the middle and lower esophagus. Upper gastrointestinal endoscopy revealed a submucosal mass with normal mucosa on the middle and lower esophageal wall. On a diagnosis of esophageal lipoma, we performed a video-assisted thoracoscopic operation and the 14.0 × 6.5 × 3.0 cm in size submucosal tumor was completely enucleated. We could successfully avoid a subtotal esophagectomy with high invasiveness. The patient was discharged on the 36th day after operation, and no symptoms had been noted. Conclusions Video-assisted thoracoscopic enucleation with minimal invasiveness may be an appropriate treatment option even for such a huge benign esophageal submucosal tumor.

Nivolumab, an immune checkpoint blocker, has been approved for advanced gastric cancer (GC), but predictive factors of nivolumab's efficacy in patients with GC, especially immune cells such as tissue-resident memory T cells or those forming tertiary lymphoid structures (TLS), remain unclear. Tissue samples were obtained from surgically resected specimens of patients with GC who were treated with nivolumab as third-line or later treatment. Immunohistochemical staining was performed to detect the presence of TLS and CD103+ T cells and assess the association between TLSs and response to nivolumab treatment. A total of 19 patients were analyzed. In patients with partial response (PR) to nivolumab, numerous TLS were observed, and CD103+ T cells were found in and around TLS. Patients with many TLS experienced immune-related adverse events more often than those with few TLS (p = 0.018). The prognosis of patients with TLS high was better than those with TLS low. Patients with a combination of TLS high and CD103 high tended to have a better prognosis than other groups. Our results suggested that TLS status might be a predictor of nivolumab effectiveness.

BackgroundWe reported that chemokine C-X-C motif receptor 2 (CXCR2) signaling appears to play an important role in the pathogenic signaling of gastric cancer (GC), and although CXCR2 may have a role in other solid cancers, the significance of CXCR2 in cholangiocarcinoma (CCA) has not been evaluated. Herein, we determined the clinicopathologic significance of CXCL1-CXCR2 signaling in CCA.Materials and methodsTwo human CCA cell lines, OCUG-1 and HuCCT1, were used. CXCR2 expression was examined by western blotting. We investigated the effects of CXCL1 on the proliferation (by MTT assay) and migration activity (by a wound-healing assay) of each cell line. Our immunohistochemical study of the cases of 178 CCA patients examined the expression levels of CXCR2 and CXCL1, and we analyzed the relationship between these expression levels and the patients' clinicopathologic features.ResultsCXCR2 was expressed on both CCA cell lines. CXCL1 significantly inhibited both the proliferative activity and migratory activity of both cell lines. CXCL1 and CXCR2 were immunohistochemically expressed in 73% and 18% of the CCA cases, respectively. The CXCL1-positive group was significantly associated with negative lymph node metastasis (p = 0.043). The CXCR2-positive group showed significantly better survival (p = 0.042, Kaplan-Meier). A multivariate logistic regression analysis revealed that CXCR2 expression (p = 0.031) and lymph node metastasis (p = 0.004) were significantly correlated with the CCA patients' overall survival.ConclusionCXCR2 signaling might exert a tumor-suppressive effect on CCA cells. CXCR2 might be a useful independent prognostic marker for CCA patients after surgical resection.

IntroductionIt 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.Patients and methodsFifty-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.ResultsAnastomotic 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.ConclusionA 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.

Adenoid cystic carcinomas (ACCs) are malignant tumors that most often occur in the salivary glands and bronchi, with occurrence in the breast being rare. ACCs of the breast reportedly give rise to few lymph node metastases or distant metastases and have a favorable prognosis. A 56-year-old woman with a left breast mass identified by mammographic screening was examined at our institute. Breast ultrasound revealed a sharply marginated, hypoechoic mass 12.7 × 9.4 × 8.7 mm in size in the upper outer quadrant of the left breast, and a vacuum-assisted biopsy (VAB) was performed at the mass site. Pathological examination of the VAB specimen revealed atypical cells with a cribriform growth pattern, and mucosal fluid surrounding tumor nests and within tumor ducts. The area around the tumor nests and inside of tumor ducts were also positively stained with alcian blue. These findings, we reached a pathological diagnosis of ACC. The preoperative diagnosis was stage I (cT1N0M0) triple-negative left breast cancer. Surgery consisted of breast-conserving surgery and sentinel node biopsy. The excised specimen was a 15.0 × 12.1 × 9.7 mm mass with a greyish white cut surface. Pathological examination of the excised specimen revealed a so-called adenoid cystic pattern. Results from immunohistochemical staining were identical to those from a VAB specimen, as they were estrogen receptor-negative, progesterone receptors-negative, and human epidermal growth factor receptor 2-negative, with low Ki67 expression. The final diagnosis, given the above findings, was left breast cancer (ACC) pT1N0M0 stage I triple-negative subtype.

