Chemotherapy treatment of cancer remains a challenge due to the molecular and functional heterogeneity displayed by tumours originating from the same cell type. The pronounced heterogeneity makes it ...difficult for oncologists to devise an effective therapeutic strategy for the patient. One approach for increasing treatment efficacy is to test the chemosensitivity of cancer cells obtained from the patient's tumour. 3D culture represents a promising method for modelling patient tumours in vitro. The aim of this study was therefore to evaluate how closely short-term spheroid cultures of primary colorectal cancer cells resemble the original tumour. Colorectal cancer cells were isolated from human tumour tissue and cultured as spheroids. Spheroid cultures were established with a high success rate and remained viable for at least 10 days. The spheroids exhibited significant growth over a period of 7 days and no difference in growth rate was observed for spheroids of different sizes. Comparison of spheroids with the original tumour revealed that spheroid culture generally preserved adenocarcinoma histology and expression patterns of cytokeratin 20 and carcinoembryonic antigen. Interestingly, spheroids had a tendency to resemble tumour protein expression more closely after 10 days of culture compared to 3 days. Chemosensitivity screening using spheroids from five patients demonstrated individual response profiles. This indicates that the spheroids maintained patient-to-patient differences in sensitivity towards the drugs and combinations most commonly used for treatment of colorectal cancer. In summary, short-term spheroid culture of primary colorectal adenocarcinoma cells represents a promising in vitro model for use in personalized medicine.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Background Incisional hernia repair is a frequent surgical procedure, but perioperative risk factors and outcomes have not been prospectively assessed in large-scale studies. The aim of this ...nationwide study was to analyze surgical risk factors for early and late outcomes after incisional hernia repair. Study Design We conducted a prospective nationwide study on all elective incisional hernia repairs registered in the Danish Ventral Hernia Database between January 1, 2007 and December 31, 2010. Main outcomes measures were surgical risk factors for 30-day readmission, reoperation (excluding recurrence), and mortality after incisional hernia repair. Late outcomes included reoperation for recurrence during the follow-up period. Follow-up was obtained by merging the Danish Ventral Hernia Database with the Danish National Patient Register. Results were evaluated by multivariate analyses. Result The study included 3,258 incisional hernia repairs. Median follow-up was 21 months (interquartile range 10 to 35 months). The 30-day readmission, reoperation, and mortality rates were 13.3%, 2.2%, and 0.5%, respectively. Advanced age, open repair, large hernia defect, and vertical incision at the primary laparotomy were significant independent risk factors for poor early outcomes (p < 0.05). The cumulated risk of recurrence repair after open and laparoscopic repair was 21.1% and 15.5%, respectively (p = 0.03). Younger age, open repair, hernia defects >7 cm, and onlay or intraperitoneal mesh positioning in open repair were significant risk factors for poor late outcomes (p < 0.05). Conclusions Elective incisional hernia repair were beset with high rates of readmission and reoperation for recurrence. Readmission and reoperation for recurrence were most pronounced after open repair and repair for hernia defects up to 20 cm. Additionally, sublay mesh position reduced the risk of reoperation for recurrence after open repairs.
Background
Available evidence on the effects of a high fraction of inspired oxygen (FIO2) of 60% to 90% compared with a routine fraction of inspired oxygen of 30% to 40%, during anaesthesia and ...surgery, on mortality and surgical site infection has been inconclusive. Previous trials and meta‐analyses have led to different conclusions on whether a high fraction of supplemental inspired oxygen during anaesthesia may decrease or increase mortality and surgical site infections in surgical patients.
Objectives
To assess the benefits and harms of an FIO2 equal to or greater than 60% compared with a control FIO2 at or below 40% in the perioperative setting in terms of mortality, surgical site infection, respiratory insufficiency, serious adverse events and length of stay during the index admission for adult surgical patients.
We looked at various outcomes, conducted subgroup and sensitivity analyses, examined the role of bias and applied trial sequential analysis (TSA) to examine the level of evidence supporting or refuting a high FIO2 during surgery, anaesthesia and recovery.
