Oncological outcomes of large gastrointestinal stromal tumors treated by laparoscopic resection.

BACKGROUND: The resection of large gastric gastrointestinal stromal tumors (GISTs) by laparoscopic has been controversial. Extending from our prior study, the long-term oncological outcome of laparoscopic resection of large (5-8 cm) gastric GISTs was reported. METHODS: From 2002 to 2018, a consecutive 66 patients with gastric GISTs of 5-8 cm were treated at National Taiwan University Hospital. Among them, 30 patients received open surgery, and 36 received laparoscopic surgery. The clinicopathological data, peri-operative and oncological outcomes were compared between groups. RESULTS: The clinical demographics including sex, age, BMI, tumor locations and ratio of wedge resection were similar between groups. The mean tumor size was 6.0 ± 0.83 cm versus 6.3 ± 1.07 cm (Open vs. Laparoscopic, p = 0.3). The operation time, blood loss, and post-operative complications, were also similar. The mean hospital stay was shorter in the laparoscopic group (8.8 ± 2.5 days) than in the open group (12.0 ± 8.9 days), though not significantly different. The median follow-up time was 108 ± 58 months (97 ± 50 in laparoscopic group; 122 ± 64 in open group). All except three patients remain disease-free. One in the open group and two in the laparoscopic group had recurrence of tumor, and they were stable of disease under Imatinib treatment. Eight patients died in non-GIST causes during follow-up. The 5-year recurrence-free survival were 100% for the open and 94.2% for the laparoscopic group (p = 0.2). CONCLUSION: Our data showed that laparoscopic surgery for gastric GIST between 5 and 8 cm was safe and oncologically feasible.

Impact of modified teaching strategies used in a gross anatomy course on the academic performance of dental students during the COVID-19 pandemic.

INTRODUCTION: Modified teaching strategies (MTS), asynchronous online teaching and smaller dissection groups, were applied to a gross anatomy course for dental students in the National Taiwan University in April 2020 in response to the COVID-19 pandemic. This study aimed to investigate the effects and perceptions of MTS on dental students. MATERIALS AND METHODS: Scores for anatomy examinations for 2018-2019 (without MTS) and 2019-2020 (with MTS) cohorts were compared to explore the effect on academic performance. Moreover, questionnaire from the 2019-2020 cohort was analysed to determine dental students' perceptions about MTS. RESULTS: The lecture performance in the final examination of the second semester for the 2019-2020 cohort was significantly higher than that of the first semester (pre-COVID-19) and that for the 2018-2019 cohort. However, the laboratory performance in the midterm examination of the second semester for the 2019-2020 cohort was significantly lower than that for the 2018-2019 cohort and showed no difference in the final examination of the first semester. The questionnaires revealed that the majority of students displayed positive attitudes towards MTS and agreed with the importance of peer discussion during laboratory dissection. CONCLUSIONS: Asynchronous online learning for anatomy lecture may be beneficial for dental students; however, a smaller dissection group accompanied by reduced peer discussion may temporarily exert negative effects on their laboratory performance at the beginning of the application. Furthermore, more dental students exhibited positive perceptions towards smaller dissection groups. These findings could illuminate the learning condition of dental students in anatomy education.

Laparoscopic versus open distal gastrectomy for elderly patients with advanced gastric cancer: a retrospective comparative study.

BACKGROUND: Laparoscopic radical distal gastrectomy (LDG) has been more frequently performed for locally advanced distal gastric cancer (AGC) than open distal gastrectomy (ODG). However, the benefits of LDG for elderly AGC patients (AGC-lap) remain unclear. METHODS: Patients aged ≥ 70 years who underwent D2 distal gastrectomy from July 2014 to July 2021 were enrolled consecutively. Perioperative parameters, pathological features, and oncological outcomes of AGC-lap patients (n = 39) were compared with those of elderly AGC patients receiving ODG (AGC-open; n = 37) and elderly early gastric cancer patients receiving LDG (EGC-lap; n = 41) respectively. RESULTS: The median age of all AGC patients was 77 years, and 28% of them had an Eastern Cooperative Oncology Group score ≥ 2. Most of the perioperative and pathological features (including the number of lymph nodes harvested) were similar between the AGC-lap and AGC-open groups. AGC-lap patients had longer median operative times (215 min versus 192 min) but significantly less surgical complications (10.3% versus 37.8%) and shorter median hospital stays (11 days versus 13 days) than did AGC-open patients (all p < 0.05). The 3-year recurrence-free and overall survival was 66.2% and 88.8% in the AGC-lap group and 51% and 66.3% in the AGC-open group (both p = 0.1). The perioperative features, including operative time, number of lymph nodes harvested, hospital stay, and complication rates, were similar between the AGC- and EGC-lap groups. CONCLUSIONS: LDG was safely and effectively performed in elderly AGC patients, resulting in faster recovery and a lower complication rate than ODG, without compromising oncological outcomes.

