World Journal of Gastroenterology
ISSN / EISSN : 1007-9327 / 2219-2840
Published by: Baishideng Publishing Group Inc. (10.3748)
Total articles ≅ 19,182
Latest articles in this journal
World Journal of Gastroenterology, Volume 27, pp 6515-6521; https://doi.org/10.3748/wjg.v27.i39.6515
In this editorial, we comment on pancreatic cancer (PC), one of the most aggressive and lethal cancers. Only minimal improvements in survival rates have been achieved over recent years. Available chemotherapeutic regimens have little impact, and surgical resection remains the only reliable curative approach. We address current treatment options for these patients, focusing on the usefulness of breast cancer (BRCA) gene mutation as a prognostic biomarker and predictor of response to chemotherapy. Superior survival outcomes have been reported in patients with PC and mutant BRCA gene treated with first-line platinum-based chemotherapy. Therefore, it appears appropriate to include BRCA gene status among clinical criteria used to select the chemotherapy regimen. In addition, maintenance treatment with poly(ADP-ribose) polymerase inhibitors has been found to improve progression-free survival in patients with PC and mutated BRCA whose disease does not progress after first-line platinum-based chemotherapy. This combination has therefore been proposed as the optimal treatment regimen for these patients.
World Journal of Gastroenterology, Volume 27, pp 6527-6550; https://doi.org/10.3748/wjg.v27.i39.6527
Pancreatic ductal adenocarcinoma (PDAC) is the third leading cause of cancer-related deaths in the United States. Although chemotherapeutic regimens such as gemcitabine+ nab-paclitaxel and FOLFIRINOX (FOLinic acid, 5-Fluroruracil, IRINotecan, and Oxaliplatin) significantly improve patient survival, the prevalence of therapy resistance remains a major roadblock in the success of these agents. This review discusses the molecular mechanisms that play a crucial role in PDAC therapy resistance and how a better understanding of these mechanisms has shaped clinical trials for pancreatic cancer chemotherapy. Specifically, we have discussed the metabolic alterations and DNA repair mechanisms observed in PDAC and current approaches in targeting these mechanisms. Our discussion also includes the lessons learned following the failure of immunotherapy in PDAC and current approaches underway to improve tumor’s immunological response.
World Journal of Gastroenterology, Volume 27, pp 6590-6600; https://doi.org/10.3748/wjg.v27.i39.6590
Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) seems to employ two routes of entrance to the host cell; via membrane fusion (with the cells expressing both angiotensin converting enzyme 2 (ACE2) and transmembrane peptidase/serine subfamily member 2/4 (TMPRSS2/4)) or via receptor-mediated endocytosis (to the target cells expressing only ACE2). The second mode is associated with cysteine cathepsins (probably cathepsin L) involvement in the virus spike protein (S protein) proteolytic activation. Also furin might activate the virus S protein enabling it to enter cells. Gastrointestinal tract (GIT) involvement in SARS-CoV-2 infection is evident in a subset of coronavirus disease 2019 (COVID-19) patients exhibiting GIT symptoms, such as diarrhea, and presenting viral-shedding in feces. Considering the abundance and co-localization of ACE2 and TMPRSS2 in the lower GIT (especially brush-border enterocytes), these two receptors seem to be mainly involved in SARS-CoV-2 invasion of the digestive tract. Additionally, in vitro studies have demonstrated the virions capability of infection and replication in the human epithelial cells lining GIT. However, also furin and cysteine cathepsins (cathepsin L) might participate in the activation of SARS-CoV-2 spike protein contributing to the virus invasiveness within GIT. Moreover, cathepsin L (due to its involvement in extracellular matrix components degradation and remodeling, the processes enhanced during SARS-CoV-2-induced inflammation) might be responsible for the dysregulation of absorption/ digestion functions of GIT, thus adding to the observed in some COVID-19 patients symptoms such as diarrhea.
World Journal of Gastroenterology, Volume 27, pp 6659-6672; https://doi.org/10.3748/wjg.v27.i39.6659
Gastric cancer is the third leading cause of cancer-related death worldwide and surgical resection remains the sole curative treatment for gastric cancer. Minimally invasive gastrectomy including laparoscopic and robotic approaches has been increasingly used in a few decades. Thus far, only a few reports have investigated the oncological outcomes following minimally invasive gastrectomy. To determine the 5-year survival following minimally invasive gastrectomy for gastric cancer and identify prognostic predictors. This retrospective cohort study identified 939 patients who underwent gastrectomy for gastric cancer during the study period. After excluding 125 patients with non-curative surgery (n = 77), other synchronous cancer (n = 2), remnant gastric cancer (n = 25), insufficient physical function (n = 13), and open gastrectomy (n = 8), a total of 814 consecutive patients with primary gastric cancer who underwent minimally invasive R0 gastrectomy at our institution between 2009 and 2014 were retrospectively examined. Accordingly, 5-year overall and recurrence-free survival were analyzed using the Kaplan–Meier method with the log-rank test and Cox regression analyses, while factors associated with survival were determined using multivariate analysis. Our analysis showed that age > 65 years, American Society of Anesthesiologists (ASA) physical status 3, total or proximal gastrectomy, and pathological T4 and N positive status were independent predictors of both 5-year overall and recurrence-free survival. Accordingly, the included patients had a 5-year overall and recurrence-free survival of 80.3% and 78.2%, respectively. Among the 814 patients, 157 (19.3%) underwent robotic gastrectomy, while 308 (37.2%) were diagnosed with pathological stage II or III disease. Notably, our findings showed that robotic gastrectomy was an independent positive predictor for recurrence-free survival in patients with pathological stage II/III [hazard ratio: 0.56 (0.33-0.96), P = 0.035]. Comparison of recurrence-free survival between the robotic and laparoscopic approach using propensity score matching analysis verified that the robotic group had less morbidity (P = 0.005). Age, ASA status, gastrectomy type, and pathological T and N status were prognostic factors of minimally invasive gastrectomy, with the robot approach possibly improving long-term outcomes of advanced gastric cancer.
