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Frontiers in Immunology 2023Immune checkpoint inhibitors (ICIs) are the standard treatment for metastatic colorectal cancer (mCRC) with high microsatellite instability (MSI-H). Among immune-related...
BACKGROUND
Immune checkpoint inhibitors (ICIs) are the standard treatment for metastatic colorectal cancer (mCRC) with high microsatellite instability (MSI-H). Among immune-related adverse events (irAEs), drug-induced sarcoidosis-like reactions (DISR) are often difficult to differentiate from cancer progression.
MAIN BODY
This is a case of a woman in her mid-60s, with mCRC (RAS wild/BRAF mutant/MSI-H) and abdominal lymph node metastasis, treated with four courses of ipilimumab + nivolumab every 3 weeks, followed by nivolumab every 2 weeks as third-line treatment. After treatment, the original lymph node metastases shrank, but hilar/mediastinal lymph nodes appeared. Endoscopic ultrasound-guided fine-needle aspiration of these lymph nodes revealed multiple epithelioid granulomas without necrosis, indicating a sarcoidosis-like reaction. Fluorodeoxyglucose-positron emission tomography scan showed abnormal subcutaneous accumulation in bilateral forearms and bilateral knee joints. Biopsy of the cutaneous lesions was also performed, which revealed epithelioid granulomas. As the patient had no symptoms in other organs, no specific therapeutic intervention was administered. After the discontinuation of immunotherapy, the sarcoidosis-like reaction regressed without cancer relapse.
CONCLUSIONS
Clinicians should be aware of the possibility of DISR as an irAE during the ICI treatment of mCRC. In suspected cases of DISR following ICI therapy, it is important to differentiate between cancer progression and DISR through histological diagnosis for the subsequent strategy, as radiological and serological findings are not definitive.
Topics: Humans; Female; Nivolumab; Immune Checkpoint Inhibitors; Neoplasm Recurrence, Local; Sarcoidosis; Colonic Neoplasms; Rectal Neoplasms; Granuloma; Lymphatic Metastasis
PubMed: 37492584
DOI: 10.3389/fimmu.2023.1203621 -
Techniques in Coloproctology Dec 2023The optimal treatment of colorectal cancer is surgical resection and primary anastomosis. Anastomotic leak can affect up to 20% of patients and creates significant...
BACKGROUND
The optimal treatment of colorectal cancer is surgical resection and primary anastomosis. Anastomotic leak can affect up to 20% of patients and creates significant morbidity and mortality. Current diagnosis of a leak is based on clinical suspicion and subsequent radiology. Peritoneal biomarkers have shown diagnostic utility in other conditions and could be useful in providing earlier diagnosis. This pilot study was designed to assess the practical utility of peritoneal biomarkers after abdominal surgery utilising an automated immunoassay system in routine use for quantifying cytokines.
METHODS
Patients undergoing an anterior resection for a rectal cancer diagnosis were recruited at University Hospital of Wales, Cardiff between June 2019 and June 2021. A peritoneal drain was placed in the proximity of the anastomosis during surgery, and peritoneal fluid was collected at days 1 to 3 post-operatively, and analysed using the Siemens IMMULITE platform for interleukin (IL)-1β, IL-6, IL-10, CXCL8, tumour necrosis factor alpha (TNFα) and C-reactive protein (CRP).
RESULTS
A total of 42 patients were recruited (22M:20F, median age 65). Anastomotic leak was detected in four patients and a further five patients had other intra-abdominal complications. The IMMULITE platform was able to provide robust and reliable results from the analysis of the peritoneal fluid. A metric based on the combination of peritoneal IL-6 and CRP levels was able to accurately diagnose three anastomotic leaks, whilst correctly classifying all negative control patients including those with other complications.
CONCLUSIONS
This pilot study demonstrates that a simple immune signature in surgical drain fluid could accurately diagnose an anastomotic leak at 48 h postoperatively using instrumentation that is already widely available in hospital clinical laboratories.
Topics: Humans; Aged; Anastomotic Leak; Interleukin-6; Pilot Projects; Biomarkers; Anastomosis, Surgical; Rectal Neoplasms; Retrospective Studies
PubMed: 37486461
DOI: 10.1007/s10151-023-02841-y -
Cancers Jun 2023Extralevator abdominoperineal excision (ELAPE) is a relatively new surgical technique for low rectal cancers, enabling a more radical approach than conventional...