The management of postoperative upper alimentary tract fistulas: A single-center experience of endoscopic tissue glue repair and recommendations of a systematic review.

BACKGROUND/PURPOSE: The appropriate management of postoperative upper alimentary tract fistula (UATF) remains uncertain. The efficacy of esophagogastroduodenoscopy (EGD) tissue glue repair in the treatment of patients with postoperative UATF was explored. We also conducted a systematic review of the literature regarding the inpatient management of UATF. METHODS: Totally 24 patients received EGD tissue glue repair for postoperative UATF at our institute from April 2014 to April 2020. Independent characteristics of size of fistula, location of the UATF, complications, and recurrences were analyzed. PubMed and Cochrane Library databases were reviewed. A pooled analysis was performed, and subgroup analysis was conducted separately for different anatomic locations and techniques. RESULTS: With a mean follow-up of 40 months, the fistula failed to close with EGD tissue glue repair in 2 of 24 patients (8.3%). Eight patients required repeated EGD tissue glue repair, which was more frequent in oral or thoracic UATF (p = 0.053), but all achieved a successful seal in the EGD tissue after glue repair alone (n = 22). The fistula size was correlated with the demand for repeated EGD tissue glue repair (p = 0.017). Besides, a total of 30 studies regarding 2356 cases of postoperative UATF between 2010 and 2021 were retrieved and analyzed. Several non-operative methods were generally accepted as the initial approach, with a non-inferior success rate compared to operative techniques. CONCLUSION: The results suggest that no single approach toward UATF is superior in terms of success rate and healing time. The potential advantages of EGD tissue glue repair after drainage were more suitable for patients with postoperative UATF and multiple comorbidities.

Adjuvant tegafur-uracil (UFT) or S-1 monotherapy for advanced gastric cancer: a single center experience.

BACKGROUND: Adjuvant tegafur-gimeracil-oteracil (S-1) is commonly used for gastric cancer in Asia, and tegafur-uracil (UFT) is another oral fluoropyrimidine when S-1 is unavailable. The real-world data of adjuvant UFT has less been investigated. METHODS: Patients with pathological stage II-IIIB (except T1) gastric cancer receiving adjuvant UFT or S-1 monotherapy after D2 gastrectomy were included. Usage of UFT or S-1 was based on reimbursement policy of the Taiwanese healthcare system. The characteristics, chemotherapy completion rates, and 5-year recurrence-free survival (RFS) and overall survival (OS), were compared between these two groups. RESULTS: From 2005 to 2016, 86 eligible patients were included. Most tumor characteristics were similar between the UFT group (n = 37; age 59.1 ± 13.9 years) and S-1 group (n = 49; age 56.3 ± 10.7 years), except there were significantly more Borrmann type III/IV (86.5% versus 67.3%; p = 0.047) and T4 (56.8% versus 10.2%; p < 0.001) lesions in the UFT group than in the S-1 group. The chemotherapy complete rates were similar in the two groups. The 5-year RFS was 56.1% in the UFT group and 59.6% in the S-1 group (p = 0.71), and the 5-year OS was 78.3% in the UFT group and 73.1% in the S-1 group (p = 0.48). The hazard ratio of adjuvant chemotherapy (S-1 versus UFT) on RFS was 1.25 (95% confidence interval = 0.53-2.94) when Borrmann type and T and N stages were adjusted. CONCLUSIONS: This small cohort study showed adjuvant UFT, and S-1 monotherapy had a comparable long-term outcome for pathological stage II-IIIB gastric cancer following D2 gastrectomy.

