The safe removal of a superior mediastinal foreign body by mediastinoscopy: a case report.

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.

Significance of tumor heterogeneity of p-Smad2 and c-Met in HER2-positive gastric carcinoma with lymph node metastasis.

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.

Clinical relevance of tertiary lymphoid structures in esophageal squamous cell carcinoma.

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.

CD103+ T Cells May Be a Useful Biomarker in Borrmann Type 4 Gastric Cancer.

BACKGROUND/AIM: Recently, several studies have reported that CD103 +  T cells are associated with antitumor immunity in gastric cancer (GC). However, the significance of CD103 +  T cells in Borrmann type 4 GC remains unclear. The aim of this study is to assess the association of CD103 + T cells with type 4 GC. MATERIALS AND METHODS: Tissue samples obtained from surgically resected specimens of patients with type 4 GC were collected, and immunohistochemical staining was performed to detect the presence of CD103 + T cells. RESULTS: A total of 46 patients were analyzed. In some patients, high CD103 expression was observed, and patients with high CD103 expression tended to have a better prognosis than those with low CD103 expression. In particular, for patients who receive doublet chemotherapy after surgery, high CD103 expression was associated with a good prognosis. CONCLUSION: CD103 + T cells may be a prognostic marker in type 4 GC.

Prognostic impact of postoperative systemic inflammatory response in patients with stage II/III gastric cancer.

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 < 0.001, p < 0.001 and p = 0.011, respectively) and relapse-free survival (RFS) (p < 0.001, p = 0.001 and p < 0.001, respectively). Multivariate analysis revealed that high-CRPmax (> 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.

Clinical efficacy of nivolumab is associated with tertiary lymphoid structures in surgically resected primary tumors of recurrent gastric cancer.

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.

Establishment of nedaplatin safety dose formula based on renal function for combination chemotherapy with nedaplatin and 5-fluorouracil in patients with esophageal cancer.

BACKGROUND: It is known that the area under the plasma concentration curve of nedaplatin (AUCNDP) is associated with the relative reduction ratio of platelets and that the AUCNDP is based on nedaplatin dose normalized by creatinine clearance (CrCL) (AUCdose/CrCL). Based on these relationships, in this retrospective study, we aimed to determine the unestablished doseNDP safe for patients with impaired renal function who received an initial combination chemotherapy with nedaplatin and 5-fluorouracil. METHODS: We performed a retrospective cohort analysis of consecutive patients with esophageal cancer who received an initial combination chemotherapy with ≤ 90 mg m-2 day-1 of nedaplatin on day 1 and 800 mg m-2 day-1 of 5-fluorouracil on days 1-5. AUCdose/CrCL was estimated using the formula, 3.2134 × doseNDP/CrCL + 4.4185. Data obtained during the first 28 days following nedaplatin administration were analyzed to compare AUCdose/CrCL between the patients with and without grade ≥ 3 thrombocytopenia. Receiver-operating characteristic (ROC) curve analysis was performed to determine the optimal AUCdose/CrCL cutoff value. RESULTS: Of the 136 patients included in this study, 8 (5.9%) presented with grade ≥ 3 thrombocytopenia. There were statistically significant differences in the AUCdose/CrCL between the patients with and those without grade ≥ 3 thrombocytopenia (11.79 vs. 10.09 µg h-1 mL-1; P = 0.00828). We found that the appropriate cutoff value for the AUCdose/CrCL using the ROC curve was 10.945 µg h-1 mL-1. CONCLUSIONS: Our results indicate that safe doseNDP should be estimated to satisfy the following formula: DoseNDP (mg) < CrCL × 2.031.

Impact of the COVID-19 Pandemic on Patients with Gastrointestinal Cancer Undergoing Active Cancer Treatment in an Ambulatory Therapy Center: The Patients' Perspective.

