The latest medical research on Gastroenterology

The research magnet gathers the latest research from around the web, based on your specialty area. Below you will find a sample of some of the most recent articles from reputable medical journals about gastroenterology gathered by our medical AI research bot.

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Management of Clinical T2N0 Esophageal and Gastroesophageal Junction Adenocarcinoma: What Is the Optimal Treatment?

Gastrointestinal Surgery

The current standard of care for locally advanced esophageal and gastroesophageal junction (GEJ) adenocarcinoma includes neoadjuvant chemoradiation and surgery. The optimal treatment for clinical T2N0M0 (cT2N0) disease is debated. This study aims to determine the optimal treatment in these patients.

The National Cancer Database was used to identify patients who underwent surgery for cT2N0 esophageal and GEJ adenocarcinoma from 2004 to 2017. Patients were grouped into surgery-alone, neoadjuvant therapy (NAT), and adjuvant therapy (AT) groups. Subgroups of high-risk patients (tumor ≥ 3 cm, poor differentiation, or lymphovascular invasion) and patients upstaged after upfront surgery were identified. Kaplan-Meier method and Cox proportional hazard ratios were used to compare overall survival.

Of 2160 patients included, 957 (44.3%) underwent surgery-alone, 821 (38.0%) underwent NAT and surgery, and 382 (17.7%) underwent surgery and AT. One thousand six hundred nineteen (75.0%) patients had high-risk features. Six hundred fourteen (45.9%) patients were upstaged after upfront surgery. In the overall cohort, AT was associated with improved survival compared to NAT (HR 0.618, p < 0.001) and surgery-alone (HR 0.699, p < 0.001). There was no difference in survival between NAT and surgery-alone (HR 1.132, p = 0.112). Similar results were observed in high-risk patients. Patients upstaged after upfront surgery who received AT had improved survival compared to those initially treated with NAT (HR 0.613, p < 0.001).

This analysis suggests that cT2N0 esophageal and GEJ adenocarcinomas may not benefit from the intensive multimodality therapy utilized in locally advanced disease. Selective use of AT for patients who are upstaged pathologically, or have high-risk features, is associated with improved outcomes.

Simultaneous whole-cell patch-clamp and calcium imaging on myenteric neurons.

Am J Physiol

Live calcium imaging is often used as a proxy for electrophysiological measurements and has been a valuable tool that allows simultaneous analysis ...

β-PIX cooperates with GIT1 to regulate eNOS in sinusoidal endothelial cells.

Am J Physiol

Previous studies have demonstrated that G-protein-coupled receptor kinase interacting-1 protein (GIT1) associates with eNOS to regulate nitric oxide production in sinusoidal endothelial cells (SECs). Here, we hypothesized that GIT1's tightly-associated binding partner, b-PIX (p21-activated kinase-interacting exchange factor beta, ARHGEF7) is specifically important in regulation of eNOS activity.

We examined b-PIX expression in normal rat liver by immunohistochemistry and explored b-PIX protein-protein interactions using immunoprecipitation and immunoblotting. The role of b-PIX in regulating eNOS enzymatic activity was studied in GIT1-deficient SECs. Finally, structural analysis of interaction sites in GIT1 and β-PIX required to regulate eNOS activity were mapped.

b-PIX was expressed primarily in SECs in normal liver, and was either absent or expressed at extremely low levels in other liver cells (stellate cells, Kupffer cells, hepatocytes). β-PIX interacted with GIT1 and eNOS to form a trimolecular signaling module in normal SECs, and was important in stimulating eNOS activity. Of note, GIT1-β-PIX interaction led to synergistic enhancement of eNOS activity, and β-PIX-driven increase in eNOS activity was GIT1 dependent. Disruption of β-PIX or GIT1 in normal SECs using β-PIX siRNA or GIT1-deficient SECs led to reduced eNOS activity. Finally, specific GIT1 domains (SHD and SLD, aa 331 to 596) and the β-PIX C terminal (aa 496 to 555) appeared to be critical in the regulation eNOS activity.

The data indicate that b-PIX regulates eNOS phosphorylation and function in normal SECs, and highlight the importance of the GIT1/b-PIX/eNOS trimolecular complex in normal liver SEC function.

Laparoscopic Proximal Gastrectomy with Novel Valvuloplastic Esophagogastrostomy vs. Laparoscopic Total Gastrectomy for Stage I Gastric Cancer: a Propensity Score Matching Analysis.

Gastrointestinal Surgery

Laparoscopic total gastrectomy for early proximal gastric cancer is widely performed. Recently, the number of laparoscopic proximal gastrectomies performed, a surgery limited to early proximal gastric cancer, has gradually increased. However, evidence for the long-term outcomes of laparoscopic total gastrectomy and laparoscopic proximal gastrectomy is insufficient. Therefore, this study aimed to clarify and compare the long-term outcomes of laparoscopic total gastrectomy and laparoscopic proximal gastrectomy with novel valvuloplastic esophagogastrostomy for treatment of clinical stage I proximal gastric cancer.

