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Molecular Cancer Research : MCR Jun 2024The pathogenesis of duodenal tumors in the inherited tumor syndromes familial adenomatous polyposis (FAP) and MUTYH-associated polyposis (MAP) is poorly understood. This...
UNLABELLED
The pathogenesis of duodenal tumors in the inherited tumor syndromes familial adenomatous polyposis (FAP) and MUTYH-associated polyposis (MAP) is poorly understood. This study aimed to identify genes that are significantly mutated in these tumors and to explore the effects of these mutations. Whole exome and whole transcriptome sequencing identified recurrent somatic coding variants of phosphatidylinositol N-acetylglucosaminyltransferase subunit A (PIGA) in 19/70 (27%) FAP and MAP duodenal adenomas, and further confirmed the established driver roles for APC and KRAS. PIGA catalyzes the first step in glycosylphosphatidylinositol (GPI) anchor biosynthesis. Flow cytometry of PIGA-mutant adenoma-derived and CRISPR-edited duodenal organoids confirmed loss of GPI anchors in duodenal epithelial cells and transcriptional profiling of duodenal adenomas revealed transcriptional signatures associated with loss of PIGA.
IMPLICATIONS
PIGA somatic mutation in duodenal tumors from patients with FAP and MAP and loss of membrane GPI-anchors may present new opportunities for understanding and intervention in duodenal tumorigenesis.
Topics: Humans; Glycosylphosphatidylinositols; Duodenal Neoplasms; Mutation; Adenomatous Polyposis Coli; Membrane Proteins; Carcinogenesis; Male; Female
PubMed: 38546397
DOI: 10.1158/1541-7786.MCR-23-0810 -
International Journal of Surgery Case... Apr 2024Lemmel's syndrome is a rare disease presenting with obstructive jaundice, secondary to common bile duct compression by duodenal diverticulum.
INTRODUCTION
Lemmel's syndrome is a rare disease presenting with obstructive jaundice, secondary to common bile duct compression by duodenal diverticulum.
PRESENTATION OF CASE
A 79-year-old female was admitted to our emergency department with cholangitis and obstructive jaundice, due to choledocal compression by two periampullary diverticula, with major papilla opening near the biggest one (periampullary diverticulum type III). Endoscopic retrograde cholangiopancreatography didn't succeed sphincterotomy, therefore laparoscopic rendez-vous was performed.
DISCUSSION
This case is an example of an unusual cause of obstructive jaundice, which should be mentioned along with choledocolithiasis and biliary or ampullary neoplasms, in order to avoid delay in diagnosis and management.
CONCLUSION
The commonest treatment of Lemmel's syndrome reported in literature is ERCP with sphincterotomy, but when endoscopic management fails, interventional radiology and surgery should also be considered.
PubMed: 38531290
DOI: 10.1016/j.ijscr.2024.109522 -
World Journal of Gastroenterology Feb 2024In this editorial we comment on the article published "Clinical significance of programmed cell death-ligand expression in small bowel adenocarcinoma is determined by...
In this editorial we comment on the article published "Clinical significance of programmed cell death-ligand expression in small bowel adenocarcinoma is determined by the tumor microenvironment". Small bowel adenocarcinoma (SBA) is a rare gastrointestinal neoplasm and despite the small intestine's significant surface area, SBA accounts for less than 3% of such tumors. Early detection is challenging and the reason arises from its asymptomatic nature, often leading to late-stage discovery and poor prognosis. Treatment involves platinum-based chemotherapy with a 5-fluorouracil combination, but the lack of effective chemotherapy contributes to a generally poor prognosis. SBAs are linked to genetic disorders and risk factors, including chronic inflammatory conditions. The unique characteristics of the small bowel, such as rapid cell renewal and an active immune system, contributes to the rarity of these tumors as well as the high intratumoral infiltration of immune cells is associated with a favorable prognosis. Programmed cell death-ligand 1 (PD-L1) expression varies across different cancers, with potential discrepancies in its prognostic value. Microsatellite instability (MSI) in SBA is associated with a high tumor mutational burden, affecting the prognosis and response to immunotherapy. The presence of PD-L1 and programmed cell death 1, along with tumor-infiltrating lymphocytes, plays a crucial role in the complex microenvironment of SBA and contributes to a more favorable prognosis, especially in the context of high MSI tumors. Stromal tumor-infiltrating lymphocytes are identified as independent prognostic indicators and the association between MSI status and a favorable prognosis, emphasizes the importance of evaluating the immune status of tumors for treatment decisions.
Topics: Humans; Tumor Microenvironment; B7-H1 Antigen; Ligands; Prognosis; Lymphocytes, Tumor-Infiltrating; Adenocarcinoma; Intestine, Small; Duodenal Neoplasms
PubMed: 38516246
DOI: 10.3748/wjg.v30.i8.794 -
Arquivos Brasileiros de Cirurgia... 2024Duodenal adenocarcinoma is a small percentage of gastrointestinal neoplasms, around 0.5%, and its treatment is based on resection of the tumor, classically by...