Search methods
We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, BIOSIS, International Web of Science, the Latin American and Caribbean Health Science Information Database (LILACS), advanced Google and the Cumulative Index to Nursing and Allied Health Literature (CINAHL) up to February 2014. We checked the references of included trials and reviews for unidentified relevant trials and reran the searches in March 2015. We will consider two studies of interest when we update the review.
Selection criteria
We included randomized clinical trials that compared a high fraction of inspired oxygen with a routine fraction of inspired oxygen during anaesthesia, surgery and recovery in individuals 18 years of age or older.
Data collection and analysis
Two review authors extracted data independently. We conducted random‐effects and fixed‐effect meta‐analyses, and for dichotomous outcomes, we calculated risk ratios (RRs). We used published data and data obtained by contacting trial authors.
To minimize the risk of systematic error, we assessed the risk of bias of the included trials. To reduce the risk of random errors caused by sparse data and repetitive updating of cumulative meta‐analyses, we applied trial sequential analyses. We used Grades of Recommendation, Assessment, Development and Evaluation (GRADE) to assess the quality of the evidence.
Main results
We included 28 randomized clinical trials (9330 participants); in the 21 trials reporting relevant outcomes for this review, 7597 participants were randomly assigned to a high fraction of inspired oxygen versus a routine fraction of inspired oxygen.
In trials with an overall low risk of bias, a high fraction of inspired oxygen compared with a routine fraction of inspired oxygen was not associated with all‐cause mortality (random‐effects model: RR 1.12, 95% confidence interval (CI) 0.93 to 1.36; GRADE: low quality) within the longest follow‐up and within 30 days of follow‐up (Peto odds ratio (OR) 0.99, 95% CI 0.61 to 1.60; GRADE: low quality). In a trial sequential analysis, the required information size was not reached and the analysis could not refute a 20% increase in mortality. Similarly, when all trials were included, a high fraction of inspired oxygen was not associated with all‐cause mortality to the longest follow‐up (RR 1.07, 95% CI 0.87 to 1.33) or within 30 days of follow‐up (Peto OR 0.83, 95% CI 0.54 to 1.29), both of very low quality according to GRADE. Neither was a high fraction of inspired oxygen associated with the risk of surgical site infection in trials with low risk of bias (RR 0.86, 95% CI 0.63 to 1.17; GRADE: low quality) or in all trials (RR 0.87, 95% CI 0.71 to 1.07; GRADE: low quality). A high fraction of inspired oxygen was not associated with respiratory insufficiency (RR 1.25, 95% CI 0.79 to 1.99), serious adverse events (RR 0.96, 95% CI 0.65 to 1.43) or length of stay (mean difference ‐0.06 days, 95% CI ‐0.44 to 0.32 days).
In subgroup analyses of nine trials using preoperative antibiotics, a high fraction of inspired oxygen was associated with a decrease in surgical site infections (RR 0.76, 95% CI 0.60 to 0.97; GRADE: very low quality); a similar effect was noted in the five trials adequately blinded for the outcome assessment (RR 0.79, 95% CI 0.66 to 0.96; GRADE: very low quality). We did not observe an effect of a high fraction of inspired oxygen on surgical site infections in any other subgroup analyses.
Authors' conclusions
As the risk of adverse events, including mortality, may be increased by a fraction of inspired oxygen of 60% or higher, and as robust evidence is lacking for a beneficial effect of a fraction of inspired oxygen of 60% or higher on surgical site infection, our overall results suggest that evidence is insufficient to support the routine use of a high fraction of inspired oxygen during anaesthesia and surgery. Given the risk of attrition and outcome reporting bias, as well as other weaknesses in the available evidence, further randomized clinical trials with low risk of bias in all bias domains, including a large sample size and long‐term follow‐up, are warranted.
