Genetic analysis and culturing techniques for gastric non-Helicobacter pylori Helicobacter (NHPH) are progressing. NHPH is reported to accompany nodular gastritis, gastric MALT lymphoma, and mild ...gastritis. However, only a few gastric cancer cases infected by NHPH have been reported. PCR analysis specific for NHPH and H. pylori was performed for DNA from gastric mucosa of 282 Korean gastric cancer patients, who were treated with endoscopic submucosal dissection. For more precise strain detection of NHPH, NHPH-positive mucosa was stained by immunohistochemistry specific for Helicobacter suis. The Cancer Genome Atlas (TCGA) classification was analyzed for these 3 gastric cancer sub-groups by in situ hybridization and immunohistochemistry. Among 281 patients, 3 patients (1.1%) were positive for NHPH. One patient (Patient 1) was also positive for H. pylori by PCR, another patient (Patient 3) was positive for serum IgG for H. pylori, and the other patient (Patient 2) had no evidence for H. pylori infection. Gastric mucosa of Patients 2 and 3 were positive for H. suis staining. All three NHPH-positive gastric cancers were located in the antrum, and belonged to the Chromosomal Instability Type of TCGA classification. Gastric NHPH can be a cause of gastric cancer, although likely with lower pathogenesis than H. pylori.
Weekly paclitaxel + ramucirumab (wPTX + RAM) therapy is recommended as the standard second-line chemotherapy regimen for unresectable advanced/recurrent gastric cancer (GC) or esophagogastric ...junction cancer. Recent subgroup analysis of the RAINBOW trial revealed a higher frequency of severe neutropenia due to wPTX + RAM in Japanese compared to Western patients. However, no risk factors for severe neutropenia have been identified.
This retrospective observational study included patients with advanced/unresectable gastric or esophagogastric junction cancer who received wPTX + RAM after failure to respond to platinum and fluoropyrimidine doublet chemotherapy between June 2015 and April 2020. We conducted multivariable logistic regression analyses to identify the risk factors associated with grade 4 neutropenia and febrile neutropenia (FN). In addition, we investigated the relationship between the number of risk factors and overall survival (OS) and progression-free survival (PFS).
Among 66 patients who met the inclusion criteria, grade 4 neutropenia and FN occurred in 21 (31.8%) and 12 (18.2%) patients, respectively. Prior treatment with oxaliplatin-containing regimens was identified as an independent risk factor for developing grade 4 neutropenia (odds ratio (OR) 20.034, 95% confidence interval (95% CI) 3.216-124.807, P = 0.001). Total bilirubin of > 1.5 mg/dL (OR 31.316, 95% CI 2.052-477.843, P = 0.013) and prior treatment with oxaliplatin-containing regimen (OR 12.502, 95% CI 1.141-137.022, P = 0.039) were identified as independent risk factors for developing FN. Next, we classified patients with 0, 1, 2 risk factor(s) as RF-0, RF-1, and RF-2 subgroups, respectively, and compared the PFS and OS among the three subgroups. PFS was not significantly different among the three subgroups, whereas OS was significantly shorter in the RF-2 subgroup (median 1.4 month, 95% CI 0.0-5.3 month) than in the RF-0 subgroup (median 10.2 month, 95% CI 6.8-13.5 month, P < 0.01 vs RF-2) and RF-1 subgroup (median 13.3 month, 95% CI 10.9-15.7 month, P < 0.01 vs RF-2).
Careful monitoring for grade 4 neutropenia and FN is needed for patients receiving wPTX + RAM therapy who have a history of treatment with oxaliplatin-containing regimens and higher total bilirubin levels.
DNA demethylation therapy is now expanding from hematological tumors to solid tumors. To exploit its maximum efficacy, long-term treatment is needed, and stratification of sensitive patients is ...critically important. Here, we identified a long non-coding RNA, LINC00162, as highly and frequently expressed in gastric cancer cell lines sensitive to 5-aza-2'-deoxycytidine (5-aza-dC). Knockdown of LINC00162 decreased the sensitivity while its overexpression increased the sensitivity. In vivo experiments also showed that LINC00162 overexpression increased the sensitivity. LINC00162 enhanced cell cycle arrest and apoptosis induced by 5-aza-dC, but did not affect its DNA demethylation effect. Mechanistically, LINC00162 interacted with an RNA splicing protein, HNRNPH1, and decreased splicing of an anti-apoptotic splicing variant, BCL-XL. LINC00162 may have translational value to predict patients who will respond to 5-aza-dC.
The aim of the present study was to clarify the association between preoperative liver function and complications after hepatectomy.
