Search Results (51)

Background and Clinical Significance: Inherited thrombocytopenia (IT) is a heterogeneous group of disorders caused by mutations in over 45 genes. Among these, ANKRD26-related thrombocytopenia (ANKRD26-RT) accounts for a notable subset and is associated with variable bleeding tendencies and an increased risk of myeloid malignancies. However, the extent of this oncogenic risk appears to vary between specific gene variants. Understanding the genotype–phenotype relationship is essential for patient counseling and management. This report presents a multigenerational family carrying the rare c.−118C > G variant in the 5′ untranslated region of ANKRD26, contributing to the discussion on variant-specific cancer predisposition. Case Presentation: Two sisters aged 57 and 60 presented with lifelong bleeding diathesis and moderate thrombocytopenia. Their symptoms included easy bruising, menorrhagia, and excessive postoperative bleeding. Genetic testing confirmed heterozygosity for the ANKRD26 c.−118C > G variant. Bone marrow analysis revealed abnormal megakaryopoiesis without evidence of dysplasia or somatic mutations. One sister underwent major surgery without complications when managed with prophylactic hemostatic therapy. Their family history included multiple female relatives with similar symptoms, although formal testing was limited. Notably, none of the affected individuals developed hematologic malignancy, and only one developed esophageal cancer, with no current evidence linking this variant to solid tumors. Conclusions: This case underscores the importance of distinguishing between ANKRD26 variants when assessing malignancy risk. While ANKRD26-RT is associated with myeloid neoplasms, the c.−118C > G variant may confer a lower oncogenic potential. Variant-specific risk stratification and genetic counseling are crucial for optimizing surveillance and avoiding unnecessary interventions in low-risk individuals. Full article

Rare presentations are surprising and may disturb the day-to-day routine of a medical unit; however, they are expected (not as individual entities, but as a group of “uncommon causes”). While reviewing the literature in relation to three clinical cases of upper gastrointestinal bleeding (UGIB) encountered in our institution—gastric metastases of breast cancer (GMB), pyloric gland adenoma, and gastrointestinal stromal tumor (GIST)—we identified seven and 29 case reports for the first two entities, and over 100 publications addressing GIST. This prompted a shift in focus from novel reporting to diagnostic contextualization. We found it difficult to obtain an overview of the spectrum of UGIB etiologies, as most publications refer to a few individual entities or to a subgroup of rare causes. The narrative review we conducted arose from this particular research methodology. Based on a broad literature search, UGIB etiologies were organized in five categories (lesions of the mucosa, neoplasms, vascular causes, bleeding predisposition, and external sources of bleeding). In the management of patients with UGIB, the underlying etiology deviates from the classic peptic ulcer disease/esophageal varices dyad in approximately half of the cases. This underscores the need for heightened clinical vigilance, particularly in complex scenarios, where endoscopic findings, imaging results, and histopathological interpretations may be unexpected or prone to misinterpretation. As an illustration, we conducted two systematic reviews of case reports of bleeding GMB and PGA. Our findings support a proactive diagnostic and research mindset and advocate for improved awareness of uncommon UGIB etiologies. Full article

Background/Objectives: TTF-1 and Napsin A are immunohistochemical markers that are widely used for the diagnosis of lung adenocarcinomas or thyroid carcinomas, as well as the characterization of metastases. However, several publications have reported the aberrant expression of one or both markers in extrathoracic malignancies, including gastrointestinal adenocarcinomas. The goal of our study was to determine the frequency of TTF-1- and Napsin A-positive neoplasms in cohorts consisting of esophageal, gastric and colorectal adenocarcinomas. Methods: Buffered formalin-fixed paraffin-embedded tumor tissues from 854 patients with primary resected gastrointestinal and esophageal carcinomas were placed in tissue microarrays (TMAs) for investigation. Between two and six tumor cores were analyzed for each case. For immunohistochemical staining, we used TTF-1 (SPT24 clone) and Napsin A (IP64 clone). Tumors were considered positive if at least 5% of their tumor cells showed weak nuclear (TTF-1) or cytoplasmic (Napsin A) staining. Results: In total, 16 cases showed positive staining for TTF-1, alongside 7 cases for Napsin A. The greatest proportion of TTF-1- and/or Napsin A-positive tumors was found among esophageal adenocarcinomas (5/125 cases; 4%). Co-expression of TTF-1 and Napsin A was found in five cases, including three esophageal and two gastric adenocarcinomas. In colorectal carcinomas, co-expression of these markers was not detected. Conclusions: TTF-1 and Napsin A are useful immunohistochemical makers for establishing the diagnosis of pulmonary adenocarcinoma. Additionally, knowing that a proportion of gastrointestinal neoplasms express these markers can help to avoid diagnostic misinterpretations. Full article