BACKGROUND: The mortality risk increases greatly in patients with cancer if they are infected with severe acute respiratory syndrome coronavirus 2. The new American Society of Clinical Oncology (ASCO) and the European Society of Medical Oncology (ESMO) guidelines for the COVID-19 pandemic suggested modifications to the standards of care to reduce harm from treatment. However, it is unclear whether these changes suit the wishes of patients. METHODS: We conducted a survey of patients with gastrointestinal cancer who were undergoing active chemotherapy in our ambulatory therapy center between 17 August and 11 September 2020. The survey comprised 18 questions on five topics: patient characteristics, lifestyle changes, disturbance in their psychological health, thoughts on the cancer treatment, and infection control in the hospital. RESULTS: Among the 63 patients who received the questionnaire, 61 participated in the study. The COVID-19 pandemic has led to changes in their lifestyles and substantially impacted their psychological wellbeing. The incidence of anxiety and insomnia has considerably increased during the pandemic. However, female patients and patients aged 70 years or older reported no notable differences. There was no significant difference in the responses to the questions regarding thoughts on the cancer treatment. CONCLUSION: Our study revealed that the COVID-19 pandemic has substantially impacted patients' lifestyles and psychological wellbeing. However, most patients preferred to continue their usual treatment without any change to their treatment plan. It is important to involve the patient in the decision-making process when formulating treatment goals.

Clinical significance of coexisting histological diffuse type in stage II/III gastric cancer.

Since 1965, the Laurén classification has been used most commonly for gastric adenocarcinoma, with two main types: intestinal type and diffuse type. Signet ring cell carcinoma (Sig) and non-solid poorly differentiated adenocarcinoma (Por2) are the histological forms of diffuse type that are often found in advanced tumors, and they seem to be associated with a poor prognosis. S-1-based adjuvant chemotherapy for patients with stage II/III gastric cancer has generally been accepted in Japan, but histological type does not alter treatment strategy. The aim of the present study was to investigate the prognostic impact of the histopathological mixture of Sig and Por2 in patients with stage II/III gastric cancer treated with S-1 adjuvant chemotherapy. The clinicopathological data of 968 patients with gastric carcinoma who underwent gastrectomy between 2007 and 2016 at Osaka City University Hospital were retrospectively analyzed. In the present study, tumors containing Sig or Por2 were classified as diffuse type, and those not containing them were classified as intestinal type. There were 307 cases of diffuse type and 661 cases of intestinal type. Diffuse type included 189 cases with Sig. A pathological diagnosis of Sig was an independent risk factor for peritoneal recurrence in patients with stage II/III gastric cancer. Patients with diffuse type had a worse overall survival rate than those with intestinal type at stage III gastric cancer. Among the patients who received S-1 adjuvant chemotherapy, the prognosis of patients with stage III gastric cancer with Sig but not Por2 was significantly worse compared with that of patients with intestinal type. Therefore, the present study revealed that the coexistence of Sig in the primary tumor was associated with a poor prognosis in patients with stage III gastric cancer. The current findings suggested that, since mixed Sig gastric cancer had a high risk of peritoneal recurrence even if adjuvant chemotherapy was performed, the pathological diagnosis should be considered when determining the therapeutic strategy for adjuvant chemotherapy in patients with stage III gastric cancer.

Preoperative C-reactive protein to albumin ratio predicts anastomotic leakage after esophagectomy for thoracic esophageal cancer: a single-center retrospective cohort study.

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.

The clinicopathologic significance of Tks5 expression of peritoneal mesothelial cells in gastric cancer patients.

BACKGROUND: Gastric 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 METHODS: A 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. RESULTS: Tks5 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. CONCLUSION: Tks5 is frequently expressed in PMCs in advanced-stage gastric cancer. Tks5 might be a useful predictor for peritoneal recurrence in GC patients.

The Optimal Definition of Sarcopenia for Predicting Postoperative Pneumonia after Esophagectomy in Patients with Esophageal Cancer.