Convolutional neural network (CNN)-based systems are increasingly used in autonomous vehicles for detecting obstacles. CNN-based object detection and per-pixel classification (semantic segmentation) ...algorithms are trained for detecting and classifying a predefined set of object types. These algorithms have difficulties in detecting distant and heavily occluded objects and are, by definition, not capable of detecting unknown object types or unusual scenarios. The visual characteristics of an agriculture field is homogeneous, and obstacles, like people, animals and other obstacles, occur rarely and are of distinct appearance compared to the field. This paper introduces DeepAnomaly, an algorithm combining deep learning and anomaly detection to exploit the homogenous characteristics of a field to perform anomaly detection. We demonstrate DeepAnomaly as a fast state-of-the-art detector for obstacles that are distant, heavily occluded and unknown. DeepAnomaly is compared to state-of-the-art obstacle detectors including "Faster R-CNN: Towards Real-Time Object Detection with Region Proposal Networks" (RCNN). In a human detector test case, we demonstrate that DeepAnomaly detects humans at longer ranges (45-90 m) than RCNN. RCNN has a similar performance at a short range (0-30 m). However, DeepAnomaly has much fewer model parameters and (182 ms/25 ms =) a 7.28-times faster processing time per image. Unlike most CNN-based methods, the high accuracy, the low computation time and the low memory footprint make it suitable for a real-time system running on a embedded GPU (Graphics Processing Unit).
Background
Laparoscopic enhanced-view totally extraperitoneal retromuscular repair (eTEP-RM) was recently introduced as a new technique for ventral hernia repair. The aim of the current study was to ...examine the outcomes of laparoscopic eTEP-RM compared with laparoscopic IPOM for patients with primary ventral and incisional hernia.
Methods
This was a retrospective cohort study of patients undergoing laparoscopic ventral hernia repair at a single University Hospital from June 2017 to November 2020. Medical charts of all patients subjected to IPOM and eTEP-RM were evaluated to identify patient- and procedure related variables, as well as postoperative 30-day outcomes.
Results
A total of 72 patients were included in the study, 43 and 29 of whom underwent IPOM and eTEP-RM repair, respectively. Patient demographics showed no differences in terms of gender, age, smoking and comorbidity. The median age was 57 years and body mass index 30.5 kg/m
2
. The rate of patients with incisional hernia was higher in the IPOM group (39.5% vs. 20.7%,
p
= 0.154). There was no difference in horizontal and vertical hernia size defect. The duration of surgery was significantly shorter for IPOM (mean 82.4 vs. 103.4 min,
p
= 0.010), whereas the length of stay was significantly longer after IPOM (median 1 days vs. 0 days (
p
< 0.001). The rate of patients requiring postoperative transversus abdominis plane (TAP) block or epidural analgesia was significantly higher after IPOM (33% vs. 0%,
p
= 0.002). A subgroup analysis on patients undergoing primary ventral hernia showed similar results.
Conclusion
The study found laparoscopic eTEP-RM safe and effective compared to traditional laparoscopic IPOM. The patients undergoing eTEP-RM had significantly reduced need for additional analgesic treatment and length of stay.
Serological biomarkers may be an option for early detection of colorectal cancer (CRC). The present study assessed eight cancer‐associated protein biomarkers in plasma from subjects undergoing first ...time ever colonoscopy due to symptoms attributable to colorectal neoplasia. Plasma AFP, CA19‐9, CEA, hs‐CRP, CyFra21‐1, Ferritin, Galectin‐3 and TIMP‐1 were determined in EDTA‐plasma using the Abbott ARCHITECT® automated immunoassay platform. Primary endpoints were detection of (i) CRC and high‐risk adenoma and (ii) CRC. Logistic regression was performed. Final reduced models were constructed selecting the four biomarkers with the highest likelihood scores. Subjects (N = 4,698) were consecutively included during 2010–2012. Colonoscopy detected 512 CRC patients, 319 colonic cancer and 193 rectal cancer. Extra colonic malignancies were detected in 177 patients, 689 had adenomas of which 399 were high‐risk, 1,342 had nonneoplastic bowell disease and 1,978 subjects had ‘clean’ colorectum. Univariable analysis demonstrated that all biomarkers were statistically significant. Multivariate logistic regression demonstrated that the blood‐based biomarkers in combination significantly predicted the endpoints. The reduced model resulted in the selection of CEA, hs‐CRP, CyFra21‐1 and Ferritin for the two endpoints; AUCs were 0.76 and 0.84, respectively. The postive predictive value at 90% sensitivity was 25% for endpoint 1 and the negative predictive value was 93%. For endpoint 2, the postive predictive value was 18% and the negative predictive value was 97%. Combinations of serological protein biomarkers provided a significant identification of subjects with high risk of the presence of colorectal neoplasia. The present set of biomarkers could become important adjunct in early detection of CRC.
