UNASSIGNED: Gastric cancer remains a challenging malignancy with a high global mortality rate. Recent advances in targeted therapy and immunotherapy have shown promise in improving patient outcomes. This paper reviews the impact of incorporating targeted agents such as trastuzumab and immunotherapeutic agents like pembrolizumab into standard chemotherapy regimens for gastric cancer treatment.
UNASSIGNED: A comprehensive analysis was conducted on pivotal clinical trials, including KEYNOTE-590, KEYNOTE-811, and ToGA, focusing on their methodologies, patient populations, treatment regimens, and outcome measures. The review also explored emerging research avenues in precision medicine, particularly genomic sequencing and biomarker identification.
UNASSIGNED: To assess the efficacy and survival benefits of adding trastuzumab and pembrolizumab to standard chemotherapy in the treatment of gastric cancer and to outline future directions in gastric cancer research.
UNASSIGNED: Including trastuzumab and pembrolizumab in treatment regimens for human epidermal growth factor receptor 2 (HER2)-positive and PD-L1-expressing gastric cancers significantly improved progression-free and overall survival rates compared to chemotherapy alone. These findings highlight the potential of personalized therapy in enhancing treatment outcomes. Furthermore, ongoing research into the gastric cancer microenvironment and the role of the microbiome suggests novel targets for future therapeutic interventions.
UNASSIGNED: The integration of targeted and immunotherapeutic agents with traditional chemotherapy represents a pivotal shift in gastric cancer treatment, moving towards more personalized and effective regimens.

BACKGROUND: Although multiple treatment options exist for gastroesophageal junction (GEJ) cancer, surgery remains the mainstay for potential cure. Extended nodal dissection with a D2 lymphadenectomy (LAD) remains controversial for Siewert II GEJ cancer. Although D2 LAD may lead to a greater lymph node harvest, its effect on survival remains elusive. The authors hypothesized that additional D2 dissection in Siewert II GEJ cancer does not lead to increased survival.
METHODS: This study reviewed Siewert II patients who received a D1 or D2 LAD in addition to minimally invasive esophagectomy (MIE) after receiving neoadjuvant chemoradiation or perioperative chemotherapy (2012-2022). The patients were followed for up to 5 years. The outcomes measured were survival, number of nodes sampled, and operative time. The association between D1 or D2 LAD and overall survival was analyzed with Kaplan-Meier methods and a multivariable Cox regression model.
RESULTS: Among 155 patients, 74 % underwent D1 and 26 % underwent D2 LAD. The patients with D2 had more than 15 lymph nodes harvested more frequently than those who had D1 (83 % vs 48 %; p < 0.001), with no difference in positive nodes (2.8 ± 5.2 vs 2.1 ± 4.2; p = 0.4). The patients with D2 LAD had a longer median operative time than those who with D1 LAD (362 vs 244 min; p < 0.001). In Kaplan-Meier and multivariable Cox regression models, overall survival did not differ significantly between the patients undergoing D2 and those who had D1 (adjusted hazard ratio [aHR], 0.52; 95 % confidence interval [CI], 0.25-1.00; p = 0.067).
CONCLUSIONS: Little consensus exists regarding the optimal lymph node harvest for GEJ cancers. In Siewert II cancer, D2 LAD may not be mandatory and may lead to increased operative morbidity with no significant difference in survival.

The signet-ring cell variant of squamous cell carcinoma (SCC) is an extremely rare histological subtype, with only 24 cases (including the present case) reported in the Medline database: 15 affecting the external surface of the body, 3 in the lung, 2 affecting the uterine cervix, 1 involving the gingiva, another one affecting the esophagus and the present case that is the first reported at the gastro-esophageal junction (GEJ). In one case, the location of the lesion was not mentioned. A 59-year-old male patient underwent segmental eso-gastrectomy for carcinoma of the GEJ. The microscopic examination showed a pT3N1-staged SCC composed of solid nests admixed in over 30% of the tumor, with cells having eccentrically located nuclei and clear vacuolated cytoplasm. The signet-ring cells did not show mucinous secretion and were positive for keratin 5/6 and vimentin, with nuclear expression of β-catenin and Sox2 and focal membrane positivity for E-cadherin. Based on these features, the case was considered a signet-ring SCC with epithelial-mesenchymal transition. Thirty-one months after surgery, the patient was disease-free, with no local recurrence and no known distant metastases. In SCC, a signet-ring cell component might be an indicator of the dedifferentiation of tumor cells towards a mesenchymal molecular subtype.