The study included 11,686 patients registered in the National ...Clinical Database for 2015 for whom data on indocyanine green at 15 min (ICG15) and hepatectomy were available. The patients were divided into four groups: group A (ICG15 <10%; n = 5,661), group B (ICG15 10% to <20%; n = 4,381), group C (ICG15 20% to <30%; n = 1,173) and group D (ICG15 >30%; n = 463). Hepatectomy procedures were classified as partial resection (n = 3,934), systematic subsegmentectomy (n = 2,055), monosectionectomy (n = 2,043), bisectionectomy (n = 2,993) and trisectionectomy (n = 208). Complications were classified using the Clavien-Dindo classification (CD) and evaluated by ICG15 category and procedure type.
Complications more severe than CD III increased significantly as the operation time lengthened and the intraoperative bleeding volume increased (P < 0.001). ICG15 category was positively associated with operative death, >CD III complications, surgical site infection (SSI), liver failure, and intractable ascites for many of the major hepatectomy procedures, but not with bile leakage. More complications were observed in patients outside the Makuuchi criteria than in those within the criteria.
Operation time and intraoperative bleeding volume are significantly associated with severe postoperative complications in patients undergoing hepatectomy. ICG15 is a good indicator predictive of operative death, >CD III complications, SSI, liver failure and intractable ascites.
Abstract
Cancer-associated fibroblasts (CAFs) tend to have tumor-promoting capacity, and can provide therapeutic targets. Even without cancer cells, CAF phenotypes are stably maintained, and DNA ...methylation and H3K27me3 changes have been shown to be involved. Here, we searched for a potential therapeutic target in primary CAFs from gastric cancer and a mechanism for its dysregulation. Expression microarray using eight CAFs and seven non-CAFs (NCAFs) revealed that serum amyloid A1 (SAA1), which encodes an acute phase secreted protein, was second most upregulated in CAFs, following IGF2. Conditioned medium (CM) derived from SAA1-overexpressing NCAFs was shown to increase migration of gastric cancer cells compared with that from control NCAFs, and its tumor-promoting effect was comparable to that of CM from CAFs. In addition, increased migration of cancer cells by CM from CAFs was mostly canceled with CM from CAFs with SAA1 knockdown. Chromatin immunoprecipitation (ChIP)-quantitative PCR showed that CAFs had higher levels of H3K27ac, an active enhancer mark, in the promoter and the two far upstream regions of SAA1 than NCAFs. Also, BET bromodomain inhibitors, JQ1 and mivebresib, decreased SAA1 expression and tumor-promoting effects in CAFs, suggesting SAA1 upregulation by enhancer activation in CAFs. Our present data showed that SAA1 is a candidate therapeutic target from gastric CAFs and indicated that increased enhancer acetylation is important for its overexpression.
Serum amyloid A1 (SAA1) was identified as highly expressed in gastric CAFs. In association with SAA1 upregulation, enhancer activation was suggested by a high H3K27ac level in CAFs. BET bromodomain inhibitors decreased SAA1 expression and tumor-promoting capacity in CAFs..
We previously reported the usefulness of droplet digital polymerase chain reaction (ddPCR) for the assessment of Human epithelial growth factor receptor 2 (HER2) gene amplification in breast cancer ...using formalin‐fixed and paraffin‐embedded sections. In our previous study, we combined HER2/CEP17 ratio (HER2 gene signals to chromosome 17 signals) with ddPCR and tumor content ratio (TCR) of each sample and determined the HER2 status by adopting a two‐dimensional chart. This “ddPCR‐TCR method” showed a high concordance with conventional HER2 status. In this study, we updated our method to assess the HER2 status of breast cancer in a more quantitative manner. We combined obtained data of the ddPCR ratio Rx and TCR x; we calculated “(Rx − 1)/x + 1” for 41 samples with primary breast cancer and named the value led by this formula as “eHER2 (estimated HER2/CEP17 ratio of a tumor cell)”. eHER2 was equivalent to conventional in situ hybridization (ISH) HER2/CEP17 ratio in most cases. eHER2 and ISH ratio showed a strong correlation (Spearman rank correlation ρ = 0.70, p < 0.0001). The obtained results indicated that eHER2 is a potential tool for HER2 status diagnosis in breast cancer.
