INTRODUCTION:Ambulatory esophageal pH monitoring is the reference standard for diagnosing gastroesophageal reflux disease (GERD), yet a subset of symptomatic patients demonstrate physiologically non-positive studies. OBJECTIVE:To evaluate whether variation in esophageal length and relative probe position influences measured reflux exposure and contributes to symptom-physiology discordance during wireless pH monitoring. METHODS:We performed a retrospective analysis of 63 patients undergoing Bravo pH monitoring. Relative probe position was defined as the ratio of capsule placement distance to esophageal length. Associations between anatomic variables and acid exposure time (AET) were assessed using multivariable regression, including analyses of overall, upright, and supine reflux exposure. RESULTS:Sixty-three patients were included (60% female). Height was strongly associated with esophageal length (β = 0.17, p < 0.001), resulting in systematic differences in relative probe position. A subset of patients with elevated symptom burden demonstrated physiologically non-positive reflux testing; these patients were more often female and shorter in stature. In multivariable models, taller height was independently associated with increased AET (β = 0.14, p = 0.02), an effect observed in upright reflux (β = 0.18, p = 0.030) but not supine reflux. Apparent sex differences in reflux detection were explained by underlying anatomic variation rather than sex itself. CONCLUSION:Fixed-distance pH probe placement results in variable relative positioning within the esophagus, producing non-equivalent physiologic sampling across patients. Probe placement farther from the gastroesophageal junction may under-sample clinically relevant distal reflux events and contribute to symptom-physiology discordance. Observed disparities in reflux detection among female patients appear to be driven by differences in esophageal length rather than intrinsic physiologic variation. These findings support prospective evaluation of anatomy-informed probe positioning to determine whether it can improve the consistency and diagnostic accuracy of ambulatory pH monitoring.
BACKGROUND:NRAS and BRAF mutations occur in approximately 5% and 12% of colorectal cancers, respectively, but their prognostic significance in Stage IV disease remains unclear. We hypothesized that NRAS and BRAF mutations confer worse survival and surgical outcomes, with effects modified by tumor location and microsatellite instability (MSI). METHODS:We conducted a retrospective cohort study using the National Cancer Database (2021-2023) of adults with clinical Stage IV colorectal cancer, stratified by NRAS and BRAF mutation status. A subset analysis included patients undergoing surgical resection. The primary outcome was two-year overall survival, with a secondary outcome of positive surgical margins. Cox proportional hazards and logistic regression were used for survival and surgical outcomes. RESULTS:Of 22,595 patients, 77.1% had no mutation, 15.3% BRAF, 6.2% NRAS, and 1.5% concurrent mutations. BRAF-mutant tumors were more often right-sided (51.2% vs. 26.0%, p<0.001) and MSI (28.8% vs. 4.6%, p<0.001), while NRAS-mutant tumors resembled those without mutations. On multivariable analysis, NRAS (HR=1.13, 95% CI 1.01-1.26, p=0.04), concurrent mutations (HR=1.29, 95% CI 1.05-1.60, p=0.02), and BRAF (HR=1.87, 95% CI 1.73-2.02, p<0.001) were associated with increased two-year mortality. MSI status modified this effect, with MSI/BRAF tumors associated with lower mortality (HR=0.54, p<0.001), while right-sided tumor location independently predicted increased mortality (HR=1.38, p<0.001). Only BRAF-mutant tumors were associated with an increased risk of positive surgical margins (OR=1.52, p<0.001). CONCLUSIONS:BRAF mutations confer worse survival and surgical outcomes than NRAS mutations. MSI modifies BRAF-associated risk, while right-sided location independently predicts survival. These findings refine risk stratification and surgical decision-making.
PURPOSE:The Affordable Care Act's Medicaid Expansion increased insurance coverage nationally; its impact on colorectal cancer surgery access and outcomes remains unclear, particularly in rural regions with structural barriers. This study evaluated whether Medicaid Expansion was associated with changes in colorectal cancer surgery utilization, access to elective surgery, and short-term outcomes within eight Midwestern states. METHODS:A population-based difference-in-difference analysis used State Inpatient Databases from 2010-2022, including four expansion and four late or non-expansion states. Adults aged 18-64 years who underwent colorectal cancer resection were included. Primary outcomes included state-level surgical utilization rates and elective surgery rates per 100,000 population. Secondary outcomes included in-hospital mortality and length of stay. RESULTS:Among 42,634 resections, 69.5% occurred in expansion states. Colorectal cancer surgical utilization rates did not increase following Medicaid expansion in either state group, regardless of rurality or insurance type. Elective surgery rates did not increase among rural patients in either group. Among rural uninsured patients, rates declined significantly more in Medicaid Expansion states, consistent with shifts in payer mix post expansion. Length of stay and in-hospital mortality remained low, with no significant differences by expansion status or rurality. CONCLUSION:Medicaid Expansion was not associated with sustained improvements in colorectal cancer surgical utilization, access to elective surgery, or outcomes in the Midwest, including rural populations. Expanded insurance coverage alone may be insufficient to overcome structural barriers to timely colorectal cancer surgery. Further research is needed to uncover drivers of gaps in rural cancer care.
