Colonic Metastasis in a Patient With Hereditary Diffuse Gastric Cancer: A Case Report.

Metastasis of gastric carcinoma to atypical locations can complicate management, often leading clinicians to rely heavily on chemotherapy. While instances of gastric carcinoma spreading to the liver, peritoneum, and lymphatics are well documented in the literature, there is limited evidence of its spread to intraintestinal organs, particularly the colon. This scarcity of reports complicates diagnosis, given the variations in histopathology. This case report highlights a 35-year-old patient diagnosed with colonic metastasis from hereditary diffuse gastric cancer (HDGC) while being evaluated for potential causes of iron deficiency anemia. A mutation in the E-cadherin (CDH1) tumor suppressor gene is associated with HDGC. Dysregulation of CDH1 leads to tumor proliferation, invasion, migration, and metastasis. Treatment options for gastric cancer include surgical resection with neoadjuvant or adjuvant chemotherapy or palliative care with chemotherapy in metastatic disease. Although colonic metastasis from gastric cancer is rare, documented incidents can offer valuable insights that avoid misdiagnosing primary tumors and help guide further management.

Role of endoscopic ultrasound-guided tissue acquisition for the diagnosis of gastric wall thickening: a retrospective study with meta-analysis.

Background: Tissue acquisition from a thickened gastric wall using biopsy forceps may not always lead to diagnosis, given the submucosal location of the pathology. Endoscopic ultrasound (EUS)-guided tissue acquisition (TA) may serve as a minimally invasive diagnostic tool in such cases. Hence, we aimed to assess the diagnostic outcome and safety of EUS-TA from thickened gastric walls. Methods: Data from patients with gastric wall thickening undergoing EUS-TA at 5 tertiary care centers from August 2020 to August 2022 were retrospectively analyzed. These data were pooled with studies obtained from a comprehensive search of Medline, Embase and Scopus from January 2000 to November 2022 and a meta-analysis was performed. Pooled event rates were calculated using an inverse variance model. Results: The search strategy yielded 13 studies that were combined with data from 30 patients from our centers; a total of 399 patients were included in the analysis. The pooled rate of sample adequacy was 94.1% (95% confidence interval [CI] 90.0-98.2), while the pooled rate of diagnostic accuracy was 91.3% (95%CI 87.0-95.5). The pooled sensitivity and specificity for diagnosing malignant lesions with EUS-TA from gastric wall thickening were 94.8% (95%CI 91.3-97.2) and 100% (95%CI 93.6-100), respectively. There were no reported adverse events in any of the studies. Conclusions: EUS-TA offers a safe and accurate diagnostic modality for the etiological diagnosis of thickened gastric walls. Further research is required to identify the needle type and optimal technique for improving outcomes.

Randomized phase II study comparing neoadjuvant 5-fluorouracil/oxaliplatin/docetaxel versus docetaxel/oxaliplatin/S-1 for patients with type 4 or large type 3 gastric cancer.

Macroscopic type 4 and large type 3 gastric cancer, mostly overlapping with scirrhous or linitis plastica type, exhibit a highly invasive nature and show unfavorable prognosis after curative surgery, even with adjuvant chemotherapy. A randomized phase III trial (JCOG0501) failed to demonstrate a survival advantage of neoadjuvant chemotherapy with S-1 plus cisplatin for this population. The current authors initiated a randomized phase II study comparing neoadjuvant chemotherapy with 5-fluorouracil/oxaliplatin/docetaxel versus docetaxel/oxaliplatin/S-1 for type 4 and large type 3 gastric cancer. 76 patients are planned to be enrolled over two years. The primary end point is the proportion of patients with a pathological response (grade 1b or higher) and secondary end points include overall survival and adverse events. Clinical Trial Registration: jRCTs031230231 (rctportal.niph.go.jp).

The Genomic Signatures of Linitis Plastica Signal the Entrance into a New Era: Novel Approaches for Diagnosis and Treatment.