World Journal of Gastroenterology, Volume 27, pp 6572-6589; https://doi.org/10.3748/wjg.v27.i39.6572
Pancreatic carcinoma (PC) is one of the leading causes of cancer-related deaths worldwide. Despite early detection and advances in therapeutics, the prognosis remains dismal. The outcome and therapeutic approach are dependent on the stage of PC at the time of diagnosis. The standard of care is surgery, followed by adjuvant chemotherapy. The advent of newer drugs has changed the landscape of adjuvant therapy. Moreover, recent trials have highlighted the role of neoadjuvant therapy and chemoradiotherapy for resectable and borderline resectable PC. As we progress towards a better understanding of tumor biology, genetics, and microenvironment, novel therapeutic strategies and targeted agents are now on the horizon. We have described the current and emerging therapeutic strategies in PC.
World Journal of Gastroenterology, Volume 27, pp 6701-6714; https://doi.org/10.3748/wjg.v27.i39.6701
Standard liver weight (SLW) is frequently used in deceased donor liver transplantation to avoid size mismatches with the recipient. However, some deceased donors (DDs) have fatty liver (FL). A few studies have reported that FL could impact liver size. To the best of our knowledge, there are no relevant SLW models for predicting liver size. To demonstrate the relationship between FL and total liver weight (TLW) in detail and present a related SLW formula. We prospectively enrolled 212 adult DDs from West China Hospital of Sichuan University from June 2019 to February 2021, recorded their basic information, such as sex, age, body height (BH) and body weight (BW), and performed abdominal ultrasound (US) and pathological biopsy (PB). The chi-square test and kappa consistency score were used to assess the consistency in terms of FL diagnosed by US relative to PB. Simple linear regression analysis was used to explore the variables related to TLW. Multiple linear regression analysis was used to formulate SLW models, and the root mean standard error and interclass correlation coefficient were used to test the fitting efficiency and accuracy of the model, respectively. Furthermore, the optimal formula was compared with previous formulas. Approximately 28.8% of DDs had FL. US had a high diagnostic ability (sensitivity and specificity were 86.2% and 92.9%, respectively; kappa value was 0.70, P < 0.001) for livers with more than a 5% fatty change. Simple linear regression analysis showed that sex (R2, 0.226; P < 0.001), BH (R2, 0.241; P < 0.001), BW (R2, 0.441; P < 0.001), BMI (R2, 0.224; P < 0.001), BSA (R2, 0.454; P < 0.001) and FL (R2, 0.130; P < 0.001) significantly impacted TLW. In addition, multiple linear regression analysis showed that there was no significant difference in liver weight between the DDs with no steatosis and those with steatosis within 5%. Furthermore, in the context of hepatic steatosis, TLW increased positively (non-linear); compared with the TLW of the non-FL group, the TLW of the groups with hepatic steatosis within 5%, between 5% and 20% and more than 20% increased by 0 g, 90 g, and 340 g, respectively. A novel formula, namely, -348.6 + (110.7 x Sex [0 = Female, 1 = Male]) + 958.0 x BSA + (179.8 x FLUS [0 = No, 1 = Yes]), where FL was diagnosed by US, was more convenient and accurate than any other formula for predicting SLW. FL is positively correlated with TLW. The novel formula deduced using sex, BSA and FLUS is the optimal formula for predicting SLW in adult DDs.
World Journal of Gastroenterology, Volume 27, pp 6647-6658; https://doi.org/10.3748/wjg.v27.i39.6647
Stigmatization is the separation of an individual from a group due to aspects that make them different. Resilience may in turn influence the perception of stigma. Patients with inflammatory bowel disease (IBD) are susceptible to stigma, although data are very limited. To validate an Italian translation of the IBD perceived stigma scale (PSS) in relation to patients’ resilience. Consecutive IBD outpatients were prospectively enrolled (December 2018-September 2019) in an Italian, tertiary referral, IBD center. Clinical and demographic data were collected. Stigma and resilience were evaluated through the IBD-PSS and the 25-item Connor-Davidson Resilience Scale, respectively. The International Quality of Life Assessment Project approach was followed to translate the IBD-PSS into Italian and to establish data quality. Higher scores represent greater perceived stigma and resilience. Multivariable analysis for factors associated with greater stigma was computed. Overall, 126 IBD patients (mean age 46.1 ± 16.9) were enrolled. The International Quality of Life Assessment criteria for acceptable psychometric properties of the scale were satisfied, with optimal data completeness. There was no ceiling effect, whilst floor effect was present (7.1%). The discriminant validity and the internal consistency reliability were good (Cronbach alpha = 0.87). The overall internal consistency was 95%, and the test-retest reliability was excellent 0.996. The median PSS score was 0.45 (0.20-0.85). Resilience negatively correlated with perceived stigma (Spearman’s correlation = -0.18, 95% confidence intervals: -0.42-0.08, P = 0.03). We herein validated the Italian translation of the PSS scale, also demonstrating that resilience negatively impacts perceived stigma.
