Pivotal role of myeloid-derived suppressor cells in infection-related tumor growth.

BACKGROUND: In this study, we investigated infection-related tumor growth, focusing on myeloid-derived suppressor cells (MDSCs) in clinical and experimental settings. PATIENTS AND METHODS: In the clinical study, a total 109 patients who underwent gastrectomy or esophagectomy were included. Blood samples were collected from a preoperative time point through 3 months after surgery, and MDSCs were analyzed using flow cytometry. In animal experiments, peritonitis model mice were created by CLP method. We investigated the number of splenic MDSCs in these mice using flow cytometry. Malignant melanoma cells (B16F10) were inoculated on the back of the mice, and tumor growth was monitored. We compared the level of MDSC infiltration around the tumor and the migration ability between CLP and sham-operated mice-derived MDSCs. Finally, we focused on PD-L1+ MDSCs to examine the effectiveness of anti-PD-L1 antibodies on tumor growth in CLP mice. RESULTS: In patients with postoperative infectious complication, MDSC number was found to remain elevated 3 months after surgery, when the inflammatory responses were normalized. CLP mice showed increased numbers of MDSCs, and following inoculation with B16F10 cells, this higher number of MDSCs was associated with significant tumor growth. CLP-mice-derived MDSCs had higher levels of accumulation around the tumor and had more enhanced migration ability. Finally, CLP mice had increased numbers of PD-L1+ MDSCs and showed more effective inhibition of tumor growth by anti-PD-L1 antibodies compared to sham-operated mice. CONCLUSION: Long-lasting enhanced MDSCs associated with infection may contribute to infection-related tumor progression.

Clinical significance of postoperative subcutaneous emphysema after video-assisted thoracoscopic surgery for esophageal cancer.

BACKGROUND: Postoperative subcutaneous emphysema (SE) is a possible complication of thoracoscopic or laparoscopic surgery. This study investigated the risk factors and clinical significance of SE after video-assisted thoracoscopic surgery for esophageal cancer (VATS-e). METHODS: This study included 135 patients who underwent VATS-e with artificial CO2 pneumothorax. Based on the X-ray images on the first postoperative day, patients were divided into two groups: N/L group (no SE or SE localized at the thoracic area, n = 65) and SE group (SE extended to the cervical area, n = 70). We compared clinicopathological features, surgical findings, and short-term outcomes between the two groups. RESULTS: In SE group, there were more patients who received neoadjuvant chemotherapy compared to N/L group. SE group had significantly lower preoperative body mass index. SE group had more frequently two-lung ventilation than N/L group. Multivariate analysis demonstrated that low BMI, NAC, and two-lung ventilation were independent risk factors for SE extended to the cervical area. Although pulmonary complication was relatively frequent in SE group, there were no significant differences in surgical outcomes between two groups, and all patients had SE disappeared within 21 days without serious complications. CONCLUSIONS: Despite extension to the cervical area, SE had a modest impact on the short-term result of VATS-e with artificial CO2 pneumothorax.

Robust Spirobifluorene Core Based Hole Transporters with High Mobility for Long-Life Green Phosphorescent Organic Light-Emitting Devices.

Using a tailored high triplet energy hole transport layer (HTL) is a suitable way to improve the efficiency and extend the lifetime of organic light-emitting devices (OLEDs), which can use all molecular excitons of singlets and triplets. In this study, dibenzofuran (DBF)-end-capped and spirobifluorene (SBF) core-based HTLs referred as TDBFSBF1 and TDBFSBF2 were effectively developed. TDBFSBF1 exhibited a high glass transition temperature of 178 °C and triplet energy of 2.5 eV. Moreover, a high external quantum efficiency of 22.0 %, long operational lifetime at 50 % of the initial luminance of 89,000 h, and low driving voltage at 1000 cd m-2 of 2.95 V were achieved in green phosphorescent OLEDs using TDBFSBF1. Further, a high-hole mobility µh value of 1.9×10-3  cm2 V-1 s-1 was recorded in TDBFSBF2. A multiscale simulation successfully reproduced the experimental µh values and indicated that the reorganization energy was the primary factor in determining the mobility differences among these SBF core based HTLs.