Linitis Plastica (LP) is a rare and aggressive tumor with a distinctive development pattern, leading to the infiltration of the gastric wall, the thickening of the gastric folds and a "leather bottle appearance". LP is an extremely heterogeneous tumor caused by mutations in oncogenic and tumor suppressive genes, as well as molecular pathways, along with mutations in stromal cells and proteins related to tight junctions. Elucidating the molecular background of tumorigenesis and clarifying the correlation between cancerous cells and stromal cells are crucial steps toward discovering novel diagnostic methods, biomarkers and therapeutic targets/agents. Surgery plays a pivotal role in LP management, serving both as a palliative and curative procedure. In this comprehensive review, we aim to present all recent data on the molecular background of LP and the novel approaches to its management.

Efficacy for diagnoses of scirrhous gastric cancer and safety of endoscopic ultrasound-guided fine-needle aspiration: A systematic review and meta-analysis.

Scirrhous gastric cancer (SGC) is diagnosed using endoscopy and/or biopsy; however, SGC diagnosis remains challenging owing to its special growth form and morphologic features. Hence, endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA), which is minimally invasive and has a high proportion of diagnostic tissue, may be an alternative investigative modality for patients with suspected SGC. This systematic review and meta-analysis aimed to identify and evaluate the evidence for the efficacy and safety of EUS-FNA in patients with suspected SGC. We conducted a systematic review using the PubMed (MEDLINE) and Ichushi-Web (NPO Japan Medical Abstracts Society) databases and included all entries in which SGC was evaluated using EUS-FNA in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement from the databases' inception to October 10, 2022. The primary outcome was the proportion of SGC diagnosed using EUS-FNA. In addition, we analyzed the proportion of adverse events associated with EUS-FNA. The electronic search identified 1890 studies; overall, four studies met the selection criteria and reported data on EUS-FNA performed on 114 patients with suspected SGC. The overall diagnostic yield of EUS-FNA for SGC was 82.6% (95% confidence interval, 74.6-90.6%) and the statistical heterogeneity was 0% (I 2 = 0%), indicating a low heterogeneity. Furthermore, the EUS-FNA diagnostic proportion for SGC lymph node metastasis was 75-100%, indicating a high diagnostic performance. The adverse event rate of EUS-FNA was 0%. EUS-FNA may be an alternative investigation mode for SGC patients with negative esophagogastroduodenoscopy-biopsy results.

Gastric Linitis Plastica: Clinical Characteristics and Outcomes from the National Cancer Database.

BACKGROUND/AIM: Gastric linitis plastica (LP) is a rare type of gastric tumor with limited data. We sought to investigate the clinical characteristics, treatment modalities, and outcomes utilizing a national database. PATIENTS AND METHODS: The National Cancer Database (NCDB) was reviewed for LP of the stomach from 2004 to 2017. Kaplan-Meier analysis and Cox proportional hazards model were utilized to evaluate overall survival and predictors of survival. RESULTS: Out of 222,488 gastric cancer cases, 896 patients with histologically confirmed primary gastric LP were included. Patients were predominantly white (78.5%), female (51.9%) and presented at advanced stage disease (stage 4=69%). A total of 369 (41.2%) patients underwent surgical resection, 520 (58.0%) received chemotherapy and 158 (17.6%) received radiation therapy. The mean OS (overall survival) of the entire cohort was 16.9 months with 1-year and 5-year OS rates of 33% and 5%, respectively. Mean OS for the patients receiving surgery with chemotherapy and/or radiation, surgery alone, chemotherapy and/or radiotherapy alone, and no treatment was 28.4, 17.1, 12.3, and, 8.1 months, respectively (p<0.001). On multivariate cox-regression analysis, advanced-stage disease (stage IV) (p<0.001), no surgical resection (p<0.001), and no receipt of chemotherapy (p<0.001) were associated with increased hazards of death. Over time, the proportion of patients receiving surgical resection (30.7% from 48.3%) and radiation therapy decreased (13.8% from 20.6%) and the use of chemotherapy increased (63.9% from 54.8%). CONCLUSION: Gastric LP is associated with a poor prognosis. Multimodal therapy including surgical resection and systemic therapy in the neoadjuvant setting seems to provide the best long-term outcomes.

Gastric Metastasis From Lung Adenocarcinoma: An Uncommon Presentation.

