RESUMO
Alternative reproductive tactics (ARTs) are discontinuous phenotypes associated with reproduction, observed in males of many species. Typically, large males adopt a tactic of competing with rivals for mating, while small males adopt a tactic of stealing fertilization opportunities from the large males. The 'birth date hypothesis', proposing that the date of birth influences the determination of each male's reproductive tactic, has been tested only in teleost fish to date. Here, the birth date hypothesis was tested in ARTs of Japanese spear squid Heterololigo bleekeri (consort/sneaker) by analysing statolith growth increments. The birth date significantly differed between consorts (early-hatched) and sneakers (late-hatched). However, no differences were detected in growth history up to 100 days from hatching. Most immature males caught during the reproductive season were larger than sneakers, and their hatch date was similar to that of consorts, suggesting that these immature males had already been following a life-history pathway as a consort. These results indicate that ARTs of H. bleekeri are determined based on their hatch date in early life. This study firstly suggests that the birth date hypothesis applies to aquatic invertebrates, suggesting that the mechanism by which birth date determines the individual phenotype is a phenomenon more common than previously believed.
Assuntos
Decapodiformes , Reprodução , Comportamento Sexual Animal , Animais , Masculino , Decapodiformes/fisiologia , FemininoRESUMO
A 47-year-old man was referred to our hospital for detailed examination of a gastric polypoid lesion. Esophagogastroduodenoscopy revealed a raspberry-like polyp at the gastric body. Pathological examination of the biopsy specimen revealed this polypoid lesion to be a gastric adenocarcinoma. Endoscopic submucosal dissection was performed, and histopathological examination revealed that lesion to be a well-differentiated adenocarcinoma. Immunohistochemical staining showed that the neoplasm was positive for MUC5AC and negative for MUC6, CD10, and pepsinogen I, indicating that this lesion was a foveolar-type gastric adenocarcinoma. From about 10 years now, this patient has been undergoing esophagogastroduodenoscopy almost every year. This lesion was absent until six years ago. Five years ago, a small polypoid lesion appeared at the gastric body, and this lesion gradually enlarged. The present case showed the growing process of the foveolar-type gastric adenocarcinoma with a raspberry-like appearance.
Assuntos
Adenocarcinoma , Ressecção Endoscópica de Mucosa , Rubus , Neoplasias Gástricas , Adenocarcinoma/diagnóstico por imagem , Adenocarcinoma/cirurgia , Mucosa Gástrica , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Gástricas/diagnóstico por imagem , Neoplasias Gástricas/cirurgiaRESUMO
Molecular irreversibleness with Helicobacter pylori (H. pylori) infection might have a role in gastric tumorigenesis after H. pylori eradication. We performed comprehensive DNA methylation profiling of gastric mucosa after H. pylori eradication with or without gastric cancer. Using four different groups of biopsies obtained from gastric body without history of H. pylori infection (Hp-), gastric body without cancer after H. pylori eradication (cancer-free body), gastric body with early gastric cancer diagnosed after H. pylori eradication (EGC body) and their paired samples from adjacent mucosa of cancer (EGC ADJ), methylation status of five candidate genes (MYOD1, SLC16A12, IGF2, RORA and PRDM5) was examined by the bisulfite pyrosequencing. An Infinium Methylation EPIC BeadChip array was also used to characterize the methylation status of greater than 850,000 CpG sites. The EGC ADJ group showed highest methylation levels of five candidate genes among the four groups of biopsies. In the gastric body (cancer-free body + EGC body), methylation levels were significantly decreased in patients with longer period after eradication, while such association was not observed in EGC ADJ group. Hyper methylated samples were associated with shorter telomere, an indicator for rapid cell turnover, and higher DNMT1 protein expression, an enzyme related to methyl transfer reaction. The genome-wide methylation analysis demonstrated strikingly higher methylation levels especially at CpG islands in the EGC ADJ group. Exclusively hypermethylated promoter CpG islands in the same group frequently coded zinc finger proteins. Our data show that DNA methylation accumulation is associated with molecular irreversibleness and gastric carcinogenesis after H. pylori eradication.
