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Increased severity or recurrence risk of some specific infectious diarrhea, such a salmonellosis or Clostridium difficile colitis, have been reported after an appendectomy in human patients. While several other mammals also possess an appendix, the suspected protective function against diarrhea conferred by this structure is known only in humans. From a retrospective collection of veterinary records of 1251 primates attributed to 45 species, including 13 species with an appendix and 32 without, we identified 2855 episodes of diarrhea, 13% of which were classified as severe diarrhea requiring a therapeutic medication or associated with a fatal issue. We identified a lower risk of severe diarrhea among primate species with an appendix, especially in the early part of life when the risk of diarrhea is maximal. Moreover, we observed a delayed onset of diarrhea and of severe diarrhea in species possessing an appendix. Interestingly, none of the primates with an appendix were diagnosed, treated or died of an acute appendicitis during the 20 years of veterinarian follow-up. These results clarify the function of the appendix among primates, as protection against diarrhea. This supports its presumed function in humans and is congruent with the existence of a selective advantage conferred by this structure.
Malignant tumours of the appendix are quite rare, especially appendiceal adenocarcinomas, which may be difficult to detect preoperatively or intraoperatively. We collected data for 1404 patients with adenocarcinoma of the appendix from the Surveillance, Epidemiology, and End Results Program (SEER) database to explore the potential associations between clinicopathological factors and overall survival. Furthermore, a novel nomogram for predicting prognosis was developed based on our analysis of the SEER data. The nomogram prediction model included seven prognostic factors derived based on different clinical estimates. When compared with the traditional tumour-node-metastasis (TNM) staging system, the nomogram prediction model showed superior discriminatory power (Harrell's C-index, 0.741 vs. 0.686) and a greater degree of similarity to actual 5-year overall survival after calibration (Akaike Information Criterion index, 5270.781 vs. 5430.141). Finally, we provide recommendations for the management of patients with adenocarcinoma of the appendix. Notably, we found the depth of adenocarcinoma invasion may be used as an indicator to determine the optimal surgical approach. For mucinous adenocarcinomas of the appendix, because these tumours are characterized by unique biological behaviour, intraoperative hyperthermic intraperitoneal chemotherapy (HIPEC) is recommended. However, whether systematic chemotherapy should be administered to patients with adenocarcinoma of the appendix requires further investigation.
The cecal appendix had been considered as a useless vestige since Darwin's work, but recent research questioned this idea demonstrating that the cecal appendix appeared among the mammals at least 80 million years ago and has made multiple and independent appearances without any obvious correlation with diet, social life, ecology, or size of the cecum. However, functions and probable selective advantage conferred by this anatomical structure still remain enigmatic. We found, through analyses of data on 258 mammalian species, that cecal appendix presence is correlated with increased maximal observed longevity. This is the first demonstration of a correlation between cecal appendix presence and life history. Interestingly, the classical evolutionary theory of aging that predicts an increased longevity when the extrinsic mortality is reduced has been questioned several times, but recent comparative studies asserted its validity in the taxa, which experience age-dependent and density-dependent mortality, as in mammals. Thus, the cecal appendix may contribute to the increase in longevity through a reduction of extrinsic mortality. A lower risk of fatal infectious diarrhea is one of the most plausible hypotheses that could explain it. However, several hypotheses coexist about the possible functions of the cecal appendix, and our results provide new insights about this much-disputed question. In addition, we show that the cecal appendix arose at least 16 times and was lost only once during the evolutionary history of the considered mammals, an asymmetry that supports the existence of a positive selective of this structure.
Three phenolic compounds are capable of activating the process that simultaneously leads to temperature rise and odor-production in the Sauromatum appendix. These compounds are salicylic acid, aspirin, and 2,6 dihydroxybenzoic acid. The objectives of the present study were to examine the effect of various concentrations of the these inducers on the temperature rise and to study the effect of mitochondrial inhibitors (KCN and SHAM) and an uncoupler (DNP) on the temperature rise.