BACKGROUND
Duodenal adenocarcinoma is a small percentage of gastrointestinal neoplasms, around 0.5%, and its treatment is based on resection of the tumor, classically by pancreaticoduodenectomy. In recent years, however, segmental resections of duodenal lesions, that do not involve the second portion or the periampullary region, have gained relevance with good surgical and oncological outcomes as well as the benefit of avoiding surgeries that can result in high morbidity and mortality.
AIMS
To report a case of an elderly female patient with malignant neoplastic lesion in the third and fourth duodenal portion, non-obstructive, submitted to surgical treatment.
METHODS
The technical option was the resection of the distal duodenum and proximal jejunum with preservation of the pancreas and reconstruction with side-to-side duodenojejunal anastomosis.
RESULTS
The evolution was satisfactory and the surgical margins were free of neoplasia.
CONCLUSIONS
Segmental resections of the duodenum are feasible and safe, offering the benefit of preventing complications of pancreaticoduodenectomies.
Topics: Humans; Female; Aged; Duodenum; Biopsy; Pancreaticoduodenectomy; Adenocarcinoma; Anastomosis, Surgical; Treatment Outcome
PubMed: 38511813
DOI: 10.1590/0102-672020240003e1796 -
Frontiers in Oncology 2024Primary appendiceal tumors are rare. Low-grade appendiceal mucinous neoplasia (LAMN) and goblet cell adenocarcinoma (GCA) account for 20% and 14% of primary appendiceal...
BACKGROUND
Primary appendiceal tumors are rare. Low-grade appendiceal mucinous neoplasia (LAMN) and goblet cell adenocarcinoma (GCA) account for 20% and 14% of primary appendiceal tumors, respectively. The coexistence of LAMN and GCA is an extremely rare event. This report presents a case of an elderly male patient with an appendiceal tumor composed of LAMN and GCA in the same appendix.
CASE PRESENTATION
A 72-year-old male patient was admitted to our institution presenting with a history of abdominal pain localized to the right lower quadrant for two months. Abdominal computed tomography (CT) showed a large dilated thickened cystic mass in the appendix, along with a small duodenal diverticulum. Laboratory tests indicated elevated levels of serum carcinoembryonic antigen (CEA) and cancer antigen 199 (CA19-9) markers. The patient underwent a laparoscopic right hemicolectomy and exploration of the duodenal diverticulum, and there was no finding of perforation of the duodenal diverticulum. Focal positivity for chromogranin A (CgA) and synaptophysin (Syn) was observed in the tumor cells of GCA. The final pathological diagnosis revealed the coexistence of LAMN staged pT4a and grade 1 GCA staged pT3 in the appendix. Unfortunately, the patient died due to severe septic shock and circulatory failure secondary to a perforated duodenal diverticulum.
CONCLUSIONS
The coexistence of LAMN and GCA are extremely rare in the appendix and may result from the proliferation of two independent cellular lines. The coexistence of distinct neoplasms poses diagnostic and management challenges. Multidisciplinary team discussion may be essential in the effective management of these patients.
PubMed: 38500658
DOI: 10.3389/fonc.2024.1313548 -
Fa Yi Xue Za Zhi Feb 2024
Topics: Humans; Stomach Neoplasms; Gastrectomy; Duodenum; Laparoscopy; Retrospective Studies; Postoperative Complications
PubMed: 38500469
DOI: 10.12116/j.issn.1004-5619.2023.430508 -
Diagnostics (Basel, Switzerland) Mar 2024Gastric cancer, a leading cause of cancer-related deaths globally, necessitates effective and early detection and treatment strategies. Endoscopic resection techniques,...
Gastric cancer, a leading cause of cancer-related deaths globally, necessitates effective and early detection and treatment strategies. Endoscopic resection techniques, particularly endoscopic mucosal resection (EMR) and endoscopic submucosal dissection (ESD), have evolved significantly, enhancing the treatment of gastric neoplasms. Underwater endoscopic mucosal resection (UEMR) is a widely used technique for the resection of duodenal and colorectal neoplasms. However, the feasibility and efficacy of UEMR in the stomach are not well established. This retrospective observational study, conducted at a tertiary medical center, evaluated the efficacy and safety of UEMR in 81 patients with gastric neoplasms. Thus, it indicates that UEMR is a highly effective and safe technique for managing small to medium-sized gastric neoplasms, achieving 100% en bloc and 93.8% R0 resection rates with a low incidence of complications. Moreover, the procedure time was found to be significantly shorter for UEMR compared to ESD, thus highlighting its efficiency. While UEMR demonstrates high safety and efficacy, it is not suitable for all patients, with some requiring conversion to ESD as a treatment option. Despite the promising results, broader validation through extensive and randomized trials is recommended to establish UEMR as a standard approach in gastric cancer management.
PubMed: 38473010
DOI: 10.3390/diagnostics14050536 -
BMC Cancer Mar 2024Ampullary adenocarcinoma (AMPAC) is a rare malignancy, treated as pancreatic or intestinal cancer based on its histologic subtype. Little is known about the genomic...
