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.

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.

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.

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.

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.

[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.

[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.

[A Case of Hyperammonemic Encephalopathy following mFOLFOX6 plus Panitumumab Therapy for Rectal Cancer].

An 80-year-old man underwent laparoscopic rectal high anterior resection with perineal dissemination for the management of RS rectal cancer. Following the diagnosis of RS rectal cancer with muc, pT4a, N3(14/15), M1c, P1, pStage Ⅳc, RAS/BRAF: wild type, treatment was initiated with mFOLFOX6 plus panitumumab(Pmab). Laboratory examination on admission revealed mild renal dysfunction(Cr 1.45 mg/dL). The patient became confused on day 3 of chemotherapy(JCS Ⅲ-200). Furthermore, laboratory findings revealed a serum ammonia level of 338µg/dL. He was diagnosed with 5-FU- induced hyperammonemic encephalopathy. Discontinuation of high-dose 5-FU and branched-chain amino acid solutions improved his mental status and decreased serum ammonia levels. We switched his chemotherapy regime to CPT-11 plus Pmab, but it was discontinued after 1 course on his request.

[Effect of Upfront Dose Reduction in the First Cycle of Chemotherapy for Unresectable/Recurrent Gastric Cancers in Patients Aged Over 80 Years].

Chemotherapy for elderly patients requires ingenuity in treatment to mitigate its high risk. Therefore, we investigated an upfront dose reduction in the first cycle of chemotherapy for unresectable/recurrent gastric cancers in patients over 80 years old. We examined 6 patients over 80 years old, who underwent S-1 plus L-OHP therapy(SOX)for unresectable/recurrent gastric cancer in our department between January 2020 and January 2021. There were no adverse events over Grade 3 in the upfront dose reduction group(U group), while 1 case(50.0%)in the normal dose group(N group)experienced an adverse event over Grade 3. Moreover, only the U group continued treatment for 4 or more courses, whereas none from the N group did. Partial response(PR)was achieved as a therapeutic effect in 3 patients of the U group. Only 2 cases of the U group advanced to the second-line regimen and both were able to transition to the third-line regimen. However, none were able to even transition to the second-line regimen in the N group. Therefore, it was suggested that by reducing the dose of chemotherapy from the first cycle for elderly patients over 80 years old, the incidence of adverse events can be kept low, which makes it possible to continue long-term chemotherapy.

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.

Clinical significance of prognostic inflammation-based and/or nutritional markers in patients with stage III gastric cancer.

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.

[A Case of Advanced Rectal Cancer with Metastasis Successfully Treated with an Anti-Vascular Endothelial Growth Factor (VEGF) Drug].

A 63-year-old asymptomatic woman was diagnosed with multiple liver tumors and a left pulmonary tumor by CT. Colonoscopy( CS)showed a Type 2, quarter circular tumor on Rb. The diagnosis was cT3N1aM1b(H3, PUL1), cStage Ⅳb rectal cancer. She was administered 8 courses of induction-adjuvant chemotherapy with CAPOX and bevacizumab(BEV). After the chemotherapy, CT and CS revealed shrinkage(up to 50%)of the metastatic liver tumor and primary tumor, and decreasing tumor marker levels. Laparoscopic abdominoperineal resection and partial hepatectomy(S5/6, S8)were performed. After the operation, she was administered 2 courses of chemotherapy with UFT and LV, after which thoracoscopy-assisted upper lobectomy of the left lung was performed. Currently, at 1 and a half years after treatment, no recurrence has been observed, and she is being followed up as an outpatient.

[A Case of Advanced Gastric Cancer with Extensive Lymph Node Metastasis That Showed pCR to Preoperative Chemotherapy Containing SP].

A 69-year-old woman, who complained of appetite loss, was diagnosed with Type 3 gastric cancer, and a biopsy resulted in the diagnosis of adenocarcinoma(tub2-por), Group 5. Abdominal computed tomography (CT) revealed bulky metastatic lymph nodes around the stomach and the aorta. The diagnosis was cT4a, cN2, cM1(LYM), cStage ⅣB, and SP therapy(a combination of S-1 and cisplatin) was immediately administered. On the completion of 3 courses of SP therapy, both the primary tumor and lymph nodes markedly decreased in size. Based on this finding, D2 total gastrectomy, No. 16 lymph node dissection, splenectomy, and right adrenal tumor resection were performed. Histopathology showed no residual tumor cells in the stomach or lymph nodes. Postoperatively, she received S-1 therapy, which was discontinued on completion of the first course due to its side effects. She survived for over 7 years postoperatively without receiving chemotherapy and showed no recurrence.

