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Zhonghua Wei Zhong Bing Ji Jiu Yi Xue May 2024To investigate the effect of mild hypothermia on macrophage polarization in lipopolysaccharide (LPS)-induced acute lung injury (ALI) mice and to clarify its role in lung...
OBJECTIVE
To investigate the effect of mild hypothermia on macrophage polarization in lipopolysaccharide (LPS)-induced acute lung injury (ALI) mice and to clarify its role in lung injury.
METHODS
According to a random number table method, 18 male C57BL/6 mice were divided into sham operation group (Sham group), ALI normothermic model group (NT group) and ALI mild hypothermia treatment group (HT group), with 6 mice in each group. The ALI model in mice was established by the method of tracheal instillation of LPS, and temperature control was administered at 1 hour after surgery. The anus temperature in NT group was kept at 36-38?centigrade, while the anus temperature in HT group was kept at 32-34?centigrade. The target anus temperature in both groups were maintained for 6 hours and then slowly rewarmed to 36-38 centigrade. The Sham group was infused with an equal amount of physiological saline through the trachea without temperature control. After 24 hours of modeling, serum was collected and mice were sacrificed to obtain lung tissue. Pathological changes in lung tissue were observed under light microscopy and semi-quantitative lung injury score was performed. Enzyme linked immunosorbent assay (ELISA) was used to detect the serum levels of interleukins (IL-1β, IL-10). Real-time quantitative polymerase chain reaction (RT-qPCR) was used to test the indicators of macrophage polarization, such as the mRNA expressions of CD86, IL-6, CD206 and arginase 1 (Arg1) in the lung tissue. The protein expression of M1 macrophage marker inducible nitric oxide synthase (iNOS) and M2 macrophage marker Arg1 were detected by Western blotting.
RESULTS
Compared with the Sham group, the NT group appeared significant pulmonary hemorrhage and edema, thickened lung septum, inflammatory cell infiltration, and lung injury score was significantly increased; serum IL-1β level was significantly elevated; IL-10 level was increased without statistical significance; the expressions of CD86 mRNA, IL-6 mRNA and iNOS protein were significantly elevated, and CD206 mRNA was significantly decreased; the mRNA and protein expressions of Arg1 decreased, but there were no significant differences. Compared with the NT group, the pathological injury of lung tissue in HT group was significantly reduced, and the lung injury score was significantly decreased (4.78±0.96 vs. 8.56±1.98, P < 0.01); serum IL-1β level was decreased (ng/L: 13.52±1.95 vs. 27.18±3.87, P < 0.01), and IL-10 level was significantly increased (ng/L: 42.59±15.79 vs. 14.62±4.47, P < 0.01); IL-6 mRNA expression was decreased in lung tissue (2: 3.37±0.92 vs. 10.04±0.91, P < 0.05), the expression of M1 macrophage markers CD86 mRNA and iNOS protein were significantly decreased [CD86 mRNA (2): 0.52±0.16 vs. 1.95±0.33, iNOS protein (iNOS/β-actin): 0.57±0.19 vs. 1.11±0.27, both P < 0.05], the expression of M2 macrophage markers CD206 mRNA, Arg1 mRNA and Arg1 protein were significantly increased [CD206 mRNA (2): 3.99±0.17 vs. 0.34±0.17, Arg1 mRNA (2): 2.33±0.73 vs. 0.94±0.23, Arg1 protein (Arg1/β-actin): 0.96±0.09 vs. 0.31±0.11, all P < 0.05].
CONCLUSIONS
Mild hypothermia can alleviate the inflammatory response and protect lung tissue in ALI mice, which may be related to the inhibition of M1 macrophage polarization and promotion of M2 macrophage polarization.
Topics: Animals; Acute Lung Injury; Male; Mice; Mice, Inbred C57BL; Macrophages; Lipopolysaccharides; Nitric Oxide Synthase Type II; Interleukin-10; Interleukin-6; Hypothermia, Induced; Interleukin-1beta; Disease Models, Animal
PubMed: 38845499
DOI: 10.3760/cma.j.cn121430-20231129-01017 -
Endoscopy Dec 2024
Topics: Humans; Anus Neoplasms; Male; Endoscopic Mucosal Resection; Carcinoma, Squamous Cell
PubMed: 38838728
DOI: 10.1055/a-2321-9527 -
Journal of the National Cancer Institute Jun 2024Squamous cell carcinoma of the anus (SCCA) incidence has been rising in the United States, particularly among older adults (≥65 years). We estimated the impact of...