Since the first successful esophagectomy for cancer in 1913 spectacular advancements have been made in diagnosis, staging, and therapy. Refinement of imaging, surgery, perioperative management together with multidisciplinary collaboration are the cornerstones. Today therapy with curative option is offered to more patients than ever. Further innovations in imaging, molecular biology, genetics, artificial intelligence, machine learning, robotics, nanotechnology will have an increasing impact. The end result being a unique therapeutic plan shaped on each patient\'s individual profile.

BACKGROUND: Blunt abdominal trauma causing Gastro-esophageal junction (GEJ), diaphragm, and gastric perforation in children is a very rare occurrence. However, the injury is serious and life-threatening with significant morbidity and mortality.
METHODS: We report an unusual case of a 14-year-old boy with an accidental fall from the tree with blunt abdomen trauma with a perforating injury to GEJ, stomach, and diaphragm.
CONCLUSIONS: Multiple vital organs in the abdominal cavity are vulnerable to damage in blunt abdominal trauma. The rarity of perforation, diagnostic delay, and early septic occurrence sums up to higher patient morbidity and mortality. A high degree of suspicion and urgent laparotomy and surgical repair forms the cornerstone in management.
CONCLUSIONS: Early suspicion along with effective resuscitation and early laparotomy and surgical repair is crucial for survival and optimal outcome of the patient.

The mechanisms associated with gastro-esophageal reflux (GER) episodes were studied using combined High-resolution Impedance Manometry (HRIM) and pH monitoring in ambulant subjects with different patterns of GERD.
Sixteen subjects with mild-moderate esophagitis (Los Angeles (LA) grade A&B) (group A) and 11 subjects with severe esophagitis (LA grade C&D) or Barrett\'s esophagus (BE) were studied before and after a meal, resting, while walking, and during standardized exercise, using a HRIM and a pH probe.
Post-prandial acid GER episodes were more common in group B (median 10 range (3-18) vs A (6.5 (0-18), p = 0.048). Postprandial acid clearance time was much longer in group B (median 0.71( 0.07-2.66 min) vs A (0.17 (0.04-2.44 min), p = 0.02). Transient lower esophageal sphincter relaxation (TLESR) was the most frequent mechanism associated with GER episodes in both groups. Post-prandial TLESRs with GER were more common in group B (median 17 (9-24) vs A 13.5 (7-34), p = 0.014), particularly during exercise (B 8 (6-9) vs A 6 (5-6.8), p = 0.007). Post-prandially TLESR with acid reflux increased during exercise in both groups (A rest median 2.4 (0-6.4) per hour vs exercise 4.7 (0-17.3), p = 0.005 and B 4 (0.8-9.6) vs 5.3 (2.7-13.3) per hour, p = 0.045).
TLESR was the most common mechanism associated with reflux episodes in all subjects. Acid reflux episodes were more common in subjects with severe esophagitis or BE and esophageal acid clearance was much slower. Post-prandial exercise increased TLESR with acid reflux and GERD patients should be encouraged to avoid exercise immediately after a meal.

For locally advanced Siewert type II and III tumors we have performed total gastrectomy including resection of the distal 2/3 of the esophagus, through separate abdominal and right chest incisions (THX-ABD). The procedure involves wide lymphadenectomy in the abdomen/chest and a Roux-en-Y jejunostomy to the level of the azygos vein or above. The aim of the study was to investigate short- and long-term results for this rarely used procedure.
Retrospective study of 83 radio-chemotherapy naïve patients with adenocarcinoma at the gastro-esophageal junction (Siewert type II n = 65 and type III n = 18) operated upon 1986-2011.
2/83 (2.4%) patients died in hospital. 70/83 (84%) patients had R0-resections. 82/83 (99%) patients had free longitudinal resection margins. Overall 5-year survival was 22/83 (27%).
THX-ABD can be performed with high rates of R0 resections and with low in-hospital mortality. Long-term survival rate was not better compared with less extensive surgical procedures.