Endoscopic submucosal dissection comparing with surgical resection in patients with early gastric cancer - A single center experience in Taiwan.

BACKGROUND/PURPOSE: The choice of endoscopic submucosal dissection (ESD) as first line treatment for selected early gastric cancer (EGC) patients was proved as effective as surgical treatment in studies over many countries. Yet there is no such cohort comparison in Taiwan. This study is aimed to describe our experience in ESD treated EGC and to compare the outcomes with those underwent surgical treatment. METHODS: This was a retrospective cohort study reviewing the patients with EGC underwent ESD and surgical treatments in a single tertiary referral center in Taiwan. The primary endpoint was disease specific survival. Recurrence free survival and length of hospital stay were also compared. RESULTS: The disease specific survival between indicated ESD and surgery showed no significant difference (cumulative survival 100% vs. 97.03%, p = 0.39), so as the recurrence free survival (cumulative survival 92.31% vs. 94.06%, p = 0.60). In subgroup analyses of ESD treated patients, a non-significant recurrence rate difference between indicated and non-indicated ESD was found (cumulative recurrence 7.69% vs. 20%, p = 0.39) and a higher recurrence rate in patients with non-R0 resection compared with R0 resection (cumulative recurrence 0% vs. 40%, p < 0.01). However, the shorter duration of hospital stay in ESD group was noted in comparison to surgery (mean 5.67 days vs. 15.75 days, p < 0.01). The ESD patients have minor complications including bleeding, perforation and fever than surgery. CONCLUSION: ESD is a reasonable first line treatment in selected early gastric cancer in additional to surgery. Pre-treatment evaluation and post-ESD review of curability is crucial to further surveillance program or definite therapy including surgery.

Laparoscopic distal gastrectomy for clinical stage I gastric adenocarcinoma: Techniques evolution and oncological outcomes of the first 100 cases.

BACKGROUND/PURPOSE: While gaining more acceptance, the use of laparoscopic distal gastrectomy (LDG) to treat gastric cancer were still limited in Taiwan. This study reviewed our experience about the technique evolution and outcome of using LDG for the patients with clinical stage (c-stage) I gastric cancers. METHODS: A retrospective review of the patients undergoing LDG for c-stage I gastric cancers at a medical center of Taiwan was performed. The demographics, peri-operative parameters, reconstruction methods, morbidities, pathologic and oncological outcomes were analyzed. RESULTS: A total of 100 patients with c-stage I gastric cancers between October 2005 and September 2016 were enrolled. Laparoscopy-assisted distal gastrectomy (LADG) was performed in the initial 69 cases. Total laparoscopic distal gastrectomy (TLDG) was done in the following 31 cases. There was no conversion of procedures, nor surgical mortality. The surgical morbidity rate was 13%, including 3 major complications. The ratio of using Billroth I reconstruction (83.9% versus 43.5%, p < 0.01) and the mean number of harvested lymph nodes (38.6 ± 14.8 versus 31.2 ± 15.2, p = 0.02) were both higher in the TLDG group than in the LADG group. The pathologic examination confirmed 78 patients were stage I, while 22 were stage II disease. Seven of the 24 patients with lymph node metastasis received adjuvant chemotherapy. Two patients had recurrence of diseases. The 3-year recurrence-free and overall survival were 93.3% and 95.8% separately. CONCLUSION: These results suggested that laparoscopic gastrectomy could be performed safely and feasibly for patients with early gastric cancers. LADG is recommended for the establishment of the demanding technique.

Postconditioning mitigates cell death following oxygen and glucose deprivation in PC12 cells and forebrain reperfusion injury in rats.