Tolerability of neoadjuvant chemotherapy for esophageal cancer in elderly patients over 76 years of age.

Although the Japan Clinical Oncology Group trial demonstrated that neoadjuvant chemotherapy (NAC) with 5-fluorouracil plus cis-diamminedichloroplatinum had significant survival benefits, it excluded elderly patients aged ≥ 76 years. Therefore, our study aimed to evaluate the tolerability of NAC in elderly patients with esophageal cancer. Classified 174 patients with clinical stage II/III esophageal cancer who underwent esophagectomy from 2010 to 2020 into the E (aged ≥ 76 years; 55 patients) and Y (aged < 76; 119 patients) groups, and retrospectively investigated for clinicopathological findings, tolerability of NAC, relative dose intensity (RDI) and short- and long-term result. Patients who received NAC were fewer in the E group than in the Y group (51% vs 77%, p = 0.001). The E group had relatively lower completion rate of NAC (71% vs 85%, p = 0.116) and significantly lower mean RDI of 5-fluorouracil and cis-diamminedichloroplatinum than the Y group (73% vs 89%, p < 0.001). However, histological and radiological were comparable between both groups. Severe adverse events (grade ≥ 3) were relatively frequent (E, 42.9%; Y, 27.5%, p = 0.091), especially, neutropenia was significantly more frequent in the E group (25.0% vs 7.7%, p = 0.022). There were no differences in the incidence of postoperative complications between with and without NAC in both E and Y groups. Elderly patients with esophageal cancer might be more susceptible to toxicity of NAC. Hence, adequate case selection and careful of dose reduction are needed for elderly with esophageal cancer.

Four Dibenzofuran-Terminated High-Triplet-Energy Hole Transporters for High-Efficiency and Long-Life Organic Light-Emitting Devices.

The weak stability of a hole-transporter upon approaching the anion state is one of the major bottlenecks for developing long-life organic light-emitting devices (OLEDs). Therefore, in this study, we developed a series of thermally and electrically stable hole-transporters that are end-capped with four dibenzofuran units. These materials exhibit i) high bond dissociation energy (BDE) toward the anion state, ii) a high glass transition temperature (Tg >130 °C), and iii) high triplet energy (ET >2.7 eV), thereby enabling approximately 20 % high external quantum efficiency (EQE) and significantly prolonging the stability of both thermally activated delayed fluorescent (TADF) and phosphorescent OLEDs with an operation lifetime at 50 % (LT50 ) of 20 000-30 000 h at 1000 cd m-2 . In addition, investigating their structure-property relationship revealed that ionization potential (IP ), BDE, and Tg are critical prerequisites for the hole-transporter to prolong lifetime in OLEDs.

Design of a gold clustering site in an engineered apo-ferritin cage.

Water-soluble and biocompatible protein-protected gold nanoclusters (Au NCs) hold great promise for numerous applications. However, design and precise regulation of their structure at an atomic level remain challenging. Herein, we have engineered and constructed a gold clustering site at the 4-fold symmetric axis channel of the apo-ferritin cage. Using a series of X-ray crystal structures, we evaluated the stepwise accumulation process of Au ions into the cage and the formation of a multinuclear Au cluster in our designed cavity. We also disclosed the role of key residues in the metal accumulation process. X-ray crystal structures in combination with quantum chemical (QC) calculation revealed a unique Au clustering site with up to 12 Au atoms positions in the cavity. Moreover, the structure of the gold nanocluster was precisely tuned by the dosage of the Au precursor. As the gold concentration increases, the number of Au atoms position at the clustering site increases from 8 to 12, and a structural rearrangement was observed at a higher Au concentration. Furthermore, the binding affinity order of the four Au binding sites on apo-ferritin was unveiled with a stepwise increase of Au precursor concentration.

Clinical Relevance of Tissue and Serum Human Epidermal Growth Factor Receptor 2 Expression in Patients With Esophageal Squamous Cell Carcinoma.

