Safety and efficacy of augmented-rectangle technique versus delta-shaped anastomosis for treating gastric cancer in total laparoscopic distal gastrectomy.

PURPOSE: This study aimed to evaluate the safety and efficacy of augmented-rectangle technique (ART) versus delta-shaped anastomosis (DA) for treating gastric cancer in total laparoscopic distal gastrectomy. METHODS: In total, 99 patients with distal gastric cancer who underwent ART (n = 60) or DA (n = 39) were considered. Operative data, postoperative recovery, complications, quality of life, and endoscopic findings of both groups were compared. RESULTS: The ART group had faster postoperative recovery than the DA group, and was better than DA regarding complications. The mode of reconstruction remained an independent predictor of complications, but not postoperative recovery. Dumping syndrome occurred in 3 (5.0%) and 2 patients (5.1%) of ART and DA groups within 30 days after surgery, and 3 (5.0%) and 2 patients (5.1%) 1 year after surgery. Regarding global health status on the EORTC-QLQ-C30 scale, the ART group had better outcomes than the DA group. Gastritis occurred in 38 (63.3%) and 27 (69.3%) patients of ART and DA groups, respectively. Residual food occurred in 8 (13.3%) and 11 (28.2%) patients of ART and DA groups. Reflux esophagitis occurred in 5 (8.3%) and 4 (10.3%) patients of ART and DA groups. Further, bile reflux occurred in 8 (13.3%) and 4 (10.3%) patients of ART and DA groups. CONCLUSIONS: ART has similar advantages to DA for total laparoscopic reconstruction and is superior to DA regarding the incidence of complications, complication grade, and global health status. Furthermore, ART may have potential advantages in postoperative recovery and anastomotic stenosis.

Safety and efficacy of laparoscopic proximal gastrectomy with SOFY versus laparoscopic total gastrectomy with Roux-en-Y for treating cT1-2 Siewert II/III adenocarcinoma of the esophagogastric junction: a single-center prospective cohort study.

PURPOSE: Side overlap with fundoplication by Yamashita (SOFY) is an anti-reflux form of esophagogastrostomy. We compared the safety and efficacy of laparoscopic proximal gastrectomy (PG) with SOFY to that of laparoscopic total gastrectomy (TG) with Roux-en-Y for treating cT1-2 Siewert II/III adenocarcinoma of the esophagogastric junction. METHODS: Fifty-two patients who underwent PG (n = 28) or TG (n = 24), without conversion to laparotomy, were included. Surgical outcomes, complications, reflux symptoms, quality of life, and nutritional status of both groups were compared. RESULTS: Significant differences between PG and TG groups regarding operative time (245.7 versus 294.6 min, P = 0.005), reconstruction time (22.1 versus 28.5 min, P < 0.001), time to pass gas (3 versus 4 days, P = 0.021), time to oral intake (4.5 versus 5 days, P = 0.043), and gastroesophageal reflux (60.7% versus 4.2%, P < 0.001) were observed. Reflux esophagitis for the PG group was 42.9% (12/28). The incidence of Los Angeles grade B and above was 10.7%. Between-group differences in terms of global health status, diarrhea, reflux, and eating were observed. Body weight maintenance was better in the PG group than in the TG group 6 months and 1 year postoperatively. CONCLUSION: SOFY is simple and more advantageous than TG in terms of postoperative recovery, body weight, eating, and diarrhea. However, the occurrence of postoperative reflux after SOFY was high. The limitations of this study are the significant differences in pathological T stage of patients in the two groups and the small sample size.

A new technique for treating hiatal hernia with gastroesophageal reflux disease: the laparoscopic total left-side surgical approach.

