The predictive and prognostic potential of plasma telomerase reverse transcriptase (TERT) RNA in rectal cancer patients

Background: Preoperative chemoradiotherapy (CRT) followed by surgery is the standard care for locally advanced rectal cancer, but tumour response to CRT and disease outcome are variable. The current study aimed to investigate the effectiveness of plasma telomerase reverse transcriptase (TERT) levels in predicting tumour response and clinical outcome. Methods: 176 rectal cancer patients were included. Plasma samples were collected at baseline (before CRT\ubcT0), 2 weeks after CRT was initiated (T1), post-CRT and before surgery (T2), and 4\u20138 months after surgery (T3) time points. Plasma TERT mRNA levels and total cell-free RNA were determined using real-time PCR. Results: Plasma levels of TERT were significantly lower at T2 (Po0.0001) in responders than in non-responders. Post-CRT TERT levels and the differences between pre- and post-CRT TERT levels independently predicted tumour response, and the prediction model had an area under curve of 0.80 (95% confidence interval (CI) 0.73\u20130.87). Multiple analysis demonstrated that patients with detectable TERT levels at T2 and T3 time points had a risk of disease progression 2.13 (95% CI 1.10\u20134.11)-fold and 4.55 (95% CI 1.48\u201313.95)-fold higher, respectively, than those with undetectable plasma TERT levels. Conclusions: Plasma TERT levels are independent markers of tumour response and are prognostic of disease progression in rectal cancer patients who undergo neoadjuvant therapy

A Multi-Institutional Analysis of Elderly Patients Undergoing a Liver Resection for Intrahepatic Cholangiocarcinoma

BACKGROUND: Little is known regarding postoperative outcomes of elderly patients undergoing liver surgery for intrahepatic cholangiocarcinoma (ICC). METHODS: Five hundred and eighty-four patients undergoing liver resection for ICC between 1990 and 2015 were identified. Perioperative morbidity, mortality, overall survival (OS), and disease-free survival (DFS) were compared between elderly (>70 year, n = 129) and non-elderly (≤70 years, n = 455) patients. RESULTS: Older patients had a higher incidence of complications (elderly vs. non-elderly; 52.7% vs. 42.6%; P = 0.03), as well as major complications (elderly vs. non-elderly; 24.0% vs. 14.9%; P = 0.01); 30-day (0.1% vs. 3.3%; P > 0.05), and 90-day mortality (2.3% vs. 5.5%; P > 0.05) were comparable. Five-year OS and DFS were comparable between the elderly and non-elderly patients (OS, 13.3% vs. 24.4%; and DFS; 7.3% vs. 12.0%; P > 0.05). On propensity score matching, DFS and OS were also comparable among non-elderly versus elderly patients. Poor tumor grade was associated with worse DFS among elderly patients (HR = 1.6, 95%CI 1.0-2.6; P = 0.04), whereas periductal invasion (HR = 1.9, 95% CI 1.1-3.5; P = 0.03) and nodal disease (HR = 2.3, 95% CI 1.3-3.9; P = 0.003) were predictive of shorter DFS among non-elderly patients. CONCLUSION: Elderly patients undergoing liver surgery for ICC demonstrated an increased risk of perioperative complications, but comparable long-term DFS and OS compared with younger patients. Rather, tumor characteristics were more predictive of worse long-term outcomes.info:eu-repo/semantics/publishedVersio

Intraperitoneal drain placement and outcomes after elective colorectal surgery: international matched, prospective, cohort study