BACKGROUND: Serum and tissue human epidermal growth factor receptor 2 (HER2) levels were evaluated in resected esophageal squamous cell carcinoma (SCC) specimens to assess the relationship between HER2 expression and long-term prognosis. METHODS: We included 95 patients who underwent esophagectomy for esophageal SCC. The serum HER2-extracellular domain (sHER2-ECD) levels were measured using an ELISA kit. A time-dependent receiver operating characteristics curve for censored survival outcomes was constructed to estimate the optimal cut-off value of sHER2-ECD (set at 4211 pg/mL). Immunohistochemical (IHC) staining was performed for HER2, and specimens were classified based on low (0 or 1+) or high HER2-IHC expression (2+ or 3+). RESULTS: Patients with low sHER2-ECD levels showed poorly differentiated tumors, nodal involvement, and larger tumor size more frequently compared to patients with high sHER2-ECD levels. There were no differences in clinicopathological features based on HER2-IHC expression. Between patients with high and low HER2-IHC expression, the former group showed significantly higher sHER2-ECD levels. Patients with high sHER2-ECD levels had significantly favorable relapse-free survival (RFS) and overall survival (OS) compared to those with low sHER2-ECD levels. Conversely, patients with high HER2-IHC expression had significantly poorer RFS than did patients with low HER2-IHC expression, although no difference was observed in OS. Additionally, patients with high sHER2-ECD levels and low HER2-IHC expression had the highest OS and RFS among the patients studied. CONCLUSIONS: The correlation among sHER2-ECD levels, HER2-IHC expression, and prognosis was demonstrated. Prospective studies are required to validate the impact of serum and tissue HER2 expression in esophageal SCC prognosis.

Oral Management of a Haematopoietic Stem Cell Transplant Recipient with Chédiak-Higashi Syndrome.

Chédiak-Higashi syndrome (CHS), a rare autosomal recessive disorder associated with leukocyte dysfunction, is characterised by partial skin and hair albinism, immunodeficiency, and abnormal bleeding. Furthermore, it may be associated with cognitive and neurological impairments. The long-term prognosis of patients is generally poor, and haematopoietic stem cell transplantation is a radical immunodeficiency treatment. Here, we report a case of successful oral management of an 18-year-old woman with CHS accompanied by aggressive periodontitis who underwent haematopoietic stem cell transplantation.

Prognostic value of platelet-related measures for overall survival in esophageal squamous cell carcinoma: A systematic review and meta-analysis.

Platelet-related measures are considered important in predicting long-term outcomes in patients with esophageal squamous cell carcinoma (ESCC). We performed a systematic electronic research of studies evaluating the prognostic value of platelet-related measures in ESCC in Google Scholar, PubMed, Cochrane Library, and Embase. Then, to synthesize publications exploring the association between platelet-related measures and survival outcomes in ESCC, a meta-analysis was conducted using hazard ratio and 95 % confidence interval. In total, 14 retrospective articles were included in this study. Among them, 4 and 10 have evaluated the clinical impact of platelet count and platelet-to-lymphocyte ratio (PLR), respectively. Further, three studies reported about platelet distribution width (PDW) and mean platelet volume (MPV). Based on the synthesized results, high PLR was significantly associated with poor overall survival (OS). However, platelet count, PDW, and MPV were non-independent prognostic factors for OS. The Begg's funnel plots for PLR, PDW, and MPV indicated low publication bias.

Correlation Between Immunoinflammatory Measures and Periostin Expression in Esophageal Squamous Cell Carcinoma: A Single-Center, Retrospective Cohort Study.