Postconditioning mitigates ischemia-induced cellular damage via a modified reperfusion procedure. Mitochondrial permeability transition (MPT) is an important pathophysiological change in reperfusion injury. This study explores the role of MPT modulation underlying hypoxic postconditioning (HPoC) in PC12 cells and studies the neuroprotective effects of ischemic postconditioning (IPoC) on rats. Oxygen-glucose deprivation (OGD) was performed for 10 hr on PC12 cells. HPoC was induced by three cycles of 10-min reoxygenation/10-min rehypoxia after OGD. The MPT inhibitor N-methyl-4-isoleucine cyclosporine (NIM811) and the MPT inducer carboxyatractyloside (CATR) were administered to selective groups before OGD. Cellular death was evaluated by flow cytometry and Western blot analysis. JC-1 fluorescence signal was used to estimate the mitochondrial membrane potential (△Ψm ). Transient global cerebral ischemia (tGCI) was induced via the two-vessel occlusion and hypotension method in male Sprague Dawley rats. IPoC was induced by three cycles of 10-sec reperfusion/10-sec reocclusion after index ischemia. HPoC and NIM811 administration attenuated cell death, cytochrome c release, and caspase-3 activity and maintained △Ψm of PC12 cells after OGD. The addition of CATR negated the protection conferred by HPoC. IPoC reduced neuronal degeneration and cytochrome c release and cleaved caspase-9 expression of hippocampal CA1 neurons in rats after tGCI. HPoC protected PC12 cells against OGD by modulating the MPT. IPoC attenuated degeneration of hippocampal neurons after cerebral ischemia.

Laparoscopic resection for large gastric gastrointestinal stromal tumor (GIST): intermediate follow-up results.

BACKGROUND: Laparoscopic wedge resection has become a widely accepted treatment for small gastrointestinal stromal tumor (GIST) of the stomach. However, its feasibility as treatment for large gastric GIST is not known. In this retrospective study, the perioperative and oncologic outcomes of laparoscopic wedge resection for gastric GIST (5-8 cm) were reviewed. METHODS: Between November 2002 and December 2012, a total of 39 patients with primary gastric GIST sized 5-8 cm underwent surgery at a tertiary care center, including 18 patients who underwent laparoscopic wedge resection of the stomach (Lap group) and 21 patients who underwent open wedge resection of the stomach (Open group). Clinicopathological parameters were reviewed and compared between the groups. RESULTS: The demographics including age, gender, and body weight were similar between groups. The operative outcomes including blood loss, hospital stay, and surgical complications were also similar, except that operative time was longer in the Lap group (146.6 ± 50.2 vs. 113.3 ± 42.9 min in the Open group, p = 0.03). There was no tumor rupture, conversion of procedures, or major surgical morbidity in either group. The overall median follow-up time was 3.6 years (1.0-11.1). Only one patient in the Lap group had liver metastasis (4 months postoperatively). This patient remains alive 5 years later under imatinib treatment. One patient in the Open group and three patients in the Lap group have died of GIST-unrelated diseases. CONCLUSIONS: Laparoscopic wedge resection of the stomach for primary gastric GIST (5-8 cm) appears to be safe and feasible, with operative and oncological outcomes comparable to those of the open method.

Dialysate Lavage: An Alternative Solution for Reducing the Peritoneal Implantation of Poorly Differentiated Gastric Cancer Cells.

