Linitis plastica: a harbinger of an unusual cause of gastric wall thickening.
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ABSTRACT:
SUBMITTER: Banerjee D
PROVIDER: S-EPMC5991917 | biostudies-literature | 2017 Sep
REPOSITORIES: biostudies-literature
Publications
Linitis plastica: a harbinger of an unusual cause of gastric wall thickening.
Banerjee Debdeep D Raghavapuram Saikiran S Jeffus Susanne S Murphy Seamus S Tharian Benjamin B
VideoGIE : an official video journal of the American Society for Gastrointestinal Endoscopy 20170119 9
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Project description:BackgroundPrimary gastric linitis plastica (GLP) is a distinct phenotype of gastric cancer with poor survival. Comprehensive molecular profiles and putative therapeutic targets of GLP remain undetermined.MethodsWe subjected 10 tumor-normal tissue pairs to whole exome sequencing (WES) and whole transcriptome sequencing (WTS). 10 tumor samples were all GLP which involves 100% of the gastric wall macroscopically. TCGA data were compared to generate the top mutated genes and the overexpressed genes in GLP.ResultsOur results reveal that GLP has distinctive genomic and transcriptomic features, dysfunction in the Hippo pathway is likely to be a key step during GLP development. 6 genes were identified as significantly highly mutated genes in GLP, including AOX1, ANKRD36C, CPXM1, PTPN14, RPAP1, and DCDC1). MUC6, as a previously identified gastric cancer driver gene, has a high mutation rate (20%) in GLP. 20% of patients in our GLP cohort had CDH1 mutations, while none had RHOA mutations. GLP exhibits high immunodeficiency and low AMPK pathway activity. Our WTS results showed that 3 PI3K-AKT pathway-related genes (PIK3R2, AKT3, and IGF1) were significantly up-regulated in GLP. Two genes were identified using immunohistochemistry (IHC), IGF2BP3 and MUC16, which specifically expressed in diffuse-type-related gastric cancer cell lines, and its knockdown inhibits PI3K-AKT pathway activity.ConclusionsWe provide the first integrative genomic and transcriptomic profiles of GLP, which may facilitate its diagnosis, prognosis, and treatment.
| S-EPMC9950178 | biostudies-literature
Project description:BackgroundEndoscopic ultrasound (EUS) is a key imaging technique in gastric cancer (GC). The aim of this study was to evaluate the performance of EUS in the staging of parietal and lymph node involvement in linitis plastica (LP) compared to "classical" GC.MethodsA retrospective multicentric French study was conducted on patients with no metastatic LP and operated by gastrectomy. A 2/1 matching based on pTNM stage and center was performed with GC.ResultsForty-three patients were included, sixteen patients in the LP group and 27 in the control group. Sensitivity and specificity of EUS for diagnosis of T3-T4 parietal invasion were 77% and 100% respectively in the LP group and 89% and 56% respectively in the control group. Sensitivity and specificity of EUS for diagnosis of lymph node involvement were 73% and 80%, respectively in the LP group and 88% and 50%, respectively in the control group. Patients from LP group had significantly more advanced histological lesion, and frequent undiagnosed peritoneal carcinomatosis.ConclusionsThis study evaluated for the first time in a European population, the preoperative EUS performance in LP. Our study identified a similar sensitivity and specificity of the EUS in LP compared to "classical" GC paving for a broader use of EUS in preoperative settings.
| S-EPMC7859799 | biostudies-literature
Project description:Gastric linitis plastica (GLP) is a descriptive term but lacks a quantitative definition. Several relatively quantitative criteria had been proposed, such as tumor involving a limit of one-third or two-thirds of the gastric surface. However, these criteria needed doctors to subjectively judge tumor infiltration area, which made diagnosis difficult to be objective and reproducible. This study aimed to propose a quantitative diagnostic criterion for distinguishing GLP. We performed a retrospective cohort study of 2,907 patients with Borrmann III and IV gastric cancer (GC) who underwent gastrectomy between 2011 and 2018 in our center. The Kaplan-Meier curves showed that patients with an observed tumor size more than 8 cm had obviously lower overall survival (OS) and disease-free survival (DFS) rates than those with a size less than 8 cm(p < 0.001; p < 0.001). However, there was no significantly different prognosis of patients with tumor sizes between more than 8 cm and more than 10 cm (p = 0.248; p = 0.534). Moreover, patients with tumor sizes greater than 8 cm more presented with advanced stage and had extremely poor 3-year OS and DFS (31.4%; 29.3%), with a stronger propensity toward peritoneal metastasis. Therefore, we considered patients' observed tumor size more than 8 cm as a critical value for distinguishing the prognosis of Borrmann III and IV GC. Furthermore, we proposed an observed tumor size more than 8 cm as a quantitative diagnostic criterion for GLP on the premise of satisfying the originally descriptive and pathological definition regardless of Borrmann type.