BACKGROUND: Immunoinflammatory measures such as the neutrophil-lymphocyte ratio (NLR), the platelet-lymphocyte ratio (PLR), and the C-reactive protein (CRP)-albumin ratio (CAR) are useful prognostic measures in various malignancies. However, no study has investigated the correlation of these measures with microenvironmental inflammation. Periostin (POSTN), a small extracellular matrix protein, strongly associates with cancer microenvironmental inflammation. The current study investigated the correlation of NLR, PLR, and CAR with periostin expression in esophageal squamous cell carcinoma (ESCC). METHODS: The study retrospectively evaluated preoperative NLR, PLR, and CAR hematologically and POSTN immunohistochemically in 171 patients. The correlation of immunoinflammatory measures, POSTN expression, and survival outcomes was measured. RESULTS: The study showed a significant correlation of POSTN-positive expression with poor overall survival (OS) (P < 0.0001) and recurrence-free survival (RFS) (P = 0.03). The POSTN-positive group had higher PLR (189.6 ± 8 vs. 159.3 ± 12; P = 0.04) and CAR (0.36 ± 0.06 vs. 0.14 ± 0.09; P < 0.05) than the POSTN-negative group, whereas NLR did not differ between the two groups (3.27 ± 0.19 vs. 2.65 ± 0.28; P = 0.07). The uni- and multivariate analyses showed that POSTN-positive expression (hazard ratio [HR], 1.595; 95% confidence interval [CI], 0.770-3.031; P = 0.03), CAR (HR, 1.663; 95% CI, 1.016-2.764; P = 0.03), gender (HR, 2.303; 95% CI, 1.067-6.019; P = 0.03), and tumor depth (HR, 1.957; 95% CI, 1.122-3.526; P = 0.01) were independent prognostic factors. CONCLUSIONS: Because POSTN-positive expression strongly correlates with immunoinflammatory measures, especially PLR and CAR, it is an independent prognostic factor in ESCC.

Postoperative pneumonia causes the loss of skeletal muscle volume and poor prognosis in patients undergoing esophagectomy for esophageal cancer.

PURPOSES: This retrospective study investigated the effect of postoperative pneumonia on the loss of skeletal muscle volume after esophagectomy for esophageal cancer. METHODS: A total of 123 patients who had undergone esophagectomy for esophageal cancer and had (30 patients) or did not have (93 patients) postoperative pneumonia were included in the analysis. The association of clinicopathological characteristics with loss of skeletal muscle volume and long-term survival were evaluated in patients with or without postoperative pneumonia. RESULTS: There were no differences in the psoas muscle volume index (PI), lymphocyte count, serum albumin level, or prognostic nutritional index between the two groups both preoperatively and at 6 months after surgery. The decrease in PI at 6 months after surgery was significant in patients with postoperative pneumonia (- 9.9 ± 2.5%) but not in those without pneumonia (- 2.6 ± 1.6%). Patients with postoperative pneumonia had a significantly increased frequency of asymptomatic pneumonia at 6 months after surgery compared with those who did not have postoperative pneumonia (36.7% vs. 19.4%). Overall survival was significantly poorer in patients with postoperative pneumonia than in those without pneumonia (p < 0.05). CONCLUSIONS: Postoperative pneumonia was associated with the loss of skeletal muscle volume and asymptomatic pneumonia within 6 months of surgery as well as poorer overall survival.

Impact of postoperative infectious complications on adjuvant chemotherapy administration after gastrectomy for advanced gastric cancer.

BACKGROUND: The aim of this study was to investigate the impact of postoperative infectious complications on adjuvant chemotherapy administration in patients with gastric cancer. METHODS: A retrospective review of 308 patients who underwent curative resection for gastric cancer was performed. Patients were divided into two groups based on the presence (90 patients, 29.2%) or absence (218 patients, 70.8%) of postoperative infectious complications to analyze clinicopathological characteristics, treatment factors and survival. RESULTS: Fewer patients with postoperative infectious complication received adjuvant chemotherapy compared to those without postoperative infectious complication. The proportion of patients who started treatment within 6 weeks after surgery was significantly lower in patients with postoperative infectious complication. The treatment completion rate was significantly lower in patients with postoperative infectious complication. The number of treatment cycles and relative dose intensity was significantly lower in patients with postoperative infectious complication. In univariate analysis, only postoperative infectious complication was significantly associated with continuation of adjuvant chemotherapy. Multivariate analysis demonstrated tumor depth, nodal involvement, postoperative infectious complication and adjuvant chemotherapy were significantly associated with overall survival. CONCLUSION: Postoperative infectious complications are significantly associated with the delay of adjuvant chemotherapy and predict adverse clinical outcome in patients with gastric cancer.