Assuntos
Transformação Celular Neoplásica/genética , Metilação de DNA , Mucosa Gástrica/metabolismo , Neoplasias Gástricas/genética , Antibacterianos/uso terapêutico , Biópsia , Ilhas de CpG/genética , Feminino , Mucosa Gástrica/microbiologia , Mucosa Gástrica/patologia , Predisposição Genética para Doença/genética , Infecções por Helicobacter/tratamento farmacológico , Infecções por Helicobacter/genética , Infecções por Helicobacter/microbiologia , Helicobacter pylori/efeitos dos fármacos , Helicobacter pylori/fisiologia , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Gástricas/microbiologia , Neoplasias Gástricas/patologia , Encurtamento do Telômero/genéticaRESUMO
To investigate the molecular mechanisms of gastric carcinogenesis after Helicobacter pylori (H. pylori) eradication, expression of miR-124a, miR-34b, and miR-34c was examined in nonneoplastic gastric specimens after successful H. pylori eradication. The magnifying narrow-band imaging (NBI) endoscopic features of gastric mucosa were also examined. The atrophic type, an informative endoscopic feature for histological intestinal metaplasia, showed lower expression of miR-124a. Lower expression of miR-124a correlated with hypermethylation of the miR-124a3 locus. The atrophic type represents gastric microarchitectures associated with irreversibility with H. pylori eradication and downregulation of miR-124a.
Assuntos
Regulação para Baixo , Mucosa Gástrica/diagnóstico por imagem , Infecções por Helicobacter/prevenção & controle , MicroRNAs/genética , Imagem de Banda Estreita/métodos , Neoplasias Gástricas/genética , Idoso , Idoso de 80 Anos ou mais , Metilação de DNA , Erradicação de Doenças , Epigênese Genética , Feminino , Mucosa Gástrica/patologia , Regulação Neoplásica da Expressão Gênica , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Gástricas/diagnóstico por imagemRESUMO
BACKGROUND: Gastric cancer develops after successful H. pylori eradication in patients with severe atrophic gastritis. We classified atrophic and non-atrophic mucosa of gastric body using magnifying NBI endoscopy in patients after successful H. pylori eradication. MATERIALS AND METHODS: One hundred and twenty-five patients after successful H. pylori eradication (median period after eradication: 36 months) were enrolled. Magnifying NBI patterns in the uninvolved gastric body were divided into the following: restored-small, round pits, accompanied with honeycomb-like subepithelial capillary networks; atrophic-well-demarcated oval or tubulovillous pits with clearly visible coiled or wavy vessels. The subjects were also classified into the three types: Grade 0-restored pattern is shown in all or almost the entire area of gastric body; Grade 1-mixture of restored and atrophic pattern, there is a considerable portion of the atrophic area in the lesser curvature; Grade 2-atrophic pattern is shown in all or almost the entire area of the gastric body. RESULTS: Sensitivity and specificity for atrophic type for detection of histological intestinal metaplasia were 95.9 and 98.3%, respectively. No association was observed between the prevalence of Grades 0, 1 and 2 and duration after eradication, while grades 1 and 2 were significantly frequent in gastric cancer patients diagnosed both before (27/35: 77%) and after (23/31: 74%) eradication, compared to the cancer-free subjects (15/59: 25%) (P < 0.001). The grades 1 and 2 were also common in patients who underwent H. pylori eradication for gastric ulcer. CONCLUSIONS: Magnifying the NBI pattern well correlates with pathological status of gastric mucosa after H. pylori eradication and may predict gastric cancer occurrence.