Objective We evaluated the utility of continuous intraoperative neuromonitoring (CIONM) during surgery for thyroid cancer (TC) in an educational university hospital. Study Design Prospective observational study. Methods During the period April 2016 to March 2017, 43 patients who underwent standardized surgery with CIONM were prospectively included: 5 men and 38 women, 24–87 years old (median 52 years); 23 lobectomies and 20 total thyroidectomies with node dissection were conducted. Thirty‐six operations were performed by a supervising surgeon, and seven were performed by trainees. Results Temporal vocal cord paresis (VCP) was identified in 9 of 63 nerves at risk (14.3%) by postoperative laryngoscopy. VCP was not related to clinical factors including the surgeon's experience or the severe nerve stress demonstrated by CIONM. A significant relation only between VCP and loss of signal (LOS) was demonstrated (P = .002). The recovery of VCP was rapid (

Abstract Background In gastrectomy, postoperative elevation of C-reactive protein (CRP) is thought to be useful for predicting complications. Laparoscopic gastrectomy (LG) is less invasive than laparotomy and the elevation of CRP is also mild. Postoperative complications such as anastomotic leakage not only increase the severity of the condition, but also carry a poor prognosis when treatment is delayed. Early treatment is therefore necessary. Method This retrospective study examined the relationship between occurrence of complications and the ratio of CRP levels on postoperative days 1 and 3 (CRP ratio) for 449 gastric cancer patients who underwent LG in the Department of Gastrointestinal Surgery at Osaka City University Hospital between 2006 and 2016. Results We observed that factors associated with postoperative complications were preoperative renal failure and CRP ratio. No significant associations with surgical procedure, operation time, bleeding volume, age, obesity, measured CRP concentration, or white blood cell count were evident. The optimal cut-off for CRP ratio to predict postoperative complications from the receiver operating characteristic curve was 2.13. Conclusion Our results suggested that the risk of severe postoperative complications after LG could be predicted using the CRP ratio.

Pure mucinous breast carcinoma with micropapillary pattern (MUMPC) was proposed as a new histopathological variant of pure mucinous carcinoma (PMC) with tumor cells forming a micropapillary architecture. The Classification of Tumours of the Breast by the World Health Organization, however, does not differentiate MUMPC as a distinct subtype. There is currently no consensus whether tumors that exhibit these features are classified as PMC or invasive micropapillary carcinoma (IMPC) with associated mucin production. A 45-year-old woman was examined for a tumor in her left breast. Upon physical examination, an elastic hard mass of around 5 cm along with accompanying skin flare and ulceration was palpated in the upper outer quadrant of the left breast. Mammary ultrasonography revealed a clearly marginated hypoechoic tumor of 55.0 × 46.9 × 37.0 mm in size in the upper outer quadrant of the left breast. A vacuum-assisted biopsy (VAB) was performed in the same site and histopathological diagnosis of PMC was made. Contrast-enhanced magnetic resonance imaging (MRI) showed a T1W1 low-intensity signal and a T2W1 high-intensity signal at the primary focus, ring enhancement of the tumor margin, and stranding enhancement inside the tumor. A preoperative diagnosis of left breast cancer (PMC), cT4bN1M0, stage IIIB, luminal B-like was made. We performed a simple mastectomy with axillary lymph node dissection. A 55.0 × 48.1 × 37.1 mm tumor with the gelatinous cut surface was excised. Histopathological examination of the excised specimen revealed mucin lake formation in the tumor containing clusters of atypical cells. The atypical cells showed swollen, irregular nuclei and a papillary growth pattern that lead to the diagnosis of MUMPC.