[Biomarkers for Immunotherapy Based on the Local Microenvironment of Gastric Cancer].

Currently, the immunotherapy approved for gastric cancer is immune checkpoint blockade( ICB) therapy. The effects of ICB depend on the T cell-mediated immune response elicited at the cancer site. Based on the results of previous clinical trials, it is clear that an enhanced immune response to cancer improves prognosis. Thus, the development of biomarkers to predict local immune responses may increase the significance of future immunotherapy for gastric cancer. Biomarker research has clearly progressed with the rapid development of genetic analysis technologies, enabling the analysis of data from clinical trials. Not only the molecular biomarkers known to date for ICB biomarkers, but immune cells that influence ICB therapy are also reviewed in this article.

C-reactive protein elevation ratio as an early predictor of postoperative severe complications after laparoscopic gastrectomy for gastric cancer: a retrospective study.

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.

[A Case of Lymph Node Recurrence Seven Years after Curative Esophagectomy for T1a(LPM)Upper Thoracic Esophageal Cancer].

Herein, we report a case of lymph node recurrence 7 years after curative esophagectomy for T1a(LPM)upper thoracic esophageal cancer. A 70's man underwent radical esophagectomy by using video-assisted thoracic surgery and hand-assisted laparoscopic surgery(VATS and HALS)with gastric tube reconstruction via a posterior mediastinal route for upper thoracic esophageal cancer cT1bN0M0, cStageⅠ in August 2010. The pathological diagnosis was pT1a(LPM), w/d, scc, ly0, v0, ie (+), inf b, pIM0, pPM0, pDM0, pRM0, pN0, pM0, pStage 0. Moreover, he was followed-up without treatment after surgery. In November 2017, 7 years after esophagectomy, follow-up CT revealed left supraclavicular lymph node swelling. FDG-PET revealed high uptake of FDG, and lymph node recurrence was suspected. In January 2018, we performed lymph node biopsy. We could not remove the lymph node completely, because the lt common carotid artery and lt jugular vein were associated with the metastatic lymph node. The pathological diagnosis was squamous cell carcinoma. Chemoradiation therapy was performed after surgery, and patient recovery was uneventful.

[A Case of Laparoscopic Abdominoperineal Resection for Rectal Cancer with Left-Sided Inferior Vena Cava].

A 66-year-old-man was hospitalizedfor the treatment of rectal cancer. Preoperative contrast-enhancedcomputedtomography revealedrectal cancer, left-sided inferior vena cava, and distant metastasis. He was diagnosed with cStage Ⅳb rectal cancer. Laparoscopic abdominoperineal resection with standard lymph node dissection was performed. There have been a few reports on laparoscopic colorectal resection for patients with left-sided inferior vena cava. We report a case of laparoscopic abdominoperineal resection for a patient with left-sided inferior vena cava.

[Efficacy and Safety of Paclitaxel plus Ramucirumab Therapy for Unresectable or Recurrent Gastric Cancer].

The RAINBOW trial showed that paclitaxel(PTX)plus ramucirumab(RAM)therapy improved the survival of patients with advanced gastric cancer, previously treated with chemotherapy. We retrospectively investigated 33 patients with unresectable or recurrent gastric cancer who underwent PTX plus RAM treatment as second- or third-line chemotherapy between September 2015 and December 2017. The median age was 68(45-84)years with 22 patients(67%)aged 65 years or older. Seventeen patients had unresectable and 16 patients had recurrent gastric cancer. ECOG PS was 2 in 5 patients(16%). PTX plus RAM was administered as second-line therapy for 24 patients, and as third-line therapy for 9 patients. Best overall response was partial response(PR)in 4 patients, stable disease(SD)in 14 patients, and progressive disease(PD)in 9 patients. Response rate(RR)and disease control rate(DCR)were 14.8% and 66.7%, respectively. Grade 3/4 adverse events were observed in 28(85%)of(leucopenia·neutropenia[64%], neuropathy[9%], etc). Median follow-up period was 7.3(0.4- 22.4)months. Median OS and PFS were 9.3(0.4-22.4)months and 4.7(0.4-22.4)months, respectively. We conclude that PTX plus RAM therapy is useful for treating unresectable or recurrent gastric cancer. In clinical practice, we have many opportunities to provide PTX plus RAM therapy for patients of older age and poorer PS; careful attention to adverse events is essential in such cases.

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

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