This study included 111 patients who underwent laparoscopic total gastrectomy or laparoscopic proximal gastrectomy for the treatment of upper third clinical stage I gastric cancer between April 2004 and December 2017. After adjusting for propensity score matching analysis, we compared the postoperative complications, nutritional status, and long-term outcomes between the two groups.

After matching the inclusion criteria, 56 patients (28 in each group) were enrolled. No significant differences were noted in the postoperative complications between the two groups. While laparoscopic proximal gastrectomy was associated with lower albumin levels, lower body weight loss was seen by 1 year after surgery and higher hemoglobin levels by 1, 2, and 3 years after surgery. No significant differences were observed in the 3-year overall survival and 3-year recurrence-free survival between the laparoscopic total gastrectomy and laparoscopic proximal gastrectomy groups (P = 0.74 and 0.72, respectively).

Laparoscopic proximal gastrectomy and laparoscopic total gastrectomy for patients with upper third clinical stage I gastric cancer are feasible as regards its safety and outcomes.

Natural History of Liver Disease in a Large International Cohort of Children with Alagille syndrome: Results from The GALA Study.


Alagille syndrome (ALGS) is a multisystem disorder, characterized by cholestasis. Existing outcome data are largely derived from tertiary centers and real-world data are lacking. This study aimed to elucidate the natural history of liver disease in a contemporary, international, cohort of children with ALGS.

Multicenter retrospective study of children with a clinically and/or genetically confirmed ALGS diagnosis, born Jan-1997 - Aug-2019. Native liver survival (NLS) and event-free survival rates were assessed. Cox models were constructed to identify early biochemical predictors of clinically evident portal hypertension (CEPH) and NLS.

1433 children (57% male) from 67 centers in 29 countries were included. 10 and 18-years NLS rates were 54.4% and 40.3%. By 10 and 18-years, 51.5% and 66.0% of ALGS children experienced ≥1 adverse liver-related event (CEPH, transplant or death). Children (>6 and ≤12 months) with median total bilirubin (TB) levels between ≥5.0 and <10.0 mg/dL had a 4.1-fold (95% CI 1.6 - 10.8) and those ≥10.0 mg/dL had an 8.0-fold (95% CI 3.4 - 18.4) increased risk of developing CEPH compared with those <5.0 mg/dL. Median TB levels between ≥5.0 and <10.0 mg/dL and >10.0 mg/dL were associated with a 4.8 (95% CI 2.4 - 9.7) and 15.6 (95% CI 8.7 - 28.2) increased risk of transplantation relative to <5.0 mg/dL. Median TB <5.0 mg/dL were associated with higher NLS rates relative to ≥5.0 mg/dL, with 79% reaching adulthood with native liver (p<0.001).

In this large international cohort of ALGS, only 40.3% of children reach adulthood with their native liver. A TB <5.0 mg/dL between 6-and-12-months of age is associated with better hepatic outcomes. These thresholds provide clinicians with an objective tool to assist with clinical decision-making and in the evaluation of novel therapies.

Rapid in vivo multiplexed editing (RIME) of the adult mouse liver.


Assessing mammalian gene function in vivo has traditionally relied on manipulation of the mouse genome in embryonic stem cells or peri-zygotic embryos. These approaches are time consuming and require extensive breeding when simultaneous mutations in multiple genes is desired. The aim of this study is to introduce a Rapid In vivo Multiplexed Editing (RIME) method, and to provide proof-of-concept of this system.

RIME, a system wherein CRISPR/Cas9 technology, paired with adeno-associated viruses (AAVs), permits the inactivation of one or more genes in the adult mouse liver. The method is quick, requiring as little as 1 month from conceptualization to knockout (KO), and highly efficient, enabling editing in >95% of target cells. To highlight its utility, we used this system to inactivate, alone or in combination, genes with functions spanning metabolism, mitosis, mitochondrial maintenance, and cell proliferation.

RIME enables the rapid, efficient, and inexpensive analysis of multiple genes in the mouse liver in vivo.

Comparing 5-Year Survival Rates Before and After Re-stratification of Stage I-III Right-Sided Colon Cancer Patients by Establishing the Presence/Absence of Occult Tumor Cells and Lymph Node Metastases in the Different Levels of Surgical Dissection.