Squamous cell carcinoma of the anus (SCCA) incidence has been rising in the United States, particularly among older adults (≥65 years). We estimated the impact of this rise on future burden (through 2035) using age-period-cohort modeling. The SCCA burden (cases/year) is expected to rise, reaching ∼2700 among men and ∼7000 among women in 2031-2035 (burden during 2016-2020 among men and women was ∼2150 and ∼4600), with most cases aged ≥65 years (61% in men and 70% in women in 2031-2035; from 40% and 46% in 2016-2020). SCCA incidence (per 100,000) is projected to rise among older men aged 65-74, 75-84, and ≥85 years (5.0, 4.9, and 4.3, in 2031-2035 vs 3.7, 3.8, 3.4 in 2016-2020) and women (11.2, 12.6, 8.0 in 2031-2035 vs 8.2, 6.8, 5.2 in 2016-2020). The projected rise in SCCA burden among older adults is troubling and highlights the importance of improving early detection and clinical care.
PubMed: 38837335
DOI: 10.1093/jnci/djae127 -
International Journal of Gynecological... Jun 2024External beam radiation with sensitizing platinum is the recommended therapy for locally advanced vulvar cancers not amenable to curative surgery and is associated with...
OBJECTIVES
External beam radiation with sensitizing platinum is the recommended therapy for locally advanced vulvar cancers not amenable to curative surgery and is associated with considerable acute and chronic side effects. Radical vulvectomy post-radiation for persistent disease is often compromised with poor wound healing. We describe clinical outcomes for patients who received neoadjuvant chemotherapy plus bevacizumab followed by radical vulvectomy for locally advanced vulvar cancer.
METHODS
We performed retrospective analyses of all patients at our institution who underwent radical vulvectomy from January 2015 to November 2023. Of 113 patients, 13 patients underwent neoadjuvant chemotherapy. Demographics and clinicopathologic data were extracted, and descriptive statistical analyses were performed. Cases with neoadjuvant chemotherapy plus bevacizumab were further evaluated for response, adverse effects, and survival.
RESULTS
Neoadjuvant chemotherapy was administered to 13 patients with stage II-IV disease that involved the urethra, vagina, or anus. Lesion sizes ranged from 4 to 20 cm (median 7 cm). Patients received 2-6 cycles of carboplatin or cisplatin, paclitaxel, and bevacizumab. Nine (69.2%) patients had partial pathologic responses, and four patients had complete responses. All patients had negative surgical margins. Ten (76.9%) patients had radiographic evidence of inguinal lymph node metastasis prior to neoadjuvant chemotherapy, and four had residual nodal disease. Only one patient developed a superficial groin seroma. Three patients developed recurrence, two locally and one distant, and there was one death. The median follow-up was 23 months (range 6-84 months).
CONCLUSIONS
Neoadjuvant chemotherapy using combination platinum/paclitaxel/bevacizumab was efficacious for locally advanced vulvar cancer, resulting in complete resections, negative margins, and excellent wound healing. A multi-institutional phase II trial is warranted to validate these findings.
PubMed: 38830645
DOI: 10.1136/ijgc-2024-005402 -
Experimental and Molecular Pathology Jun 2024Shallow whole genome sequencing (Shallow-seq) is used to determine the copy number aberrations (CNA) in tissue samples and circulating tumor DNA. However, costs of NGS...
BACKGROUND
Shallow whole genome sequencing (Shallow-seq) is used to determine the copy number aberrations (CNA) in tissue samples and circulating tumor DNA. However, costs of NGS and challenges of small biopsies ask for an alternative to the untargeted NGS approaches. The mFAST-SeqS approach, relying on LINE-1 repeat amplification, showed a good correlation with Shallow-seq to detect CNA in blood samples. In the present study, we evaluated whether mFAST-SeqS is suitable to assess CNA in small formalin-fixed paraffin-embedded (FFPE) tissue specimens, using vulva and anal HPV-related lesions.
