Colorectal Cancer Stage at Diagnosis Before vs During the COVID-19 Pandemic in Italy

IMPORTANCE Delays in screening programs and the reluctance of patients to seek medical attention because of the outbreak of SARS-CoV-2 could be associated with the risk of more advanced colorectal cancers at diagnosis. OBJECTIVE To evaluate whether the SARS-CoV-2 pandemic was associated with more advanced oncologic stage and change in clinical presentation for patients with colorectal cancer. DESIGN, SETTING, AND PARTICIPANTS This retrospective, multicenter cohort study included all 17 938 adult patients who underwent surgery for colorectal cancer from March 1, 2020, to December 31, 2021 (pandemic period), and from January 1, 2018, to February 29, 2020 (prepandemic period), in 81 participating centers in Italy, including tertiary centers and community hospitals. Follow-up was 30 days from surgery. EXPOSURES Any type of surgical procedure for colorectal cancer, including explorative surgery, palliative procedures, and atypical or segmental resections. MAIN OUTCOMES AND MEASURES The primary outcome was advanced stage of colorectal cancer at diagnosis. Secondary outcomes were distant metastasis, T4 stage, aggressive biology (defined as cancer with at least 1 of the following characteristics: signet ring cells, mucinous tumor, budding, lymphovascular invasion, perineural invasion, and lymphangitis), stenotic lesion, emergency surgery, and palliative surgery. The independent association between the pandemic period and the outcomes was assessed using multivariate random-effects logistic regression, with hospital as the cluster variable. RESULTS A total of 17 938 patients (10 007 men [55.8%]; mean [SD] age, 70.6 [12.2] years) underwent surgery for colorectal cancer: 7796 (43.5%) during the pandemic period and 10 142 (56.5%) during the prepandemic period. Logistic regression indicated that the pandemic period was significantly associated with an increased rate of advanced-stage colorectal cancer (odds ratio [OR], 1.07; 95%CI, 1.01-1.13; P = .03), aggressive biology (OR, 1.32; 95%CI, 1.15-1.53; P < .001), and stenotic lesions (OR, 1.15; 95%CI, 1.01-1.31; P = .03). CONCLUSIONS AND RELEVANCE This cohort study suggests a significant association between the SARS-CoV-2 pandemic and the risk of a more advanced oncologic stage at diagnosis among patients undergoing surgery for colorectal cancer and might indicate a potential reduction of survival for these patients

Correction to: Two years later: Is the SARS-CoV-2 pandemic still having an impact on emergency surgery? An international cross-sectional survey among WSES members

Background: The SARS-CoV-2 pandemic is still ongoing and a major challenge for health care services worldwide. In the first WSES COVID-19 emergency surgery survey, a strong negative impact on emergency surgery (ES) had been described already early in the pandemic situation. However, the knowledge is limited about current effects of the pandemic on patient flow through emergency rooms, daily routine and decision making in ES as well as their changes over time during the last two pandemic years. This second WSES COVID-19 emergency surgery survey investigates the impact of the SARS-CoV-2 pandemic on ES during the course of the pandemic. Methods: A web survey had been distributed to medical specialists in ES during a four-week period from January 2022, investigating the impact of the pandemic on patients and septic diseases both requiring ES, structural problems due to the pandemic and time-to-intervention in ES routine. Results: 367 collaborators from 59 countries responded to the survey. The majority indicated that the pandemic still significantly impacts on treatment and outcome of surgical emergency patients (83.1% and 78.5%, respectively). As reasons, the collaborators reported decreased case load in ES (44.7%), but patients presenting with more prolonged and severe diseases, especially concerning perforated appendicitis (62.1%) and diverticulitis (57.5%). Otherwise, approximately 50% of the participants still observe a delay in time-to-intervention in ES compared with the situation before the pandemic. Relevant causes leading to enlarged time-to-intervention in ES during the pandemic are persistent problems with in-hospital logistics, lacks in medical staff as well as operating room and intensive care capacities during the pandemic. This leads not only to the need for triage or transferring of ES patients to other hospitals, reported by 64.0% and 48.8% of the collaborators, respectively, but also to paradigm shifts in treatment modalities to non-operative approaches reported by 67.3% of the participants, especially in uncomplicated appendicitis, cholecystitis and multiple-recurrent diverticulitis. Conclusions: The SARS-CoV-2 pandemic still significantly impacts on care and outcome of patients in ES. Well-known problems with in-hospital logistics are not sufficiently resolved by now; however, medical staff shortages and reduced capacities have been dramatically aggravated over last two pandemic years