INTRODUCTION: Although the traditional bilateral surgical approach to treat hiatal hernia (HH) with gastroesophageal reflux disease (GERD) can provide local protection of the vagus nerve, the integrity of the entire vagus nerve cannot be evaluated. Therefore, we developed and described the total left-side surgical approach (TLSA), which theoretically reduces injury to the vagus nerve, and described the detailed surgical procedure. METHODS: Initially, we performed a cadaver study to explore the characteristics of the vagus nerve. Then, we prospectively evaluated the TLSA in 5 patients with HH and GERD between June 2020 and September 2020. Demographic characteristics, surgical parameters, perioperative outcomes, and follow-up findings were analyzed. RESULTS: The TLSA was successfully used in five patients (40-64 years old), and no major complications were noted. The median total operative time was 114 min, median blood loss was 50 mL, and median postoperative hospital stay was 3.8 days. Gastrointestinal function recovered within 4 days of surgery in all the patients. The 6-month follow-up gastroscopy examination showed well-established gastroesophageal flap valves. Compared with the baseline results, the 6-month follow-up results showed lower values for the total GerdQ score (12.4 vs. 6.2) and the total esophageal acid exposure time (3.48% vs. 0.38%). Based on the European Organization for Research and Treatment of Cancer quality of life questionnaire-stomach module 52 results, the incidence of dysphagia and flatulence decreased over time after the TLSA. CONCLUSIONS: The TLSA provides a clear and broad surgical field, less trauma, and rapid recovery; moreover, it is technically simple. Although our results suggest that the TLSA provides safety and short-term efficacy and is feasible for patients with HH and GERD, long-term results from a larger clinical trial are needed to validate these findings. Trial registration ChiCTR2000034028, registration date is June 21, 2020. The study was registered prospectively.

Aneuploidy and improved growth are coincident but not causal in a yeast cancer model.

Cancer cells have acquired mutations that alter their growth. Aneuploidy that typify cancer cells are often assumed to contribute to the abnormal growth characteristics. Here we test the idea of a link between aneuploidy and mutations allowing improved growth, using Saccharomyces cerevisiae containing a mcm4 helicase allele that was shown to cause cancer in mice. Yeast bearing this mcm4 allele are prone to undergoing a "hypermutable phase" characterized by a changing karyotype, ultimately yielding progeny with improved growth properties. When such progeny are returned to a normal karyotype by mating, their improved growth remains. Genetic analysis shows their improved growth is due to mutations in just a few loci. In sum, the effects of the mcm4 allele in mice are recapitulated in yeast, and the aneuploidy is not required to maintain improved growth.

Impact of preoperative biliary drainage on postoperative complications and prognosis after pancreaticoduodenectomy: A single-center retrospective cohort study.

Background and objectives: Obstructive jaundice is common in patients with pancreaticobiliary malignancies. Preoperative biliary drainage (PBD) can alleviate cholestasis; however, no consensus has been reached on the impact of PBD on the incidence of surgery-related complications and patient survival. This study aimed to evaluate the effect among patients treated with PBD. Methods: This retrospective study examined the clinical and follow-up prognostic data of 160 patients with pancreaticobiliary malignancies who underwent pancreaticoduodenectomy (PD) at Beijing Friendship Hospital, Capital Medical University, from January 2016 to July 2020. Outcomes were compared between patients who underwent PBD (PBD group) and those who did not (control group). Changes in biochemical indicators were evaluated before and after drainage in the PBD group. Between-group differences in inflammatory indicators after PD were assessed using the Wilcoxon signed-rank test. Postoperative complications were classified according to the Clavien-Dindo classification system. The effects of PBD and biliary drainage efficiency on postoperative complications were evaluated using the chi-square test and binary logistics regression. The Kaplan-Meier analysis was used for between-group comparison of survival analysis. Univariate and multivariate regression analyses were performed to identify prognostic factors of survival. Results: Total 160 patients were enrolled,the mean age of the study sample was 62.75 ± 6.75 years. The distribution of pancreaticobiliary malignancies was as follows: 34 cases of pancreatic head cancer, 61 cases of distal bile duct cancer, 20 cases of duodenal papilla cancer, 39 cases of duodenal ampullary cancer, and 6 cases of malignant intraductal papillary mucinous neoplasm (IPMN). PBD was performed in 90 of the 160 patients, with PBD performed using an endoscopic retrograde cholangiopancreatography (ERCP) approach in 55 patients and with percutaneous transhepatic cholangiography (PTC) used in the remaining 35 cases. The mean duration of drainage in the PBD group was 12.8 ± 8.8 days. The overall rate of complications was 48.05% (37/77) in the control group and 65.55% (59/90) in the PBD group with non-significant difference (χ2 = 3.527, p=0.473). In logsitics regression analysis, PBD was also not a risk factor for postoperative complications OR=1.77, p=0.709). The overall rate of postoperative complications was significantly higher among patients who underwent PBD for >2 weeks (χ2 = 6.102, p=0.013), with the rate of severe complications also being higher for this subgroup of PBD patients (χ2 = 4.673, p=0.03). The overall survival time was 47.9 ± 2.45 months, with survival being slightly lower in the PBD group (43.61 ± 3.26 months) than in the control group (52.24 ± 3.54 months), although this difference was not significant (hazard ratio (HR)=0.65, p=0.104). Conclusion: In patients with malignant biliary obstruction, PBD does not affect the incidence of postoperative complications after pancreaticoduodenectomy nor does it affect patient survival. Prolonged biliary drainage (>2 weeks) may increase the incidence of overall postoperative complications and severe complications.

