Development of an algorithm combining blood-based biomarkers, fecal immunochemical test, and age for population-based colorectal cancer screening.

BACKGROUND AND AIMS: Implementation of screening modalities have reduced the burden of colorectal cancer (CRC), but high false positive rates pose a major problem for colonoscopy capacity. We aimed to create a tailored screening algorithm that expands the fecal immunochemical test (FIT) with a blood specimen and current age to improve selection of individuals for diagnostic colonoscopy. METHODS: In this prospective multi-center study, eight blood-based biomarkers (CEA, Ferritin, hsCRP, HE4, Cyfra21-1, Hepsin, IL-8 and OPG) were investigated in 1,977 FIT positive individuals from the Danish national CRC screening program undergoing follow-up colonoscopy. Specimens were analyzed on ARCHITECT i2000®, ARCHITECT c8000® or Luminex xMAP® machines. FIT analyses and blood-based biomarker data were combined with clinical data (i.e., age and colonoscopy findings) in a cross-validated logistic regression model (algorithm) benchmarked against a model solely using the FIT result (FIT model) applying different cutoffs for FIT positivity. RESULTS: The cohort included individuals with CRC (n = 240), adenomas (n = 938) or no neoplastic lesions (n = 799). The cross-validated algorithm combining the eight biomarkers, quantitative FIT result and age performed superior to the FIT model in discriminating CRC versus non-CRC individuals (AUC 0.77 versus 0.67, p < 0.001). When discriminating individuals with either CRC or high- or medium-risk adenomas versus low-risk adenomas or clean colorectum, the AUCs were 0.68 versus 0.64 for the algorithm and FIT model, respectively. CONCLUSIONS: The algorithm presented here can improve patient allocation to colonoscopy, reducing colonoscopy burden without compromising cancer and adenomas detection rates or vice versa.

Prospective evaluation of bowel function and quality of life after colon cancer surgery - is it time for routine screening for late sequelae?

AIM: Bowel dysfunction after colon cancer (CC) surgery is widely neglected in current follow up programmes. This study explored changes in bowel function and quality of life (QoL) from three (3 m) to twelve months (12 m) after surgery in CC patients undergoing right- or left-sided colon resection (RightSCR/LeftSCR) and investigated differences between the two groups 12 m after surgery. METHOD: CC patients undergoing surgical resection in 2018-2020 at five surgical departments were included in this population-based prospective cohort study. Included patients completed electronic surveys consisting of a collection of validated scores 3 m and 12 m after surgery. RESULTS: A total of 708 CC patients (423 RightSCR, 285 LeftSCR) were included. In RightSCR, no improvement was observed from 3 m to 12 m in most scores/items, on the contrary, symptom worsening in flatus- and faecal incontinence and urgency was observed (p < 0.05). Also, the proportion of patients rating their bowel function as very good/good decreased (p < 0.05) in this group. In LeftSCR improvement was found in flatus and faecal incontinence, urgency and night-time defaecation (p < 0.02), while no improvement was observed in the remaining scores/items. At 12 m, higher proportions of RightSCR than LeftSCR reported loose stools, incontinence and urgency (all p < 0.001), whereas LeftSCR more often reported hard stools and flatus incontinence (p < 0.05). Among all CC patients 18.3% reported bowel-related impairment of QoL at 12 m with no differences between the two groups. CONCLUSION: From 3 m to 12 m no significant change was observed in the majority of bowel function and QoL scores/items, however, some symptoms worsened in RightSCR, while a few improved in LeftSCR. Bowel dysfunction and impaired QoL were still common in both groups at 12 m, although the symptom pattern differed between the groups. These findings call for a systematic screening for bowel dysfunction to ensure early treatment of symptoms.

Impression of the stomach wall at gastroscopy may be due to giant a. lienalis aneurysm.

Splenic artery aneurysms are rare but can be fatal. The majority are asymptomatic and small (less-than 2cm). The diagnosis is often incidental on abdominal CT, but this case report presents of a 78-year-old woman who was diagnosed with a splenic artery aneurysm through a gastroscopy. The posterior gastric wall in the fundus-corpus junction showed a 7 cm area that was bulging into the lumen. The subsequent CT showed a gigantic splenic artery aneurysm measuring 9 cm in diameter. EUS is recommended because it has a high precision in diagnosing subepithelial lesions compared to abdominal CT scan.

The Laparoscopic Implantation of Neuroprosthesis Procedure Increases Leg Lean Mass in Individuals With Paraplegia Due To Traumatic Spinal Cord Injury.