Despite current guidelines, intraperitoneal drain placement after elective colorectal surgery remains widespread. Drains were not associated with earlier detection of intraperitoneal collections, but were associated with prolonged hospital stay and increased risk of surgical-site infections.Background Many surgeons routinely place intraperitoneal drains after elective colorectal surgery. However, enhanced recovery after surgery guidelines recommend against their routine use owing to a lack of clear clinical benefit. This study aimed to describe international variation in intraperitoneal drain placement and the safety of this practice. Methods COMPASS (COMPlicAted intra-abdominal collectionS after colorectal Surgery) was a prospective, international, cohort study which enrolled consecutive adults undergoing elective colorectal surgery (February to March 2020). The primary outcome was the rate of intraperitoneal drain placement. Secondary outcomes included: rate and time to diagnosis of postoperative intraperitoneal collections; rate of surgical site infections (SSIs); time to discharge; and 30-day major postoperative complications (Clavien-Dindo grade at least III). After propensity score matching, multivariable logistic regression and Cox proportional hazards regression were used to estimate the independent association of the secondary outcomes with drain placement. Results Overall, 1805 patients from 22 countries were included (798 women, 44.2 per cent; median age 67.0 years). The drain insertion rate was 51.9 per cent (937 patients). After matching, drains were not associated with reduced rates (odds ratio (OR) 1.33, 95 per cent c.i. 0.79 to 2.23; P = 0.287) or earlier detection (hazard ratio (HR) 0.87, 0.33 to 2.31; P = 0.780) of collections. Although not associated with worse major postoperative complications (OR 1.09, 0.68 to 1.75; P = 0.709), drains were associated with delayed hospital discharge (HR 0.58, 0.52 to 0.66; P < 0.001) and an increased risk of SSIs (OR 2.47, 1.50 to 4.05; P < 0.001). Conclusion Intraperitoneal drain placement after elective colorectal surgery is not associated with earlier detection of postoperative collections, but prolongs hospital stay and increases SSI risk

No evidence of association between prothrombotic gene polymorphisms and the development of acute myocardial infarction at a young age

Background : we investigated the association between 9 polymorphisms of genes encoding hemostasis factors and myocardial infarction in a large sample of young patients chosen because they have less coronary atherosclerosis than older patients, and thus their disease is more likely to be related to a genetic predisposition to a prothrombotic state Methods and Results : this nationwide case-control study involved 1210 patients who had survived a first myocardial infarction at an age of 45 years who underwent coronary arteriography in 125 coronary care units and 1210 healthy subjects matched for age, sex, and geographical origin. None of the 9 polymorphisms of genes encoding proteins involved in coagulation (G-455A -fibrinogen: OR, 1.0; CI, 0.8 to 1.2; G1691A factor V: OR, 1.1; CI, 0.6 to 2.1; G20210A factor II: OR, 1.0; CI, 0.5 to 1.9; and G10976A factor VII: OR, 1.0; CI, 0.8 to 1.3), platelet function (C807T glycoprotein Ia: OR, 1.1; CI, 0.9 to 1.3; and C1565T glycoprotein IIIa: OR, 0.9; CI, 0.8 to 1.2), fibrinolysis (G185T factor XIII: OR, 1.2; CI, 0.9 to 1.6; and 4G/5G plasminogen activator inhibitor type 1: OR, 0.9; CI, 0.7 to 1.2), or homocysteine metabolism (C677T methylenetetrahydrofolate reductase: OR, 0.9; CI, 0.8 to 1.1) were associated with an increased or decreased risk of myocardial infarction Conclusions : this study provides no evidence supporting an association between 9 polymorphisms of genes encoding proteins involved in hemostasis and the occurrence of premature myocardial infarction or protection against it

Actinomycosis mimicking pancreatic neuroendocrine tumor. Case report and review of the literature