BACKGROUND: Peritoneal lavage after cancer surgery is performed to reduce microscopic residual tumors in the peritoneum. This study evaluated the effects and mechanism of dialysate lavage in reducing the peritoneal implantation of gastric cancer cells. METHODS: Gastric cancer cells (MKN45 or AGS) were cultured with 1.5% peritoneal dialysate (PD) or normal saline (NS) for 30 min. The in vitro cell susceptibility to dialysate, including cell proliferation, cell death, cleaved PARP expression, and mitochondrial membrane potential, was evaluated. A murine model for gastric cancer cell peritoneal seeding was established to test the effects of PD and NS lavage on animal survival and tumor growth. RESULTS: A significant decrease in cell proliferation in PD and NS (75.2 ± 0.1 vs. 12.4 ± 0.2% in MKN45, p = 0.009; 58.2 ± 0.01 vs. 28.0 ± 0.01% in AGS, p = 0.008), an increase in mitochondrial permeability transition (93.0 ± 2.6 vs. 18.0 ± 2.9% in MKN45, p = 0.021; 86.8 ± 4.6 vs. 47.7 ± 10.2% in AGS, p < 0.001), and an increase in the expression of cleaved PARP and increased death (25.6 ± 9.4 vs. 16.9 ± 5.3% in MKN45, p = 0.031; 39.5 ± 5.1 vs. 20.9 ± 3.9% in AGS, p = 0.008) were recorded for gastric cancer cells separately exposed to PD and NS. Twenty-four days after inoculating MKN45 cells (5 × 10(6)/0.1 ml) in the peritoneal cavity, the average number of seeded tumors was 67.3 ± 10.8, 92.3 ± 6.0, and 29.2 ± 16.7 (p = 0.032), and the total weight of tumors was 0.98 ± 0.21, 0.58 ± 0.12, and 0.31 ± 0.17 g (p = 0.008), respectively, for mice receiving sham operation, NS lavage, and PD lavage. The 45-day survival rate for the PD lavage group was 22% compared to 0% for the sham injection and NS lavage groups (p = 0.034). CONCLUSION: PD induced significant cytotoxicity in gastric cancer cells that was related to mitochondrial perturbation. The use of PD lavage was effective in reducing the peritoneal implantation of gastric cancers in a murine model.

ß-1,4-Galactosyltransferase III suppresses ß1 integrin-mediated invasive phenotypes and negatively correlates with metastasis in colorectal cancer.

Metastasis often occurs in colorectal cancer (CRC) patients and is the main difficulty in cancer treatment. The upregulation of poly-N-acetyllactosamine-related glycosylation is found in CRC patients and is associated with progression and metastasis in cancer. ß-1,4-Galactosyltransferase III (B4GALT3) is an enzyme responsible for poly-N-acetyllactosamine synthesis, and therefore, we investigated its expression in CRC patients. We found that B4GALT3 negatively correlated with poorly differentiated histology (P < 0.001), advanced stages (P = 0.0052), regional lymph node metastasis (P = 0.0018) and distant metastasis (P = 0.0463) in CRC patients. B4GALT3 overexpression in CRC cells suppressed cell migration, invasion and adhesion, whereas B4GALT3 knockdown enhanced malignant cell phenotypes. The ß1 integrin-blocking antibody reversed the B4GALT3-mediated increase in cell invasion. B4GALT3 expression altered glycosylation on the N-glycan of ß1 integrin probably through changes in poly-N-acetyllactosamine expression. Furthermore, more activated ß1 integrin along with the activation of its downstream signaling transduction were found in B4GALT3 knockdown cells, whereas overexpression of B4GALT3 suppressed the expression of active ß1 integrin and inhibited its downstream signaling. Our results suggest that B4GALT3 is negatively associated with CRC metastasis and suppresses cell invasiveness through inhibiting activation of ß1 integrin.

Clinicopathological features and cancer transcriptomic profiling of poorly cohesive gastric carcinoma subtypes.

Gastric poorly cohesive carcinoma (PCC) manifests with a diffuse pattern and diverse tumor cell morphologies, often indicating a more unfavorable prognosis. Recent consensus has reclassified PCC based on the proportion of signet-ring cells (SRCs) in tumors for research purposes. The two most distinct subtypes, poorly cohesive carcinoma not otherwise specified (PCC-NOS) and signet-ring cell carcinoma (SRCC), are characterized by less than 10% and more than 90% SRCs, respectively. However, research comparing the clinicopathological and transcriptomic differences between these subtypes remains limited. In this study, we conducted a comparative analysis of clinicopathological features in 55 advanced-stage PCCs, consisting of 43 PCC-NOS and 12 SRCC cases. Subsequently, 12 PCC-NOS and 5 SRCC cases were randomly selected for initial cancer-related gene expression profiling and pathway enrichment analysis using the GeoMx digital spatial profiler, followed by validation in a separate validation group comprising 16 PCC-NOS and 6 SRCC cases. These transcriptomic findings were then correlated with tumor morphology and clinicopathological data. PCC-NOS cases exhibited larger tumor size, a higher prevalence of pathological N3 disease, and a worse 1-year progression-free survival rate compared to SRCC cases. Clustering of PCC-NOS and SRCC was successfully achieved using the GeoMx Cancer Transcriptome Atlas. Among all studied genes, only MMP7 showed differential expression, with its overexpression significantly associated with the PCC-NOS subtype, increased perineural invasion, and earlier disease progression. Pathway analysis revealed significantly enriched pathways in PCC-NOS related to vesicle-mediated transport, adaptive immune systems, oncogenic signaling, and extracellular matrix organization, while SRCC displayed significant enrichment in pathways associated with respiratory electron transport and the cell cycle. In conclusion, this study compares and correlates clinicopathological features and transcriptomic data between PCC-NOS and SRCC at advanced stages, employing the latest consensus classification and a novel platform for analysis.

