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Abstract Background/Aim The effectiveness of a transanal drainage tube (TAT) for the prevention of anastomotic leakage after double stapling technique (DST) anastomosis in colorectal cancer has been reported. Previously, TATs had been placed and connected to drainage bags. It was considered that a higher decompression effect could be expected by inserting an open-type TAT, without connection to a drainage bag. In this study, the relation between anastomotic leakage and the application of this type of TAT in left-sided colorectal cancer surgery was investigated, using propensity score matching (PSM). Materials and methods From January 2016 to July 2023, 233 consecutive patients underwent radical surgery for sigmoid colon and rectal cancers and reconstruction using DST at Osaka Metropolitan University Hospital. Patients were divided into two groups: those who had a closed TAT inserted (CLOSED group), and those who had an open TAT inserted (OPEN group). Results Overall, open TATs were inserted in 43 patients, and closed TATs were inserted in 190 patients. PSM was performed between the OPEN and CLOSED groups on the basis of the following 13 factors: age, sex, BMI, diabetes mellitus (DM), smoking history, modified Glasgow prognostic score (mGPS), ASA-PS, location of distal tumor edge, operative procedure, surgical approach, operative time, intraoperative blood loss, and pathological stage. The multivariate analysis of significant factors identified a BMI of 25 or more, a location of distal edge on middle to lower rectum, and a closed TAT, as independent risk factors for anastomotic leakage (HR: 8.72; p = 0.038, HR: 10.06; p = 0.034 and HR: 17.43; p = 0.033). Conclusion An open TAT may be effective in preventing anastomotic leakage in left-sided colorectal cancer surgery.

Abstract Background The number of older patients with cancer is increasing with the progression of aging societies. In the current study, we sought to clarify the prognostic values of the geriatric nutritional risk index (GNRI) as a nutritional index and the neutrophil-to-lymphocyte ratio (NLR) as an inflammatory index in older patients with gastric cancer. Methods Between January 2007 and December 2016, a total of 197 consecutive gastric cancer patients aged ≥ 75 years who underwent radical gastrectomy were enrolled in this study. The prognostic values of preoperative GNRI and NLR were assessed using time-dependent receiver operating characteristic curve analysis, log-rank tests, and Cox regression analysis. Results The areas under the curve (AUCs) predicting 5-year overall survival (OS) were 0.668 for GNRI and 0.637 for NLR. The 5-year OS rates in the groups with low GNRI and NLR were 40.1% and 74.1% (p

Abstract Background Robotic-assisted surgery is steadily becoming more prominent. The majority of reports regarding port site hernias (PSHs) have involved laparoscopic procedures. Currently, it is common to suture the fascia at port sites that are 10 mm or larger; however, the closure of 5-mm port sites is not considered mandatory. The da Vinci® surgical system (Intuitive Surgical Inc., Sunnyvale, CA, USA) utilizes a distinctive 8-mm port. We report a case of an early-onset PSH at an 8-mm port site after robotic-assisted ileocecal resection. Case presentation A 74-year-old male patient with a body mass index of 19.7 kg/m2 was diagnosed with cecal cancer and underwent robotic-assisted ileocecal resection. A 3-cm midline incision was made at the umbilicus for insufflation. Under laparoscopic visualization, three ports (12 mm, 8 mm, and 8 mm) were inserted in the lower abdomen. An 8-mm port was inserted in the left subcostal region, and a 5-mm port was inserted in the left lateral abdomen. The procedure was performed without significant intraoperative complications. The fascia was closed only at the umbilicus and 12-mm port site; the fascia at the 8-mm port sites was not closed. The patient was initially discharged without complications; however, on postoperative day 11, the patient was urgently hospitalized again because of PSH incarceration. After manual reduction, the fascia was sutured closed under local anesthesia. The hernial defect was small and barely allowed the insertion of a little finger. There was no evidence of compression or significant damage to the fascia. On postoperative day 27, the patient was discharged after experiencing good recovery. Conclusions Robotic-assisted colectomy could contribute to the risk of PSHs because of its surgical characteristics. Although routine closure of the fascia at 8-mm port sites is not mandatory, it may be beneficial in certain cases.