Bilateral Approach for Thoracoscopic Esophagectomy in a Patient with Esophageal Cancer and Solitary Posterior Thoracic Para-aortic Lymph Node Metastasis.

We report a successful dissection of metastatic posterior thoracic para-aortic lymph node (No. 112aoP) via bilateral thoracoscopic surgery. With the anesthetized patient (a 73-year-old Japanese woman) in the prone position, two working ports were inserted for the left-side approach, and artificial pneumothorax was created. Thoracoscopic examination revealed a swollen LN posterior to the descending aorta. Fat and metastatic LNs posterior to the aorta were dissected from the aortic arch level to the diaphragm while preserving intercostal arteries. For the right-side approach, two working ports were inserted and a routine thoracoscopic esophagec-tomy was performed. Gastric conduit reconstruction was achieved laparoscopically. Operation time for the left thoracic procedure: 54 min; estimated blood loss: almost none. No recurrence was detected 24 months post-operatively. There are several surgical options for approaching No. 112aoP, including transhiatal, left thora-cotomy, and thoracoscopy. Although a wide dissection of the posterior thoracic para-aortic area has not been reported, it may be feasible and safe if the artery of Adamkiewicz and intercostal arteries are preserved. A min-imally invasive bilateral thoracoscopic approach for a thoracoscopic esophagectomy is safe and useful for esophageal cancer patients with solitary No. 112aoP metastasis.

Differences Between Laparoscopic and Open Gastrectomy on the Impact of Postoperative Infectious Complications on Prognosis.

BACKGROUND/AIM: The aim of this study was to evaluate the impact of laparoscopic gastrectomy (LG) for gastric cancer on long-term survival in patients with postoperative infectious complications (PIC). PATIENTS AND METHODS: A total of 608 patients who underwent gastrectomy were classified into two groups based on the surgical approach: LG (385 patients) and open gastrectomy (OG: 211 patients). Long-term survival after gastrectomy was compared between patients with and without PIC in both LG and OG groups. RESULTS: Although the patients with PIC in OG group tended to have worse overall survival (OS) than those without PIC, the OS was not significantly different between the patients with and without PIC in LG group. Although multivariate analysis demonstrated that nodal involvement and PIC were significantly associated with OS in OG group, age and tumor depth, and not PIC, were associated with OS in LG group. CONCLUSION: PIC were negative predictors of clinical outcomes in patients with gastric cancer, particularly those who underwent OG, and long-term prognosis may be impacted less by PIC in patients undergoing LG.

A Novel Systemic Inflammatory Score Combined With Immunoinflammatory Markers Accurately Reflects Prognosis in Patients With Esophageal Cancer.

AIM: To establish a novel systemic inflammatory score (SIS) combined with neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and C-reactive protein/albumin ratio (CAR) and to validate its prognostic value and relation with serum cytokine levels in patients who underwent esophagectomy for esophageal cancer (EC). PATIENTS AND METHODS: Preoperative NLR, PLR, and CAR were evaluated in 102 patients undergoing esophageal resection for EC from 2009 to 2014. Receiver operating characteristic (ROC) curves censored for 5-year survival were plotted to determine the cutoff values of each measure. Each measure was scored 1 if it was above the cutoff value (NLR >3.12, PLR >230, and CAR >0.085) and scored 0 if it was below that. The SIS was defined as the sum of these values and was divided into the two groups: High SIS (SIS=2-3) and low SIS (SIS=0-1). Univariate and multivariate analyses were used to determine the prognostic significance. The area under the ROCs (AUROC) was compared to verify the discriminative power of survival prediction. In addition, we analyzed the relationship between SIS and perioperative serum interleukin (IL)-6 and IL-10 levels. RESULTS: In the clinicopathological findings, only tumor depth was significantly related to SIS (p=0.004). At 0.732, the AUROC of SIS was the highest (NLR=0.618, PLR=0.545), and CAR=0.712). The high-SIS group had a significantly poorer prognosis than the low-SIS group (p=0.011). SIS was identified as an independent prognostic factor in the multivariate analysis (hazard ratio=1.96, 95% confidence intervaI=1.11-3.41, p=0.020). The preoperative serum interleukin-6 level was significantly low (p=0.046) and postoperative serum interleukin-10 level was significantly high in the high-SIS group (p=0.047). CONCLUSION: SIS was a superior predictor of prognosis compared with existing immunoinflammatory markers and closely reflected the fluctuation of peripheral inflammatory cytokines in patients with EC.