Assuntos
Erradicação de Doenças , Mucosa Gástrica/diagnóstico por imagem , Infecções por Helicobacter/diagnóstico por imagem , Helicobacter pylori , Imagem de Banda Estreita/métodos , Neoplasias Gástricas/diagnóstico por imagem , Adulto , Idoso , Idoso de 80 Anos ou mais , Erradicação de Doenças/tendências , Feminino , Mucosa Gástrica/microbiologia , Infecções por Helicobacter/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade , Imagem de Banda Estreita/tendências , Estudos Prospectivos , Fatores de Risco , Neoplasias Gástricas/epidemiologia , Neoplasias Gástricas/microbiologiaRESUMO
BACKGROUND AND AIMS: Fusobacterium species are part of the gut microbiome in humans, but some species have been recognized as opportunistic pathogens implicated in inflammatory diseases including inflammatory bowel diseases. Here, we performed prevalence screening of Fusobacterium in ulcerative colitis (UC) in Japanese patients. METHODS: We examined Fusobacterium nucleatum (F. nucleatum) and whole Fusobacterium species (Pan-fusobacterium) by quantitative real-time PCR in 163 inflamed mucosae from 152 UC patients. Data were correlated with clinical subtypes of UC. RESULTS: In an initial prevalence screen, F. nucleatum and Pan-fusobacterium were detected in 6.3 % (4/64) and 53.1 % (34/64). For all 163 mucosae, the prevalence of Pan-fusobacterium was 54.6 % (89/163). Pan-fusobacterium status was concordant in inflamed and normal adjacent samples, and the matched cases during 1-year follow-up colonoscopy. The higher amount of Pan-fusobacterium was observed in chronic continuous type compared to one attack and relapse/remitting type (p = 0.039). The higher amount of Pan-fusobacterium was also associated with rather mild clinical course of disease, such as non-steroid dependency (p = 0.015), non-refractory phenotype (p = 0.013), and non-severe phenotype (p = 0.04). Based on the distribution of Pan-fusobacterium measurable cases, we identified 10 cases as having a high amount of Pan-fusobacterium (FB-high). The clinicopathological features of FB-high UC cases were also highlighted by chronic continuous type and mild phenotypes of disease. CONCLUSION: Whole Fusobacterium species, but not F. nucleatum, are common in UC patients and have a role in persistence of colonic inflammation in UC. However, Fusobacterium infection is associated with rather mild clinical phenotypes of UC.
Assuntos
Colite Ulcerativa/microbiologia , Colite Ulcerativa/patologia , Colo/microbiologia , Infecções por Fusobacterium/complicações , Fusobacterium/isolamento & purificação , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Colo/patologia , Feminino , Humanos , Mucosa Intestinal/microbiologia , Japão , Masculino , Pessoa de Meia-Idade , Fenótipo , Adulto JovemRESUMO
A poorly known epialtid crab species, Pugettia pellucens Rathbun, 1932, is redescribed and a closely allied new species P. vulgaris n. sp. is described and illustrated on the basis of material from Sagami Bay, Japan. Pugettia pellucens was originally described as a subspecies of P. quadridens (De Haan, 1839), but it is confirmed that the taxon is distinct from P. quadridens. The superficially similar Pugettia vulgaris n. sp. can be distinguished from P. pellucens by several morphological characters. The new species is also similar to P. elongata Yokoya, 1933, and P. intermedia Sakai, 1938, but can also be separated by various carapace and gonopodal characters.
Assuntos
Braquiúros/anatomia & histologia , Braquiúros/classificação , Animais , Braquiúros/fisiologia , Demografia , Feminino , Japão , Masculino , Oceano Pacífico , Especificidade da EspécieRESUMO
Visual display is a crucial aspect of courtship, and their success relies on both display quality and the surrounding environment, such as the visual background. Cephalopods may release ink when attacked by predators or during aggressive interactions with conspecifics. Here, we report that ink is used as a part of the courtship display by males of the cuttlefish species Sepia andreana. Males of this species engage in a highly ritualized multimodal courtship using a pair of markedly long sexually dimorphic arms. At the climax of the courtship, the male releases a diffuse backdrop of ink near himself and then performs the specific courtship display by extending his sexually dimorphic arms and altering his body pattern to pale in front of this ink backdrop, and then proceeds to mate. This novel use of cephalopod ink could make the surroundings darker and more homogeneous, potentially serving as a temporary modification of the visual environment for courtship display.
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Objective In general, surface ulceration in gastric gastrointestinal stromal tumor (GIST) is considered a malignant feature; however, the mechanism underlying its formation has not been evaluated in detail. In this study, we analyzed the factors involved in ulceration using resected specimens of gastric GIST. Methods A total of 48 samples were retrospectively analyzed. We examined the association of surface ulceration of gastric GIST with the MIB-1 labeling index, mitotic number, tumor size, endoscopic ultrasound (EUS) findings and growth pattern on computed tomography (CT). Results The proportion of men was significantly higher in the ulceration group than in the non-ulceration group (p=0.04146), whereas age was not significantly different between the groups. Tumor was significantly larger in the ulceration group than in the non-ulceration group (p=0.0048). There was no correlation between tumor size and ulcer number. The MIB-1 index was not related to ulceration, nor were EUS findings. The number of mitotic cells tended to be higher in the ulceration group than in the non-ulceration group (p=0.05988). Intraluminal growth pattern was strongly associated with ulceration (p=0.00019). After a multivariate analysis, the growth pattern was the only factor associated with ulceration of gastric GIST. Conclusion Although formation of surface ulceration in gastric GIST was partially associated with the degree of malignancy, the growth pattern was the most important factor associated with ulceration in gastric GIST.