METHODS
Seventy-two FFPE samples, including 36 control samples (19 vulva;17 anal) for threshold setting and 36 samples (24 vulva; 12 anal) for clinical evaluation, were analyzed by mFAST-SeqS. CNA in vulva and anal lesions were determined by calculating genome-wide and chromosome arm-specific z-scores in comparison with the respective control samples. Sixteen samples were also analyzed with the conventional Shallow-seq approach.
RESULTS
Genome-wide z-scores increased with the severity of disease, with highest values being found in cancers. In vulva samples median and inter quartile ranges [IQR] were 1[0-2] in normal tissues (n = 4), 3[1-7] in premalignant lesions (n = 9) and 21[13-48] in cancers (n = 10). In anal samples, median [IQR] were 0[0-1] in normal tissues (n = 4), 14[6-38] in premalignant lesions (n = 4) and 18[9-31] in cancers (n = 4). At threshold 4, all controls were CNA negative, while 8/13 premalignant lesions and 12/14 cancers were CNA positive. CNA captured by mFAST-SeqS were mostly also found by Shallow-seq.
CONCLUSION
mFAST-SeqS is easy to perform, requires less DNA and less sequencing reads reducing costs, thereby providing a good alternative for Shallow-seq to determine CNA in small FFPE samples.
Topics: Humans; Female; DNA Copy Number Variations; Paraffin Embedding; High-Throughput Nucleotide Sequencing; Formaldehyde; Tissue Fixation; Whole Genome Sequencing; Vulvar Neoplasms; Papillomavirus Infections; Anus Neoplasms
PubMed: 38820761
DOI: 10.1016/j.yexmp.2024.104906 -
Journal of the American College of... May 2024The long-term risk of pouch failure after restorative proctocolectomy with ileal-pouch anal anastomosis (IPAA) range from 5 and 15%. Salvage surgery for failing IPAA's...
BACKGROUND
The long-term risk of pouch failure after restorative proctocolectomy with ileal-pouch anal anastomosis (IPAA) range from 5 and 15%. Salvage surgery for failing IPAA's may be achieved by disconnecting the IPAA and either repairing and re-using the existing pouch (REP) or constructing a neo-pouch (NEO). We aimed to evaluate whether there are differences in long-term functional pouch survival and functional outcomes between the REP group and the NEO group. We hypothesized patients undergoing REP have higher long-term pouch survival rates compared to patients who require NEO pouch construction.
METHODS
Our prospectively maintained Pouch Registry was queried for patients who underwent a pouch salvage surgery with either pouch REP or NEO from 1988 - 2020. Patients who underwent pouch repair without disconnection from the anus were excluded. The primary endpoint was long-term pouch survival after redo pouch surgery. Secondary outcomes were patient reported quality of life and pouch function.
RESULTS
Of 653 patients undergoing redo IPAA, 462 met inclusion criteria of transabdominal redo surgery with pouch reconnection: 243 (52.6%) had REP and 219 (47.4%) had NEO. Median age was 39 years and 59% were female. Median time between index and redo IPAA was 34 months for REP vs 54 months for NEO (p=0.002). The 5-year pouch survival after redo IPAA was similar between REP (79.5%) and NEO (76.8%) groups (p=0.4). Fewer patients in the REP group reported nighttime pad use (51.4% vs 68.2%, p=0.04).
CONCLUSION
Pouch survival and functional outcomes after salvage surgery for failing ileoanal pouch was similar regardless of pouch salvage procedure. When performing redo pouch surgery, surgeons should not hesitate to construct a new pouch if indicated.