BACKGROUND: Esophageal cancer (EC) is associated with malnutrition in the vast majority of patients, and this often leads to sarcopenia, which is characterised by loss of skeletal muscle mass (SMM). Although sarcopenia could be one of the risk factors for postoperative pneumonia (PP), the optimal definition of sarcopenia using skeletal muscle mass index (SMI) by bioelectrical impedance analysis (BIA) remains unknown for predicting PP after esophagectomy in patients with EC. Therefore, this study aimed to identify high-risk patients for PP after esophagectomy through evaluating SMI by BIA and set an appropriate cut-off value for this purpose. METHOD: A total of 73 patients with EC who underwent subtotal esophagectomy with lymph node dissection at Osaka City University Hospital between 2017 and 2019 were reviewed retrospectively. The association between PP and perioperative factors including SMI by BIA were analysed. When SMI was lower than the cut-off values proposed by two study groups (Asian Working Group for Sarcopenia (AWGS) and original European Working Group on Sarcopenia in Older People (EWGSOP)) or SMM was less than 90% of standard, the patient was diagnosed with sarcopenia. Receiver operating characteristic analysis was performed to set the appropriate cut-off value of SMI, and a new criterion (modified EWGSOP) was formulated by using the value. Clinicopathological factors and postoperative complications between sarcopenia and non-sarcopenia groups were compared, which were classified by four different criteria: (1) AWGS, (2) original EWGSOP, (3) < 90% standard and (4) modified EWGSOP criteria. RESULTS: Nine patients (12.3%) were with PP grade III or higher. Total SMI as well as body mass index (BMI), transthyretin and % vital capacity (%VC) were found to be significantly associated with PP (Clavien-Dindo grade ≥ III). BMI, total and appendicular SMI of sarcopenic patients were found to be lower than those of non-sarcopenic patients. Low serum albumin and %VC were significantly associated with sarcopenia defined by modified EWGSOP criteria. The rate of PP was significantly higher in sarcopenic patients when the original and modified EWGSOP criteria were used (p = 0.0079 and 0.0015, respectively). A multivariate analysis revealed that sarcopenic state by modified EWGSOP criteria was the significant independent predictive factor of PP [p = 0.0031, hazard ratio (HR) = 10.1; 95% confidential interval (CI): 2.12-76.9]. CONCLUSION: Preoperative sarcopenia by modified EWGSOP criteria could be the best indicator using BIA for predicting PP after esophagectomy in patients with EC.

Clinicopathologic significance of TROP2 and phospho-TROP2 in gastric cancer.

Trophoblast cell-surface antigen 2 (TROP2) is a transmembrane glycoprotein expressed in epithelial cells. Increased TROP2 expression has been reported to be associated with malignant progression in most carcinomas; however, TROP2 has a tumor-suppressive function in certain types of cancer. Since the function of TROP2 is controversial, the present study subsequently aimed to clarify the clinicopathologic significance of TROP2 and pTROP2 expression in human gastric cancer (GC). The cases of 704 patients with GC who underwent gastrectomy were retrospectively analyzed. The expression levels of TROP2 and pTROP2 in each tumor were evaluated by immunohistochemistry. The association between the clinicopathologic features of patients with GC and the levels of TROP2 and pTROP2 in their tumors was analyzed. Increased TROP2 and pTROP2 expression was identified in 330 (46.9%) and 306 (43.5%) of the 704 patients with GC, respectively. Increased TROP2 expression was associated with the histological intestinal type, high tumor invasion depth (T3/T4), lymph node metastasis, lymphatic invasion and venous invasion. By contrast, increased pTROP2 expression was associated with intestinal type, low tumor invasion depth (T1/2), no lymph node metastasis and no lymphatic invasion. Increased TROP2 expression was associated with poorer overall survival (OS) (P<0.01; log rank test), whereas increased pTROP2 expression was significantly associated with improved OS (P<0.01; log rank test). In conclusion, increased expression levels of TROP2, but not pTROP2, may be associated with the metastatic ability of GC, resulting in poor prognosis of patients with GC.

[A Case of the Large Rectal GIST Treated by Laparoscopic Anus Preserving Operation after Neoadjuvant Therapy with Imatinib Mesylate].

A 50s old woman admitted to our hospital with anal pain, who was diagnosed as rectal gastrointestinal stromal tumor (GIST). After neoadjuvant therapy with imatinib mesylate for 6 months, the tumor reduced by 75% from its original size and anus preserving operation(low anterior resection)was performed. After operation adjuvant therapy with imatinib mesylate was performed for 2 years and 6 months. The patient is alive without recurrence 5 years after surgery. It is suggested that neoadjuvant therapy with imatinib mesylate is useful and safety for large rectal GIST, from the standpoint of anal preservation.

Tertiary lymphoid structures show infiltration of effective tumor-resident T cells in gastric cancer.