Assuntos
Tumores do Estroma Gastrointestinal , Neoplasias Gástricas , Masculino , Humanos , Tumores do Estroma Gastrointestinal/complicações , Tumores do Estroma Gastrointestinal/diagnóstico por imagem , Tumores do Estroma Gastrointestinal/patologia , Estudos Retrospectivos , Úlcera/etiologia , Úlcera/complicações , Neoplasias Gástricas/complicações , Neoplasias Gástricas/patologia , Endossonografia/métodosRESUMO
Pugettia quadridens (De Haan, 1837) and its closely similar congener, P. intermedia Sakai, 1938, are redescribed and illustrated and their possible infraspecific variations related to sexual, ontogenetic, and environmental differences are discussed. As a result, a new species, Pugettia ferox, which had long been believed to be a local variant of P. quadridens sensu lato in the northeast Japan, is described. Despite moderate sexual dimorphism and considerable variability related to their ontogeny, the three species can be distinguished from each other by the combination of various morphological characters including the structure of the orbital region and male first gonopods. The patterns of ontogenetic morphological and morphometric changes in the chelipeds, gonopods, and pleons are also differentiated among the three species. The updated distribution ranges of three species greatly overlap in the northeast Asian waters, although P. quadridens sensu stricto is distributed more southward than P. ferox n. sp.. Distinguishing characters between P. quadridens s.s. and P. pellucens Rathbun, 1932, and between P. intermedia and P. vulgaris Ohtsuchi, Kawamura Takeda, 2014, are revised.
Assuntos
Braquiúros , Animais , Japão , Masculino , Caracteres SexuaisRESUMO
In April 2014 and 2015, field samplings were conducted in a subtropical seagrass-seaweed mixed bed in Ishigaki Island, southwest Japan in order to collect macrophytes and mobile epi-benthic invertebrates. This article describes macrophyte biomass of 16 species or groups and invertebrate abundance of 66 species or groups. This data is associated with "Phylogenetically diverse macrophyte community promotes species diversity of mobile epi-benthic invertebrates" (Nakamoto et al., 2018) [1].
RESUMO
The molecular mechanisms of gastric carcinogenesis after Helicobacter pylori (H. pylori) eradication remain unclear. We examined the telomere length of gastric mucosa samples after successful H. pylori eradication in patients without and those with gastric cancer. Telomere length was measured by the real-time PCR among four different groups of biopsies: gastric body from subjects without history of H. pylori infection (Hp-: n = 23), gastric body from cancer-free subjects after H. pylori eradication (cancer-free body: n = 24), gastric body from early gastric cancer patients diagnosed after H. pylori eradication (EGC body: n = 35) and its paired samples from adjacent mucosa of cancerous area (EGC ADJ: n = 35). The Hp-group presented the longest telomeres among the all groups (Hp- vs. all others, all P < 0.05). Samples from EGC body group showed shorter telomere length than the samples from cancer-free body groups (P < 0.05). Conversely, samples from EGC ADJ group showed rather longer telomere length compared to the EGC body group (P < 0.05), which was also confirmed by the comparison of 35 matched samples (P = 0.0007). Among the samples after H. pylori eradication, shorter telomere length was associated with higher expression of IL-1B and NF-kB (P < 0.0001, 0.0006, respectively). Longer telomere length was also associated with higher expression of TNF-A (P = 0.01). Telomere shortening seems to be important initial steps in gastric cancer predisposition after H. pylori eradication, while it might shift to lengthening to acquire more aggressive pathway to develop cancer.