Abstract Purposes Subtotal esophagectomy for esophageal cancer (EC) is associated with high morbidity rates. Tight glycemic control using an artificial pancreas (AP) is one of the promising strategies to reduce postoperative inflammation and morbidities. However, the effects of tight glycemic control using AP in patients with EC are yet to be fully elucidated. Method This study reviewed 96 patients with EC who underwent subtotal esophagectomy. The postoperative inflammation parameters and morbidity rates were compared between patients who used the AP (n = 27) or not (control group, n = 69). AP is a closed-loop system that comprises a continuous glucose monitor and an insulin pump. Results The numbers of white blood cells (WBC) and Neutrophils (Neut) were noted to be lower in the AP group than in the control group, but with no significant difference. The ratio in which the number of WBC, Neut, and CRP on each postoperative day (POD) was divided by those tested preoperatively was used to standardize the results. The ratio of WBC and Neut on 1POD was significantly lower in the AP group than in the control group. The rate of surgical site infection was lower in the AP group than in the control group. Conclusion AP significantly decreased WBC and Neut on 1POD; this suggests the beneficial effects of AP in alleviating postoperative inflammation.

Abstract Background Gastric cancer is primarily treated by surgery; however, little is known about the changes in the intraperitoneal immune environment and the prognostic impact of surgery. Surgical stress and cancer-associated inflammation cause immune cells to mobilize into the abdominal cavity via numerous cytokines. One such cytokine, CX3CR1, has various immune-related functions that remain to be fully explained. We characterized the intraperitoneal immune environment by investigating CX3CR1+ cells in intraperitoneal lavage fluid during gastric cancer surgery. Methods Lavage fluid samples were obtained from a total of 41 patients who underwent gastrectomy. The relative expression of various genes was analyzed using quantitative real-time PCR. The association of each gene expression with clinicopathological features and surgical outcomes was examined. The fraction of CX3CR1+ cells was analyzed by flow cytometry. Cytokine profiles in lavage fluid samples were investigated using a cytometric beads array. Results CX3CR1high patients exhibited higher levels of perioperative inflammation in blood tests and more recurrences than CX3CR1low patients. CX3CR1high patients tended to exhibit higher pathological T and N stage than CX3CR1low patients. CX3CR1 was primarily expressed on myeloid-derived suppressor cells and tumor-associated macrophages. In particular, polymorphonuclear myeloid-derived suppressor cells were associated with perioperative inflammation, pathological N, and recurrences. These immunosuppressive cells were associated with a trend toward unfavorable prognosis. Moreover, CX3CR1 expression was correlated with programmed death–1 expression. Conclusions Our results suggest that CX3CR1+ cells are associated with an acute inflammatory response, tumor-promotion, and recurrence. CX3CR1 expression could be taken advantage of as a beneficial therapeutic target for improving immunosuppressive state in the future. In addition, analysis of intra-abdominal CX3CR1+ cells could be useful for characterizing the immune environment after gastric cancer surgery.

Abstract Background Immune checkpoint inhibitors (ICIs), including nivolumab, have been approved to treat esophageal cancer. However, these remedies are not fit for all patients with esophageal cancer; therefore, a predictive surrogate marker is needed to assess their effectiveness. CD103+CD8+ tumor-infiltrating lymphocytes, defined as tissue-resident memory T cells (TRM), are promising indicators of response to ICIs, but it remains to be elucidated. This study investigated the association between the efficacy of ICIs and TRM. Methods The relationships between TRM infiltrating esophageal cancer, clinicopathological features, and prognosis after nivolumab initiation were examined using immunostaining. Tissue samples were obtained from surgically resected specimens of 37 patients with esophageal cancer who received nivolumab as a secondary or subsequent therapy. In addition, TRM infiltration was compared with programmed death-ligand 1 (PD-L1) expression and blood count parameters as predictors of nivolumab effectiveness. Results TRM-rich patients had a significant survival benefit after nivolumab initiation (12-months overall survival 70.8% vs 37.2%, p = 0.0485; 12-months progression-free survival 31.2% vs 0%, p = 0.0153) and experienced immune-related adverse events more frequently than TRM-poor patients (6 vs 2 patients). TRM infiltration was weakly correlated with PD-L1 positivity (r = 0.374, p = 0.022), but TRM may indicate more sensitive response to ICIs than PD-L1 expression in this study. Some blood test parameters also weakly correlated with TRM but did not impact prognosis. Conclusions TRM-rich patients have a favorable prognosis after nivolumab initiation. Our results suggest that TRM are vital for antitumor immunity and are a promising predictor of ICIs effectiveness.