| S-EPMC8377468 | biostudies-literature
Project description:BackgroundTo explore the efficacy of treatment strategies for non-metastatic gastric linitis plastica (GLP).MethodsPatients with non-metastatic GLP from 2004 to 2014 were identified from the National Cancer Database (NCDB). We compared overall survival (OS) of those patients who received different treatments, including surgery alone, a combination of surgery with chemotherapy and/or radiotherapy (S + C/R), chemotherapy and/or radiotherapy (C/R), and no treatment.ResultsThe cohort included 474 patients with non-metastatic GLP. Overall, the median survival was significantly different among four groups (13.90 months in S + C/R, 8.38 months in surgery alone, 8.94 months in C/R and 2.50 months in no treatment). Then, we compared the efficacy of surgery alone and surgery with postoperative chemotherapy and/or radiotherapy (S + post C/R). When the tumor size was greater than 8 cm in stage III patients, S + post C/R was associated with a better survival benefit than surgery alone. S + post C/R also conferred an obvious survival advantage compared to surgery alone for R0 patients with positive lymph nodes and patients with positive margins.ConclusionsSurgery plays the fundamental role in improving the OS of patients with non-metastatic GLP. S + post C/R would benefit patients in stage III with large-sized tumors (>8 cm), patients with negative margins and positive lymph nodes, and/or patients with positive margins.
| S-EPMC7723551 | biostudies-literature
Project description:For gastric lesions in a patient with a history of breast cancer, it is essential to distinguish between primary gastric cancer and gastric metastasis from breast cancer. However, gastric metastasis from breast cancer often mimics primary linitis plastica, and histological diagnosis may be difficult with conventional endoscopic biopsies. Herein, we describe the case of a 75-year-old woman who presented at our hospital with epigastralgia and vomiting. She had a history of mastectomy for carcinoma of the right breast and had received hormone therapy as adjuvant therapy. Computed tomography at arrival showed thickening of the gastric wall at the antrum and peritoneal dissemination. Esophagogastroduodenoscopy showed mucosal swelling of the antrum and stenosis of the pylorus, and histological diagnosis failed with conventional endoscopic biopsies. Endoscopic ultrasound-guided fine-needle biopsy using a Franseen needle was performed, and a diagnosis of gastric metastasis from breast cancer was made. She received hormone therapy and chemotherapy after deployment of a metallic stent for gastric outlet obstruction. To the best of our knowledge, this is the first case of gastric metastasis from breast cancer diagnosed using endoscopic ultrasound-guided fine-needle biopsy.
| S-EPMC9302264 | biostudies-literature
Project description:The molecular landscape and the intratumor heterogeneity (ITH) architecture of gastric linitis plastica (LP) are poorly understood. We performed whole-exome sequencing (WES) and T-cell receptor (TCR) sequencing on 40 tumor regions from four LP patients. The landscape and ITH at the genomic and immunological levels in LP tumors were compared with multiple cancers that have previously been reported. The lymphocyte infiltration was further assessed by immunohistochemistry (IHC) in LP tumors. In total, we identified 6339 non-silent mutations from multi-samples, with a median tumor mutation burden (TMB) of 3.30 mutations per Mb, comparable to gastric adenocarcinoma from the Cancer Genome Atlas (TCGA) cohort (P = 0.53). An extremely high level of genomic ITH was observed, with only 12.42%, 5.37%, 5.35%, and 30.67% of mutations detectable across 10 regions within the same tumors of each patient, respectively. TCR sequencing revealed that TCR clonality was substantially lower in LP than in multi-cancers. IHC using antibodies against CD4, CD8, and PD-L1 demonstrated scant T-cell infiltration in the four LP tumors. Furthermore, profound TCR ITH was observed in all LP tumors, with no T-cell clones shared across tumor regions in any of the patients, while over 94% of T-cell clones were restricted to individual tumor regions. The Morisita overlap index (MOI) ranged from 0.21 to 0.66 among multi-regions within the same tumors, significantly lower than that of lung cancer (P = 0.002). Our results show that LP harbored extremely high genomic and TCR ITH and suppressed T-cell infiltration, suggesting a potential contribution to the frequent recurrence and poor therapeutic response of this adenocarcinoma.
| S-EPMC10399711 | biostudies-literature
Project description:Chronic exposure to hypoxia causes pulmonary hypertension and pulmonary arterial remodeling. Although the exact mechanisms of this remodeling are unclear, there is evidence that it is dependent on hemodynamic stress, rather than on hypoxia alone. Pulmonary supernumerary arteries experience low hemodynamic stress as a consequence of reduced perfusion due to 90° branching angles, small diameters, and "valve-like" structures at their orifices. We investigated whether or not intra-acinar supernumerary arteries undergo structural remodeling during the moderate pulmonary hypertension induced by chronic hypoxia. Rats were exposed to either normoxia or hypoxia for 6 weeks. The chronically hypoxic rats developed pulmonary hypertension. For both groups, pulmonary arteries were selectively filled with barium-gelatin mixture, and the wall thickness of intra-acinar pulmonary arteries was measured in histological samples. Only thin-walled arteries were observed in normoxic lungs. In hypertensive lungs, we found both thin- and thick-walled pulmonary arteries with similar diameters. Disproportionate degrees of arterial wall thickening between parent and daughter branches were observed with supernumerary branching patterns. While parent arteries developed significant wall thickening, their supernumerary branches did not. Thus, chronic hypoxia-induced pulmonary hypertension did not cause wall thickening of intra-acinar pulmonary supernumerary arteries. These findings are consistent with the idea that hemodynamic stress, rather than hypoxia alone, is the cause of structural remodeling during chronic exposure to hypoxia.