Several studies have reported that tissue-resident memory T cells (TRM cells) or tertiary lymphoid structures (TLSs) are associated with a good prognosis. The aim of this study was to clarify the association of TRM cells and TLSs in the tumor immune microenvironment in gastric cancer (GC). We performed immunohistochemical and immunofluorescence staining to detect the presence of CD103+ T cells and to assess the association between CD103+ T cells and TLSs. CD103+ T cells were observed in the tumor epithelium accompanied by CD8+ T cells and were associated with a better prognosis in GC. Furthermore, CD103+ T cells were located around TLSs, and patients with CD103high had more rich TLSs. Patients who had both CD103high cells and who were TLS-rich had a better prognosis than patients with CD103low cells and who were TLS-poor. Moreover, for patients who received PD-1 blockade therapy, CD103high and TLS-rich predicted a good response. Flow cytometry was performed to confirm the characteristics of CD103+ CD8+ T cells and showed that CD103+ CD8+ T cells in GC expressed higher levels of PD-1, granzyme B, and interferon-γ than CD103- CD8+ T cells. Our results suggested that CD103+ CD8+ cells in GC are correlated with TLSs, resulting in enhanced antitumor immunity in GC.

Association between the preoperative neutrophil-to-lymphocyte ratio and tertiary lymphoid structures surrounding tumor in gastric cancer.

The neutrophil-to-lymphocyte ratio (NLR) has been reported to be associated with a poor prognosis in various types of cancer. We previously reported that an antitumor immune response was induced by tertiary lymphoid structures (TLSs) surrounding tumor, and increased TLS was an independent prognostic factor in patients with gastric cancer. The present study examined the stratification based on the correlation between the preoperative NLR and TLS density in gastric cancer. A total of 199 patients who underwent surgery for stage Ib-IV gastric cancer were included in the study. Receiver operating characteristic curve analysis was used to determine the appropriate cut-off values of the preoperative NLR and the TLS density. The prognostic factors were evaluated in a multivariate analysis. The median NLR was 2.18 (mean ± SD, 2.7±2.04). A total of 91 patients with an NLR ≥2.33 was classified into the high NLR group. The overall survival was significantly improved in patients with a low NLR than in those with a high NLR. Additionally, the low NLR group tended to have a high TLS density. The multivariate analysis indicated that the preoperative NLR and TLS density were independent risk factors. When the patients were classified into the high and low NLR and TLS groups and the survival rates were compared, the prognosis was significantly improved in the low NLR and high TLS group than in the other groups. The preoperative NLR may be associated with the presence of TLSs surrounding the tumor, and the combination of NLR and TLS may be useful for the stratification of patient prognosis. The present results suggested that the NLR and TLS density may be surrogate markers for immunotherapy against gastric cancer.

Induction of Immunogenic Cell Death of Esophageal Squamous Cell Carcinoma by 5-Fluorouracil and Cisplatin.

BACKGROUND/AIM: Neoadjuvant chemotherapy (NAC) using 5-FU (5-fluorouracil)/CDDP (cisplatin) is a standard therapy for stage II/III thoracic esophageal squamous cell carcinoma (ESCC) in Japan. The aim of this study was to investigate whether 5-FU/CDDP could induce immunogenic cell death in ESCC cell lines. MATERIALS AND METHODS: Tumor samples for immunohistochemistry were obtained from 50 patients (mean age=63.1 years) with pathological stage 0-IVa ESCC who underwent NAC followed by surgery. Cell lines T.T and KYSE30 were used for the in vitro experiments. RESULTS: The concentrations of HMGB1 were elevated in the cell line supernatants treated with 5-FU/CDDP. 5-FU/CDDP treated dendritic cells (DCs) showed a mature phenotype, and enhanced T cell proliferation capacity. In addition, mature DCs were observed in surgical specimens with a histological response after treatment with 5-FU/CDDP chemotherapy. CONCLUSION: 5-FU/CDDP could induce immunogenic cell death in the tumor microenvironment of ESCC.

Clinical benefit for clinical sequencing using cancer panel testing.