Assuntos
Carcinogênese , Mucosa Gástrica/patologia , Infecções por Helicobacter/complicações , Infecções por Helicobacter/tratamento farmacológico , Helicobacter pylori/efeitos dos fármacos , Neoplasias Gástricas/patologia , Telômero , Adulto , Idoso , Idoso de 80 Anos ou mais , Biometria , Biópsia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase em Tempo RealRESUMO
Epstein-Barr virus (EBV) infection is involved in a subset of gastric carcinoma (GC) cases, and is associated with distinct clinicopathological features. The present study reports a unique case of EBV-associated early-stage GC compared with the other cases experienced in our hospital. A 72-year-old male receiving treatment for cerebral infarction underwent an esophagogastroduodenoscopy (EGD) for suspicion of gastrointestinal bleeding. EGD revealed a type 0-I protruding lesion in the lesser curvature of the upper gastric corpus. Biopsy indicated well-differentiated adenocarcinoma. As the tumor diameter was >3 cm and the thickness of the tumor suggested submucosal invasion, laparoscopic gastrectomy was performed. Histological assessment revealed polypoid growth of an intramucosal, differentiated, tubular or papillary adenocarcinoma, with dense infiltration of lymphocytes. The carcinoma crypts were found to be EBV-positive on in situ hybridization. A review of the clinicopathological features of 25 EBV-associated GCs from 20 patients treated in our hospital between 2005 and 2014 was performed. All of these tumors, except that in the current case, appeared as shallow, depressed or ulcerative lesions. Thus, the current case appears to represent an unusual growth of EBV-positive GC.
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DNA methylation of leukocyte DNA has been proposed to be a biomarker for cancer that can be used to target patients for appropriate clinical implementation. We investigated IGF2 DMR and LINE1 methylation in the leukocyte DNA and their association with clinicopathological features and prognosis of gastric cancer (GC) patients. Methylation status of IGF2 DMR and LINE1 in the leukocyte DNA was quantified using bisulfite pyrosequencing in 207 GC patients. Methylation of both IGF2 DMR and the LINE1 was significantly higher in the undifferentiated histologic type compared to the differentiated histologic type (both P = 0.0002). Hypermethylation of both the IGF2 DMR and the LINE1 was associated with more aggressive features of GC such as advanced stage (IGF2 DMR, P = 0.0002; LINE1, P < 0.0001), lymphatic invasion positive (IGF2 DMR, P = 0.004; LINE1, P = 0.002), venous invasion positive (IGF2 DMR, LINE1, both P = 0.03), lymph node metastasis positive (IGF2 DMR, P = 0.01; LINE1, P = 0.001), peritoneal dissemination positive (IGF2 DMR, P = 0.04; LINE1, P = 0.002), liver metastasis positive (IGF2 DMR, P = 0.008; LINE1, P = 0.001), and other distant metastasis positive (IGF2 DMR, P = 0.04). Our data suggest that high LINE1 and IGF2 DMR methylation status would be a phenomenon that is observed with the progression of GC, supporting their potential utility as a biomarker in GC patients.
Assuntos
Metilação de DNA , Fator de Crescimento Insulin-Like II/genética , Leucócitos/química , Elementos Nucleotídeos Longos e Dispersos , Neoplasias Gástricas/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Progressão da Doença , Feminino , Humanos , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Análise de Sequência de DNA , Neoplasias Gástricas/sangue , Neoplasias Gástricas/genéticaRESUMO
BACKGROUND AND AIM: Early-stage gastric cancer (EGC) found after H. pylori eradication often has non-tumorous epithelium on the tumorous tissue and/or surface differentiation of tumors, which may confuse endoscopic and histologic diagnosis. We investigated the diagnostic reliability of EGC using conventional white light endoscopy (WLE), chromoendoscopy (CE) using indigo carmine, and magnifying endoscopy with narrow band imaging (ME-NBI) in patients with EGC with or without history of prior H. pylori eradication therapy. METHODS: Diagnostic reliability of EGC by using the WLE, CE and ME-NBI was investigated in 71 EGC lesions diagnosed after successful H. pylori eradication (eradication group) and 115 EGC lesions with current H. pylori infection (control group). RESULTS: Diagnostic reliability of EGC was lower in the eradication group than in the control group using all three modalities. In particular, the diagnostic accuracy of CE in the eradication group was especially lower compared to that of the control group (WLE: 74.6% vs. 86.1%, P=0.05; CE: 64.8% vs. 91.3%, P<0.0001; ME-NBI: 88.7% vs. 98.2%, P=0.01). The ME-NBI scored better in comparison with WLE and CE in the eradication group (both P<0.05). The indistinct EGC lesions in the eradicated group by using CE were associated with the presence of histological changes such as non-tumorous epithelium on the tumor and/or surface differentiation of tumors (P=0.005). CONCLUSIONS: It should be noted that the diagnostic reliability of EGC after H. pylori eradication becomes lower especially using CE. Indistinguishable cases using CE are associated with histological findings such as non-tumorous epithelium on the tumor and/or surface differentiation of tumors.