Background Abdominal actinomycosis is an uncommon subacute or chronic inflammatory disease due to a filamentous, gram-positive, anaerobic bacterium: Actinomyces israelii. The pathogen invades surrounding tissues, spreads by contiguity causing a suppurative and granulomatous inflammation with formation of abscess. Methods Case report: A 66-year-old asymptomatic woman with incidentally radiological finding of a pancreatic head solid mass. Approximately 35 years before, she underwent cholecystectomy and choledocotomy for gallstones of the biliary tract. Suspecting of a neuroendocrine tumor, the patient was enrolled to pancreaticoduodenectomy. Results Histologic examination revealed pancreatic actinomycosis. Foci of severe dysplasia of the pancreatic ductal epithelium were found, and bacteria referable to Actinomyces were isolated. Conclusions Pancreatic actinomycosis is extremely rare but it should be considered in the differential diagnosis with other pancreatic disease. In the literature, it was been reported that the abdominal location could be related to contamination by gallstone spillage during biliary surgery. Prognosis is excellent if actinomycosis is well treated; early diagnosis is mandatory but remains a challenge, and often is achieved only after surgery

Impact of Age on Short- And Long-Term Outcomes after Pancreatoduodenectomy for Periampullary Neoplasms

Background. Although mortality and morbidity of pancreatoduodenectomy (PD) have improved significantly over the past years, the impact of age for patients undergoing PD is still debated. This study is aimed at analyzing short- and long-term outcomes of PD in elderly patients. Methods. 124 consecutive patients who have undergone PD for pancreas neoplasms in our center between 2012 and 2017 were analyzed. Patients were divided into two groups: group I (<75 years) and group II ( 6575 years). Demographic features and intraoperative and clinical-pathological data were collected. Primary endpoints were perioperative morbidity and mortality; complications were classified according to the Clavien-Dindo Score. Secondary endpoints included feasibility of adjuvant treatment and overall survival rates. Results. A total of 106 patients were included in this study. There were 73 (68.9%) patients in group I and 33 (31.1%) in group II. Perioperative deceases were 4 (3.6%), and postoperative pancreatic fistulas were 34 (32.1%). Significant difference between two groups was demonstrated for the ASA Score (p=0.004), Karnofsky Score (p=0.025), preoperative jaundice (p=0.004), and pulmonary complications (p=0.034). No significance was shown for diabetes, radicality of resection, stage of disease, operative time, length of stay, postoperative complications according to the Clavien-Dindo Score, postoperative mortality, pancreatic fistula, and reoperation rates. 69.9% of the patients in group I underwent adjuvant treatment vs. 39.4% of the older ones (p=0.012). Mean overall survival was 28.5 months in group I vs. 22 months in group II (p=0.909). Conclusion. PD can be performed safely in elderly patients. Advanced age should not be an absolute contraindication for PD, even if greater frailty should be considered. The outcome of elderly patients who have undergone PD is similar to that of younger patients, even though adjuvant treatment administration is significantly lower, demonstrating that surgery remains the main therapeutic option

Women in thoracic, cardiac and vascular surgery claim for a change in the working situation: an Italian national survey

Background: Women’s participation in the surgical workforce has increased. The aim of the study is to acquire objective data regarding practice, training, satisfaction, and discrimination of women surgeons working in cardiothoracic and vascular surgery in Italy. Methods: An 83-item questionnaire was distributed through social media and sent to e-mails of women surgeons from November through December 2020. A sub-analysis on women working in cardiac, thoracic, and vascular surgery was performed. Results: Overall, 222 respondents were included (48 cardiac, 62 thoracic, and 112 vascular surgeons). Thirty-six percent partially abandoned surgical activities in favor of other professional activities, not including the operating room. On average, our respondents took part in 33% of all surgical cases performed in their units; however, of 12 high complexity surgeries per month, less than one is performed by them. Only 7 female participants who answered the questionnaire were in leadership positions. Many respondents struggle with lack of mentorship and missing opportunities in operating room. A high percentage of women experienced discrimination due to their gender in their professional life, and 59% claimed to have been subject to sexual harassment. Conclusions: In Italy, women thoracic, cardiac, and vascular surgeons face lack of mentorship, opportunities in the operating room, and gender-related issues including some episodes of sexual harassment. Diversity, equity, and inclusion should become strategic priorities in all institutions. Among our respondents, surgical exposure is limited, which may deter a surgical career and play a crucial role in surgeons’ dissatisfaction, that also include poor work-life-balance, and a large amount of administrative work. Surgical societies may address these issues by providing structured mentorship programs and networking opportunities. Societies’ contributions might substantially impact supporting and retaining women at different stages of their careers