Helicobacter pylori-Mediated Immunity and Signaling Transduction in Gastric Cancer.

Helicobacter pylori infection is a leading cause of gastric cancer, which is the second-most common cancer-related death in the world. The chronic inflammatory environment in the gastric mucosal epithelia during H. pylori infection stimulates intracellular signaling pathways, namely inflammatory signals, which may lead to the promotion and progression of cancer cells. We herein report two important signal transduction pathways, the LPS-TLR4 and CagA-MET pathways. Upon H. pylori stimulation, lipopolysaccharide (LPS) binds to toll-like receptor 4 (TLR4) mainly on macrophages and gastric epithelial cells. This induces an inflammatory response in the gastric epithelia to upregulate transcription factors, such as NF-κB, AP-1, and IRFs, all of which contribute to the initiation and progression of gastric cancer cells. Compared with other bacterial LPSs, H. pylori LPS has a unique function of inhibiting the mononuclear cell (MNC)-based production of IL-12 and IFN-γ. While this mechanism reduces the degree of inflammatory reaction of immune cells, it also promotes the survival of gastric cancer cells. The HGF/SF-MET signaling plays a major role in promoting cellular proliferation, motility, migration, survival, and angiogenesis, all of which are essential factors for cancer progression. H. pylori infection may facilitate MET downstream signaling in gastric cancer cells through its CagA protein via phosphorylation-dependent and/or phosphorylation-independent pathways. Other signaling pathways involved in H. pylori infection include EGFR, FAK, and Wnt/ß-Catenin. These pathways function in the inflammatory process of gastric epithelial mucosa, as well as the progression of gastric cancer cells. Thus, H. pylori infection-mediated chronic inflammation plays an important role in the development and progression of gastric cancer.

Impact of Antiplatelet and Anticoagulant Therapies on Platelet-related Prognostic Markers in Patients With Esophageal Cancer.

BACKGROUND/AIM: In recent years, platelet-related markers were recognized as useful prognostic factors in various malignancies. We investigated the relationship between platelet-related prognostic markers and anti-platelet or anti-coagulant therapies for survival outcomes in esophageal squamous cell carcinoma. PATIENTS AND METHODS: Preoperative platelet-related prognostic markers were evaluated from peripheral blood testing and statistical analyses were performed to evaluate the prognostic value of these markers and reveal the effects of antiplatelets and/or anticoagulants regarding their prognostic relevance. RESULTS: In all 176 patients, preoperative platelet-to-lymphocyte ratio (PLR) was not found to be a predictor of overall survival (OS). However, in patients without antiplatelet or anticoagulant therapies, PLR was significantly associated with a poor OS (p=0.03). Although platelet large cell ratio (P-LCR) was not associated with the prognosis in patients with antiplatelet and/or anticoagulant therapies, higher P-LCR was associated with a poor prognosis in patients without antiplatelet or anticoagulant therapies (p<0.0001). CONCLUSION: Researching detailed antiplatelet and anticoagulant therapies could reinforce the prognostic value of platelet-related prognostic markers in ESCC.

Clinical Significance of Programmed Death Ligand-1 Expression in Esophageal Squamous Cell Carcinoma.