The gastrointestinal tract may be a site of origin for α-synuclein pathology in idiopathic Parkinson's disease (PD). Disruption of the autophagy-lysosome pathway (ALP) may contribute to α-synuclein aggregation. Here we examined epigenetic alterations in the ALP in the appendix by deep sequencing DNA methylation at 521 ALP genes. We identified aberrant methylation at 928 cytosines affecting 326 ALP genes in the appendix of individuals with PD and widespread hypermethylation that is also seen in the brain of individuals with PD. In mice, we find that DNA methylation changes at ALP genes induced by chronic gut inflammation are greatly exacerbated by α-synuclein pathology. DNA methylation changes at ALP genes induced by synucleinopathy are associated with the ALP abnormalities observed in the appendix of individuals with PD specifically involving lysosomal genes. Our work identifies epigenetic dysregulation of the ALP which may suggest a potential mechanism for accumulation of α-synuclein pathology in idiopathic PD.
Although appendectomy may reduce colorectal inflammation in patients with ulcerative colitis (UC), this surgical procedure has been suggested to be associated with an increased risk of colitis-associated cancer (CAC). Our aim was to explore the mechanism underlying the appendectomy-associated increased risk of CAC.
Neuroendocrine neoplasms (NENs) are the most common tumor of the appendix and have an excellent prognosis. Appendiceal tumors diagnosed between 1989 and 2019 were reviewed, and clinical data were collected from patient files. Part of the series was immuno-profiled for markers related to cell cycle proliferation and/or senescence-type, apoptotic, and metastatic potential. Appendix NENs were detected in 74 patients, with 0.47% of incidence per appendectomy. The median age of the patients was 21.5 years, with two age peaks of incidence at 17.0 and 55.2 years. The median tumors size was 5.8 mm, and most were smaller than 10 mm. Lymphovascular and perineural invasion, as well as necrosis, was associated with larger tumor size. G1 tumors composed 96.0% of the cohort. The presence of moderate/strong p16 and the absent/low Bcl-2 expression was frequently observed and associated with a smaller size. This study represents one of the largest cohorts and with a long follow-up. For tumors smaller than 10 mm appendicectomy was sufficient as a curative procedure, as revealed by the good outcome. This series presented a 100% disease-free survival. The indolent phenotype of appendix NENs is supported by the expression of markers that point towards a strong inhibition of cell replication and growth inhibition.
The interstitial cells of Cajal (ICC) are located within and around the digestive tract's muscle layers. They function as intestinal muscle pacemakers and aid in the modification of enteric neurotransmission. The appendix's unique position requires an appropriate contraction pattern of its muscular wall to adequately evacuate its contents. We investigated the development and distribution of nervous structures and ICC in the human fetal appendix.
Molecular-targeted therapies have demonstrated disappointing results against most advanced solid cancers. This may largey be attributed to irrational drug use against unselected cancers. We investigated the efficacy of dual MEK-PI3K drug therapy against KRAS mutated mucin 2 (MUC2)-secreting LS174T cells and patient-derived ex vivo and in vivo models of KRAS mutated mucinous colon/appendix cancers. These tumors demonstrate unique phenotypic and genotypic features that likely predict sensitivity to this targeted co-therapy. Co-treatment with MEK inhibitor (trametinib) and PI3K inhibitor (pictilisib)-induced synergistic cytotoxicity and intrinsic mitochondrial-mediated apoptosis in LS174T cells and tumor explants in vitro. Dual drug therapy also induced endoplasmic reticulum stress (ERS)-associated proteins (GRP78/BiP, ATF4, and CHOP). However, CHOP knock-down assays demonstrated that mitochondrial-mediated apoptosis in LS174T cells was not ERS-dependent. Dual drug therapy also significantly decreased MUC2 expression, MUC2 post-translational modification (palmitoylation) and secretion in LS174T cells, suggesting a simultaneous cytotoxic and mucin suppressive mechanism of action. We also demonstrated effective mucinous tumor growth suppression in ex vivo epithelial organoid (colonoid) cultures and in in vivo intraperitoneal patient-derived xenograft models derived from mucinous colon/appendix cancer. These promising preclinical data support a role for dual MEK-PI3K inhibitor therapy in mucinous colon/appendix cancers. We postulate that mucinous KRAS mutated cancers are especially vulnerable to this co-treatment based on their unique phenotypic and genotypic characteristics.