Feasibility of Perineal Defect Reconstruction with Simplified Fasciocutaneous Inferior Gluteal Artery Perforator (IGAP) Flaps after Tumor Resection of the Lower Rectum: Incidence and Outcome in an Interdisciplinary Approach.
BACKGROUND
Extralevator abdominoperineal excision (ELAPE) is a relatively new surgical technique for low rectal cancers, enabling a more radical approach than conventional abdominoperineal excision (APE) with a potentially better oncological outcome. To date, no standard exists for reconstruction after extended or extralevator approaches of abdominoperineal (ELAPE) resection for lower gastrointestinal cancer or inflammatory tumors. In the recent literature, techniques with myocutaneous flaps, such as the VY gluteal flap, the pedicled gracilis flap, or the pedicled rectus abdominis flaps (VRAM) are primarily described. We propose a tailored concept with the use of bilateral adipo-fasciocutaneous inferior gluteal artery perforator (IGAP) advancement flaps in VY fashion after ELAPE surgery procedures. This retrospective cohort study analyzes the feasibility of this concept and is, to our knowledge, one of the largest published series of IGAP flaps in the context of primary closure after ELAPE procedures.
METHODS
In a retrospective cohort analysis, we evaluated all the consecutive patients with rectal resections from Jan 2017 to Sep 2021. All the patients with abdominoperineal resection were included in the study evaluation. The primary endpoint of the study was the proportion of plastic reconstruction and inpatient discharge.
RESULTS
Out of a total of 560 patients with rectal resections, 101 consecutive patients with ELAPE met the inclusion criteria and were included in the study evaluation. The primary direct defect closure was performed in 72 patients (71.3%). In 29 patients (28.7%), the defect was closed with primary unilateral or bilateral IGAP flaps in VY fashion. The patients' mean age was 59.4 years with a range of 25-85 years. In 84 patients, the indication of the operation was lower rectal cancer or anal cancer recurrence, and non-oncological resections were performed in 17 patients. Surgery was performed in a minimally invasive abdominal approach in combination with open perineal extralevatoric abdominoperineal resection (ELAPE) and immediate IGAP flap reconstruction. The rate of perineal early complications after plastic reconstruction was 19.0%, which needed local revision due to local infection. All these interventions were conducted under general anesthesia (Clavien-Dindo IIIb). The mean length of the hospital stay was 14.4 days after ELAPE, ranging from 3 to 53 days.
CONCLUSIONS
Since radical resection with a broad margin is the standard choice in primary, sphincter-infiltrating rectal cancer and recurrent anal cancer surgery in combination with ELAPE, the choice technique for pelvic floor reconstruction is under debate and there is no consensus. Using IGAP flaps is a reliable, technical, easy, and safe option, especially in wider defects on the pelvic floor with minimal donor site morbidity and an acceptable complication (no flap necrosis) rate. The data for hernia incidence in the long term are not known.
PubMed: 37444455
DOI: 10.3390/cancers15133345 -
Journal of Crohn's & Colitis Jan 2024The risk of relapse after anti-tumour necrosis factor [TNF] therapy discontinuation in Crohn's disease patients with perianal fistulas [pCD] is unclear. We aimed to... (Meta-Analysis)
Meta-Analysis
Discontinuation of Anti-Tumour Necrosis Factor Therapy in Patients with Perianal Fistulizing Crohn's Disease: Individual Participant Data Meta-Analysis of 309 Patients from 12 Studies.
BACKGROUND
The risk of relapse after anti-tumour necrosis factor [TNF] therapy discontinuation in Crohn's disease patients with perianal fistulas [pCD] is unclear. We aimed to assess this risk.
METHODS
A systematic literature search was conducted to identify cohort studies on the incidence of relapse following anti-TNF discontinuation in pCD patients. Individual participant data were requested from the original study cohorts. Inclusion criteria were age ≥16 years, pCD as a (co)indication for start of anti-TNF therapy, more than three doses, and remission of luminal and pCD at anti-TNF discontinuation. The primary outcome was the cumulative incidence of CD relapse using Kaplan-Meier estimates. Secondary outcomes included response to re-treatment and risk factors associated with relapse as assessed by Cox regression analysis.