World Journal of Gastroenterology, Volume 27, pp 6551-6571; https://doi.org/10.3748/wjg.v27.i39.6551
Information about the coronavirus disease 2019 (COVID-19) pandemic is still evolving since its appearance in December 2019 and has affected the whole world. Particularly, a search for an effective and safe treatment for COVID-19 continues. Botanical mixtures contain secondary metabolites (such as flavonoids, phenolics, alkaloids, essential oils etc.) with many therapeutic effects. In this study, the use of herbal treatments against COVID-19 was evaluated. Medical synthetic drugs focus mainly on respiratory symptoms, however herbal therapy with plant extracts may be useful to relieve overall symptoms of COVID-19 due to the variety of bioactive ingredients. Since COVID-19 is a virus that affects the respiratory tract, the antiviral effects of botanicals/plants against respiratory viruses have been examined through clinical studies. Data about COVID-19 patients revealed that the virus not only affects the respiratory system but different organs including the gastrointestinal (GI) system. As GI symptoms seriously affect quality of life, herbal options that might eliminate these problems were also evaluated. Finally, computer modeling studies of plants and their active compounds on COVID-19 were included. In summary, herbal therapies were identified as potential options for both antiviral effects and control of COVID-19 symptoms. Further data will be needed to enlighten all aspects of COVID-19 pathogenesis, before determining the effects of plants on severe acute respiratory syndrome coronavirus 2.
World Journal of Gastroenterology, Volume 27, pp 6601-6614; https://doi.org/10.3748/wjg.v27.i39.6601
Gastroesophageal reflux disease has an increasing incidence and prevalence worldwide. A significant proportion of patients have a suboptimal response to proton pump inhibitors or are unwilling to take lifelong medication due to concerns about long-term adverse effects. Endoscopic anti-reflux therapies offer a minimally invasive option for patients unwilling to undergo surgical treatment or take lifelong medication. The best candidates are those with a good response to proton pump inhibitors and without a significant sliding hiatal hernia. Transoral incisionless fundoplication and nonablative radiofrequency are the techniques with the largest body of evidence and that have been tested in several randomized clinical trials. Band-assisted ligation techniques, anti-reflux mucosectomy, anti-reflux mucosal ablation, and new plication devices have yielded promising results in recent noncontrolled studies. Nonetheless, the role of endoscopic procedures remains controversial due to limited long-term and comparative data, and no consensus exists in current clinical guidelines. This review provides an updated summary focused on the patient selection, technical details, clinical success, and safety of current and future endoscopic anti-reflux techniques.
World Journal of Gastroenterology, Volume 27, pp 6631-6646; https://doi.org/10.3748/wjg.v27.i39.6631
Different types of pathogenic mutations may produce different clinical phenotypes, but a correlation between Peutz-Jeghers syndrome (PJS) genotype and clinical phenotype has not been found. Not all patients with PJS have detectable mutations of the STK11/LKB1 gene, what is the genetic basis of clinical phenotypic heterogeneity of PJS? Do PJS cases without STK11/LKB1 mutations have other pathogenic genes? Those are clinical problems that perplex doctors. The aim was to investigate the specific gene mutation of PJS, and the correlation between the genotype and clinical phenotype of PJS. A total of 24 patients with PJS admitted to the Air Force Medical Center, PLA (formerly the Air Force General Hospital, PLA) from November 1994 to January 2020 were randomly selected for inclusion in the study. One hundred thirty-nine common hereditary tumor-related genes including STK11/LKB1 were screened and analyzed for pathogenic germline mutations by high-throughput next-generation sequencing (NGS). The mutation status of the genes and their relationship with clinical phenotypes of PJS were explored. Twenty of the 24 PJS patients in this group (83.3%) had STK11/LKB1 gene mutations, 90% of which were pathogenic mutations, and ten had new mutation sites. Pathogenic mutations in exon 7 of STK11/LKB1 gene were significantly lower than in other exons. Truncation mutations are more common in exons 1 and 4 of STK11/LKB1, and their pathogenicity was significantly higher than that of missense mutations. We also found SLX4 gene mutations in PJS patients. PJS has a relatively complicated genetic background. Changes in the sites responsible for coding functional proteins in exon 1 and exon 4 of STK11/LKB1 may be one of the main causes of PJS. Mutation of the SLX4 gene may be a cause of genetic heterogeneity in PJS.