PubMed: 38814287
DOI: 10.1097/XCS.0000000000001122 -
La Revue Du Praticien Apr 2024
Topics: Humans; Papillomavirus Infections; Anus Neoplasms; Mass Screening
PubMed: 38814020
DOI: No ID Found -
Journal of Medical Virology Jun 2024Persistent infection with high-risk human papillomavirus (HPV) is recognized as the main cause for the development of anogenital cancers. This study prospectively... (Comparative Study)
Comparative Study
Persistent infection with high-risk human papillomavirus (HPV) is recognized as the main cause for the development of anogenital cancers. This study prospectively evaluated the diagnostic performance of the novel Allplex-HPV28 assay with the Anyplex-II-HPV28 to detect and genotype HPV in 234 consecutive swabs and 32 biopsies of the anogenital tract from 265 patients with atypical findings in cytomorphological screening. Agreement in HPV-DNA detection between the Anyplex-II and Allplex-HPV28 assays was 99%. There was a notable diversity in the HPV-virome, with the most prevalent high-risk HPV types being 16, 53, 66, and 68. The agreement rates for detecting these genotypes exceeded 93% between the Anyplex-II and Allplex-HPV28 assays. Discrepancies in test results were solely noted for Anyplex-II-HPV28 results with a low signal intensity of "+", and for Allplex-HPV28 results with cycle thresholds of ≥36. The semi-quantitative analysis of HPV-DNA loads showed significant agreement between the Anyplex-II-HPV28 and Allplex-HPV28 assays (p < 0.001). Furthermore, HPV-DNA detection rates and mean HPV-DNA loads significantly correlated with the grade of abnormal changes identified in cytopathological assessment, being highest in cases of HSIL, condyloma accuminatum, and squamous cell carcinoma. Overall agreement rates for detecting specific HPV-types among the Anyplex-II and Allplex-HPV28 assays exceeded 99.5% in cases of atypical squamous cells, condyloma accuminatum, and squamous cell carcinoma. The novel Allplex-HPV28 assay shows good diagnostic performance in detecting and genotyping HPV commonly associated with anogenital cancers. Consequently, this assay could offer substantial potential for incorporation into future molecular screening programs for anogenital cancers in clinical settings.
Topics: Humans; Papillomavirus Infections; Female; Male; Papillomaviridae; Middle Aged; Genotype; Early Detection of Cancer; Adult; Aged; Prospective Studies; Molecular Diagnostic Techniques; DNA, Viral; Genotyping Techniques; Young Adult; Sensitivity and Specificity; Anus Neoplasms; Human Papillomavirus Viruses; Alphapapillomavirus
PubMed: 38812416
DOI: 10.1002/jmv.29649 -
Clinical Case Reports Jun 2024Inflammatory bowel disease is rare in infants and it includes perianal Crohn's disease, which is inflammation at or near the anus. An early diagnosis is essential to...
Inflammatory bowel disease is rare in infants and it includes perianal Crohn's disease, which is inflammation at or near the anus. An early diagnosis is essential to prevent the complications that may affect the development and growth of the child.
PubMed: 38803326
DOI: 10.1002/ccr3.8963 -
Techniques in Coloproctology May 2024Gastrointestinal stromal tumours (GISTs) can develop throughout the entire gastrointestinal tract, but these tumours are usually found in the stomach and small...
Gastrointestinal stromal tumours (GISTs) can develop throughout the entire gastrointestinal tract, but these tumours are usually found in the stomach and small intestine. In this case, a rare GIST arising from the anal canal was investigated using high-frequency endoanal ultrasound and external three-dimensional ultrasound with tomographic ultrasound imaging. The endoanal approach revealed the inner structure of the tumour. External ultrasound was used to determine the relationship between the lesion and surrounding tissues. In the limited reports of anal canal GISTs, no other lesions have been correctly diagnosed preoperatively or displayed in detail on imaging. The multilayer structure of the anal sphincter and these lesions can be clearly displayed by a variety of ultrasound imaging methods, which are nonradiative, low-cost and easily accessible. Modern ultrasound has the potential for broad application in anal canal tumour diagnosis and surveillance.
Topics: Humans; Gastrointestinal Stromal Tumors; Anus Neoplasms; Anal Canal; Endosonography; Imaging, Three-Dimensional; Ultrasonography; Male; Middle Aged; Female; Aged
PubMed: 38801613
DOI: 10.1007/s10151-024-02934-2