Abstract Background Thoracic duct cysts are extremely rare mediastinal tumors. We report a case of a thoracic duct cyst extending from the caudal aspect of the left main bronchus to the left renal artery that was safely and completely resected via bilateral thoracoscopic surgery in the prone position. Case presentation A 77-year-old male was referred to our hospital for follow-up computed tomography (CT) of prostate cancer, which revealed a mediastinal tumor and fatty low-density along the posterior mediastinum of the para-aortic artery with a slightly high-density component. Magnetic resonance imaging revealed a T2-weighted image with high intensity. The preoperative radiological diagnosis was lipoma or well-differentiated liposarcoma. CT in the prone position suggested that the tumor could be resected from the thoracic cavity to the caudal side, and bilateral thoracoscopic surgery was performed in the prone position. Based on the surgical findings, the tumor was diagnosed as a thoracic duct cyst rather than a lipoma. Dissection around the thoracic duct cyst was performed using a vessel-sealing system to prevent leakage of the chyle, and reliable clipping was performed to resect the cisterna chyli. Histopathological examination revealed smooth muscle structures around the cyst, suggestive of a thoracic duct cyst. The diagnosis of a thoracic duct cyst was made based on a high triglyceride level of 1310 mg/dL on examination of the milky-white cyst fluid. The patient's postoperative course was uneventful, and he was discharged 4 days postoperatively. A CT scan performed 13 months after surgery showed no recurrence. Conclusions A rare thoracic duct cyst extending from the mediastinum to the cisterna chyli was safely and completely resected using bilateral thoracoscopic surgery, with the patient in the prone position.

BackgroundSubtotal esophagectomy with lymph node dissection followed by neoadjuvant chemotherapy (NAC) is the standard treatment for stage II-III esophageal cancer. Esophagectomy is still associated with high morbidity rates, and reducing these rates remains challenging. Among several complications, postoperative pneumonia (PP) is sometimes fatal, which has been reportedly caused by sarcopenia. Thus, nutritional support and rehabilitation may be promising for preventing skeletal muscle mass loss and reduce the incidence of PP.MethodsThis single-center, randomized, open-label, pilot trial will randomize a total of 40 patients with esophageal cancer in a 1:1 ratio either to ISOCAL Clear + rehabilitation arm or only rehabilitation arm. Although all patients will be educated about rehabilitation by a specialized physician and will be asked to undergo the prespecified rehabilitation program, patients treated with ISOCAL Clear + rehabilitation arm will be supplemented by 400 mL of ISOCAL Clear (Nestlé Japan Ltd, Tokyo, Japan) per day during two courses of NAC with docetaxel, cisplatin, and fluorouracil. Body composition will be assessed using Inbody (Inbody Co., Ltd., Tokyo, Japan) just before starting NAC and surgery. The primary endpoint is the change of skeletal muscle index (SMI) during NAC. Secondary endpoints include (i) body weight, total skeletal muscle mass, appendicular skeletal muscle mass, and lean body mass index changes; (ii) the percentage of ISOCAL Clear continuation; (iii) appetite evaluation; (iv) the percentage of targeted calorie achievement; (v) adverse events of NAC; (vi) postoperative complication rates; and (vii) postoperative hospital stay.DiscussionThis prospective trial assesses the efficacy of nutritional support in addition to rehabilitation during NAC for patients with esophageal cancer. The results will be utilized in assessing whether the effects of nutritional support by ISOCAL Clear are promising or not and in planning future larger clinical trials.