What's new?
How can colorectal cancer be detected earlier? ‘Colonoscopies for everyone’ might be effective, but it is far too expensive. Instead, these authors propose a set of eight protein biomarkers that could signal the presence of cancer. They tested the blood‐based biomarker screening in patients who were already seeking a colonoscopy after experiencing bowel‐related symptoms. Of the nearly 4,700 subjects tested, colonoscopy uncovered 512 colorectal cancers and 399 high‐risk adenomas. The panel of biomarkers, in combination, successfully predicted the cancers. Next, the markers will need to be tested on asymptomatic subjects, to determine their usefulness as a general screening tool.
OBJECTIVE:To investigate the impact of anastomotic leak (AL) on disease recurrence and long-term mortality in patients alive 120 days after curative resection for colonic cancer.
BACKGROUND:There is ...no solid data as to whether AL after colonic cancer surgery increases the risk of disease recurrence.
METHODS:This was a nationwide cohort study of 9333 patients, prospectively registered in the database of the Danish Colorectal Cancer Group and merged with data from the Danish Pathology Registry and the National Patient Registry. Multivariable Cox regression analysis was used to adjust for confounding.
RESULTS:The incidence of AL was 6.4%, 744 patients died within 120 days. Of the remaining 8589 patients, 861 (10.0%) developed local recurrence with no association to AL adjusted hazard ratio (HR) = 0.78; 95% confidence interval (CI)0.55–1.12; P = 0.184. Distant recurrence developed in 1281 (14.9%) patients and more frequently after AL (adjusted HR = 1.42; 95% CI1.13–1.78; P = 0.003). AL was also associated with increased long-term mortality (adjusted HR = 1.20; 95% CI1.01–1.44; P = 0.042). In 2841 patients with stage III cancer, AL was associated with both decreased likelihood of receiving adjuvant chemotherapy (adjusted HR = 0.58; 95% CI0.45–0.74; P < 0.001) and a delay to initial administration (16 days; 95% CI12–20 days; P < 0.001).
CONCLUSIONS:AL was significantly associated with increased rates of distant recurrence and long-term all-cause mortality. Cancelled or delayed administration of adjuvant chemotherapy may partly account for these findings.
OBJECTIVE:The aim of the study was to examine abdominal wall function in patients undergoing abdominal wall reconstruction (AWR) for incisional hernia.
BACKGROUND:The literature on abdominal wall ...function in patients with incisional hernia is sparse. It has been suggested that AWR leads to improvement in function, but it is unknown whether this is specific to the abdominal wall or due to an improvement in overall physical fitness.
METHODS:We performed a prospective case-control study of 18 consecutive patients with large incisional hernia undergoing AWR with linea alba restoration. Truncal flexion and extension strength, hand grip strength, leg extension power, and quality of life (SF-36 and Carolinas Comfort Scale) were assessed preoperatively and 1 year postoperatively. Patients were compared with a control group of patients with an intact abdominal wall undergoing colorectal resection (n = 18). The study was registered at ClinicalTrials.gov (NCT02011048).
RESULTS:Compared with preoperative measurements, 1-year follow-up after AWR demonstrated an increase of both truncal flexion strength (from mean 505.6 N to 572.3 N, P < 0.001) and truncal extension strength (from 556.7 to 606.0 N, P = 0.005). There was no significant change of either hand grip strength or leg extension power. After AWR, the physical component of overall quality of life improved, whereas the mental component score remained unchanged. In the control group, surgery resulted in a decrease in both truncal flexion and truncal extension.