Gastrointestinal Surgery

"Safe Radical D3 Right Hemicolectomy for Cancer through Preoperative Biphasic Multi-Detector Computed Tomography (MDCT) Angiography" registered at

Consecutive patients were drawn from a multicenter prospective trial. After surgery, the surgical specimen was divided into the D1/D2 and D3 volumes before being further analyzed separately. All lymph nodes were examined with cytokeratin CAM 5.2 immunohistochemically. Lymph nodes containing metastases and OTC (micrometastases; isolated tumor cells) were identified. Re-stratification was as follows: RS1, stages I/II, no OTC in D1/D2 and D3 volumes; RS2, stages I/II, OTC in D1/D2 and/or D3; RS3, stage III, lymph node metastases in D1/D2, with/without OTC in D3; RS4, stage III, lymph node metastases in D3, with/without OTC in D3.

Eighty-seven patients (39 men, 68.4 + 9.9 years) were included. The standard stratified (SS) group contained the following: stages I/II (SS1) 57 patients; stage III (SS2) 30 patients. Re-stratified (RS) contained RS1 (38), RS2 (19), RS3 (24), and RS4 (6) patients. Lymph node ratio (OTC) RS2: 0.157 D1/D2; 0.035 D3 and 0.092 complete specimens. Lymph node ratio RS3: 0.113 D1/D2; complete specimen 0.056. Overall survival and disease-free survival were p = 0.875 and p = 0.049 for SS and p = 0.144 and p = 0.001 for RS groups, respectively.

This re-stratification identifies a patient group with poor prognosis (RS4). Removing this group from SS2 eliminates all the differences in survival between RS2 and RS3 groups. The level of dissection of the affected nodes may have an impact on survival.

RIPK3 dampens mitochondrial bioenergetics and lipid droplet dynamics in metabolic liver disease.


Receptor-interacting protein kinase 3 (RIPK3) mediates non-alcoholic fatty liver disease (NAFLD) progression, but its metabolic function is unclear. Here, we aimed to investigate the role of RIPK3 in modulating mitochondria function, coupled with lipid droplet (LD) architecture in NAFLD.

Functional studies evaluating mitochondria and LD biology were performed in wild-type (WT) and Ripk3-/- mice fed a choline-deficient, amino acid-defined (CDAA) diet for 32 and 66 weeks and in CRISPR-Cas9 Ripk3-null fat-loaded immortalized hepatocytes. The association between hepatic perilipin (PLIN) 1 and 5, RIPK3 and disease severity was also addressed in a cohort of NAFLD patients and in PLIN1-associated familial partial lipodystrophy. Ripk3 deficiency rescued impairment in mitochondrial biogenesis, bioenergetics and function in CDAA diet-fed mice and fat-loaded hepatocytes. Ripk3 deficiency was accompanied by a strong upregulation of antioxidant systems, leading to diminished oxidative stress upon fat loading both in vivo and in vitro. Strikingly, Ripk3-/- hepatocytes displayed smaller size LD in higher numbers than WT cells after incubation with free fatty acids. Ripk3 deficiency upregulated adipocyte and hepatic levels of LD-associated proteins PLIN1 and PLIN5. PLIN1 upregulation controlled LD structure and diminished mitochondrial stress upon free fatty acid overload in Ripk3-/- hepatocytes and was associated with diminished human NAFLD severity. Conversely, a pathogenic PLIN1 frameshift variant was associated with NAFLD and fibrosis, as well as with increased hepatic RIPK3 levels in familial partial lipodystrophy.

Ripk3 deficiency restores mitochondria bioenergetics and impacts LD dynamics. RIPK3 inhibition is promising in ameliorating NAFLD.

Factors affecting prognosis in hepatocellular carcinoma patients post-transarterial chemoembolization.

Indian Journal of Gastroenterology

To evaluate the factors influencing the achievement of a sustained complete response (CR) and overall survival (OS) in hepatocellular carcinoma (HCC) patients undergoing transarterial chemoembolization (TACE).

We retrospectively reviewed the records of HCC patients who underwent TACE as the first modality of treatment between 2014 and 2019. We investigated the factors affecting sustained CR (no recurrence within 6 months) and OS (time from diagnosis until either death or last follow-up).

The study enrolled 161 patients; 159 (98.8%) had cirrhosis. Post-TACE, 19.9% (32/161) achieved sustained CR. In the multivariate analysis, a tumor size < 5 cm was a positive factor for achieving sustained CR (odds ratio, 5.012; p = 0.006). In the proportional hazards model, the factors associated with decreased survival included alcohol-related liver disease (hazards ratio [HR] 1.683; p = 0.036), presence of symptoms (HR 1.816; p = 0.005) and portal hypertension (HR 1.608; p = 0.038) at initial diagnosis, serum alpha-fetoprotein (AFP) > 100 ng/mL (HR 2.082; p < 0.001), and higher Child-Pugh classification (HR 1.1.639; p = 0.024). Achievement of sustained CR (HR, 0.355; p = 0.002) was independently associated with increased survival.