Abstract Background A higher density of tumor-infiltrating lymphocytes (TILs) can lead to greater therapeutic effects and improved prognoses in cancer treatment. Similar results have been observed in breast cancer, particularly in triple-negative breast cancer (TNBC) and human epidermal growth factor receptor 2-enriched breast cancer. Calcium channel blockers (CCBs) are antihypertensive drugs (AHTs) that have also been reported to suppress the functions of T cells and macrophages. In this study, we evaluated TILs before pre-operative chemotherapy (POC) in breast cancer and retrospectively analyzed the correlation between CCBs and TILs or prognosis. Methods Of the patients treated with POC, 338 who had evaluable TILs were enrolled in this study. The correlations among TILs were evaluated according to standard methods, and CCB use and prognosis were investigated retrospectively. Results Before POC, 65 patients (19.2%) took AHTs (CCBs: 41/338, 12.1%). The TIL density was significantly lower among patients administered CCBs for the group of all patients and for patients with TNBC (p = 0.040, p = 0.009, respectively). Additionally, patients with TNBC who were administered CCBs showed significantly lower response rates for POC (p = 0.040). In all patients receiving POC, no significant differences in disease-free survival (DFS) or overall survival (OS) were observed in patients administered CCBs (p = 0.712, p = 0.478, log-rank tests, respectively). Furthermore, no significant differences were found, even in patients with TNBC (DFS: p = 0.441, OS: p = 0.727, log-rank tests, respectively). Conclusions In patients with TNBC undergoing treatment for hypertension with CCBs, TILs in the needle biopsy specimens before treatment were significantly lower, and the response rate of POC was not sufficient. Thus, the immunosuppressive effects of CCBs may also affect the immune microenvironment.

Abstract Background Pancreatic cancer is a refractory malignancy, and the development of a new effective treatment strategy is needed. We generated a dendritic cell vaccine by culturing monocytes obtained by apheresis of blood from each patient, inducing their differentiation into dendritic cells, and pulsing with tumor antigen peptides. However, the clinical efficacy of the vaccine has not been established. We therefore decided to conduct an exploratory clinical trial of dendritic cell vaccine loaded with Wilms’ tumor gene 1 peptides (TLP0-001) as a potential new treatment for patients with advanced pancreatic cancer refractory to standard chemotherapy. Methods This is an investigator-initiated, double-blind, comparative trial. The patients were allocated to two groups in a 1:1 ratio through a central registration by dynamic allocation. A total of 185 patients with inoperable or metastatic pancreatic cancer who were refractory or intolerant to standard primary chemotherapy with gemcitabine plus nab-paclitaxel will be allocated to secondary treatment either with placebo in combination with S-1 (the control group) or TLP0-001 in combination with S-1 (the investigational product group). The primary objective of this trial is to evaluate the safety and efficacy (as measured by overall survival) of the investigational product by comparing the two groups. This clinical trial will be performed in accordance with Japanese Good Clinical Practice guidelines. Discussion Clinical trials of the standard regimen, including gemcitabine, for advanced pancreatic cancer are ongoing worldwide. However, a strategy for after the primary treatment has not been established. We therefore decided to conduct this study to evaluate the safety and efficacy of TLP0-001 as a secondary treatment for pancreatic cancer in anticipation of the approval of this new drug in Japan. This trial is conducted with full consideration of safety, as it is the first-in-human clinical trial of TLP0-001; thus, the trial will be conducted only at the Second Department of Surgery at Wakayama Medical University until the safety is confirmed by interim analysis. We plan to conduct a multicenter trial at 18 institutions in Japan after confirmation of the safety. Trial registration University Hospital Medical Information Network Clinical Trials Registry, UMIN000027179. Registered on 9 April 2017.

Abstract Background Alveolar soft part sarcoma (ASPS) is an extremely rare neoplasm that tends to occur in the lower limbs of children and adolescents. Metastatic breast tumors constitute 0.5–2.0% of all malignant mammary neoplasms, and cases of ASPS with mammary metastases are very rare. Case presentation Three years ago, an 11-year-old girl presented to the hospital with pain in the right jaw after becoming aware of a mass in the right cheek. After detailed examination, the patient was diagnosed with ASPS with the primary tumor in the right cheek and multiple lung metastases, and chemotherapeutic treatment was initiated. One year later, accumulation of fluorodeoxyglucose (FDG) was observed in the right front of the skull (standardized uptake value (SUV)-max 2.8) and left breast (SUV-max 2.4) using FDG-positron emission tomography (PET) / computed tomography (CT). Ultrasonography revealed the mammary tumor as a hypoechoic, internally heterogeneous mass measuring 22.4 × 16.2 × 21.1 mm with a rich blood supply. Using pathological findings of core-needle biopsy, we diagnosed it as ASPS. Based on the above information, we made a diagnosis of ASPS with left mammary and cranial metastases. Due to chemoresistance, surgical excision was selected as the mode of treatment; resection of the metastatic cranial bone was performed first, and partial mastectomy of the left breast was performed in two stages. Postoperative conditions were good, and we are currently performing regular follow-ups (visual palpation every 3 months and semi-annual mammary gland ultrasonography). Conclusions We have reported an extremely rare case of ASPS with mammary metastasis with some reference-based discussion. In our case, disease control was obtained by a combination of drug therapy and surgical treatment.

