The Diverticular Disease Registry (DDR Trial) by the Advanced International Mini-Invasive Surgery Academy Clinical Research Network: Protocol for a Multicenter, Prospective Observational Study

Diverticular disease is an increasingly common issue, with a variety of clinical presentations and treatment options. However, very few prospective cohort studies explore outcomes between the different presentations and treatments. The Diverticular Disease Registry (DDR Trial) is a multicenter, prospective, observational cohort study on behalf of the Advanced International Mini-Invasive Surgery (AIMS) academy clinical research network. The DDR Trial aims to investigate the short-term postoperative and long-term quality of life outcomes in patients undergoing surgery or medical treatments for diverticular disease. DDR Trial is open to participation by all tertiary-care hospitals. DDR Trial has been registered at ClinicalTriats.gou (NCT 04907383). Data collection will be recorded on Research Electronic Data Capture (REDCap) starting on June 1 , 2021 and will end after 5 years of recruitment. All adult patients with imaging-proven colonic diverticular disease (i.e., symptomatic colonic diverticulosis including diverticular bleeding, diverticulitis, and Symptomatic Uncomplicated Diverticular Disease) will be included. The primary outcome of DDR Trial is quality of life assessment at 12-month according to the Gastrointestinal Quality of Life Index (GIQLI). The secondary outcome is 30-day postoperative outcomes according to the Clavien-Dindo classification. DDR Trial will significantly advance in identifying the optimal care for patients with diverticular disease by exploring outcomes of different presentations and treatments

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

Thoracic duct identification with indocyanine green fluorescence during minimally invasive esophagectomy with patient in prone position

Chylothorax is a serious complication of transthoracic esophagectomy. Intraoperative thoracic duct (TD) identification represents a possible tool for preventing or repairing its lesions, and it is most of the time difficult, even during high-definition thoracoscopy. The aim of the study is to demonstrate the feasibility of using near-infrared fluorescence-guided thoracoscopy to identify TD anatomy and check its intraoperative lesions during minimally invasive esophagectomy. A 0.5 mg/kg solution of indocyanine green (ICG) was injected percutaneously in the inguinal nodes of 19 patients undergoing minimally invasive esophagectomy in a prone position, before thoracoscopy. TD anatomy and potential intraoperative lesions were checked with the KARL STORZ OPAL1\uae Technology. In all of the 19 patients where transthoracic esophagectomy was feasible, the TD was clearly identified after a mean of 52.7 minutes from injection time. The TD was cut for oncological radicality in two patients, and it was successfully ligated under the ICG guide. No postoperative chylothorax or adverse reactions from the ICG injection occurred. The TD identification with indocyanine green fluorescence during minimally invasive esophagectomy is a simple, effective, and non-time-demanding tool; it may become a standard procedure to prevent postoperative chylothorax

Role of topoisomerase I and thymidylate synthase expression in sporadic colorectal cancer: Associations with clinicopathological and molecular features

Topoisomerase I (Topo I) and thymidylate synthase (TS) are essential enzymes for the replication, transcription and repair of DNA, and are potential biomarkers in colorectal cancer (CRC). The aim of the study was to correlate the tissue expression of Topo I and TS in sporadic CRCs with relevant pathological and molecular features and patients' outcome. Topo I and TS expression was assessed by immunostaining in 112 consecutive primary CRCs. Increased expression of Topo I was found in 36% of tumors, preferentially rectal (50%) and with not otherwise specified (NOS) histology (44%). Topo I expression was associated with 18q allelic loss (LOH), (p=0.013), microsatellite stable phenotype (p=0.002) and normal expression of mismatch proteins hMLH1 and hMSH2 (p=0.0012 and p=0.02, respectively). High TS expression was found in 60% of tumors, more frequently in distal sites (62%) and with NOS histology (66%); no association with microsatellite instability was observed. Topo I seems to be involved in the chromosomal instability pathway of sporadic CRCs. Conversely, high TS expression is unlikely to affect the clinical behavior of microsatellite unstable CRCs

Synthesis and Photochemical Characterization of Indolizine Fluorophores Obtained by a Multicomponent Palladium Iodide‒Catalyzed Oxidative Aminocarbonylation Approach

A catalytic carbonylative method for the direct, multicomponent synthesis of indolizine fluorophores has been developed. The process is based on the PdI2/KI‐catalyzed oxidative aminocarbonylation of 2‐(pyridin‐2‐yl)pent‐4‐yn‐1‐carbonyl compounds leading to the corresponding 2‐ynamide intermediates, followed in situ by 5‐exo‐dig cyclization (by amine‐promoted conjugate addition of the pyridine ring nitrogen) and aromatization, to give the finally isolated N,N‐disubstituted 2‐(indolizin‐3‐yl)acetamides. Reactions are carried out under relatively mild conditions (100 °C under 20 atm of a 4:1 mixture CO‒air for 6‐15 h) in MeCN as the solvent and with a low catalyst loading (0.33 mol% PdI2), in the presence of 0.5 equiv of KI and 3 equiv of a secondary amine. The optical properties of representative 2‐(indolizin‐3‐yl)acetamide products have also been investigate