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 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 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.

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.

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.

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.

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.

BackgroundGastric cancer (GC) patients frequently develop peritoneal metastasis. Recently, it has been reported that peritoneal mesothelial cells (PMCs) activated by GC cells acquire a migratory capacity and promote GC cell invasion. The invasiveness of PMCs reportedly depends on the activity of Tks5, an adaptor protein required for invadopodia formation. However, the relationship between clinicopathologic features and Tks5 expression in PMCs has been poorly documented. In this study, we evaluated the clinicopathologic significance of the Tks5 expression of PMCs in GC patients.Materials and methodsA total of 110 GC patients who underwent gastrectomy were enrolled in this study. Tks5 expressions in PMCs from the greater omentum, lesser omentum and retroperitoneum were evaluated by immunohistochemistry. We analyzed the correlation between Tks5 expressions in PMCs and the patients' clinicopathologic features.ResultsTks5 expression was found in 71 (64.5%) of the 110 patients, while 39 (35.5%) were Tks5-negative. Tks5 positivity was significantly (p = 0.038) associated with a greater tumor depth (i.e., T3/4 compared with T1/T2). Peritoneal recurrence was found in 12 of 98 cases within 3 years of surgery. The 3-year peritoneal recurrence-free survival (PRFS) rate in Tks5-positive cases was significantly poorer than that in Tks5-negative cases (80.1% vs 97.4%, p = 0.024). Multivariate analysis revealed that Tks5 positivity and lymph node metastasis were independent factors for PRFS.ConclusionTks5 is frequently expressed in PMCs in advanced-stage gastric cancer. Tks5 might be a useful predictor for peritoneal recurrence in GC patients.

Abstract 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.

Abstract Background Common complications of pelvic fractures include visceral injury, large-volume hemorrhage, genitourinary injury, rectal injury, and pulmonary embolism. On the other hand, traumatic hernia is a rare complication, especially in association with pelvic fractures. We report a case of bowel perforation due to traumatic hernia at a pelvic fracture site. Case presentation A 65-year-old female was presented at our hospital for further examination and treatment of ileus. She was diagnosed with bowel perforation due to traumatic hernia at a pelvic fracture site, and an emergency operation was thus immediately performed. We performed segmental jejunum resection and constructed jejunostomy, and the iliac bone fracture was fixed with four pins. In the postoperative course, she received antibiotics and vasopressors for septic shock. However, there was no need for either a ventilator, dialysis or admission to the ICU. At seven days after the operation, a residual abscess was detected in the pouch of Douglas. We performed percutaneous drainage (Clavien-Dindo IIIa) and jejunostomy closedown 35 days after the first operation. The postoperative course was without complication, but she received rehabilitation until she was able to walk unaided. She was discharged 64 days after the first operation. Conclusion The occurrence of traumatic hernia is rare, especially in association with pelvic fractures. Although its rarity, traumatic hernia follows a severe course. Thus, proper diagnosis and effective treatment are necessary. Surgeons treating patients with pelvic injuries should consider the possibility of any complications and perform a work-up examination in order to achieve an accurate diagnosis at an earlier time point.