BACKGROUNDS
Ampullary adenocarcinoma (AMPAC) is a rare malignancy, treated as pancreatic or intestinal cancer based on its histologic subtype. Little is known about the genomic features of Chinese patients with AMPAC.
MATERIALS AND METHODS
We enrolled 145 Chinese AMPAC patients in our local cohort and performed a compressive somatic and germline genetic testing using a 156 gene panel. Expression of PD-L1 (clone 28 - 8) was also assessed in tumor specimens from 64 patients.
RESULTS
The frequency of genetic alterations (GAs) in Chinese patients with AMPAC was found to be distinctive, with TP53, KRAS, SMAD4, APC, CTNNB1, ARID1A, and CDKN2A emerged as the most frequently mutated genes. Comparing with Western patients, significant differences were observed in the prevalence of PIK3CA and ARID2. Furthermore, the incidence of MSI-H was lower in the Chinese cohort, with only two patients identified as MSI-H. Conversely, 11 patients (8.27%) had pathogenic/likely pathogenic germline alterations, all of which were in the DNA damage response (DDR) pathway. In our cohort, 34.48% (22/64) of patients exhibited positive PD-L1 expression in tumor cells, and this expression was associated with GAs in CTNNB1 and BLM. Importantly, over three-fourths of Chinese AMPAC patients in our study had at least one actionable GA, with more than one-fifth of them having actionable GAs classified as Level 3. These actionable GAs were primarily involved in the DDR and PI3K pathways. Notably, GAs in the DDR pathway were detected in both Chinese and Western patients, and regardless of their functional impact, these alterations demonstrated enhanced overall survival rates and higher tumor mutational burden (TMB) levels.
CONCLUSION
These findings underscore the distinct genomic landscape of Chinese AMPAC patients and highlight the potential for targeted therapies based on the identified GAs.
Topics: Humans; B7-H1 Antigen; Phosphatidylinositol 3-Kinases; Genomics; Duodenal Neoplasms; Pancreatic Neoplasms; Adenocarcinoma; Common Bile Duct Neoplasms; China
PubMed: 38439030
DOI: 10.1186/s12885-024-11949-9 -
Cureus Jan 2024Gastrointestinal stromal tumours (GISTs) are rare gastrointestinal (GI) malignancies, but the most prevalent mesenchymal tumours of the GI tract arise from the...
Gastrointestinal stromal tumours (GISTs) are rare gastrointestinal (GI) malignancies, but the most prevalent mesenchymal tumours of the GI tract arise from the interstitial cells of Cajal. They account for 1-3% of all GI malignancies, and only 3-5% of all cases of GIST are located at the duodenal. We present a case of a young adult who presented to the ED with symptoms of GI bleeding.
PubMed: 38435882
DOI: 10.7759/cureus.53331 -
Journal of Gastroenterology May 2024The clinicopathological features and prognosis of primary small bowel adenocarcinoma (PSBA), excluding duodenal cancer, remain undetermined due to its rarity in Japan.
BACKGROUND
The clinicopathological features and prognosis of primary small bowel adenocarcinoma (PSBA), excluding duodenal cancer, remain undetermined due to its rarity in Japan.
METHODS
We analyzed 354 patients with 358 PSBAs, between January 2008 and December 2017, at 44 institutions affiliated with the Japanese Society for Cancer of the Colon and Rectum.
RESULTS
The median age was 67 years (218 males, 61.6%). The average tumor size was 49.9 (7-100) mm. PSBA sites consisted of jejunum (66.2%) and ileum (30.4%). A total of 219 patients (61.9%) underwent diagnostic small bowel endoscopy, including single-balloon endoscopy, double-balloon endoscopy, and capsule endoscopy before treatment. Nineteen patients (5.4%) had Lynch syndrome, and 272 patients (76.8%) had symptoms at the initial diagnosis. The rates for stages 0, I, II, III, and IV were 5.4%, 2.5%, 27.1%, 26.0%, and 35.6%, respectively. The 5-year overall survival rates at each stage were 92.3%, 60.0%, 75.9%, 61.4%, and 25.5%, respectively, and the 5-year disease-specific survival (DSS) rates were 100%, 75.0%, 84.1%, 59.3%, and 25.6%, respectively. Patients with the PSBA located in the jejunum, with symptoms at the initial diagnosis or advanced clinical stage had a worse prognosis. However, multivariate analysis using Cox-hazard model revealed that clinical stage was the only significant predictor of DSS for patients with PSBA.
CONCLUSIONS
Of the patients with PSBA, 76.8% had symptoms at the initial diagnosis, which were often detected at an advanced stage. Detection during the early stages of PSBA is important to ensure a good prognosis.
Topics: Aged; Humans; Male; Adenocarcinoma; Capsule Endoscopy; Duodenal Neoplasms; Ileal Neoplasms; Intestinal Neoplasms; Japan; Jejunal Neoplasms; Prognosis
PubMed: 38411920
DOI: 10.1007/s00535-024-02081-3