A 78-year-old woman was referred to our hospital for close examination of an extramural submucosal tumor in the gastroesophageal region, suspected based on an imaging test performed for a chief complaint of epicardial pain while eating. Contrast-enhanced computed tomography revealed a 3 cm sized mass with well-defined margins and a homogeneous interior near the gastroesophageal junction. Endoscopic ultrasonography (EUS) revealed a large (28 mm) unilocular cystic lesion with a heterogeneous hypoechoic internal structure. The cyst wall was layered with a hypoechoic layer that appeared to be muscular and continuous with the external longitudinal muscle of the esophagus. Based on the EUS findings, an esophageal duplication cyst was diagnosed. Cystectomy was performed because the patient was symptomatic. Pathological examination revealed that the specimen was covered with columnar and pseudostratified ciliated epithelium without atypia and that the cyst wall comprised two layers of smooth muscle. No cartilaginous tissue was present, which is consistent with esophageal duplication cysts. Retrospectively, the EUS findings were consistent with the pathological findings. Full article

Background: Robot-assisted minimally invasive esophagectomy (RAMIE) has gained global popularity. Recent randomized controlled trials have demonstrated that RAMIE results in reduced operative times and a greater number of dissected lymph nodes compared to conventional minimally invasive esophagectomy (MIE). This study provides an initial analysis of single-port (SP) robot-assisted minimally invasive esophagectomy (SRAMIE) using the SP robotic system via the subcostal approach. The primary objective is to examine perioperative outcomes of SRAMIE compared to multi-port RAMIE (MRAMIE) using the Xi robotic system and video-assisted thoracoscopic esophagectomy (VAE). Methods: In this retrospective study, patients who underwent MIE at a single center between February 2017 and December 2024 were analyzed. Patients were divided into SRAMIE (n = 17), MRAMIE (n = 13), and VAE (n = 23) groups. The primary outcome was the incidence of postoperative complications. Secondary outcomes included chest tube duration, length of postoperative hospital stay, postoperative pain levels, and 30-day mortality. Results: The SRAMIE group did not experience conversions to thoracotomy or VAE. Compared with VAE, SRAMIE resulted in significantly shorter chest tube duration (p = 0.038), shorter postoperative hospital stays (p = 0.036), and lower peak postoperative pain (p = 0.003). No significant differences were observed among the groups regarding the total operative time, number of resected lymph nodes, or incidence of postoperative complications. Conclusions: SRAMIE is a feasible approach offering advantages over VAE in recovery and postoperative pain. The comparable perioperative outcomes suggest that SRAMIE may be a viable alternative to conventional MIE, warranting further large-scale studies. Full article

Background: Barrett’s esophagus (BE) is a known precursor to esophageal adenocarcinoma (EAC). However, reports on incidence and progression-to-neoplasm rates have been very variable and conflicting. The aims of the study were to evaluate the characteristics of BE and its progression to neoplasm in a large homogeneous population. Methods: This was a retrospective population-based study with patients identified from 11 institutions through the databases in two centralized pathology laboratories. Demographics and relevant clinicopathological features were obtained from medical records among patients with a pathologically confirmed BE by the presence of intestinal metaplasia between 2003 and 2022. Results: A total of 1388 patients were identified with BE: 948 were men (69%); the median age at diagnosis was 62 years (IQR, 53–72). The ratio of long-segment BE to short-segment BE was significantly higher in patients ≥ 60 years (1.15, 284/248) than those ≤ 60 years (0.77, 205/265) (p = 0.0025). At BE diagnosis, 9.4% had neoplasms: LGD (n = 65), HGD (n = 16), and EAC (n = 49). Among 1258 non-dysplastic BE (NDBE) patients, 4.6% developed a neoplasm—LGD (n = 35), HGD (n = 8), and EAC (n = 15)—with a median observation-period of 5 years (IQR, 3–7). Overall, 160 cases with neoplasms were diagnosed in this BE cohort; 130 (74%) were present at initial BE diagnosis, and 58 (26%) progressed to neoplasms from NDBE. Conclusions: The ratio of long-segment BE was found to be significantly higher in patients ≥ 60 years. Around 9% of the patients were diagnosed as harboring a neoplasm concomitantly with BE, accounting for approximately 74% of all neoplasms. After a median follow-up of 5 years, about 5% of BE showed dysplastic or malignant progression. Full article