Current Advancement on the Dynamic Mechanism of Gastroesophageal Reflux Disease.

Gastroesophageal reflux disease (GERD) is a common clinical disease associated with upper gastrointestinal motility disorders. Recently, with improvements in living standards and changes in lifestyle and dietary habits, the incidence of GERD has been increasing yearly. However, the mechanism of GERD has not been fully elucidated due to its complex pathogenesis, and this had led to unsatisfactory therapeutic outcomes. Currently, the occurrence and development of GERD involve multiple factors. Its pathogenesis is mainly thought to be related to factors, such as lower esophageal sphincter pressure, transient lower esophageal sphincter relaxation, crural diaphragmatic dysfunction, hiatus hernia, and impaired esophageal clearance. Therefore, explaining the pathogenesis of GERD more clearly and systematically, exploring potential and effective therapeutic targets, and choosing the best treatment methods have gradually become the focus of scholars' attention. Herein, we reviewed current advancements in the dynamic mechanism of GERD to better counsel patients on possible treatment options.

Laparoscopic total left-sided surgical approach versus traditional bilateral surgical approach for treating hiatal hernia: a study protocol for a randomized controlled trial.

BACKGROUND: In China, guidelines for the treatment of hiatal hernia (HH) are lacking. Furthermore, efficacy and safety assessments of surgical approaches for HH and for the protection of the vagus nerve and organ function are needed. Therefore, the present clinical trial is being conducted to establish the normative treatment for HH. METHODS: The current trial is an ongoing, single-center, randomized controlled trial of patients with HH. The total sample size required for the trial (July 2020-December 2023) is approximately 114 patients. Patients will be randomly assigned to either an experimental group (total left-sided surgical approach; TLSA) or a control group (traditional bilateral surgical approach; TBSA) at a ratio of 1:1 using the block randomization method. We will use case report forms (CRFs) and electronic data capture (EDC) systems to obtain demographic information, preoperative laboratory tests, auxiliary examination results, operation information, and postoperative condition. The patients will be followed up for 3 years after surgery. The primary endpoint is the gastrointestinal quality-of-life index (GIQLI) at 1 year. The secondary endpoints include an efficacy evaluation index [consisting of the incidence of gallstones and gastric emptying disorders, gastrointestinal function recovery time, visual analog scale (VAS) scores, objective evaluation of postoperative indices, and surgical information] and a safety evaluation index (consisting of the incidence of postoperative complications, the 30-day postoperative mortality rate, and the HH recurrence rate at 1 and 3 years after surgery). DISCUSSION: TLSA can protect the normal physiological function of organs to a certain extent by protecting the vagus nerve from injury, and has satisfactory short- and long-term efficacy. There is no significant difference in the incidence of postoperative complications and surgical safety between TLSA and TBSA. Our findings will facilitate clinical decision-making for HH and improve the life quality of patients. TRIAL REGISTRATION: Chinese Clinical Trial Registry, ChiCTR2000034028 (registration date: June 21, 2020).

Mouse pachytene checkpoint 2 (trip13) is required for completing meiotic recombination but not synapsis.

In mammalian meiosis, homologous chromosome synapsis is coupled with recombination. As in most eukaryotes, mammalian meiocytes have checkpoints that monitor the fidelity of these processes. We report that the mouse ortholog (Trip13) of pachytene checkpoint 2 (PCH2), an essential component of the synapsis checkpoint in Saccharomyces cerevisiae and Caenorhabditis elegans, is required for completion of meiosis in both sexes. TRIP13-deficient mice exhibit spermatocyte death in pachynema and loss of oocytes around birth. The chromosomes of mutant spermatocytes synapse fully, yet retain several markers of recombination intermediates, including RAD51, BLM, and RPA. These chromosomes also exhibited the chiasmata markers MLH1 and MLH3, and okadaic acid treatment of mutant spermatocytes caused progression to metaphase I with bivalent chromosomes. Double mutant analysis demonstrated that the recombination and synapsis genes Spo11, Mei1, Rec8, and Dmc1 are all epistatic to Trip13, suggesting that TRIP13 does not have meiotic checkpoint function in mice. Our data indicate that TRIP13 is required after strand invasion for completing a subset of recombination events, but possibly not those destined to be crossovers. To our knowledge, this is the first model to separate recombination defects from asynapsis in mammalian meiosis, and provides the first evidence that unrepaired DNA damage alone can trigger the pachytene checkpoint response in mice.