RESULTS
In total, 309 patients from 12 studies in ten countries were included. The median duration of anti-TNF treatment was 14 months [interquartile range 5.8-32.5]. Most patients were treated for pCD without active luminal disease [89%], received first-line anti-TNF therapy [87%], and continued immunomodulatory therapy following anti-TNF discontinuation [78%]. The overall cumulative incidence of relapse was 36% (95% confidence interval [CI] 25-48%) and 42% [95% CI 32-53%] at 1 and 2 years after anti-TNF discontinuation, respectively. Risk factors for relapse included smoking (hazard ratio [HR] 1.5 [1.0, 2.1]) and history of proctitis (HR 1.7 [1.1, 2.5]). The overall re-treatment response rate was 82%.
CONCLUSIONS
This individual participant data meta-analysis, on predominantly patients with pCD without active luminal disease and first-line anti-TNF therapy, shows that over half of patients remain in remission 2 years after anti-TNF discontinuation. Therefore, anti-TNF discontinuation may be considered in this subgroup.
Topics: Humans; Adolescent; Crohn Disease; Infliximab; Tumor Necrosis Factor-alpha; Tumor Necrosis Factor Inhibitors; Recurrence; Necrosis; Treatment Outcome; Retrospective Studies; Rectal Fistula
PubMed: 37437094
DOI: 10.1093/ecco-jcc/jjad118 -
International Journal of Pharmaceutics:... Dec 2023Infliximab is a monoclonal antibody that plays an important role in the management and treatment of chronic inflammatory bowel diseases (IBD). Due to its macromolecular...
Infliximab is a monoclonal antibody that plays an important role in the management and treatment of chronic inflammatory bowel diseases (IBD). Due to its macromolecular structure, its delivery through the oral route is challenging, limiting its administration to only via the parenteral route. The rectal route offers an alternative way for administering infliximab, allowing it to be localised at the disease site and circumventing its passage across the alimentary canal and thus, maintaining its integrity and bioactivity. Three-dimensional (3D) printing is an advanced production technology that permits the creation of dose-flexible drug products from digital designs. The current study assessed the feasibility of utilising semi-solid extrusion 3D printing for the fabrication of infliximab-loaded suppositories for the local treatment of IBD. Various printing inks composed of Gelucire® (48/16 or 44/14) mixed with coconut oil and/or purified water were investigated. It was shown that following reconstitution in water, the infliximab solution can be directly incorporated into the printing ink of Gelucire® 48/16 and can withstand the extrusion process, resulting in well-defined suppositories. Since water content and temperature are critical for safeguarding infliximab's potency, the effect of changing the composition of the printing inks and printing parameters on infliximab's biologic efficiency was evaluated by measuring its binding capacity (i.e., the amount of infliximab that actively binds to its antigen to exert an effect). Despite drug loading assays showing that infliximab remains intact following printing, it was found that the incorporation of water in isolation results in only ∼65% binding capacity. However, when oil is added to the mixture, infliximab's binding capacity increases up to ∼85%. These promising results demonstrate that 3D printing has the potential to be exploited as a novel platform for fabricating dosage forms containing biopharmaceuticals, avoiding patients' compliance issues observed with injectables and addressing their unmet needs.
PubMed: 37396625
DOI: 10.1016/j.ijpx.2023.100176 -
Medicina (Kaunas, Lithuania) Jun 2023: Renal infarction is an extremely rare disease. Although more than 95% of cases are symptomatic, there have been no previously reported asymptomatic cases, without any...
: Renal infarction is an extremely rare disease. Although more than 95% of cases are symptomatic, there have been no previously reported asymptomatic cases, without any abnormal blood and urine test findings. Furthermore, the efficacy of long-term treatment of idiopathic renal infarction remains unknown. A 63-year-old Japanese male underwent laparoscopy; a very low anterior resection of the rectum for lower rectal cancer (stage II) four years and five months prior to diagnosis with renal infarction. During the follow-up imaging studies, asymptomatic idiopathic renal infarction was found incidentally. The blood and urine test findings were normal. Contrast-enhanced computed tomography revealed a linearly bordered area of poor contrast in the dorsal region of the right kidney; however, no renal artery lesions, thromboembolic disease, or coagulation abnormalities were observed. Initial treatment with rivaroxaban 15 mg/day resulted in the remission of the infarcted lesion. The anticoagulation therapy was terminated after about 18 months without any incidences of re-infarction or bleeding events. We reported a very rare case of asymptomatic idiopathic renal infarction where blood and urine tests revealed no abnormal findings, and it was diagnosed incidentally during a post-treatment follow-up examination for lower rectal cancer. Long-term anticoagulant therapy for idiopathic renal infarction should be terminated at an appropriate time, taking the risk of bleeding into account.