Background/Objectives: Superficial esophageal cancer is diagnosed by evaluating the vascular architecture, including dilation, tortuosity, caliber change, and shape, of a lesion. However, this diagnosis is subjective and requires extensive experience. Endoscopically distinguishing squamous intraepithelial neoplasia (SIN) from esophageal cancer is difficult. Thus far, only a few studies have described the endoscopic findings of SIN. Therefore, the present study aimed to investigate whether endoscopic observation of the vascular architecture of tumors is useful in differentiating SIN from superficial esophageal cancer (SCC). Methods: This study included 141 patients who were histopathologically diagnosed with SIN or SCC between 2007 and 2023. Based on endoscopic images, patients were divided into those with a regular vascular arrangement (regular group) and those with an irregular vascular arrangement (irregular group). After evaluating the clinical characteristics, propensity score matching was used to assess the association between the groups and their pathological diagnoses. Results: Of the 141 patients, 44 and 97 were in the regular and irregular groups, respectively, with a ratio of 1:2. After propensity score matching, 33 and 66 patients were included in the regular and irregular groups, respectively. There were no significant differences between the groups after matching for age, alcohol consumption, smoking status, lesion site, sex, or lesion size. The regular group had significantly more patients with SIN, whereas the irregular group had significantly more patients with esophageal cancer (p < 0.001). Conclusions: The regularity of the vascular architecture may be useful for endoscopically distinguishing between SIN and esophageal cancer. Full article

Several techniques exist to maintain oral and/or enteral feeding among esophageal cancer (EC) patients, but their impact on patient-reported outcomes (PROs) remains unclear. This systematic review aimed to assess the impact of nutritional support techniques on PROs in EC patients. We searched Medline, Web of Science, and CINAHL Complete from inception to 3 April 2024. Eligible studies included those evaluating EC patients, reporting PROs using standardized measures, and providing data on different nutritional support techniques or comparing them to no intervention. The reference lists of the included studies were also screened for additional eligible articles. The Mixed Methods Appraisal Tool was used to evaluate the quality of the included studies. Of the 694 articles identified from databases and 224 from backward citation, 11 studies met the inclusion criteria. Nine studies evaluated the overall quality of life (QoL), four assessed pain, and one evaluated depression. Among those submitted to esophagectomy, jejunostomy may be associated with higher QoL scores and less postoperative pain, compared to a nasojejunal tube, but no significant differences were found when compared to no intervention. For patients undergoing chemotherapy or receiving palliative/symptomatic treatment, expandable metal stents (SEMSs) were associated with higher levels of emotional functioning when compared with laparoscopic gastrostomy. Moreover, percutaneous endoscopic gastrostomy or SEMSs were associated with a higher QoL compared with nasogastric tubes. This review underscores the importance of considering PRO measures when evaluating nutritional support techniques in cancer patients, though further robust evidence is needed to fully understand these associations. Full article

Background/Objectives: Trefoil factor 1 (TFF1) plays a role in the mucus barrier. Methods: To evaluate the prevalence of TFF1 expression in cancer, a tissue microarray containing 18,878 samples from 149 tumor types and 608 samples of 76 normal tissue types was analyzed through immunohistochemistry (IHC). Results: TFF1 staining was detectable in 65 of 149 tumor categories. The highest rates of TFF1 positivity were found in mucinous ovarian carcinomas (76.2%), colorectal adenomas and adenocarcinomas (47.1–75%), breast neoplasms (up to 72.9%), bilio-pancreatic adenocarcinomas (42.1–62.5%), gastro-esophageal adenocarcinomas (40.4–50.0%), neuroendocrine neoplasms (up to 45.5%), cervical adenocarcinomas (39.1%), and urothelial neoplasms (up to 24.3%). High TFF1 expression was related to a low grade of malignancy in non-invasive urothelial carcinomas of the bladder (p = 0.0225), low grade of malignancy (p = 0.0003), estrogen and progesterone receptor expression (p < 0.0001), non-triple negativity (p = 0.0005) in invasive breast cancer of no special type, and right-sided tumor location (p = 0.0021) in colorectal adenocarcinomas. Conclusions: TFF1 IHC has only limited utility for the discrimination of different tumor entities given its expression in many tumor entities. The link between TFF1 expression and parameters of malignancy argues for a relevant biological role of TFF1 in cancer. TFF1 may represent a suitable therapeutic target due to its expression in only a few normal cell types. Full article

