July 2025

Using mouse models, patient-derived biospecimens, and tumor organoids, this study aimed to investigate the mechanism by which Roux-en-Y gastric bypass (RYGB) surgery reduces colorectal cancer (CRC) risk. The authors developed a novel RYGB-CRC mouse model and demonstrated that RYGB reduced CRC progression and metastasis. Further mechanistic studies revealed that the reduced CRC tumor progression in both the mouse model and patient-derived samples was primarily driven by alterations in circulating bile acids.

Summary: Obesity is associated with a wide range of diseases, including increased cancer risk. Metabolic surgery, such as RYGB, is an effective and sustainable treatment for obesity and has been shown to reduce the risk of malignancy. In RYGB surgery, an anastomosis is created between the biliopancreatic and alimentary limbs, rerouting food and digestive metabolites through the gastrointestinal tract. This study aimed to elucidate the antitumoral mechanisms of RYGB in CRC carcinogenesis.

The authors developed an RYGB-CRC mouse model in which mice were fed a high-fat diet (HFD) for six weeks, followed by either RYGB or sham surgery and an additional six weeks of HFD or normal chow (NC). Tumor organoids were then orthotopically implanted into the cecum, leading to primary tumor growth and spontaneous metastasis to the liver and lungs, as well as peritoneal carcinomatosis, after six weeks (Figure 1). Mice that underwent RYGB had a two-thirds reduction in tumor volume (RYGB: ~50 mm³ vs. sham-NC: ~150 mm³, P<0.05) and an almost complete reduction in liver metastases compared to sham-operated mice on HFD or NC (RYGB: 1/20, sham-HFD: 16/20, sham-NC: 13/20).

To explore the mechanism behind the reduced tumor burden, the authors analyzed intraluminal and serum bile acid (BA) composition. They found that RYGB mice on NC had similar levels of primary and secondary BAs in the intestinal lumen compared to sham-NC mice, but exhibited a ~50% decrease in circulating primary BAs and ~50% increase in circulating secondary BAs. This suggests that while diet controls luminal BAs, RYGB specifically alters serum BA composition. To test whether serum BA composition directly influenced CRC progression, the authors created a second mouse model in which a cholecysto-intestinal shunt (CIS) was performed by connecting the gallbladder to the terminal ileum. CIS mice exhibited similar tumor volumes and rates of liver metastasis as RYGB mice, with significantly reduced tumor volumes (CIS: ~50 mm³ vs. sham-HFD: ~175 mm³, P<0.0001) and fewer liver metastases (CIS: 2/20 vs. sham-HFD: 16/20). No significant differences were found in the fecal/intertumoral microbiome or tumor-infiltrating immune cells between groups. Finally, human and murine tumor organoids exposed to primary BAs in-vitro showed a dose-dependent increase in proliferation and upregulation of pathways associated with metabolism and stemness, such as Wnt/β-catenin.

The authors then analyzed BA composition in a human cohort of stage IV CRC patients with metachronous colorectal liver metastases. Elevated serum levels of total and primary BAs were associated with shorter time to metastasis (P = 0.00004, HR = 3.077 for total BAs; P<0.0001, HR = 3.365 for primary BAs). Key primary BA drivers included cholic acid, taurocholic acid, and glycocholic acid.

Notably, the study did not include an RYGB + HFD group, which would have helped delineate the role of diet following surgery. Additionally, no human RYGB cohort was analyzed; rather, BA levels were measured in patients already diagnosed with CRC. Nonetheless, the study provides novel mechanistic insights into how metabolic surgery may reduce CRC tumor progression.

Bottom line: Metabolic surgery reduces colorectal cancer progression primarily through alterations in bile acid composition, rather than changes in the gut microbiome or systemic inflammation. 

This study is a secondary analysis of patient data from seven randomized clinical trials included in the ARDS Network or the Prevention Early Treatment of Acute Lung Injury Network, which revealed that after controlling for confounders, baseline ventilator driving pressure was independently associated with the development of acute kidney injury (AKI).

Summary: This secondary analysis or prior randomized clinical trials included 2,960 patients with acute respiratory distress syndrome (ARDS) of which 1,000 patients developed an AKI. Regarding the association between baseline driving pressure and development of late AKI (between two and seven days of ARDS diagnosis), the authors performed a multivariable logistic regression including the variables of age, sex, body mass index, diabetes mellitus, other organ failure present, fluid balance, baseline Pao2:Fio2 ratio, respiratory rate, tidal volume, respiratory system compliance, PEEP, and driving pressure as the independent variables, with the development of a late AKI as the dependent variable. AKI was defined only regarding blood creatinine as hourly urine output was not available as a variable, and patients with the development of AKI within two days of ARDS diagnosis (‘early AKI’) were excluded. After controlling for confounders, driving pressure was independently associated with the development of a late AKI (odds ratio [OR], 1.046; 95% CIs, 1.021–1.072; p < 0.001). 