A gasless laparoscopic technique of wide excision for gastric gastrointestinal stromal tumor versus open method.

BACKGROUND: Traditional open surgery for gastrointestinal stromal tumors (GIST) requires a long incision. Moreover, the gas-filling laparoscopic technique used in GIST surgery still has its limitations. Therefore, we developed a gasless laparoscopic (GL) surgery for GIST and compared it with traditional open surgery. METHODS: Between October 2007 and September 2009, 62 GIST patients in the National Taiwan University Hospital received wide excisions. Of these 62 patients, 30 underwent the new procedure (GL group) and 32 had open surgery (OS group). Preoperative and postoperative clinicopathologic characteristics were compared between the groups. RESULTS: There were no significant differences in preoperative characteristics or blood loss. However, the days to first flatus, postoperative hospital stay, wound length, white blood cell count at postoperative day one, and peak daily body temperature were all significantly improved in the GL group. Usage of postoperative analgesia on postoperative days one to five was also significantly lower in the GL group. CONCLUSIONS: Wide-excision laparoscopy for gastric GIST can be performed more safely, more effectively, and with faster postoperative recovery using the gasless technique as compared with the open method. We, therefore, recommend this new surgical technique, which hybridizes the advantages of both the traditional open method and pure laparoscopic surgery.

Plasma riboflavin fluorescence as a diagnostic marker of mesenteric ischemia-reperfusion injury in rats.

Due to the delayed and vague symptoms, it is difficult to early diagnose mesenteric ischemia injuries in the dynamics of acute illness, leading to a 60-80 % mortality rate. Here, we found plasma fluorescence spectra can rapidly assess the severity of mesenteric ischemia injury in animal models. Ischemia-reperfusion damage of the intestine leads to multiple times increase in NADH, flavins, and porphyrin auto-fluorescence of blood. The fluorescence intensity ratio between blue-fluorophores and flavins can reflect the occurrence of shock. Using liquid chromatography and mass spectroscopy, we confirm that riboflavin is primarily responsible for the increased flavin fluorescence. Since humans absorb riboflavin from the intestine, its increase in plasma may indicate intestinal mucosa injury. Our work suggests a self-calibrated and reagent-free approach to identifying the emergence of fatal mesenteric ischemia in emergency departments or intensive care units.

Relationship Between Symptom Distress and Fatigue Characteristics in Patients with Gastric Cancer During 1 Month after Gastrectomy.

This study's purpose was to describe changes in symptom distress and fatigue characteristics identifying which symptoms significantly impacted fatigue characteristics of patients with Gastric Cancer (GC) within 1 month after gastrectomy. A prospective longitudinal study was conducted. Patients with GC who were scheduled for gastrectomy were recruited from surgical outpatient clinics and surgery wards in northern Taiwan. Data were collected using a set of questionnaires before (T0) and 7 (T1) and 28 days (T2) after gastrectomy. Over all, 86 patients experienced mild levels of fatigue and symptom distress. The changes in worst fatigue and fatigue interference were greatest at T1. Anxiety had a significant negative effect on both worst fatigue and fatigue interference. Dry mouth, pain, and body image had significant deleterious effects on worst fatigue. The co-occurring symptoms affecting fatigue for patients with GC in the acute phase after gastrectomy should be actively assessed to ensure optimal fatigue management.

Coronavirus Disease Pandemic Effect on Medical-Seeking Behaviors Even in One Resource-Competent Community: A Case Controlled Study.