BACKGROUND:Peritoneal recurrence is one of the most frequent recurrent diseases in gastric cancer. Although the exposure of cancer cells to the serosal surface is considered a common risk factor for peritoneal recurrence, there are some cases of peritoneal recurrence without infiltration to the serosal surface even after curative surgery. This study sought to clarify the risk factors of peritoneal recurrence in the absence of invasion to the serosal surface. MATERIALS AND METHODS:Ninety-six patients with gastric cancer who underwent curative surgery were enrolled. In all 96 cases, the depth of tumor invasion was subserosal (T3). The microscopic distance from the tumor invasion front to the serosa (DIFS) was measured using tissue slides by H&E staining and pan-cytokeratin staining. E-cadherin expression was evaluated by immunohistochemical staining. RESULTS:Among the 96 patients, 16 developed peritoneal recurrence after curative surgery. The DIFS of the tumors with peritoneal recurrence (156±220 μm) was significantly shorter (p = 0.011) than that without peritoneal recurrence (360±478 μm). Peritoneal recurrence was significantly correlated with DIFS ≤234 μm (p = 0.023), but not with E-cadherin expression. The prognosis of DIFS ≤234 μm was significantly poorer than that of DIFS >234 μm (log rank, p = 0.007). A multivariate analysis of the patients' five-year overall survival revealed that DIFS ≤234 μm and lymph node metastasis were significantly correlated with survival (p = 0.005, p = 0.032, respectively). CONCLUSION:The measurement of the DIFS might be useful for the prediction of peritoneal recurrence in T3-gastric cancer patients after curative surgery.

[This corrects the article DOI: 10.1371/journal.pone.0225958.].

INTRODUCTION:Thrombospondin-4 [1] is an extracellular glycoprotein involved in wound healing and tissue remodeling. Although THBS4 is reportedly frequently expressed in solid tumors, there are few reports of the clinicopathological features of carcinomas with THBS4 expression. We evaluated the clinicopathologic significance of THBS4 expression in gastric carcinoma (GC). MATERIALS AND METHODS:We retrospectively analyzed the cases of 584 GC patients. The expression of THBS4 in each tumor was evaluated by immunohistochemistry. We then divided the patients into the THBS4-high (n = 223, 38.2%) group and THBS4-low (n = 361, 61.8%) group. THBS4 expression in cancer-associated fibroblasts (CAFs), normal-associated fibroblasts (NFs) and gastric cancer cell lines was examined by western blotting. RESULTS:THBS4 is expressed on stromal cells with αSMA or Podoplanin expression in the GC microenvironment, but not expressed on cancer cells with cytokeratin expression. The western blot analysis results showed that CAFs (but not NFs and cancer cells) expressed THBS4. Compared to the THBS4-low expression status, the THBS4-high expression status was correlated with higher αSMA expression, higher invasion depth, lymph-node metastasis, lymphatic invasion, peritoneal cytology, peritoneal metastasis, larger tumor size, microscopic diffuse type, and the macroscopic diffuse infiltrating type. The THBS4-high group's 5-year overall survival rate was significantly poorer than that of the THBS4-low group. A multivariate analysis revealed that THBS4 expression was an independent prognostic factor. CONCLUSION:THBS4 is expressed on CAFs in the gastric cancer microenvironment. THBS4 from CAFs is associated with the metastasis of cancer cells, and is a useful prognostic indicator for gastric cancer patients.

Background/Aim: Despite the remarkable developments in chemotherapy for gastric cancer (GC), rapid tumor growth is sometimes experienced during chemotherapy. This study investigated the association of tumor growth rate (TGR) during second-line chemotherapy with the prognosis of patients with GC. Patients and Methods: We retrospectively reviewed 29 patients with GC treated with nab-paclitaxel plus ramucirumab as second-line chemotherapy between 2017 and 2019 at Osaka Metropolitan University. Of them, 13 cases with target lesions were classified into two groups according to TGR using a cutoff value of 0.25. Clinicopathological factors and survival outcomes were compared between the high TGR (n=5) and low TGR (n=8) groups. Results: The median duration of first-line chemotherapy was significantly longer in the high TGR group than in the low TGR group [median 298 days vs. 72.5 days, p=0.030]. Progressive disease (PD) was observed in 60% of patients with high TGR, whereas stable disease (SD) was observed in 75% patients with low TGR. The median survival time (MST) after starting chemotherapy was 488 days in the low TGR group but was not reached in the high TGR group (log rank p=0.215). The MST after PD was 145 days in the low TGR group but was not estimated in the high TGR group (log rank p=0.345). Conclusion: Based on the absence of significant differences in survival outcomes between the high and low TGR groups, sequential late-line chemotherapy might be considered important, even for patients with high TGR. [ABSTRACT FROM AUTHOR]