Gastric metastasis is an infrequent occurrence, especially when derived from lung adenocarcinomas. They can grossly resemble advanced gastric cancer and require comprehensive evaluations of the patients and their symptoms. Here, we present the case of a 71-year-old patient admitted to our hospital due to intense, cramping abdominal pain. He had been previously diagnosed with a right lower lobe adenocarcinoma of the lung, which was treated in the previous year with chemotherapy and radiotherapy with good clinical response. The abdominal CT scan and the esophagogastroduodenoscopy showed a gastric infiltrating lesion resembling advanced gastric cancer. However, the biopsy showed malignant epithelial neoplasia with features of adenocarcinoma of pulmonary origin. Even though they are an uncommon finding, gastrointestinal metastases may be life-threatening and should be diagnosed as soon as possible, as the advent of molecular studies and new therapies may result in better survival rates.

Analysis of genomic and immune intratumor heterogeneity in linitis plastica via multiregional exome and T-cell receptor sequencing.

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.

pCLE detects mucosal neoplastic vascular pattern in gastric linitis plastica.

Linitis plastica (LP) is a very aggressive and rare carcinoma with a scirrhous stroma that affects the submucosal and muscular layers of the stomach even without mucosal alterations. Lack of timely diagnosis is a crucial problem related to its prognosis and treatment. In this study, we investigated the LP-associated vascular pattern as a possible means to improve the diagnosis of these patients. During standard endoscopy, mucosal architecture, tortuosity and enlargement of vessels, as well as the presence of vascular leakage and efficiency of the blood flow were assessed in six LP patients using probe-based Confocal Laser Endomicroscopy (pCLE). In all LP patients, we detected abnormal changes in vasculature. The aberrant features of the vascular network were common to all LP patients examined and consisted of vessel enlargement, tortuosity, and leakage associated with the affected submucosal layer. This is the first study to highlight the presence of marked vascularization associated with LP, characterized by the presence of abnormal and non-functional vessels, similar to what is observed in neoplastic tissues. Therefore, the analysis of LP by pCLE may provide a new endoscopic approach and strategy to better define these patients.

Comprehensive transcriptomic profiling and mutational landscape of primary gastric linitis plastica.

BACKGROUND: Primary 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. METHODS: We 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. RESULTS: Our 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. CONCLUSIONS: We provide the first integrative genomic and transcriptomic profiles of GLP, which may facilitate its diagnosis, prognosis, and treatment.

Yeyunostomía laparoscópica / Laparoscopic jejunostomy / Jejunostomia laparoscópica

La yeyunostomía implica el abocamiento del yeyuno a la piel y se utiliza como vía de nutrición enteral en pacientes con imposibilidad de alimentarse por vía oral; en quienes la gastrostomía no es una opción adecuada. La misma puede realizarse por vía mínimamente invasiva, como percutánea y laparoscópica

[Chronic ischemic gastropathy as a simulator of plastic linitis]. / Gastropatía isquémica crónica como simuladora de linitis plástica.

Chronic ischemic gastropathy is a rare entity, being the atheroesclerotic vascular the most prevalent cause. Clinical and endoscopic manifestations are unspecific and may simulate more frequent pathologies. Cardiovascular risk factors allow us to diagnose and treat these patients earlier. We present the case of a patient with chronic ischemic gastropathy that manifested abdominal pain, weight loss and endoscopic findings as a simulator of linitis plastica. The diagnosis was made with an endoscopic block biopsy after two inconclusive biopsies.

La gastropatía isquémica es una entidad rara, cuya etiología más frecuente es la obstrucción al flujo sanguíneo secundaria a aterosclerosis. Sus manifestaciones clínicas y endoscópicas son inespecíficas, pudiendo simular afecciones más prevalentes. La sospecha clínica en pacientes con factores de riesgo cardiovascular permite un diagnóstico precoz y tratamiento adecuado. Presentamos el caso de una paciente con gastropatía isquémica crónica que se manifestó con dolor abdominal, pérdida de peso y hallazgos endoscópicos compatibles con linitis plástica. Se arribó al diagnóstico con una biopsia endoscópica en bloque luego de haber obtenido dos biopsias previas no concluyentes.