C-Reactive Protein and Procalcitonin as Predictors of Postoperative Inflammatory Complications After Pancreatic Surgery

The association between postoperative inflammatory markers and risk of complications after pancreaticoduodenectomy (PD) is controversial. We sought to assess the diagnostic value of perioperative C-reactive protein (CRP) and procalcitonin (PCT) levels in the early identification of patients at risk for complications after PD. In 2014, 84 patients undergoing elective PD were enrolled in a prospective database. Clinicopathological characteristics, CRP and PCT, as well as short-term outcomes, such as complications and pancreatic fistula, were analyzed. Complications and pancreatic fistula were defined based on the Clavien-Dindo classification and the International Study Group on Pancreatic Fistula (ISGPF) classification, respectively. High CRP and PCT were classified using cut-off values based on ROC curve analysis. The majority (73.8 %) of patients had pancreatic adenocarcinoma. CRP and PCT levels over the first 5 postoperative days (POD) were higher among patients who experienced a complication versus those who did not (p 84 mg/l on POD 1 (AUC 0.77) and > 127 mg/l on POD 3 (AUC 0.79) was associated with the highest risk of overall complications (OR 6.86 and 9.0, respectively; both p 0.7 mg/dl on POD 1 (AUC 0.67) were at higher risk of developing a postoperative complication (OR 3.33; p = 0.024). On POD 1, a CRP > 92 mg/l (AUC 0.72) and a PCT > 0.4 mg/dl (AUC 0.70) were associated with the highest risk of pancreatic fistula (OR 5.63 and 5.62, respectively; both p < 0.05). CRP and PCT concentration were associated with an increased risk of developing complications and clinical relevant pancreatic fistula after PD. Use of these biomarkers may help identify those patients at highest risk for perioperative morbidity and help guide postoperative management of patients undergoing PD

Artificial neural networks for multi-omics classifications of hepato-pancreato-biliary cancers: towards the clinical application of genetic data

Purpose: Several multi-omics classifications have been proposed for hepato-pancreato-biliary (HPB) cancers, but these classifications have not proven their role in the clinical practice and been validated in external cohorts. Patients and methods: Data from whole-exome sequencing (WES) of The Cancer Genome Atlas (TCGA) patients were used as an input for the artificial neural network (ANN) to predict the anatomical site, iClusters (cell-of-origin patterns) and molecular subtype classifications. The Ohio State University (OSU) and the International Cancer Genome Consortium (ICGC) patients with HPB cancer were included in external validation cohorts. TCGA, OSU and ICGC data were merged, and survival analyses were performed using both the ‘classic’ survival analysis and a machine learning algorithm (random survival forest). Results: Although the ANN predicting the anatomical site of the tumour (i.e. cholangiocarcinoma, hepatocellular carcinoma of the liver, pancreatic ductal adenocarcinoma) demonstrated a low accuracy in TCGA test cohort, the ANNs predicting the iClusters (cell-of-origin patterns) and molecular subtype classifications demonstrated a good accuracy of 75% and 82% in TCGA test cohort, respectively. The random survival forest analysis and Cox’ multivariable survival models demonstrated that models for HPB cancers that integrated clinical data with molecular classifications (iClusters, molecular subtypes) had an increased prognostic accuracy compared with standard staging systems. Conclusion: The analyses of genetic status (i.e. WES, gene panels) of patients with HPB cancers might predict the classifications proposed by TCGA project and help to select patients suitable to targeted therapies. The molecular classifications of HPB cancers when integrated with clinical information could improve the ability to predict the prognosis of patients with HPB cancer