Epstein-Barr virus (EBV)-associated gastric carcinoma (EBVaGC), one of four major gastric cancer types, consists of clonal growth of EBV-infected epithelial cells. However, the significance of viral ...loads in each tumor cell has not been evaluated. EBV-DNA is stably maintained in episomal form in the nucleus of each cancer cell. To estimate EBV copy number per genome (EBV-CN), qPCR of viral EBNA1 and host GAPDH, standardized by Namalwa DNA (one copy/genome), was applied to the formalin-fixed paraffin embedded (FFPE) surgically resected EBVaGC specimens (n = 43) and EBVaGC cell lines (SNU-719 and NCC-24). In surgical specimens, the cancer cell ratio (CCR) was determined with image analysis, and EBV-CN was obtained by adjusting qPCR value with CCR. Fluorescent in situ hybridization (FISH) was also applied to the FFPE sections using the whole EBV-genome as a probe. In surgical specimens, EBV-CN obtained by qPCR/CCR was between 1.2 and 185 copies with a median of 9.9. EBV-CN of SNU-719 and NCC-24 was 42.0 and 1.1, respectively. A linear correlation was observed with qPCR/CCR data up to 20 copies/genome (40 signals/nucleus), the limit of FISH analysis. In addition, substantial variation in the number of EBV foci was observed. Based on qPCR/CCR, high EBV-CN (>10 copies) correlated with PD-L1 expression in cancer cells (P = 0.015), but not with other pathological indicators. Furthermore, EBVaGC with high EBV-CN showed worse disease-specific survival (P = 0.041). Our findings suggest that cancer cell viral loads may contribute to expression of the immune checkpoint molecule and promotion of cancer progression in EBVaGC.
Microbial food cultures have directly or indirectly come under various regulatory frameworks in the course of the last decades. Several of those regulatory frameworks put emphasis on “the history of ...use”, “traditional food”, or “general recognition of safety”. Authoritative lists of microorganisms with a documented use in food have therefore come into high demand. One such list was published in 2002 as a result of a joint project between the International Dairy Federation (IDF) and the European Food and Feed Cultures Association (EFFCA). The “2002 IDF inventory” has become a de facto reference for food cultures in practical use. However, as the focus mainly was on commercially available dairy cultures, there was an unmet need for a list with a wider scope. We present an updated inventory of microorganisms used in food fermentations covering a wide range of food matrices (dairy, meat, fish, vegetables, legumes, cereals, beverages, and vinegar). We have also reviewed and updated the taxonomy of the microorganisms used in food fermentations in order to bring the taxonomy in agreement with the current standing in nomenclature.
► Up to date inventory of microbial species used in production of fermented foods. ► The inventory covers species of starter cultures and “natural floras”. ► Species with a documented beneficial technological purpose are included. ► We present a history of use also for newly established taxonomic units. ► The inventory consists of 195 bacterial species and 69 species of yeasts and molds.
Background Lymph node status is one of the most important clinical outcome determinants in gastric cancer patients. Categorization based on the metastatic node count alone, however, would presumably ...be influenced by the extent of lymphadenectomy and the stage migration phenomenon. Methods We statistically analyzed relevant clinicopathologic data of 351 gastric cancer patients with node metastasis who had undergone R0 surgery to compare the reliability of the negative to positive lymph nodes ratio to those of other classifications of lymph node metastasis for predicting outcomes. Results Survival analyses demonstrated the negative to positive lymph nodes ratio to be an independent predictor of overall survival in the 351 gastric cancer patients (hazard ratio = 0.414; P < .001) and revealed significant superiority ( P < .001) for evaluating overall survival based on direct comparison with other categories of lymph node metastasis applying case-control matching. In addition, the negative to positive lymph nodes ratio was found to correlate significantly with the number of negative lymph nodes ( P < .001), pN stage ( P < .001), and the positive to dissected lymph nodes ratio ( P < .001) by multinomial logistic regression analysis. Finally, the interplay effect analyses revealed the negative to positive lymph nodes ratio to yield information similar to that provided by the positive to dissected lymph nodes ratio (R2 = 1.000), while providing more information on both the number of dissected lymph nodes and the number of negative lymph nodes than the positive to dissected lymph nodes ratio. Conclusion The negative to positive lymph nodes ratio, which reflects comprehensive information on dissected, positive, and negative node counts, appears to be a useful alternative for predicting the outcomes of node-positive gastric cancer patients.
Malignant transformation of gastric leiomyoma has not been reported, and therefore it is considered to have virtually no malignant potential. We report a case of gastric leiomyosarcoma arising from ...leiomyoma. The patient is a 72‐year‐old man with a submucosal mass measuring 20 mm in diameter, which was incidentally identified by an endoscopic surveillance. A biopsy suggested a diagnosis of leiomyosarcoma, and local excision was performed. Pathological examination revealed that the tumor was composed of two distinct components: typical leiomyoma‐like area in the periphery and leiomyosarcoma component exhibiting higher cellularity, prominent nuclear atypia, necrosis, and increased mitosis. Immunohistochemically, in the latter, p53 overexpression, increased Ki‐67 labeling index, and attenuated expression of smooth muscle markers were noted. This is the first report to demonstrate the presence of leiomyoma–leiomyosarcoma sequence in the stomach that is well recognized in the uterus. Our observation highlights the potential occurrence of malignant transformation of gastrointestinal leiomyoma.
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