Anticancer potential of novel α,β-unsaturated γ-lactam derivatives targeting the PI3K/AKT signaling pathway

Six recently synthesized alkyl (Z)-2-(2-oxopyrrolidin-3-ylidene)acetates were evaluated for their potential as cytotoxic and anticancer agents. All compounds were tested in the ERα positive MCF-7, triple negative MDA-MB-231, and Her2+ SKBR-3 breast cancer cell lines. The most lipophilic derivatives, bearing the 4-isopropylphenyl (2) or 4-tert-butylphenyl (3) group at the γ-lactam nitrogen, proved to be cytotoxic against all the cancer cell lines tested (IC50 values ranging from 18 to 63 μM), exerting their greatest activity in SKBR-3 cells, with IC50 values of 33 and 18 μM, respectively. Biological studies showed that the cytotoxic effects of 2 and 3 are accompanied by apoptotic death in breast cancer cells, and both compounds showed no significant toxicity on healthy cells (e.g., MCF-10A) and red blood cells. An in-depth mechanistic study based on molecular biology, immunoblotting analysis and in silico docking calculations suggested that α,β-unsaturated γ-lactam derivatives could interfere with the functioning of PI3K and PDK-1, two key enzymes in the PI3K/AKT signaling pathway, whose overactivation is related to the regulation of cell growth and survival in several malignancies

Road Running After Gastric Bypass For Morbid Obesity: Rationale And Preliminary Results Of A New Protocol

Introduction: In recent years, the pandemic explosion of obesity has led to the definition of a pre-eminent therapeutic role for bariatric surgery, confining physical activity to a success parameter of surgery rather than a primary prevention measure. The aim of this study is to re-define a role for aerobic physical activity (road running) in strengthening the metabolic and psycho-social effects of bariatric surgery. Methods: 10 patients who underwent gastric bypass (RYGB) for morbid obesity were submitted to an intensive program of road running training. After a preparatory trimester, a six-month intensive training program started, aimed at completing a 10 km competition in September 2013. Inclusion criteria included age (<50), BMI (<35), suitability for sport activity and good compliance. A cohort of 10 patients excluded for logistical issues were enrolled as a control group. During the training period patients were submitted to biometrical measurements, sport performance tests (Cooper), and cardio-pulmonary, metabolic, nutritional and psychiatric evaluations. Results: Protocol compliance was 80%. After the preparatory phase mean weight significantly decreased (78.6 vs 86.8 kg, p: 0.03), slightly more than in the control group. Cooper test performance significantly increased for all the patients. Glycemic values remained normal during the entire period. All the participants (100%) expressed satisfaction at participating in the program. Conclusions: Road running seems to have an important supporting role in boosting bariatric surgery results. The utilization of monitorized and regulated training programs represents a fundamental prerequisite to achieving satisfactory results and adequate patient compliance

Sarcopenia and Patient's Body Composition: New Morphometric Tools to Predict Clinical Outcome After Ivor Lewis Esophagectomy: a Multicenter Study

Background: The impact of preoperative body composition as independent predictor of prognosis for esophageal cancer patients after esophagectomy is still unclear. The aim of the study was to explore such a relationship. Methods: This is a multicenter retrospective study from a prospectively maintained database. We enrolled consecutive patients who underwent Ivor-Lewis esophagectomy in four Italian high-volume centers from May 2014. Body composition parameters including total abdominal muscle area (TAMA), visceral fat area (VFA), and subcutaneous fat area (SFA) were determined based on CT images. Perioperative variables were systematically collected. Results: After exclusions, 223 patients were enrolled and 24.2% had anastomotic leak (AL). Sixty-eight percent of patients were sarcopenic and were found to be more vulnerable in terms of postoperative 90-day mortality (p = 0.028). VFA/TAMA and VFA/SFA ratios demonstrated a linear correlation with the Clavien-Dindo classification (R = 0.311 and 0.239, respectively); patients with anastomotic leak (AL) had significantly higher VFA/TAMA (3.56 ± 1.86 vs. 2.75 ± 1.83, p = 0.003) and VFA/SFA (1.18 ± 0.68 vs. 0.87 ± 0.54, p = 0.002) ratios. No significant correlation was found between preoperative BMI and subsequent AL development (p = 0.159). Charlson comorbidity index correlated significantly with AL (p = 0.008): these patients had a significantly higher index (≥ 5). Conclusion: Analytical morphometric assessment represents a useful non-invasive tool for preoperative risk stratification. The concurrent association of sarcopenia and visceral obesity seems to be the best predictor of AL, far better than simple BMI evaluation, and potentially modifiable if targeted with prehabilitation programs