The tumor size was a predictive factor for sustained CR. Alcohol-related liver disease, presence of symptoms and portal hypertension at initial diagnosis, elevated serum AFP, liver reserve status, and achieved sustained CR were independent factors affecting survival. We demonstrated the effect of alcohol-related liver disease on survival after TACE. Our results will aid physicians in the management and prognostication of HCC.

What Is the Optimal Time on a Low-Calorie Diet Prior to Laparoscopic Anti-reflux Surgery? A Prospective Case-Controlled Study.

Gastrointestinal Surgery

A very low-calorie diet (VLCD) or low-calorie diet (LCD) is often used prior to laparoscopic surgery to optimize access to the hiatus. Much debate exists in the literature regarding the required duration for a VLCD or LCD, and how to evaluate the presence of a fatty liver. The aim of our study was to determine the optimal amount of time on an LCD to achieve maximal liver volume reduction, and to assess the accuracy of the InBody 230® vs. bedside ultrasonography vs. magnetic resonance imaging (MRI) in the measurement of liver volume.

Seventeen consecutive patients undergoing laparoscopic anti-reflux surgery were recruited into the study. Each patient underwent body composition analysis with the InBody® 230, liver ultrasound, and liver MRI. Patients then began an LCD with a weekly ultrasound assessment until the day before surgery when they underwent repeat body composition analysis, liver ultrasound, and MRI.

The mean age was 54 years (range 21, 74). Maximal liver volume loss was noted within 3 weeks for 88% of participants, with 47% achieving their maximal liver volume reduction after the first week of an LCD. The mean reduction in liver volume was 16%, 18.6%, and 19% for MRI, ultrasound, and body composition analysis, respectively.

Close to 90% of patients require 3 weeks or less on an LCD to achieve maximal liver volume loss prior to laparoscopic anti-reflux surgery. Body composition analysis and bedside ultrasonography were both as accurate as the gold standard MRI in the assessment of liver volume.

Bile Leakage After Hepatic Resection for Hepatocellular Carcinoma: Does It Impact the Short- and Long-term Outcomes?

Gastrointestinal Surgery

Bile leakage (BL) is one of the commonest morbidities after hepatic resection for hepatocellular carcinoma (HCC). The current study was conducted to evaluate the incidence and different predictive factors for BL after hepatic resection for HCC, and to evaluate of the impact of BL on the long-term survival outcomes.

We reviewed the patients' data who underwent hepatic resection for HCC during the period between June 2010 and June 2019.

A total of 293 patients were included in the study. BL occurred in 17 patients (5.8%). More Child-Pugh class B patients were found in BL group. There were no significant differences between the two groups except for tumor site, macroscopic portal vein invasion, extent of liver resection, Pringle maneuver use, intraoperative blood loss, and transfusions. Longer hospital stay, higher grades of post-hepatectomy liver failure, and abdominal collections were noted in BL group. After median follow-up duration of 17 months (4-110 months), there were no significant differences between BL and non-BL group regarding overall survival (log-rank, p = 0.746) and disease-free survival (log-rank, p = 0.348). In multivariate analysis, Child-Pugh class, macroscopic portal vein invasion, liver resection extent (minor/major), and Pringle's maneuver use were the only significant predictors of BL.

BL did not significantly impair the long-term outcomes after hepatic resection for HCC. Child-Pugh class, macroscopic portal vein invasion, liver resection extent (minor/major), and Pringle's maneuver use were the main risk factors of BL in the current study.

Counter-Clockwise Approach for Robotic Pylorus-Preserving Pancreatoduodenectomy.

Gastrointestinal Surgery

This multi-media article aims to describe a counter-clockwise approach for pancreatoduodenectomy (CCA-PD) in robotic surgery.

A CCA-PD was used as a strategy for robotic surgery to treat a 69-year-old woman without comorbidities who presented a ductal adenocarcinoma of the head of the pancreas (2.7 cm) in contact with the portal vein (less than 180°), preoperatively treated with FOLFIRINOX. The procedure was entirely done in the abdominal right upper quadrant (RUQ) following the main steps of CCA-PD resection: section of the first portion of the duodenum; biliary duct transection; Kocherization of the duodenum and retropancreatic lymphadenectomy; section of the jejunum; portal vein dissection; transection of the pancreas and uncinate detachment. The reconstruction also followed the counter-clockwise direction with a single jejunal loop with end-to-side anastomoses: pancreato-jejunal; choledoco-jejunal; duodenojejunal.

The total operation time was 435 min, and the estimated blood loss was 200 mL. The postoperative course was uneventful without complications, with hospital discharge on the fifth postoperative day. The final pathology was ductal adenocarcinoma (G2), ypT2ypN2 (07/31), with negative surgical margins.

The entire surgery happens in a unique surgical field, the RUQ, which saves time by avoiding unnecessary mobilization of the bowel and favors a layer-by-layer dissection with enough space for both dissections and sutures on each step of the procedure and improving bleeding control if necessary.