(1) Background: The coronavirus disease 2019 (COVID-19) pandemic had overwhelming impacts on medical services. During its initial surge, Taiwan was unique in maintaining its medical services without imposing travel restrictions, which provided an ideal environment in which to test if the fear of becoming infected with COVID-19 interfered with health-seeking behavior (HSB). We tested this hypothesis among adults with acute complicated appendicitis (ACA). (2) Methods: Adults with acute appendicitis were enrolled between 1 January and 30 June 2020 (COVID-19 period). The first two quarters of the preceding 3 years were defined as a historical control group. Outcome measures included the rate of ACA and the number of hospital stays. (3) Results: The COVID-19 era included 145 patients with acute appendicitis. Compared to the historical control (320 patients), the COVID-19 era was significantly associated with a higher length of symptom duration until presentation to the emergency room within >48 h (17.2% vs. 9.1%, p = 0.011), a higher incidence of ACA (29.7% vs. 19.4%, p = 0.014), and a longer length of hospital stays (5.0 days vs. 4.0 days, p = 0.043). The adjusted models showed that the COVID-19 period had a significant relationship with a higher rate of ACA (odds ratio (OR) = 1.87; 95% confidence interval (CI): 1.23-2.52; p = 0.008) and longer length of hospital stays (OR= 2.10; 95% CI: 0.92 to 3.31; p < 0.001). (4) Conclusions: The fear of COVID-19 may prohibit patients from seeking medical help, worsening their clinical outcomes. The surgical community should take action to provide scientific information to relive mental stress.

EGF-induced Grb7 recruits and promotes Ras activity essential for the tumorigenicity of Sk-Br3 breast cancer cells.

Co-amplification and co-overexpression of ErbB2 and Grb7 are frequently found in various cancers, including breast cancer. Biochemical and functional correlations of the two molecules have identified Grb7 to be a pivotal mediator downstream of ErbB2-mediated oncogenesis. However, it remains largely unknown how Grb7 is involve in the ErbB2-mediated tumorigenesis. In this study, we show that Grb7-mediated cell proliferation and growth are essential for the tumorigenesis that occurs in ErbB2-Grb7-overexpressing breast cancer cells. Intrinsically, EGF-induced de novo Grb7 tyrosine phosphorylation/activation recruits and activates Ras-GTPases and subsequently promotes the phosphorylation of ERK1/2, thereby stimulating tumor growth. Furthermore, we also found the anti-tumor effect could be synergized by co-treatment with Herceptin plus Grb7 knockdown in Sk-Br3 breast cancer cells. Our findings illustrate an underlying mechanism by which Grb7 promotes tumorigenesis through the formation of a novel EGFR-Grb7-Ras signaling complex, thereby highlighting the potential strategy of targeting Grb7 as an anti-breast cancer therapy.

Phosphorylation of focal adhesion kinase at Tyr397 in gastric carcinomas and its clinical significance.

Focal adhesion kinase (FAK) has been implicated in tumorigenesis in various cancers; however, it remains unclear how FAK participates in tumor malignancy in vivo. This study seeks to understand the role of FAK activation in gastric cancer progression. Using immunohistochemical staining and Western blotting, we found that pY397 FAK, an autophosphorylation site on FAK activation, was abundant in the cancerous tissues of 21 of 59 patients with gastric carcinomas. We attempted to correlate clinicopathological parameters, including histological types, TNM staging, and cancer recurrence, with the expression of FAK and pY397 FAK in cancerous tissues. Intriguingly, patients with higher levels of pY397 FAK displayed higher incidences of gastric cancer recurrence after surgery and poor 5-year recurrence-free survival. Furthermore, multivariate analyses showed that pY397 FAK was an independent predictor of gastric cancer recurrence. As a result, expression of pY397 FAK is a significant prognostic factor for the recurrence of gastric cancer. Additionally, in vitro studies showed that overexpression of Y397F, a dominant-negative mutant of FAK, in AGS human gastric carcinoma cells impaired cell migration, invasion, and proliferation compared with cells overexpressing wild-type FAK. Thus, activation of FAK through autophosphorylation at Tyr397 leads to the progression of gastric carcinomas by promoting cell migration, invasion, and proliferation. Collectively, our results have provided valuable insights for the development of novel diagnoses and therapeutic targets for gastric cancer treatments.