Topics: Humans; Male; Middle Aged; Kidney Diseases; Tomography, X-Ray Computed; Kidney; Infarction; Rectal Neoplasms
PubMed: 37374380
DOI: 10.3390/medicina59061176 -
Asian Pacific Journal of Cancer... May 2023Ulcerative colitis (UC) is an inflammatory bowel disease that affects people worldwide. The causes of UC are diverse, and symptoms include diarrhea, weight loss, anemia,...
BACKGROUND
Ulcerative colitis (UC) is an inflammatory bowel disease that affects people worldwide. The causes of UC are diverse, and symptoms include diarrhea, weight loss, anemia, rectal bleeding, and bloody stools. Tenebrio molitor larvae have recently gained attention as edible insects with various physiological and medical effects. Research on the anti-inflammatory effects of ingesting Tenebrio molitor larvae powder (TMLP) is being actively conducted. In this study, TMLP was administered to mice with dextran sodium sulfate (DSS)-induced colitis to investigate its effects in reducing colitis symptoms.
METHODS
Mice were initially given 3% DSS in water to induce colitis and then feed containing 0%, 2%, or 4% TMLP. Pathologic changes in colon tissues were assessed by histology, and neutrophil levels were measured by myeloperoxidase (MPO) assay. Levels of IL-1β, IL-6, and TNF-α were measured using real-time PCR and ELISA assays, and IκB and NF-kB protein levels were measured by western blotting.
RESULT
Disease Activity Index (DAI) scores and MPO activity were reduced in TMLP-treated mice, and colon length increased as much as normal mice. Pathologic changes in the colon tissues of DSS-induced mice were attenuated, and the expression of inflammatory cytokine genes IL-1β, IL-6, and TNF-α decreased. Concomitant decreases in the protein expression of IL-1β and IL-6 were confirmed using ELISA. Western blotting revealed that levels of phosphorylated forms of IκB and NF-κB also decreased.
CONCLUSION
These results show that feeding TMLP to DSS-induced mice inhibited the typical inflammatory pathway of colitis. Therefore, TMLP shows potential as a food additive that can help treat colitis.
.Topics: Animals; Mice; Tenebrio; Dextrans; Powders; Tumor Necrosis Factor-alpha; Larva; Interleukin-6; Signal Transduction; Colitis; Colitis, Ulcerative; Colon; NF-kappa B; Dextran Sulfate; Disease Models, Animal
PubMed: 37247298
DOI: 10.31557/APJCP.2023.24.5.1751 -
Annals of Medicine and Surgery (2012) May 2023The extragastrointestinal stromal tumor (EGIST) is defined as a mesenchymal neoplasm arising from soft tissues outside the gastrointestinal tract, and the prostate is a...
UNLABELLED
The extragastrointestinal stromal tumor (EGIST) is defined as a mesenchymal neoplasm arising from soft tissues outside the gastrointestinal tract, and the prostate is a rare presentation site.
CASE PRESENTATION
A 58-year-old man was presented with lower urinary tract symptoms for 6 months. A digital rectal examination revealed a markedly enlarged prostate with a smooth, bulging surface. Prostate-specific antigen density was 0.5 ng/ml. MRI of the prostate showed an enlarged prostatic mass with hemorrhagic necrosis. Transrectal ultrasound-guided prostate biopsy was performed and pathological reports suggested a gastrointestinal stromal tumor. The patient refused radical prostatectomy and received only imatinib treatment.
CLINICAL DISCUSSION
The diagnosis of EGIST of the prostate is extremely rare and depends on the histopathologic features with immunohistochemical results. The treatment is essentially based on radical prostatectomy, but there are other therapeutic modalities associating surgery with adjuvant or neoadjuvant chemotherapy. For patients refusing surgery, treatment with imatinib alone appears to be a therapeutic solution.
CONCLUSION
Despite the rarity, EGIST of the prostate should be included in the differential diagnosis of patients presenting with lower urinary tract symptoms. There is no consensus regarding the treatment of EGIST, and the patients are treated as per the risk stratification.
PubMed: 37228978
DOI: 10.1097/MS9.0000000000000373 -
Frontiers in Immunology 2023The prevalence of food allergy (FA) is increasing. Decreases in the diversity of gut microbiota may contribute to the pathogenesis of FA by regulating IgE production of...