BACKGROUND: Clinical sequencing using a panel of genes has recently been applied worldwide for patients with refractory solid tumors, but the significance of clinical sequencing using gene panel testing remains uncertain. Here we sought to clarify the feasibility and utility of clinical sequencing in the treatment of refractory tumors at our hospital. METHODS: A total of 39 patients with advanced solid tumors treated at our hospital between 2018 and 2020 were enrolled in the clinical sequencing. Among them, we identified 36 patients whose tissue samples were of suitable quality for clinical sequencing, and we analyzed the genomic profiles of these tumors. RESULTS: Pathogenic alterations were detected in 28 (78%) of the 36 patients. The most common mutation was TP53 (55%), followed by KRAS (22%), and the highest frequency of gene amplification was ERBB2 (17%). Nine of the 36 patients were identified as candidates for novel molecular-targeted therapy based on their actionable gene alterations, but only one case ended up receiving novel targeted therapy following the genetic tests. CONCLUSIONS: Our current results suggested that clinical sequencing might be useful for the detection of pathogenic alterations and the management of additional cancer treatment. However, molecular target based on actionable genomic alteration does not always bridge to subsequent therapy due to clinical deterioration, refusal for unapproved drug, and complexity of clinical trial access. Both improved optimal timing of clinical sequencing and a consensus about its off-label use might help patients receive greater benefit from clinical sequencing.

The duration of systemic inflammatory response syndrome is a reliable indicator of long-term survival after curative esophagectomy for esophageal squamous cell carcinoma.

BACKGROUND: We focused on the Systemic Inflammatory Response Syndrome (SIRS) duration after surgery for esophageal squamous cell carcinoma (ESCC) as the prognostic marker. METHODS: We enrolled a total of 222 patients with local ESCC, who underwent curative esophagectomy between 2005 and 2015. SIRS was diagnosed according to the criteria as a condition involving two or more of the following factors after surgery: (a) body temperature of > 38 °C or < 36 °C; (b) heart rate > 90 beats/min; (c) respiratory rate > 20 breaths/min (d) WBC count > 12,000 or < 4000 cells/mm3. We defined SIRS duration as the total sum of the days defined as SIRS conditions during 7 days after surgery. The SIRS duration was analyzed by Cox hazards modeling to determine the independent prognostic factors for overall survival (OS) and Cancer-specific survival (CSS). RESULTS: The cutoff point of SIRS duration was determined to be set at 5.0 days according to the receiver operating characteristic (ROC) curve, which was plotted using 5-year OS as the endpoint. Of the 222 patients, 165 (74.4%) and 57 (25.6%) were classified as having short (< 5.0) and long (≥ 5.0) SIRS, respectively. The long SIRS was significantly associated with postoperative pneumonia (Hazard Ratio (HR):9.07; P < 0.01), great amount of blood loss during surgery (HR: 2.20: P = 0.04), preoperative high CRP value (HR: 2.45: P = 0.04) and preoperative low albumin (HR: 2.79: P = 0.03) by logistic-regression multivariate analysis. Cox Hazard Multivariate analyses revealed that long SIRS was a worse prognostic factor for OS (HR: 2.36; 95% Confidence Interval (CI):1.34-4.20, P < 0.01) and CSS (HR: 2.07; 95% CI:1.06-4.06, P = 0.03), while postoperative pneumonia and postoperative high CRP value were not worse prognostic factors for OS and CSS. CONCLUSION: SIRS duration is a more reliable prognostic marker than the development of pneumonia and high postoperative CRP value after surgery for ESCC. The surgeons should aim to reduce the SIRS duration to improve the prognosis of ESCC patients.

[Two Cases of Advanced and Recurrent Gastric Cancer with Long-Term Survival Due to Successful Chemotherapy].

Case 1: A 73-year-old man underwent total gastrectomy for residual gastric cancer, and final pathological diagnosis was pStage ⅠB. Adjuvant chemotherapy was not performed. CT findings showed multiple liver metastasis 16 months after procedure. S-1 and CDDP were administered for 28 months. Although chemotherapy regimen was changed to S-1, paclitaxel plus ramucirumab, nivolumab, irinotecan and S-1 plus oxaliplatin(SOX)after progression, he died 73 months after operation, and 57 months after recurrence. Case 2: A 72-year-old man was pointed out swelling of gastric lymph nodes in CT imaging. He was diagnosed as advanced gastric cancer with para-aortic lymph node metastasis by followed examination. S- 1 plus CDDP was administrated for 30 months. S-1 and SOX were administered after progressive findings, but he died 48 months after diagnosis. We report 2 cases of recurrent and advanced gastric cancer with long-term survival because of successful chemotherapy.