OBJECTIVES: We hypothesized that the laparoscopic implantation of neuroprosthesis (LION) procedure would significantly alter the body composition of patients with chronic traumatic spinal cord injury (SCI). The objectives were to determine the effect of the LION procedure on lean mass (LM), fatty mass (FM), and bone mineral content (BMC) in patients with SCI. MATERIALS AND METHODS: Five consecutive patients underwent dual-energy x-ray absorptiometry scans before the LION procedure and at the one-year postoperative follow-up to determine changes in LM, FM, and BMC. Student paired t-test was used to determine significance. RESULTS: The patients gained 2506 ± 565 g of LM in the legs (p < 0.001), which was an 18% total increase in leg LM. Total body LM was significantly increased by 3523 ± 1048 g (p < 0.003). FM was unaffected, whereas total BMC showed a small but significant increase of 99 ± 42 g (p = 0.009). CONCLUSIONS: The LION procedure and subsequent neurostimulation procedures resulted in substantial increases in leg LM in patients with chronic traumatic SCI and paraplegia. A possible incremental effect on total BMC also was observed. Further studies are needed to confirm and expand these promising results.

Comparing single-target and multitarget approaches for postoperative circulating tumour DNA detection in stage II-III colorectal cancer patients.

Circulating tumour DNA (ctDNA) detection for postoperative risk stratification in cancer patients has great clinical potential. However, low ctDNA abundances complicates detection. Multitarget (MT) detection strategies have been developed to increase sensitivity. Yet, empirical evidence supporting performance gains of MT vs. single-target (ST) strategies in a postoperative setting is limited. We compared ctDNA detection in 379 paired plasma samples from 112 stage II-III colorectal cancer patients by ST digital PCR and MT sequencing of 16 patient-specific variants. The strategies exhibited good concordance (90%, Cohen's Kappa 0.79), with highly correlated ctDNA quantifications (Pearson r = 0.985). A difference was observed in ctDNA detection preoperatively (ST 72/92, MT 88/92). However, no difference was observed immediately after surgery in recurrence (ST 11/22, MT 10/22) or nonrecurrence (both 2/34) patients. In serial samples, detection was similar within recurrence (ST 13/16, MT 14/16) and nonrecurrence (ST 3/49, MT 1/49) patients. Both approaches yielded similar lead times to standard-of-care radiology (ST 4.0 months, MT 4.1 months). Our findings do not support significant performance gains of the MT strategy over the ST strategy for postoperative ctDNA detection.

[Use of the sentinel lymph node procedure in colorectal cancer].

The use of a sentinel lymph node procedure (SN) in various cancer treatments including breast cancer is well examined. Little is known however, regarding the use of SN in colorectal cancer treatment. In this review, we explain the use of SN and its implications for future colorectal cancer treatment.

Gastric perforation during second intragastric balloon treatment: a case report.

Intragastric balloon (IGB) is a widely used, minimal invasive treatment for obesity. The IGB reduce gastric capacity and enhance feeling of fullness, thereby inducing weight loss. A rare, but severe complication to IGB treatment is gastric perforation. We present a rare case of gastric perforation, occurring shortly after a second IGB treatment. The patient was first treated with an Orbera® IGB for 12 months, exceeding the recommended treatment period of 6 months. Upon removal, esophagitis and gastritis was found. Therefore, insertion of the second IGB was postponed. After only 9 treatment-free days, a new endoscopy revealed a macroscopical normal gastric mucosa, and the second Orbera® IGB was inserted. The day after the insertion the patient was admitted to the hospital, due to extensive vomiting and mild epigastric pain. Three days after the insertion a gastric perforation was found. The patient underwent endoscopic removal of the IGB and laparoscopic suture of the perforation. The postoperative course was complicated due to recurrent multiple intra abdominal abscesses, treated with antibiotics, drainage and abscess puncture on several occasions. We suggest that patients should be carefully evaluated before IGB treatments are repeated, especially when gastritis is present. If the gastric mucosa is affected, sufficient time to let it heal is needed. The recommended treatment period should not be exceeded, and perforation should always be suspected as a differential diagnosis when patients present with abdominal symptoms after IGB insertion.

Effect of pelvic laparoscopic implantation of neuroprosthesis in spinal cord injured subjects: a 1-year prospective randomized controlled study.

STUDY DESIGN: 1-year prospective RCT. OBJECTIVE: Examine the effect of implantable pulse generator and low-frequency stimulation of the pelvic nerves using laparoscopic implantation of neuroprosthesis (LION) compared with neuromuscular electrical stimulation (NMES) in SCI. METHODS: Inclusion criteria: traumatic spinal cord injury (SCI), age 18-55 years, neurological level-of-injury Th4-L1, time-since-injury >1 year, and AIS-grades A-B. Participants were randomized to (A) LION procedure or (B) control group receiving NMES. PRIMARY OUTCOME MEASURE: Walking Index for Spinal Cord Injury (WISCI-II), which is a SCI specific outcome measure assessing ability to ambulate. SECONDARY OUTCOME MEASURES: Spinal Cord Independence Measure III (SCIM III), Patient Global Impression of Change (PGIC), Penn Spasm Frequency Scale (PSFS), severity of spasticity measured by Numeric Rating Scale (NRS-11); International Spinal Cord Injury data sets-Quality of Life Basic Data Set (QoLBDS), and Brief Pain Inventory (BPI). RESULTS: Seventeen SCI individuals, AIS grade A, neurological level ranging from Th4-L1, were randomized to the study. One individual was excluded prior to intervention. Eight participants (7 males) with a mean age (SD) of 35.5 (12.4) years were allocated to the LION procedure, 8 participants (7 males) with age of 38.8 (15.1) years were allocated to NMES. Significantly, 5 LION group participants gained 1 point on the WISCI II scale, (p < 0.013; Fisher´s exact test). WISCI II scale score did not change in controls. No significant changes were observed in the secondary outcome measures. CONCLUSION: The LION procedure is a promising new treatment for individuals with SCI with significant one-year improvement in walking ability.