| S-EPMC4760391 | biostudies-other
Project description:A 54-year-old man had previously undergone curative sigmoidectomy for poorly differentiated adenocarcinoma with a signet-ring cell component of the sigmoid colon, which was characterized morphologically by stenosis and inelasticity of the colon (linitis plastica). Six weeks after surgery, the patient developed stenosis of the right ureter. Disseminated sigmoid cancer was suspected, and chemotherapy was started. Nine months after initiation of chemotherapy, obstructive jaundice was observed which was due to stenosis of the distal bile duct (BD). Although computed tomography showed no evident metastatic lesion that could cause the stenosis, swelling of the entire pancreas was evident compared to that of 11 months earlier. Endoscopic ultrasound (EUS) also did not detect any focal masses in the head of the pancreas, although there was a diffuse hypoechoic change in the entire pancreas. Histopathology of the stenotic BD and biopsy specimen from the head of the pancreas showed no malignant cells. Two months after the initial endoscopic bile duct drainage, the patient was admitted again for epigastric pain. A second EUS fine needle aspiration (EUS-FNA) of the head of the pancreas was performed and showed poorly differentiated carcinoma with some signet-ring cells. This finding provided histological confirmation of a disseminated pancreatic lesion of the previously resected linitis plastica of the sigmoid colon. This is a rare case of disseminated pancreatic lesion from primary linitis plastica of the colon diagnosed by EUS-FNA.
| S-EPMC8828226 | biostudies-literature
Project description:A 40-year-old Japanese male presented with epigastric pain and loss of appetite at a general hospital three years ago. Computed tomography revealed massive thickening of the gastric wall, and gastroscopy revealed diffuse erythema and edematous thickening of the gastric mucosa. Thereafter, epigastric pain and gastric wall thickening recurred frequently, causing an inability to intake food. Conservative treatment was marginally effective; therefore, a distal gastrectomy was performed. Postoperatively, the patient resumed food intake without complications. Histopathological examination of the surgical specimen revealed Heinrich type 1 gastric ectopic pancreas (EP) with pancreatitis. In this case, the gastric wall's massive thickening was caused by gastric EP's pancreatitis. Although there are some reports of pancreatitis of gastric EP, there are no detailed reports of endoscopic findings, including endoscopic ultrasonography and the disease progression. Recurrent pancreatitis of EP leads to forming a septum within the gastric wall, resulting in a hematoma. Eventually, irreversible narrowing of the gastric lumen may occur, as observed in the present case. We consider this an important case report presenting detailed pathogenesis supported by endoscopic and pathohistological findings of surgical specimens. Our study will help in the early diagnosis and better management of the condition.
| S-EPMC9691903 | biostudies-literature
Project description:OBJECTIVE: In this article we present a simplified algorithm-based approach to the thickening of the small and large bowel wall detected on routine computed tomography (CT) of the abdomen. BACKGROUND: Thickening of the small or large bowel wall may be caused by neoplastic, inflammatory, infectious, or ischaemic conditions. First, distinction should be made between focal and segmental or diffuse wall thickening. In cases of focal thickening further analysis of the wall symmetry and perienteric anomalies allows distinguishing between neoplasms and inflammatory conditions. In cases of segmental or diffuse thickening, the pattern of attenuation in light of clinical findings helps narrowing the differential diagnosis. CONCLUSION: Focal bowel wall thickening may be caused by tumours or inflammatory conditions. Bowel tumours may appear as either regular and symmetric or irregular or asymmetric thickening. When fat stranding is disproportionately more severe than the degree of wall thickening, inflammatory conditions are more likely. With the exception of lymphoma, segmental or diffuse wall thickening is usually caused by benign conditions, such as ischaemic, infectious and inflammatory diseases. KEY POINTS: • Thickening of the bowel wall may be focal (<5 cm) and segmental or diffuse (6-40 cm or >40 cm) in extension. • Focal, irregular and asymmetrical thickening of the bowel wall suggests a malignancy. • Perienteric fat stranding disproportionally more severe than the degree of wall thickening suggests an inflammatory condition. • Regular, symmetric and homogeneous wall thickening is more frequently due to benign conditions, but can also be caused by neoplasms such as well-differentiated adenocarcinoma and lymphoma. • Segmental or diffuse bowel wall thickening is usually caused by ischaemic, inflammatory or infectious conditions and the attenuation pattern is helpful in narrowing the differential diagnosis.
| S-EPMC3999365 | biostudies-other