How future surgery will benefit from SARS-COV-2-related measures: a SPIGC survey conveying the perspective of Italian surgeons

COVID-19 negatively affected surgical activity, but the potential benefits resulting from adopted measures remain unclear. The aim of this study was to evaluate the change in surgical activity and potential benefit from COVID-19 measures in perspective of Italian surgeons on behalf of SPIGC. A nationwide online survey on surgical practice before, during, and after COVID-19 pandemic was conducted in March-April 2022 (NCT:05323851). Effects of COVID-19 hospital-related measures on surgical patients' management and personal professional development across surgical specialties were explored. Data on demographics, pre-operative/peri-operative/post-operative management, and professional development were collected. Outcomes were matched with the corresponding volume. Four hundred and seventy-three respondents were included in final analysis across 14 surgical specialties. Since SARS-CoV-2 pandemic, application of telematic consultations (4.1% vs. 21.6%; p < 0.0001) and diagnostic evaluations (16.4% vs. 42.2%; p < 0.0001) increased. Elective surgical activities significantly reduced and surgeons opted more frequently for conservative management with a possible indication for elective (26.3% vs. 35.7%; p < 0.0001) or urgent (20.4% vs. 38.5%; p < 0.0001) surgery. All new COVID-related measures are perceived to be maintained in the future. Surgeons' personal education online increased from 12.6% (pre-COVID) to 86.6% (post-COVID; p < 0.0001). Online educational activities are considered a beneficial effect from COVID pandemic (56.4%). COVID-19 had a great impact on surgical specialties, with significant reduction of operation volume. However, some forced changes turned out to be benefits. Isolation measures pushed the use of telemedicine and telemetric devices for outpatient practice and favored communication for educational purposes and surgeon-patient/family communication. From the Italian surgeons' perspective, COVID-related measures will continue to influence future surgical clinical practice

GsαR201C and estrogen reveal different subsets of bone marrow adiponectin expressing osteogenic cells

The Gsalpha/cAMP signaling pathway mediates the effect of a variety of hormones and factors that regulate the homeostasis of the post-natal skeleton. Hence, the dysregulated activity of Gsalpha due to gain-of-function mutations (R201C/R201H) results in severe architectural and functional derangements of the entire bone/bone marrow organ. While the consequences of gain-of-function mutations of Gsalpha have been extensively investigated in osteoblasts and in bone marrow osteoprogenitor cells at various differentiation stages, their effect in adipogenically-committed bone marrow stromal cells has remained unaddressed. We generated a mouse model with expression of Gsalpha R201C driven by the Adiponectin (Adq) promoter. AdqGsalpha R201C mice developed a complex combination of metaphyseal, diaphyseal and cortical bone changes. In the metaphysis, Gsalpha R201C caused an early phase of bone resorption followed by bone deposition. Metaphyseal bone formation was sustained by cells that were traced by Adq-Cre and eventually resulted in a high trabecular bone mass phenotype. In the diaphysis, Gsalpha R201C, in combination with estrogen, triggered the osteogenic activity of Adq-Cre-targeted perivascular bone marrow stromal cells leading to intramedullary bone formation. Finally, consistent with the previously unnoticed presence of Adq-Cre-marked pericytes in intraosseous blood vessels, Gsalpha R201C caused the development of a lytic phenotype that affected both cortical (increased porosity) and trabecular (tunneling resorption) bone. These results provide the first evidence that the Adq-cell network in the skeleton not only regulates bone resorption but also contributes to bone formation, and that the Gsalpha/cAMP pathway is a major modulator of both functions

The mPGES-1 inhibitor AF3485 reduces VEGF and FGF-2 expression in tumors and in A431 cells.