Parenteral glutamine supplementation improves serum albumin values in surgical cancer patients.

INTRODUCTION: Patients with gastric adenocarcinoma (GA) often develop malnutrition, which deteriorates after cancer surgery and negatively affects surgical outcomes. Despite being an abundant and versatile amino acid involved in the immune system and metabolic functions, glutamine levels are significantly depleted among patients who are critically ill or hypercatabolic. Therefore, this study aimed to investigate whether parenteral glutamine supplementation may improve nutritional status and surgical outcomes. METHODS: This retrospective, single-center cohort study included patients with GA who underwent gastrectomy between January 2007 and June 2019. Patients were classified into either the non-glutamine or glutamine group. Propensity score matching was used to minimize the bias in patient demographics. Furthermore, the average parenteral glutamine dose from the day of surgery to postoperative day four was calculated in g/kg/day. Surgical outcomes (length of hospitalization, major complication, and mortality) and changes in lymphocyte count and serum albumin levels 7 days post-surgery were assessed in both matched groups using adjusted models. RESULTS: A total of 1950 patients were reviewed, among whom 522 (26.8%) received parenteral glutamine supplementation (glutamine dose ranging from 0.05 to 0.49 g/kg/day). Among the included patients, 57.2% were males, and the median age was 64.9 years. After matching, there were 478 cases in each group. No differences in surgical outcomes and changes in lymphocyte count were observed between both matched groups. The glutamine group exhibited a smaller decrease in serum albumin levels compared to the non-glutamine group (-0.6 vs. -1.1 g/dL; P < 0.001). The adjusted matched model showed that glutamine dose contributed significantly toward increasing serum albumin levels (coefficient = 0.08 per 0.1 g/day/kg increment in glutamine; 95% confidence interval: 0.04 to 0.10; P < 0.001). CONCLUSIONS: Perioperative parenteral glutamine supplementation had a positive dose-dependent impact on the recovery of serum albumin levels among patients with GA undergoing gastrectomy, implying that glutamine supplementation improved postoperative nutritional suppression and ameliorated stress-associated inflammation. Although glutamine supplementation was not associated with surgical outcomes, further studies should be conducted to evaluate the clinical significance of serum albumin restoration.

Loss of SFRP1 expression is a key progression event in gastrointestinal stromal tumor pathogenesis.

The mechanism of high-grade transformation in gastrointestinal stromal tumors (GISTs) remains to be clarified. We aim to discover the key progression events by studying biphasic GISTs. The study group included 101 GISTs. Nineteen of these had been screened from 263 GISTs to represent the early stage of GIST high-grade transformation, characterized by juxtaposed low-grade and high-grade regions in the same tumor (so-called biphasic GISTs). Mutational analyses, fluorescence in situ hybridization (FISH), NanoString analyses, telomere analysis, and gene expression profiling were carried out, followed by in silico analyses, cell line study, and immunohistochemical validation. Using gene expression analysis, downregulation of SFRP1 was revealed to be the main event in GIST high-grade transformation (p = 0.013), accompanied by upregulation of EZH2. In silico analyses revealed that downregulation of SFRP1 was a common feature in GIST progression across several different series. Immunohistochemically, the expression of SFRP1 was validated to be significantly lower in high-grade GISTs (WHO risk group 3a or higher) than in low-grade GISTs (p < 0.001), and attenuation/loss of SFRP1 was associated with GIST tumor progression (p < 0.001). By NanoString and FISH analyses, chromosomal 9/9p loss was the only recurrent large-scale chromosome aberration in biphasic GISTs, with a correlation with SFRP1 downregulation. Subclones containing chromosome 9/9p loss could be appreciated in the low-grade parts of biphasic GISTs. TP53 mutation, RB1 loss, KIT/PDGFRA mutation, and alternative lengthening of telomeres did not play a significant role in GIST high-grade transformation. In conclusion, high-grade transformation of GISTs features SFRP1 downregulation and chromosome 9/9p loss.