Assuntos
Detecção Precoce de Câncer/métodos , Gastroscopia/métodos , Infecções por Helicobacter/tratamento farmacológico , Helicobacter pylori , Neoplasias Gástricas/diagnóstico , Idoso , Idoso de 80 Anos ou mais , Corantes , Feminino , Infecções por Helicobacter/complicações , Humanos , Índigo Carmim , Masculino , Pessoa de Meia-Idade , Imagem de Banda Estreita/métodos , Reprodutibilidade dos Testes , Neoplasias Gástricas/microbiologia , Neoplasias Gástricas/patologiaRESUMO
Residual DNA methylation in the gastric mucosa after Helicobacter pylori (H. pylori) eradication may have a role in gastric carcinogenesis. We examined the association between morphologic features and promoter methylation status of non-neoplastic gastric mucosa especially after H. pylori eradication. A total of 140 gastric specimens from 99 participants who had at least 6 months of post-eradication period were examined. The magnifying narrow-band imaging (NBI) endoscopic feature of gastric mucosa was divided into two types: restored-small, round pits, accompanied with honeycomb-like subepithelial capillary networks; atrophic-well-demarcated oval or tubulovillous pits with clearly visible coiled or wavy vessels. Methylation status of five candidate genes (MYOD1, SLC16A12, IGF2, RORA, and PRDM5) were examined by bisulfite pyrosequencing. The atrophic type, informative endoscopic features of intestinal metaplasia, demonstrated higher methylation levels in all five genes compared to the restored type (all P < 0.0001). In the restored type, methylation levels were significantly lower among the samples with longer post-eradication period (for all genes, P < 0.0001), which was not observed in atrophic type (for all genes, P > 0.1). Multivariate analysis demonstrated that atrophic type or presence of intestinal held an independent factor for hyper methylation (odds ratio: 24.69, 95% confidence interval: 6.95-87.76, P < 0.0001). The atrophic type by the magnifying NBI and presence of intestinal metaplasia are the morphologic characteristics of residual DNA methylation of after H. pylori eradication, regardless of the post-eradication period and it might be considered as the epigenetic irreversible point with H. pylori eradication.
Assuntos
Transformação Celular Neoplásica/genética , Metilação de DNA , Mucosa Gástrica/metabolismo , Mucosa Gástrica/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Endoscopia Gastrointestinal , Mucosa Gástrica/microbiologia , Regulação da Expressão Gênica , Infecções por Helicobacter/complicações , Infecções por Helicobacter/tratamento farmacológico , Infecções por Helicobacter/microbiologia , Helicobacter pylori/efeitos dos fármacos , Helicobacter pylori/fisiologia , Humanos , Pessoa de Meia-Idade , Razão de Chances , Regiões Promotoras Genéticas , Fatores de Risco , Neoplasias Gástricas/etiologia , Neoplasias Gástricas/patologiaRESUMO
Neoadjuvant chemotherapy may improve outcomes for patients with locally advanced gastric cancer (GC). To explore useful predictive factors for the response of advanced GC to neoadjuvant chemotherapy, tumor responses were assessed using computed tomography (CT) with histological based criteria. A total of 78 patients with advanced GC undergoing neoadjuvant chemotherapy were included. CT-based response assessment was performed following 2 courses of treatment. Histological evaluation of resected specimens was also performed according to the Japanese classification of gastric carcinoma. Grade 1b, 2 and 3 (viable tumor cells remaining in <2/3 of the tumorous area) were defined as histological responders. The results were associated with overall survival (OS) and progression-free survival (PFS). The majority of the cases underwent tegafur/gimeracil/oteracil based preoperative chemotherapy as the first line of treatment (n=76, 96%). A total of 25 (32%) and 29 (37%) cases were considered to be CT and histological responders, respectively. CT-based evaluation was not associated with OS or PFS, while histological evaluation was significantly associated with OS and PFS. Histological based evaluation was not associated with CT and GI X-ray or endoscopy-based evaluation of primary lesions. Multivariate survival analysis using Cox's regression model demonstrated that histological non-response was an independent prognostic factor for predicting worse OS. Histological-based evaluation of primary lesions was independently associated with prognosis in patients with GC who underwent neoadjuvant chemotherapy.