Circulating tumor cells (CTCs) in cancer-draining veins have diagnostic and prognostic value. However, studies on esophageal squamous cell carcinoma (ESCC) are limited. This study aimed to compare CTCs obtained from different sampling sites (peripheral vein vs. cancer-draining azygos vein) and to investigate their association with the clinicopathological characteristics of ESCC patients. Blood samples were collected preoperatively from both veins in 40 ESCC patients at Pusan National University Hospital from June 2020 to April 2022. CTCs were detected using a centrifugal microfluidic method with fluid-assisted separation. CTCs and TWIST (+) CTCs were detected more frequently in the azygos vein blood than in the peripheral vein blood; however, the difference was not statistically significant (85.0% [34/40] vs. 77.5% [31/40], p = 0.250 and 82.5% [33/40] vs. 75.0% [30/40], p = 0.586, respectively). CTC and TWIST (+) CTC counts were significantly higher in the azygos vein blood than in the peripheral vein blood (7 vs. 3, p < 0.001, and 6 vs. 2, p < 0.001, respectively). CTCs and TWIST (+) CTCs from peripheral and azygos veins showed no association with clinicopathological characteristics. Further large-scale studies are needed to clarify their role as predictive biomarkers for prognosis and chemotherapy responses in ESCC patients. Full article

Objective: This study explores the potential causal association between proprotein convertase subtilisin/kexin 9 (PCSK9) inhibitors and tumor development using Mendelian randomization (MR) based on drug targets. Methods: Instrumental variables within ±100 kb of the PCSK9 gene locus, impacting low-density lipoprotein cholesterol (LDL-C), were utilized for MR analysis. Coronary heart disease (CHD) served as a positive control to validate the causal relationship between PCSK9 inhibitors and various cancers. We employed reverse MR to address the reverse causation concerns. Data from positive controls and tumors were sourced from OpenGWAS. Results: MR analysis suggested a negative causal relationship between PCSK9 inhibitors and both breast and lung cancers (95%CI_{Breast cancer} 0.81~0.99, p = 2.25 × 10⁻²; 95%CI_{Lung cancer} 0.65~0.94, p = 2.55 × 10⁻³). In contrast, a positive causal link was observed with gastric, hepatic, and oral pharyngeal cancers and cervical intraepithelial neoplasia (95%CI_{Gastric cancer} 1.14~1.75, p = 1.88 × 10⁻²; 95%CI_{Hepatic cancer} 1.46~2.53, p = 1.16 × 10⁻²; 95%CI_{Oral cavity and pharyngeal cancer} 4.49~6.33, p = 3.36 × 10⁻⁴; 95%CI_{Carcinoma in situ of cervix uteri} 4.56~7.12, p = 6.91 × 10⁻³), without heterogeneity or pleiotropy (p > 0.05). Sensitivity analyses confirmed these findings. The results of MR of drug targets suggested no causal relationship between PCSK9 inhibitors and bladder cancer, thyroid cancer, pancreatic cancer, colorectal cancer, malignant neoplasms of the kidney (except for renal pelvis tumors), malignant neoplasms of the brain, and malignant neoplasms of the esophagus (p > 0.05). Reverse MR helped mitigate reverse causation effects. Conclusions: The study indicates a divergent causal relationship of PCSK9 inhibitors with certain cancers. While negatively associated with breast and lung cancers, a positive causal association was observed with gastric, hepatic, oral cavity, and pharyngeal cancers and cervical carcinoma in situ. No causal links were found with bladder, thyroid, pancreatic, colorectal, certain kidney, brain, and esophageal cancers. Full article