<p>(A) VEGF and FGF-2 levels in tumors specimens and (B) in A431 cells treated with or without IL-1β (10 ng/ml, 18 h) in presence/absence of AF3485 (10 µM). *P<0.05, **P<0.01. ADU =  arbitrary density unit ± standard deviation. (C) Pseudocapillary formation of EC exposed for 16 h to conditioned media from A431 treated with 0.1% FBS (panel a: control), IL-1β (panel b: 10 ng/ml, 18 h), AF3485 (panel c: 10 µM, 24 h), IL-1β + AF3485 (panel d: 24 h) *P<0.01 vs. cont, #p<0.01 vs. IL-1β. (D) VEGF and FGF-2 expression in A431 cells co-cultured with NIH-3T3 for 24 h.</p

The mPGES-1 inhibitor AF3485 reduces A431 tumor growth in xenograft nude mice.

<p>(A) Tumor volume measured in athymic mice inoculated with A431 cells and treated with vehicle (Ctr, 0.5% MTC), AF3485 (20, 1, or 0.1 mg/kg/mouse), or AG1478 (400 µg/mouse). (B) EGFR phosphorylation in xenograft tumor tissues reported as optical density (OD  =  ratio between phospho-tyr and EGFR expression). *P<0.05 vs Cont. (C) Representative images of the proliferative Ki67 index in tumor sections.</p

AF3485 inhibits tumor growth and angiogenesis.

<p>Representative images of histological analysis of CD31 in tumor sections from (a) control, (b) AF3485-treated mice. Images taken at 40X. Quantification of microvessel density in tumors. **P<0.01 vs Cont.</p

Effects of AF3485 on PGE2 release and growth in non tumor cells.

<p>Human fibroblasts (HF), human endothelial cells (EC) and mouse fibroblasts (NIH-3T3) were exposed to AF3485 (1–10 µM), and PGE₂ release and cell growth was evaluated by EIA and MTT assay, respectively.</p

Effects of AF3485 on leukotriene biosynthesis.

<p>A23187 (5 µM) stimulated-HL-60 cells were exposed to AF3485 (10 µM) for 30 min at 37°C, then LTB4 and LTC4 secretion was measured by EIA. Nordihydroguiaretic acid (NDGA) and (Phorbol 12-myristate 13-acetate) PMA were used as reference compounds. Inhibition values were obtained in 3 separate experiments.</p

AF3485 inhibits IL-1β-induced PGE₂ production in A431 cells.

<p>(A) COX-1, -2 and mPGES-1 mRNA expression in A431 cells in presence/absence of IL-1β (10 ng/ml, 18 h). Data reported as fold increase vs. unstimulated control. **P<0.01 vs Control. (B) Western blot of COX-1, -2, and mPGES-1 expression in A431 cells in presence/absence of IL-1β (10 ng/ml, 18 h). (C) PGE₂ levels in unstimulated A431 cells treated with AF3485 (0–100 µM, 30 min). PGE₂ levels measured by ELISA (24 h from plating.) Data reported as ng/ml. *P<0.05; **P<0.01; ***P<0.001 vs Control. (D) PGE₂ levels in unstimulated or IL-1β (10 ng/ml, 24 h) pre-treated A431 cells, and treated with AF3485 (10 µM, 30 min). The data are reported as ng/ml. **P<00.1 vs Cont; ##P<0.01 vs Cont; §§P<0.01 vs IL-1β (10 ng/ml).</p