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BACKGROUND: Chemotherapy may improve outcomes in gastric cancer (GC), especially for the patients with advanced stage. To explore useful predictive factor for GC performing chemotherapy, we compared the tumor responses assessed using computed tomography (CT) with endoscopy based criteria. METHODS: 192 GC patients performing chemotherapy were retrospectively studied. CT based response assessment was performed after 2 courses of treatment. Endoscopic evaluation according to The Japanese classification of gastric carcinoma was also performed at same period. Data were correlated with overall survival (OS) and progression-free survival (PFS). RESULTS: Majority of the cases (n = 178, 93%) received S-1 based chemotherapy as the first line treatment. 55 (29%) and 91 (47%) cases were considered to be CT and endoscopic responders. Endoscopic responder was more clearly associated with better OS and PFS compared to CT based responder by the log-rank test (P<0.0001 vs. 0.01 and P<0.0001 vs. 0.008, respectively). The association was more striking among patients performing neoadjuvant chemotherapy (P<0.0001 vs. 0.15 and P<0.0001 vs. 0.1, respectively). Multivariate survival analysis using Cox's regression model revealed that endoscopic non-responder was the independent predictive factor, being more strongly associated with worse OS when compared to CT non-responder (hazard ratio: 4.60 vs. 1.77, 95% confidence interval: 2.83-7.49 vs.1.08-2.89, P<0.0001 vs. 0.02). More advanced T, N stage and cases who had peritoneal dissemination were significantly associated with endoscopic non-responder (all P values <0.01). CONCLUSION: Endoscopy based evaluation of primary lesions are clearly associated with prognosis in patients with GC who perform chemotherapy.
Assuntos
Gastroscopia/métodos , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Intervalo Livre de Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Terapia Neoadjuvante , Prognóstico , Estudos Retrospectivos , Neoplasias Gástricas/diagnóstico por imagem , Neoplasias Gástricas/mortalidade , Tomografia Computadorizada por Raios X/métodos , Resultado do TratamentoRESUMO
DNA methylation is associated with "field defect" in the gastric mucosa. To characterize "field defect" morphologically, we examined DNA methylation of non-neoplastic gastric mucosa in relation to their morphology seen by narrow-band imaging (NBI) with magnifying endoscopy. Magnifying NBI of non-neoplastic gastric body was classified as follows: normal-small and round pits with uniform subepithelial capillary networks; type 1-a little enlarged round pits with indistinct subepithelial capillary networks; type 2-remarkably enlarged pits with irregular vessels; and type 3-clearly demarcated oval or tubulovillous pits with bulky coiled or wavy vessels. Methylation of nine candidate genes (MYOD1, SLC16A12, GDNF, IGF2, MIR 124A1, CDH1, PRDM5, RORA and MLF1) were determined by bisulfite pyrosequencing. Infinium HumanMethylation450 array was used to characterize the methylation of >450,000 CpG sites. Mean Z score methylation of nine genes positively correlated with the changes of mucosal patterns from normal to types 1, 2, and 3 (P < 0.0001). Genome-wide analysis showed that development of mucosal patterns correlated with methylation accumulation especially at CpG islands. Genes with promoter CpG islands that were gradually methylated with the development of mucosal patterns significantly enriched the genes involved in zinc-related pathways. The results indicates that gastric mucosal morphology predicts a "field defect" in this tissue type. Accumulation of DNA methylation is associated with "field defect" in the non-neoplastic gastric mucosa. Endoscopic identification of "field defect" has important implications for preventing gastric cancer. Our results suggest that magnifying NBI of gastric mucosal morphology predicts a "field defect" in the gastric mucosa.