[Distributions and pollution status of heavy metals in the suspended particles of the estuaries and coastal area of eastern Hainan].

The distributions and pollution status of heavy metals in the suspended particles were investigated in the Wanquan and Wenchang/Wenjiao estuaries and the coastal area of eastern Hainan in July 2008. The concentrations of metal elements (Al, Fe, Mn, Cr, Cu, Ni, V, Zn) were determined by ICP-AES after microwave digestion. Multivariate statistical methods (e. g. correlation analysis and principal factor analysis) were used to discuss the major factors controlling the variability of heavy metal concentrations and the pollution status in those areas. There was an obvious variability in particulate metal concentrations from upstream to estuary of both rivers. The concentrations first increased with increasing salinity and then decreased with further increase of the salinity; the concentrations were slightly higher at the coastal area in the east. The variability of particulate metal concentrations reduced significantly after the normalization by Al, indicating the effects of grain size. Enrichment factor calculation results showed that there was heavy metal pollution (especially Cu, Ni) in the Wenchang/Wenjiao River and estuary, while the situation in Wanquan River remained at pristine level. Concentrations of particulate metals in the study area were mainly controlled by source geology and provenance, as well as contamination from the discharge of waste water and biological activity.

Ploidy dictates repair pathway choice under DNA replication stress.

This study reports an unusual ploidy-specific response to replication stress presented by a defective minichromosome maintenance (MCM) helicase allele in yeast. The corresponding mouse allele, Mcm4(Chaos3), predisposes mice to mammary gland tumors. While mcm4(Chaos3) causes replication stress in both haploid and diploid yeast, only diploid mutants exhibit G2/M delay, severe genetic instability (GIN), and reduced viability. These different outcomes are associated with distinct repair pathways adopted in haploid and diploid mutants. Haploid mutants use the Rad6-dependent pathways that resume stalled forks, whereas the diploid mutants use the Rad52- and MRX-dependent pathways that repair double strand breaks. The repair pathway choice is irreversible and not regulated by the availability of repair enzymes. This ploidy effect is independent of mating type heterozygosity and not further enhanced by increasing ploidy. In summary, a defective MCM helicase causes GIN only in particular cell types. In response to replication stress, early events associated with ploidy dictate the repair pathway choice. This study uncovers a fundamental difference between haplophase and diplophase in the maintenance of genome integrity.

Genetic evidence that synaptonemal complex axial elements govern recombination pathway choice in mice.

Chiasmata resulting from interhomolog recombination are critical for proper chromosome segregation at meiotic metaphase I, thus preventing aneuploidy and consequent deleterious effects. Recombination in meiosis is driven by programmed induction of double strand breaks (DSBs), and the repair of these breaks occurs primarily by recombination between homologous chromosomes, not sister chromatids. Almost nothing is known about the basis for recombination partner choice in mammals. We addressed this problem using a genetic approach. Since meiotic recombination is coupled with synaptonemal complex (SC) morphogenesis, we explored the role of axial elements--precursors to the lateral element in the mature SC--in recombination partner choice, DSB repair pathways, and checkpoint control. Female mice lacking the SC axial element protein SYCP3 produce viable, but often aneuploid, oocytes. We describe genetic studies indicating that while DSB-containing Sycp3-/- oocytes can be eliminated efficiently, those that survive have completed repair before the execution of an intact DNA damage checkpoint. We find that the requirement for DMC1 and TRIP13, proteins normally essential for recombination repair of meiotic DSBs, is substantially bypassed in Sycp3 and Sycp2 mutants. This bypass requires RAD54, a functionally conserved protein that promotes intersister recombination in yeast meiosis and mammalian mitotic cells. Immunocytological and genetic studies indicated that the bypass in Sycp3-/- Dmc1-/- oocytes was linked to increased DSB repair. These experiments lead us to hypothesize that axial elements mediate the activities of recombination proteins to favor interhomolog, rather than intersister recombinational repair of genetically programmed DSBs in mice. The elimination of this activity in SYCP3- or SYCP2-deficient oocytes may underlie the aneuploidy in derivative mouse embryos and spontaneous abortions in women.