[Omental infarction with omental torsion, arare condition very seldom suspected clinically].

This is a case report of an adult female with omental infarction caused by internal herniation and omental torsion. The patient, who had no previous surgical record, presented with three days of pain in the right upper quadrant. Ultrasound evaluation showed no signs of cholecystitis, after which an abdominal computed tomography confirmed the diagnosis. The patient underwent laparoscopic omentectomy, with an uneventful recovery. This case highlights the importance of radiological and surgical awareness of this rare condition.

[The use of self-expanding metal stents as treatment for colonic stenosis].

An estimated 14% of patients diagnosed with colonic cancer present with acute obstruction. An increasing number of colonic obstructions is observed on the basis of benign causes. The use of a self-expanding metal stent (SEMS) is one of the treatment options, and in this review the background and the recommendations for the application in different settings is described. The use of SEMS has clinical outcomes similar to acute resection and is the first line of choice in palliation. Moreover, recent studies have shown SEMS to be an efficient and safe treatment for benign colonic stenosis.

Influence of anastomoses on intestine ischemia and cefuroxime concentrations: Evaluated in the ileum and colon in a porcine model.

BACKGROUND: Anastomotic leakage is a serious complication following gastrointestinal surgery and is associated with increased morbidity and mortality. The incidence of anastomotic leakage is determined by anatomy and is reported to be between 4%-33% for colon anastomosis and 1%-3% for small intestine anastomosis. The etiology of anastomotic leakage of the intestine has been divided into three main factors: healing disturbances, communication between intra- and extra-luminal compartments, and infection. All three factors interact, and one factor will inevitably lead to the other two factors resulting in tissue ischemia, tissue necrosis, and anastomotic leakage. AIM: To evaluate ischemic metabolites and cefuroxime concentrations in both anastomosis and non-anastomosis ileum and colon in a porcine model. METHODS: Eight healthy female pigs (Danish Landrace breed, weight 58-62 kg) were included in this study. Microdialysis catheters were placed for sampling of ischemic metabolites (glucose, lactate, glycerol, and pyruvate) and cefuroxime concentrations in both anastomosis and non-anastomosis ileum and colon. Cefuroxime 1.5 g was administered as an intravenous infusion over 15 min. Subsequently, dialysates and blood samples were collected over 8 h and the ischemic metabolites and cefuroxime concentrations were quantified in all samples. The concentrations of glucose, lactate, glycerol and pyruvate were determined using the CMA 600 Microdialysis Analyzer with Reagent Set A (M Dialysis AB, Sweden), and the concentrations of cefuroxime and meropenem were quantified using a validated ultra-high-performance liquid chromatography assay. RESULTS: Only the colon anastomosis induced mean ischemic lactate/pyruvate ratios above 25 (ischemic cut-off) throughout the entire sampling interval, and simultaneously decreased glucose concentrations. The mean time for which cefuroxime concentrations were maintained above the clinical breakpoint minimal inhibitory concentration for Escherichia coli (8 µg/mL) ranged between 116-128 min across all the investigated compartments, and was similar between the anastomosis and non-anastomosis ileum and colon. For all pigs and in all the investigated compartments, a cefuroxime concentration of 8 µg/mL was reached within 10 min after administration. When comparing the pharmacokinetic parameters between the anastomosis and non-anastomosis sites for both ileum and colon, only colon Tmax and half-life differed between anastomosis and non-anastomosis (P < 0.03). Incomplete tissue penetrations were found in all tissues except for the non-anastomosis colon. CONCLUSION: Administering 1.5 g cefuroxime 10 min prior to intestine surgery seems sufficient, and effective concentrations are sustained for approximately 2 h. Only colon anastomosis was locally vulnerable to ischemia.

[Neuromodulation in spinal cord injury rehabilitation].

Suffering a spinal cord injury is a devastating event often entailing a significant and demanding inpatient rehabilitation regime to improve the level of functioning post-injury. Neuromodulation has been applied in spinal cord injury rehabilitation for decades and carries promise for ameliorating the chronic complications associated with lesions of the spinal cord. Conventional methods of rehabilitation may be augmented by different modes of neuromodulation offering better rehabilitation outcomes, and combining techniques not currently in clinical use may convey additional benefits.