Background: Endoscopic submucosal dissection (ESD) is a well–established method for treating early esophageal carcinomas. However, data on the safety and efficacy of esophageal ESD in older patients in the United States are limited. Methods: This retrospective study investigated the outcomes of esophageal ESD in patients aged ≥80 years and included those who underwent esophageal ESD between June 2018 and April 2023 at a single center in the United States. Patients were divided into two age groups for comparison: ≥80 and <80 years. Treatment outcomes and complications were evaluated and compared between these groups. Results: A total of 53 cases of esophageal ESD for malignant neoplasms were included, with 12 patients in the ≥80 years age group. No significant differences were observed in the patients’ background and characteristics, except for a prior history of interventions (p = 0.04). The en bloc resection rate was 100% in both groups. The R0 resection rate was lower in the ≥80 years age group (75% vs. 88%). There were no complications requiring additional intervention in the ≥80 years age group, such as post–ESD bleeding, perforation, mediastinal emphysema, or pneumonia. Conclusions: Esophageal ESD may be a safe and feasible procedure for treating esophageal carcinomas in older patients. Full article

Gastrointestinal (GI) cancers are an increasingly common type of malignancy, caused by the unhealthy lifestyles of people worldwide. Limited methods of treatment have prompted the search for new compounds with antitumor activity, in which betulin (BE) is leading the way. BE as a compound is classified as a pentacyclic triterpene of the lupane type, having three highly reactive moieties in its structure. Its mechanism of action is based on the inhibition of key components of signaling pathways associated with proliferation, migration, interleukins, and others. BE also has a number of biological properties, i.e., anti-inflammatory, hepatoprotective, neuroprotective, as well as antitumor. Due to its poor bioavailability, betulin is subjected to chemical modifications, obtaining derivatives with proven enhanced pharmacological and pharmacokinetic properties as a result. The method of synthesis and substituents significantly influence the effect on cells and GI cancers. Moreover, the cytotoxic effect is highly dependent on the derivative as well as the individual cell line. The aim of this study is to review the methods of synthesis of BE and its derivatives, as well as its pharmacological properties and molecular mechanisms of action in colorectal cancer, hepatocellular carcinoma, gastric cancer, and esophageal cancer neoplasms. Full article

Surgery is a crucial treatment option for patients with resectable esophageal cancer. The emergence of minimally invasive esophageal techniques has led to the popularity of video-assisted thoracoscopic esophagectomy, which has proven to be more advantageous than traditional thoracotomy. However, some patients with esophageal cancer may not benefit from this procedure. Individualized treatment plans may be necessary for patients with varying conditions and tolerances to anesthesia, making conventional surgical methods unsuitable. Inflatable video-assisted mediastinoscopic transhiatal esophagectomy (IVMTE) has emerged as a promising treatment option for esophageal cancer because it does not require one-lung ventilation, reduces postoperative complications, and expands surgical indications. This technique also provides surgical opportunities for patients with impaired pulmonary function or thoracic lesions. It is crucial to have a comprehensive understanding of the advancements and limitations of IVMTE to tailor treatment plans and improve outcomes in patients with esophageal cancer. Understanding the advantages and limitations of this surgical method will help specific patients with esophageal cancer. We conducted a thorough review of the relevant literature to examine the importance of IVMTE for individualized treatment of this disease. Full article

(1) Background: Epidermolysis bullosa (EB) comprises a group of rare skin diseases. We assessed diagnostic procedures, comorbidity profiles, length of hospital stay (LOHS), costs, and in-hospital mortality (IHM) associated with EB. (2) Methods: A retrospective, population-based observational study was performed using the Spanish National Hospital Discharge Database. Hospitalized patients with EB in Spain were identified for the period 2016 to 2021. (3) Results: A total of 677 hospitalizations were identified among 342 patients with a diagnosis of EB. Fifty percent of patients had at least one readmission during the 6-year follow-up. Notably, rehospitalizations were more common among patients aged 2–17 years. The most prevalent comorbidity was digestive disorders, which were associated with the frequency of esophageal dilatation procedures and percutaneous endoscopic gastrostomy. The longest LOHS was recorded for the 0- to 1-year age group. IHM increased with age, and the difference was statistically significant. The prevalence of malignant neoplasm was 36.88%, with cutaneous squamous cell carcinoma being the most frequent. The overall cost per hospitalized patient was estimated to be EUR 10,895.22 (SD EUR 13,394.81), with significant variations between age groups. (4) Conclusions: Readmissions are very frequent among people with EB. We observed a higher LOHS in the 0- to 1-year age group, while the highest rates of IHM were observed in patients older than 50 years. There was a substantial prevalence of comorbidities, namely, digestive disorders, infectious diseases, and especially cancer. Full article