Abstract Background Growing evidence indicates that inflammation contributes to cancer progression, and several inflammatory markers have been reported to be associated with the clinical outcomes in patients with various types of cancer. Recently, the advanced lung cancer inflammation index (ALI) has been developed as a prognostic marker in patients with lung cancer. The difference between the ALI and the inflammatory markers reported in the previous studies is that the ALI contains not only indices related to inflammation but also the body mass index (BMI), which was reported to correlate with the sarcopenic status. The aim of this study was to evaluate the prognostic significance of the ALI in patients with unresectable metastatic colorectal cancer. Methods We retrospectively reviewed a database of 159 patients who underwent combination chemotherapy for unresectable metastatic colorectal cancer between 2008 and 2016. The BMI was calculated by dividing the weight by height squared. The neutrophil-to-lymphocyte ratio (NLR) was calculated from a blood sample by dividing the absolute neutrophil count by the absolute lymphocyte count. The ALI was defined as follows: ALI=BMI × serum albumin concentration/NLR. Results The overall survival rate was significantly worse in the low-ALI group than in the high-ALI group (p

Abstract Background Pancreatic injuries are rare, and no treatment plan has yet been established for grade III injuries. In many cases, pancreatic stent placement has resulted in saving patients. However, some cases of perforation of a pancreatic duct during the placement of a stent have been described, and there are also a few cases of delayed perforation by a pancreatic stent. Case presentation A 62-year-old man had obstructive jaundice and pancreatitis due to locally advanced pancreatic head cancer. Both biliary and pancreatic stent were placed by endoscopy, after which chemoradiotherapy was performed. Four months later, he visited our hospital with severe abdominal pain. We performed enhanced CT and diagnosed the patient as having a perforation of a pancreatic duct by a pancreatic stent; therefore, we performed an emergency operation. Since we deemed pancreatectomy risky, we inserted pancreatic tubes into both sides of the perforated site and performed percutaneous transgastric drainage. The postoperative course was uneventful. We thereafter cut the tubes and switched to internal drainage. Conclusion Many cases of pancreatic injuries have reported that pancreatic stent placement results in saving the patient, but there have been few cases in which a pancreatic stent causes perforation of a pancreatic duct. External drainage by pancreatic tubes is very effective in resolving perforation of a pancreatic duct.

Abstract Background The immune tumor microenvironment (iTME) is thought to affect the response to chemotherapy, and tumor-infiltrating lymphocytes (TILs) are often used as an indicator to evaluate the iTME. Smoking is involved in carcinogenesis, the relationship between smoking and the iTME of lung cancer has been reported. We hypothesized that smoking would affect the iTME of breast cancer and aimed to examine this relationship based on the amount of pre-diagnosis smoking and the subsequent effects on treatment response and prognosis. Methods This retrospective study evaluated data from 149 patients who underwent preoperative chemotherapy for triple-negative or HER2-enriched breast cancer. TILs were assessed in biopsy specimens at diagnosis. The data of all patients were used to calculate each patient’s smoking amount based on pack-years. Results Relative to the low smoking group, the high smoking group had a significant greater TILs density (p = 0.043) and a significantly better pathological complete response (pCR) rate (p = 0.042). However, there was no significant difference according to smoking amount in disease-free survival (p = 0.114) or overall survival (p = 0.347). Conclusions Smoking may influence the iTME, with an activated iTME being associated with pCR rate. Therefore, controlled activation of the microenvironment in this setting may help improve patients’ prognosis.

Abstract Background The diagnosis of metastasis by sentinel lymph node biopsy (SLNB) in early breast cancer surgery provides an accurate view of the state of metastases to the axillary lymph nodes, and it has now become the standard procedure. In the present study, whether omission of axillary lymph node dissection (ALND) after neoadjuvant chemotherapy (NAC) is possible by evaluation of tumor-infiltrating lymphocytes (TILs) before NAC in cases without metastasis on diagnostic imaging, but with metastasis on SLNB, was retrospectively investigated. Methods A total of 91 patients with resectable, early-stage breast cancer, diagnosed as cT1–2, N0, M0, underwent SLNB and were treated with NAC. A semi-quantitative evaluation of lymphocytes infiltrating the peritumoral stroma as TILs in biopsy specimens of primary tumors prior to treatment was conducted. Results In cases with a low number of TILs, estrogen receptor expression was significantly higher (p = 0.044), and human epidermal growth factor receptor 2 (HER2) expression was significantly lower than in other cases (p = 0.019). The number of TILs was significantly lower in cases in which the intrinsic subtype was hormone receptor-positive breast cancer (HRBC) (p = 0.044). Metastasis to axillary lymph nodes was significantly more common in HER2-negative cases and cases with a low number of TILs (p = 0.019, p = 0.005, respectively). Conclusions Even if macrometastases are found on SLNB in cN0 patients, it appears that ALND could be avoided after NAC in cases with a good immune tumor microenvironment of the primary tumor.