BACKGROUND
The prevalence of food allergy (FA) is increasing. Decreases in the diversity of gut microbiota may contribute to the pathogenesis of FA by regulating IgE production of B cells. Intermittent fasting (IF) is a popular diet with the potential to regulate glucose metabolism, boosting immune memory and optimizing gut microbiota. The potential effect of long-term IF on the prevention and treatment of FA is still unknown.
METHODS
Two IF protocols (16 h fasting/8 h feeding and 24 h fasting/24 h feeding) were conducted on mice for 56 days, while the control mice were free to intake food (free diet group, FrD). To construct the FA model, all mice were sensitized and intragastrical challenged with ovalbumin (OVA) during the second half of IF (day 28 to day 56). Rectal temperature reduction and diarrhea were recorded to evaluate the symptoms of FA. Levels of serum IgE, IgG1, Th1/Th2 cytokines, mRNA expression of spleen T cell related transcriptional factors, and cytokines were examined. H&E, immunofluorescence, and toluidine blue staining were used to assess the structural changes of ileum villi. The composition and abundance of gut microbiota were analyzed by 16srRNA sequencing in cecum feces.
RESULTS
The diarrhea score and rectal temperature reduction were lower in the two fasting groups compared to the FrD groups. Fasting was associated with lower levels of serum OVA-sIgE, OVA-sIgG1, interleukin (IL)-4 and IL-5, and mRNA expression of IL-4, IL-5, and IL-10 in the spleen. While no significant association was observed in interferon (IFN)-γ, tumor necrosis factor (TNF)-α, IL-6, IL-2 levels. Less mast cell infiltration in ileum was observed in the 16h/8h fasting group compared to the FrD group. ZO-1 expression in the ileum of the two fasting groups was higher in IF mice. The 24h/24h fasting reshaped the gut microbiota, with a higher abundance of and strains compared to the other groups.
CONCLUSION
In an OVA-induced mice FA model, long-term IF may attenuate FA by reducing Th2 inflammation, maintaining the integrity of the intestinal epithelial barrier, and preventing gut dysbiosis.
Topics: Mice; Animals; Gastrointestinal Microbiome; Intermittent Fasting; Disease Models, Animal; Interleukin-5; Food Hypersensitivity; Cytokines; Immunoglobulin E; Diarrhea; RNA, Messenger
PubMed: 37228621
DOI: 10.3389/fimmu.2023.1167562 -
BMC Gastroenterology May 2023To evaluate the value of transrectal ultrasound (TRUS) guided biopsy in endoscopy negative biopsy patients with rectal lesions.
OBJECTIVE
To evaluate the value of transrectal ultrasound (TRUS) guided biopsy in endoscopy negative biopsy patients with rectal lesions.
METHODS
150 endoscopy negative biopsy result rectal lesions adopted the transrectal ultrasound-guided biopsy. Based on whether the patients received contrast-enhanced ultrasound examination or not before the biopsies, all enrolled cases were divided into TRUS guided group and contrast-enhanced TRUS (CE-TRUS) guided group, and the safety and diagnostic performances were analyzed retrospectively.
RESULTS
We obtained adequate specimens in the majority of cases (98.7%,148/150); There were no complications identified in our study. 126 patients received contrast-enhanced TRUS examination before biopsy to evaluate vascular perfusion and necrosis. The sensitivity, specificity, PPV, NPV, and overall accuracy of all biopsies were 89.1%, 100%,100%, 70.4%, and 91.3% respectively; The sensitivity, specificity, PPV, NPV, and accuracy for TRUS-guided biopsy and CE-TRUS guided biopsy were 73.7%, 100%,100%, 50%,79.2% and 92.1%,100%,100%,75%,93.6% separately; The increase in correct diagnoses was significant (p < 0.05) between TRUS guided biopsy and CE-TRUS guided biopsy.
CONCLUSION
TRUS-guided biopsy is a reliable procedure that can be augmented by endoscopic biopsy techniques if the biopsy yields negative results. CE-TRUS might assist in the location of the biopsy and decrease sampling errors.
Topics: Humans; Retrospective Studies; Rectum; Biopsy; Ultrasonography; Ultrasonography, Interventional; Image-Guided Biopsy
PubMed: 37217841
DOI: 10.1186/s12876-023-02806-3