The aim of the study is to evaluate feasibility, safety, toxicity profile, and dosimetric results of volumetric modulated arc therapy (VMAT) to deliver definitive or pre-operative radiation in locally advanced esophageal cancer patients. A total of 68 patients were treated with VMAT between March 2014 and March 2018 (44% vs 56% for definitive and neoadjuvant settings, respectively). Dose prescription differed depending on the clinical scenario (54-60 Gy in 30 fractions for definitive treatments; 41.4/45 Gy in 23-25 fractions in the pre-operative setting). Most of the patients were given concurrent chemotherapy. Two coplanar and one non-coplanar arcs were employed for VMAT delivery. Treatment was generally well tolerated. Acute toxicity was generally mild. In patients treated with definitive intent, ≥ G3 toxicities were observed for esophagitis (30%), anorexia (26.7%), fatigue (26.7%), nausea (6.7%), and vomiting (3.3%). In patients treated within a neoadjuvant approach, ≥ G3 anorexia (21%), esophagitis (15.8%), fatigue (13.3%), nausea (5.3%), and vomiting (2.6%) were observed. Dosimetric results were consistent in term of both target coverage and normal tissue sparing. In conclusion, VMAT proved to be a feasible, safe, and effective strategy to deliver definitive or pre-operative radiation in locally advanced esophageal cancer patients.

In the modern era of surgery, minimally invasive surgery is increasingly applied for excision of gastrointestinal stromal tumors. Site, size and tumor location are important factors that affect the surgical approach and excision. We performed a laparoendoscopic transgastric enucleation of a 4-cm pericardial endophytic gastrointestinal stromal tumor (GIST) using an energy device. The surgery was successful and post-operative recovery uneventful. No tumor recurrence was detected on surveillance gastroscopy. In the safe hands of a well-trained laparoscopic upper gastrointestinal surgeon, pericardial GIST can be enucleated safely by this method. The avoidance of surgical staplers is not only cost-effective, but also reduces the risk of associated complications.

OBJECTIVE: An important premise for obtaining diagnostically relevant histology specimens is an appropriate biopsy technique. Goal of this study was to determine if biopsies of adequate quality can be obtained from the canine esophagus at the gastro-esophageal junction (GEJ) during routine upper gastrointestinal endoscopy.
METHODS: Over the course of one year, 58 dogs undergoing upper gastrointestinal endoscopy because of the presence of esophageal (n = 22) or gastrointestinal (n = 36) clinical signs were prospectively included. Five biopsies were repeatedly collected from the same dorsal and ventral locations of the GEJ, fixated individually in 4% neutral buffered formaldehyde, and evaluated histopathologically after standard preparation and haematoxylin and eosin staining. The presence of esophageal squamous epithelium with a basal cell layer and lamina propria mucosae in conjunction with foveolar columnar epithelium and cardiac glands, and the absence of fundic glands in one specimen, respectively, was judged as an adequately sampled biopsy.
RESULTS: Adequately sampled biopsies were reported in 45 out of 58 dogs, with 31 samples originating from the dorsal GEJ, 36 samples originating from the ventral GEJ, and with 22 samples originating from both sites, respectively. The incidence of adequately sampled biopsies increased significantly over time (r = 0,22; p < 0,05), with these biopsies being reported significantly more often during the last 6 months compared to the first 6 months of the study (p = 0,03). Histopathological evaluation of the esophageal squamous epithelium showed fibrosis, inflammation, elongation of the stromal papillae, and increased thickness of the basal cell layers in 14 out of 58 dogs. Stromal papillae of the ventral esophageal epithelium were significantly elongated in dogs with esophageal clinical signs compared to dogs with gastrointestinal clinical signs (p = 0,03).
CONCLUSIONS: After an initial learning phase adequate esophageal biopsies from the GEJ can be obtained in canine patients undergoing upper gastrointestinal endoscopy, and histological lesions can be found in these biopsies.