INTRODUCTION:Circumferential resection margin (CRM) positivity is an established predictor of local recurrence and survival in rectal cancer. The prognostic impact of CRM positivity specifically attributable to tumour within lymph nodes at the CRM (node-positive CRM) is unclear. We performed a systematic review to determine whether CRM positivity caused by lymph node metastases confers similar oncological risk to CRM positivity from direct tumour extension. METHODS:A systematic search of MEDLINE, EMBASE, CINAHL and Cochrane Library was conducted in March 2026 for studies reporting outcomes for patients with CRM positivity specifically due to lymph node involvement. Search strings combined terms for "rectal cancer", "circumferential resection margin" and "lymph node". Two reviewers screened records and extracted data. Study quality was assessed with the Newcastle-Ottawa Scale. Outcomes of interest were overall survival, disease-free survival, local recurrence and distant recurrence. Due to heterogenous outcome reporting and small numbers no meta-analysis was performed and a structured narrative synthesis was conducted. RESULTS:From 138 records screened, 5 studies (published between 2002-2024) including 5,303 patients met inclusion criteria; 162 patients were CRM-positive due to lymph nodes. Across all studies, node-positive CRM patients generally demonstrated more favourable outcomes than patients with CRM positivity due to direct tumour extension: 5-year overall survival ranged 49-51% for node-positive CRM versus 20-29% for tumour-extension CRM. Local recurrence in node-positive CRM ranged from 5-12% versus 22-52% for tumour-extension CRM. CONCLUSION:CRM positivity due solely to metastatic lymph nodes may be associated with more favourable oncological outcomes than CRM positivity resulting from direct tumour extension. Prospective multicentre studies with standardised pathological classification and reporting are required to determine whether the mechanism of CRM involvement represents an independent prognostic factor before these findings can inform clinical practice.
BACKGROUND:Intraoperative ultrasound is central to liver surgery, but its incremental staging value in intrahepatic cholangiocarcinoma remains poorly defined. METHODS:We retrospectively analyzed a prospectively maintained database of patients considered for curative-intent liver resection for suspected intrahepatic cholangiocarcinoma from January 2004 to December 2024. The primary endpoint was the incremental intraoperative staging yield of IOUS/LUS, defined as the proportion of resected patients with at least one additional pathologically confirmed ICC nodule. Secondary endpoints were changes in surgical strategy, factors associated with incremental detection, and oncologic outcomes. RESULTS:Of 208 patients considered for resection, 17 were found to have unresectable disease at staging laparoscopy/LUS and 191 underwent hepatectomy. IOUS/LUS prompted resection of 35 additional suspicious nodules; 33 were confirmed as ICC in 21 patients (11.0%), whereas two were benign. The surgical plan changed in 34 patients (17.8%): in 21 because of additional nodules and in 13 because of previously unrecognized vascular relationships. Time to first recurrence was shorter in patients with additional ICC nodules (6.6 vs 16.7 months, p<0.001). CONCLUSION:IOUS/LUS provided clinically relevant incremental staging, refined surgical strategy, and identified patients at increased risk of early recurrence. These findings support its routine use during curative-intent surgery for intrahepatic cholangiocarcinoma.
BACKGROUND:Hepatic ischemia-reperfusion injury (HIRI) is a major cause of graft dysfunction and postoperative complications following liver transplantation and hepatic resection. Increasing evidence indicates that the gut-liver axis plays a central role in modulating hepatic injury, inflammation, and tissue regeneration during HIRI. METHODS:This narrative review synthesizes current experimental and clinical evidence regarding the mechanisms linking intestinal barrier dysfunction, gut microbiota dysbiosis, microbial metabolites and immune signaling pathways to the pathogenesis of HIRI. Recent advances in pharmacological strategies targeting the gut-liver axis were also evaluated. RESULTS:Hepatic ischemia disrupts intestinal microcirculation, leading to epithelial barrier breakdown, bacterial translocation and activation of innate immune responses through pathogen-associated molecular patterns and Toll-like receptor signaling. Microbiota-derived metabolites exert both protective and deleterious effects. Short-chain fatty acids promote anti-inflammatory responses through histone deacetylase inhibition, whereas trimethylamine N-oxide amplifies NLRP3 inflammasome activation and pyroptosis. Disruption of the FXR-FGF15/19 signaling pathway further compromises intestinal barrier integrity and hepatic regeneration. Emerging therapeutic approaches, including FXR agonists, non-mitogenic FGF19 analogs, recombinant IL-22, postbiotics and TMAO-targeted interventions, demonstrate promising hepatoprotective potential in preclinical studies. DISCUSSION:The gut-liver axis is a key regulator of HIRI pathophysiology and represents a promising therapeutic target. Strategies aimed at preserving intestinal barrier integrity, modulating the gut microbiota, and restoring immunometabolic homeostasis may reduce hepatic injury and improve outcomes following liver transplantation and major hepatic surgery.