CONCLUSIONS:AWR for incisional hernia specifically improved long-term abdominal wall muscular function and quality of life.
Background
The effect of organized colorectal cancer (CRC) screening on type of primary treatment remains sparsely investigated. This study evaluated the difference in primary treatment strategy ...between patients diagnosed with screen-detected (SD-CRC) and non-screen-detected colorectal cancer (NSD-CRC) in a national CRC screening program.
Methods
This was a retrospective national register-based cohort study. Data on patients aged between 50 and 75 years and diagnosed with SD-CRC or NSD-CRC were retrieved from the national colorectal cancer screening database and the Danish Colorectal Cancer Group database. Outcomes related to surgical invasiveness were compared between the two cohorts. Differences were expressed as relative risks using log-binomial generalized linear regression models. UICC stage IV specific outcomes were analyzed using the same method. All analyses were adjusted for sex, age, type of cancer (colonic/rectal), and Charlson comorbidity index.
Results
The study included 4707 patients with SD-CRC and 7328 with NSD-CRC. Therapeutic flexible endoscopy (SD-CRC:
n
= 636 vs. NSD-CRC:
n
= 334, RR: 2.50,
P
< 0.001), (robotic-assisted) laparoscopic resection ((
n
= 616 vs.
n
= 773, RR: 1.27,
P
< 0.001),
n
= 2759 vs.
n
= 3471, RR: 1.11,
P
< 0.001), and radical resection (
n
= 3890 vs.
n
= 4834, RR: 1.02,
P
= 0.002) were significantly more frequent in the SD-CRC group. The rates of emergency priority (
n
= 32 vs.
n
= 562, RR: 0.09,
P
< 0.001), open surgery (
n
= 391 vs.
n
= 1410, RR: 0.53,
P
< 0.001), supplementary organ resection (
n
= 259 vs.
n
= 860, RR: 0.56,
P
< 0.001), and stoma formation (
n
= 526 vs.
n
= 1040, RR: 0.89,
P
= 0.007) were significantly lower in the SD-CRC group. The rate of patients undergoing surgery with UICC stage IV disease was significantly higher in the SD-CRC group (SD-CRC:
n
= 262, NSD-CRC:
n
= 994, RR: 1.43,
P
< 0.001).
Conclusion
SD-CRC remained associated with less invasive primary surgical treatment following adjustment for potential healthy user bias. UICC stage IV disease may be less advanced in patients with SD-CRC.
A high perioperative inspiratory oxygen fraction (80%) has been recommended to prevent postoperative wound infections. However, the most recent and one of the largest trials, the PROXI trial, found ...no reduction in surgical site infection, and 30-day mortality was higher in patients given 80% oxygen. In this follow-up study of the PROXI trial we assessed the association between long-term mortality and perioperative oxygen fraction in patients undergoing abdominal surgery.
From October 8, 2006, to October 6, 2008, 1386 patients underwent elective or emergency laparotomy and were randomized to receive either 80% or 30% oxygen during and for 2 hours after surgery. The follow-up date was February 24, 2010. Survival was analyzed using Kaplan-Meier statistics and the Cox proportional hazards model.
Vital status was obtained in 1382 of 1386 patients after a median follow-up of 2.3 years (range 1.3 to 3.4 years). One hundred fifty-nine of 685 patients (23.2%) died in the 80% oxygen group compared to 128 of 701 patients (18.3%) assigned to 30% oxygen (HR, 1.30 95% confidence interval, 1.03 to 1.64, P = 0.03). In patients undergoing cancer surgery, the HR was 1.45; 95% confidence interval, 1.10 to 1.90; P = 0.009; and after noncancer surgery, the HR was 1.06; 95% confidence interval, 0.69 to 1.65; P = 0.79.
Administration of 80% oxygen in the perioperative period was associated with significantly increased long-term mortality and this appeared to be statistically significant in patients undergoing cancer surgery but not in noncancer patients.
PDF