BACKGROUND: The aim of this study was to evaluate the association between the expression of programmed death ligand-1 (PD-L1) and clinical outcomes in patients with surgically resected esophageal squamous cell carcinoma (ESCC). MATERIALS AND METHODS: We included 76 patients with primary ESCC who underwent surgical resection between January 2009 and December 2014 at National Defense Medical College Hospital. Using the tumor tissues, we evaluated PD-L1 expression in tumor cells and stromal reactive lymphocytes via immunohistochemistry. Furthermore, the relationship between PD-L1 expression and the clinicopathological status of patients with ESCC was investigated. RESULTS: PD-L1 expression in tumor cells was detected in 39.5% of the patients. In addition, 51.3% of the patients had PD-L1-positive stromal reactive lymphocytes and exhibited significantly longer overall survival than those with lack of PD-L1 expression in stromal reactive lymphocytes (median survival time, 56.0 versus 27.3 mo; log-rank test, P = 0.04). Patients with lack of PD-L1 expression in both tumor cells and stromal reactive lymphocytes showed worse overall survival than those with the PD-L1-positive expression in tumor cells and/or stromal reactive lymphocytes (P = 0.02). CONCLUSIONS: PD-L1-positive expression in stromal reactive lymphocytes, rather than in tumor cells, is associated with a longer survival in patients with ESCC.

Predictive value of immuno-inflammatory and nutritional measures modulated by neoadjuvant chemotherapy on the response of neoadjuvant chemotherapy and long-term outcomes in patients with esophageal cancer.

It has been reported that immuno-inflammatory and nutritional parameters are associated with long-term survival in various malignancies. However, little is known regarding the associations between alterations of these parameters during neoadjuvant chemotherapy (NAC) and the response to NAC in patients with esophageal cancer. The present study examined the clinical significance of alterations in these parameters during NAC in terms of the response to NAC and the long-term outcomes in patients with esophageal cancer. Various systemic immuno-inflammatory and nutritional measures including the systemic neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), C-reactive protein (CRP)-to-albumin ratio (CAR) and psoas muscle index (PMI) were examined before and after NAC. Statistical analyses were performed to determine the significance of immuno-inflammatory and nutritional parameters prior to NAC and alterations during NAC regarding the response to NAC and long-term outcomes. The NLR, PMI, neutrophil count and platelet count declined significantly following NAC, whereas no alterations in PLR, CAR, lymphocyte counts, CRP levels and albumin concentration were observed. The decreases in NLR and neutrophil counts following NAC were strongly associated with a favorable overall survival (P=0.006). In conclusion, decreases in NLR and neutrophil counts following NAC were clinically significant predictors of the response to NAC and of survival in esophageal cancer, respectively.

Mixed adenoneuroendocrine carcinoma with loss of HER2 positivity after trastuzumab-based chemotherapy for HER2-positive gastric cancer: a case report.

BACKGROUND: Trastuzumab (T-mab)-based chemotherapy is a standard regimen for human epithelial growth factor 2 (HER2)-positive gastric cancer. However, some patients have demonstrated a change in HER2 status after T-mab-based treatment of breast cancer. We report a rare case of mixed adenoneuroendocrine carcinoma with loss of HER2 positivity after T-mab-based chemotherapy for HER2-positive gastric cancer. CASE PRESENTATION: A 60-year-old man presented with a mass of the upper abdomen, which was diagnosed as adenocarcinoma with a HER2 score of 3+ by endoscopic biopsy. He received seven cycles of combination chemotherapy with capecitabine, cisplatin, and T-mab. Subsequently, he underwent open total gastrectomy, distal pancreatosplenectomy, and extended left hepatic lobectomy as a conversion surgery. The surgically resected specimen demonstrated both adenocarcinoma and neuroendocrine components; therefore, it was diagnosed as HER2-negative mixed adenoneuroendocrine carcinoma. Although the patient received additional chemotherapy, multiple liver metastases appeared at 3 months postoperatively and he died at 6 months postoperatively because of the rapidly progressing metastatic tumor. CONCLUSIONS: We encountered a rare case of rapidly progressive mixed adenoneuroendocrine carcinoma that was negative for HER2 expression after T-mab treatment combined with chemotherapy.