In a further sensitivity analysis, the authors repeated the main analysis without excluding patients with an early AKI. When controlling for all factors as listed in the above multivariable logistic regression, baseline driving pressure remained independently associated with development of AKI (OR, 1.038; 95% CI, 1.020-1.056; p < 0.001). Finally, authors included all patients who developed AKI, even if later than seven days post-ARDS diagnosis, and found that baseline driving pressure remained independently associated with development of AKI (OR, 1.060; 95% CI, 1.036-1.084; p < 0.001).

If we use baseline driving pressure as a surrogate marker for injurious mechanical ventilation, these results may indicate that injurious mechanical ventilation contributes to acute kidney injury. This is thought to be via a mechanism discussed in the literature as ‘biotrauma,’ or the release of inflammatory cytokines contributing to extrapulmonary end organ damage, including in the kidneys. This is consistent with other studies in literature linking ventilator-induced lung injury with renal inflammation and microvascular dysfunction.

The chief limitation of this study is its observational nature; it cannot prove that ventilator-associated lung injury causes AKI. Other limitations include a lack of detailed data regarding urine output, and its inclusion of only North American patient populations, limiting its generalizability.

Bottom line: Patients with higher baseline driving pressures following acute respiratory distress syndrome were more likely to experience acute kidney injury in a secondary analysis of national data.

This retrospective, multicenter study assessed lymph node metastasis, recurrence patterns, and prognosis in patients with clinical stage 0 to IA non-small cell lung cancer (NSCLC) presenting as radiologic ground-glass opacity (GGO)-dominant tumors ≤3 cm. Among 988 patients treated with curative-intent surgery, lymph node involvement was rare, and oncologic outcomes were excellent regardless of surgical approach. These findings suggest that resection without lymph node dissection may be appropriate for small, peripheral, GGO-dominant adenocarcinomas, offering a less invasive strategy while preserving oncologic outcomes. 

Summary: This retrospective study evaluated clinicopathologic outcomes in 988 patients with clinical stage 0 to IA lung adenocarcinoma presenting as ≤3 cm GGO-dominant tumors on preoperative imaging. Patients underwent curative-intent resection (lobectomy, segmentectomy, or wedge resection) between 2010 and 2020 at two academic centers in Japan. The primary objective was to determine whether lymph node dissection is necessary in this subset of NSCLC, which is thought to represent a more indolent form of the disease. 

With a median follow-up of 54.5 months, among all patients, only one (0.1%) had evidence of lymph node metastasis on final pathology (an intrapulmonary station 13 node). This tumor was slightly central, measured 1.9 cm, and histologically revealed an invasive component despite its GGO-dominant radiologic appearance. There were no cases of hilar or mediastinal lymph node metastasis in the entire cohort.

Surgical procedures included 206 wedge resections (21%), 372 segmentectomies (38%), and 410 lobectomies (42%). Lymph node dissection was performed in 95% of lobectomies and 98% of segmentectomies but in only 5% of wedge resections. Among those undergoing wedge resection, 3% had lymph node sampling, 0.5% underwent hilar dissection, and 1.5% had both hilar and mediastinal dissection. Nearly all tumors (99%) were adenocarcinomas. Lymphatic, vascular, and pleural invasion were observed in 1%, 2%, and 2% of patients, consistent with the low-grade behavior of GGO-dominant tumors.

Among all patients, the five-year overall survival (OS) and recurrence-free survival (RFS) were 96.7% (95% CI, 95.1–97.8%) and 96.6% (95% CI, 94.9–97.7%), respectively. Survival outcomes were comparable across all surgical approaches. Patients undergoing lobectomy had an OS of 97.1%, segmentectomy 96.9%, and wedge resection 95.7%, while RFS was 97.1%, 96.9%, and 94.9%, respectively. There were no lung cancer related deaths. Four patients (0.4%) experienced recurrences, two with local recurrence at the surgical stump, and two with distant disease. 

This study is limited by its retrospective design, and the dataset lacks certain clinical variables, such as surgical margin size. Additionally, a median follow-up of 54.5 months may be insufficient to detect all late recurrences in this indolent subset. Nonetheless, the study’s findings may help guide surgical decision-making regarding the extent of lymph node dissection in GGO-dominant NSCLC, ultimately improving patient outcomes by minimizing operative morbidity.

Bottom line: Small, peripheral, GGO-dominant adenocarcinomas can be safely treated with wedge resection with omission of lymph node dissection, if complete resection with negative margins is achieved. For more centrally located tumors or those with high-risk features, segmentectomy or lobectomy may still be preferred to ensure appropriate margin along with complete nodal assessment.