Gastropatía isquémica crónica como simuladora de linitis plástica / Chronic ischemic gastropathy as a simulator of plastic linitis

Resumen La gastropatía isquémica es una entidad rara, cuya etiología más frecuente es la obstrucción al flujo sanguíneo secundaria a aterosclerosis. Sus manifestaciones clínicas y endoscópicas son inespe cíficas, pudiendo simular afecciones más prevalentes. La sospecha clínica en pacientes con factores de riesgo cardiovascular permite un diagnóstico precoz y tratamiento adecuado. Presentamos el caso de una paciente con gastropatía isquémica crónica que se manifestó con dolor abdominal, pérdida de peso y hallazgos endoscópicos compatibles con linitis plástica. Se arribó al diagnóstico con una biopsia endoscópica en bloque luego de haber obtenido dos biopsias previas no concluyentes.

Abstract Chronic ischemic gastropathy is a rare entity, being the atheroesclerotic vascular the most prevalent cause. Clinical and endoscopic manifestations are unspecific and may simulate more frequent pathologies. Cardio vascular risk factors allow us to diagnose and treat these patients earlier. We present the case of a patient with chronic ischemic gastropathy that manifested abdominal pain, weight loss and endoscopic findings as a simula tor of linitis plastica. The diagnosis was made with an endoscopic block biopsy after two inconclusive biopsies.

Gastric linitis plastica with autoimmune pancreatitis diagnosed by an endoscopic ultrasonography-guided fine-needle biopsy: A case report.

BACKGROUND: Gastric linitis plastica (GLP) is a subset of gastric cancer with a poor prognosis. It is difficult to obtain a definitive diagnosis by endoscopic mucosal biopsies, and the usefulness of an endoscopic ultrasonography-guided fine-needle biopsy (EUS-FNB) for GLP has been recently reported. Meanwhile, autoimmune diseases are occasionally known to coexist with malignant tumors as paraneoplastic syndrome. We herein report the usefulness of an EUS-FNB for detecting GLP and the possibility of paraneoplastic syndrome coexisting with GLP. CASE SUMMARY: An 81-year-old man was admitted to our hospital for a 1-mo history of epigastric pain that increased after eating. His laboratory data revealed high levels of serum carbohydrate antigen 19-9 and immunoglobulin-G4. Endoscopic examinations showed giant gastric folds and reddish mucosa; however, no epithelial changes were observed. The gastric lumen was not distensible by air inflation, suggesting GLP. Computed tomography showed the thickened gastric wall, the diffuse enlargement of the pancreas, and the peripancreatic rim, which suggested autoimmune pancreatitis (AIP) coexisting with GLP. Because the pathological findings of the endoscopic biopsy showed no malignancy, he underwent an EUS-FNB and was diagnosed with GLP. He received chemotherapy for unresectable gastric cancer due to peritoneal metastasis, after which both the gastric wall thickening and diffuse enlargement of the pancreas were improved. CONCLUSION: An EUS-FNB for GLP with a negative endoscopic biopsy is useful, and AIP may develop as a paraneoplastic syndrome.

Rectal linitis plastica as the first presentation of metastatic lobular breast cancer: an endoscopic ultrasound diagnosis.

Gastrointestinal tract is an uncommon site of breast cancer metastasis. Rectal linitis plastica (RLP) is a rare presentation of rectal neoplasia, both primary and secondary, and refers to a diffuse infiltration of the wall by an infiltrating carcinoma. Diagnostic assessment of RLP may be challenging since cross-sectional imaging and endoscopic findings may be nonspecific, and endoscopic biopsies are frequently non-diagnostic due to the submucosal disease localization. Endoscopic ultrasound (EUS) with fine needle biopsy (FNB) is widely used for the diagnostic assessment of sub-epithelial lesions of upper and lower gastrointestinal tract. However, data about the use of EUS in case of rectal linitis plastica are very poor. We present a case of rectal metastasis as the first presentation of lobular breast cancer, presenting as rectal linitis plastica and diagnosed with EUS-FNB.