Abstract Background The lymphocyte-to-monocyte ratio (LMR) has been used as a parameter reflecting systemic inflammation in several tumors, and is reportedly associated with prognosis in cancer patients. In this study, we evaluated the predictive value of LMR for progression and chemosensitivity in breast cancer patients treated with preoperative chemotherapy. Methods LMR was evaluated in 239 patients with breast cancer treated with neoadjuvant chemotherapy (NAC) with 5-fluorouracil, epirubicin, and cyclophosphamide, followed by weekly paclitaxel with or without trastuzumab, and subsequent curative surgery. The correlations between LMR and clinicopathological features, prognosis, and pathological complete response (pCR) rate of NAC were evaluated retrospectively. We also evaluated the predictive value of neutrophil-to-lymphocyte ratio (NLR), and compared the predictive values of LMR and NLR. Results We set 6.00 as the cut-off level for LMR based on the receiver operating characteristic (ROC) curve. A total of 119 patients (49.8%) were classified in the high-LMR group and 120 (50.2%) were classified in the low-LMR group. The low-LMR group had significantly worse disease-free survival rate (DFS) in all patients (p = 0.005) and in triple-negative breast cancer patients (p = 0.006). However, there was no significant correlation between LMR and pCR. Multivariate analysis showed that low LMR was an independent risk factor for DFS (p = 0.008, hazard ratio = 2.245). However, there was no significant difference in DFS (p = 0.143, log-rank) between patients in the low- and high-NLR groups. Conclusions LMR may be a useful prognostic marker in patients with breast cancer.

With advances in new cytotoxic drugs and molecular-targeted drugs, the prognosis of patients with metastatic colorectal cancer (mCRC) has improved. However, physicians often hesitate to administer intensive standard regimens to elderly patients with mCRC. Recently, first-line regimens that are effective in and well-tolerated by patients who are not eligible for intensive chemotherapy have been established. However, the therapeutic strategies to adopt after the failure of first-line treatment for patients who are not eligible for intensive chemotherapy remain unclear. We herein report two cases of long-term control of mCRC via FTD/TPI+bevacizumab (Bmab) as second- or third-line treatment in elderly patients without severe adverse events. In case 1, first-line treatment with Tegafur-Uracil, which is a prodrug of 5-FU, caused disease progression in a short period after the initiation of chemotherapy. In case 2, intensive first-line treatment caused severe adverse events, and treatment was discontinued. However, in both cases, disease control was obtained for a long time without severe adverse events by subsequent treatment with FTD/TPI+Bmab. The success in these present cases indicates that FTD/TPI+Bmab as a second- or third-line treatment is a therapeutic option for elderly patients with mCRC who are not eligible for intensive chemotherapy, even after failure of treatment with 5-FU.

Abstract Background The prognosis of breast cancer and the treatment response to neoadjuvant chemotherapy (NAC) differ depending on the intrinsic molecular subtypes. We evaluated the prognostic significance of immunohistological subtypes in patients with recurrent breast cancer after treatment with NAC and surgery. Methods A total of 237 patients with breast cancer treated with NAC and subsequent curative surgery between 2007 and 2015 were analyzed. The correlation between intrinsic molecular subtypes and clinicopathological features, prognosis, and pathological complete response (pCR) rate of NAC were investigated retrospectively. Results There were 55 (23.2%) patients with recurrence after surgery. No significant difference in post-recurrence survival (PRS) was noted among the subtypes (p = 0.397). In patients with estrogen receptor-positive human epidermal growth factor receptor (HER) 2-negative (luminal) malignancy, PRS was significantly better in the pCR group than in the non-pCR group (p = 0.031). Conversely, pCR was not a significant predictor of improved PRS in patients with triple-negative breast cancer (TNBC; p = 0.329). Multivariate analysis revealed that the efficacy of NAC [hazard ratio (HR) 300.204, p