Endoscopic ultrasound-guided fine-needle biopsy for the diagnosis of gastric metastasis from breast cancer mimicking primary linitis plastica: A case report.

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.

Endoscopic ultrasound-guided fine-needle biopsy for the diagnosis of gastric linitis plastica.

We report two cases of patients with gastric linitis plastica (GLP), in which the histopathological diagnosis was made by endoscopic ultrasound-guided fine-needle biopsy (EUS-FNB) using a Franseen-tip needle. Esophagogastroduodenoscopy findings showed mucosal swelling and poor distensibility of the gastric antrum. Abdominal computed tomography findings showed significant thickening of the gastric wall at the antrum. Conventional endoscopic and bite-on-bite biopsy were attempted but resulted in failure to diagnose the lesions. We performed EUS-FNB to obtain histopathological samples from a deeper site, which confirmed the diagnosis. We considered this method safe and effective for the diagnosis of GLP.

Endoscopic ultrasound guided fine needle biopsy in patients with suspected gastric linitis plastica.

BACKGROUND: Gastric linitis plastica (GLP) is a diffuse infiltrating type of gastric adenocarcinoma. It is associated with a poor prognosis and a five-year survival of 3-10%. The infiltrating profile of this tumor explains the low yield of the superficial mucosal biospies. The objective of this study was to investigate the role of endoscopic ultrasound-fine needle biopsy (EUS-FNB) in the diagnosis of GLP. METHODS: We performed a retrospective analysis including all patients who had an EUS-FNB, at a tertiary referral center, over the last 3 years. The primary outcome was the sensitivity of EUS-FNB in patients with suspected GLP. RESULTS: Between January 2017 and December 2020, 34 patients had an EUS-FNB for suspected GLP. Ten patients had a diagnostic of GLP. This diagnosis was obtained by EUS-FNB in 90% (9/10) of the cases. Eight patients had at least one previous esophagogastroduodenoscopy (EGD) with negative mucosal biopsies. Gastric EUS-FNB helped diagnose other serious conditions in 47% (16/34) of cases with inconclusive mucosal biopsies. CONCLUSION: Gastric EUS-FNB in patients with suspected GLP and normal endoscopic mucosal biopsies may lead to a positive diagnosis of GLP in 90% of cases without notable adverse events. This technique should be considered as a second step in the setting of suspicion of GLP after inconclusive mucosal biopsies.

Usefulness of endoscopic ultrasound for acquiring the pathological diagnosis of gastrointestinal lymphoma.

BACKGROUND AND STUDY AIMS: This study aims to assess the value of endoscopic ultrasound (EUS) for acquiring a pathological diagnosis of gastrointestinal lymphoma (GIL). PATIENTS AND METHODS: We retrospectively reviewed all GIL patients who underwent EUS from November 2011 to July 2020 at Fudan University Shanghai Cancer Center. All patients with pathologically confirmed GIL were included. The characteristics of the lesions were recorded, and the efficacy for acquiring pathologic diagnosis between white light endoscopy (WLE) and EUS was analyzed. RESULTS: In total, 404 patients with GIL who underwent EUS examination were included in this study. GIL was confirmed in 143 cases by after EUS judgment biopsy (AEJ biopsy), 11 cases by endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA), 293 cases by WLE biopsy, and 10 cases by surgical pathology for repeated negative pathologic results from EUS and WLE. Among all cases, 78.71% (318/404) were T1-T2, whereas 32.18% (130/404) were determined to have multiple lesions in the digestive tract wall. The positive rates of the WLE biopsy and AEJ biopsy of the involved gastric wall were 77.93% (293/376) and 89.38% (143/160), respectively. Twelve cases showed diffuse thickening of the gastric wall, and the total positive rate of EUS was 91.67% but 0% for WLE with this type of GIL. The total positive rate and positive rate during the first examination of EUS were all significantly higher than those of WLE. Moreover, 19.68% of the patients showed negative results during their WLE examination and then received a positive pathologic diagnosis upon EUS examination, but none had the opposite process. CONCLUSIONS: EUS was found to be a better tool for acquiring a pathological diagnosis of GIL than conventional WLE, especially for GIL similar to linitis plastica.