Gut microbiota contributes to human health. Plenty of studies demonstrate that antibiotics can disrupt gut ecosystem leading to dysbiosis. Little is known about the microbial variation of appendix and its up/downstream intestine after antibiotic treatment. This study aimed to investigate the microbiome and mucosal morphology of jejunum, appendix, and colon of rats in health and dysbiosis. A rodent model of antibiotic-induced dysbiosis was employed. Microscopy was used to observe mucosal morphological changes. 16S rRNA sequencing was performed for identifying bacterial taxa and microbiome structure. The appendices of dysbiosis were found enlarged and inflated with loose contents. Microscopy revealed the impairment of intestinal epithelial cells. High-throughput sequencing showed the Operational Taxonomic Units changed from 361 ± 33, 634 ± 18, 639 ± 19 in the normal jejunum, appendix, colon to 748 ± 98, 230 ± 11, 253 ± 16 in the disordered segments, respectively. In dysbiosis, Bacteroidetes translocated inversely from the colon and appendix (0.26%, 0.23%) to the jejunum (13.87% ± 0.11%); the relative abundance of all intestinal Enterococcaceae increased, while Lactobacillaceae decreased. Several bacterial clusters were found correlated to the normal appendix, whereas nonspecific clusters correlated to the disordered appendix. In conclusion, species richness and evenness reduced in the disordered appendix and colon; similar microbiome patterns were shared between the appendix and colon regardless of dysbiosis; site-specific bacteria were missing in the disordered appendix. Appendix is likely a transit region involving in upper and lower intestinal microflora modulation. The limitation of this study is all the data were derived from rats. We must be cautious about translating the microbiome results from rats to humans.
The function of the appendix is largely unknown, but its microbiota likely contributes to function. Alterations in microbiota may contribute to appendicitis, but conventional culture studies have not yielded conclusive information. We conducted a pilot, culture-independent 16S rRNA-based microbiota study of paired appendix and rectal samples.
The common technique used in securing the base of the appendix is Endoloop ligature (Ethicon, Somerville, NJ, USA). Vicryl (polyglactin 910) (Ethicon) and polydioxanone (PDS) (Ethicon) Endoloop ligatures can be used. There are potential benefits of the use of PDS Plus (Ethicon) Endoloop ligature. However, the use of different materials may vary in terms of inflammation, foreign-body reaction, rate of infection in the surgical area, or rate of adhesion formation. An ideal suture would induce minimal inflammatory response and adhesion formation.
Diversification of the primary antibody repertoire occurs in young rabbit appendix. As a prelude to molecular investigation of whether human appendix has a similar role, we compared the lymphoid morphology and distribution of common B- and T-cell subsets in frozen and/or paraffin-embedded normal appendix specimens at various ages. IgA, IgM and IgG staining patterns were similar in frozen human and rabbit appendices. The elongated follicles of the young human and rabbit appendices regressed with age to resemble Peyer's patches. Although similar in morphology to the bursa, human and rabbit appendix follicles differ in that they do not involute completely with age and contain significant numbers of germinal center (GC) T cells although the number is low early in life. If the human appendix functions as a primary lymphoid organ, it may occur during the first few months of age when the GC T-cell density is low.
The appendix is the third most common place for neuroendocrine tumors (NETs) along the digestive tract and NETs are the most common neoplasms of the appendix. However, there are limited population-based data on the epidemiology of this disease. Using a large database, we sought to describe the epidemiology and risk association of NETs of the appendix.
Introduction and importance: More than 600 cases of De Garengeot's hernia, characterized by a femoral hernia containing the vermiform appendix, have been reported. The surgical method of choice has been an appendectomy and a primary hernia repair. Since the emergence of laparoscopy, this is undoubtedly an option. However, the treatment of the appendix remains in most reports as an appendectomy. Successful appendix-sparing treatment of De Garengeot's hernia via laparotomy or laparoscopy has been described, mainly since the COVID-19 pandemic. Case presentation: We report a new case of an 80-year-old woman with an incarcerated De Garengeot's appendiceal femoral-crural hernia, successfully treated entirely laparoscopically. She had noticed the protrusion of a lump in her right inguinal region for two months. Radiological studies, ultrasonography (US), and computed tomography (CT) were inconclusive. Due to the failure in the preoperative diagnosis, a minimally invasive endoscopic approach was performed. Although the distal appendix appeared incarcerated in the femoral ring, there was no evidence of appendicitis. Thus, a fully laparoscopic appendix-sparing transabdominal preperitoneal (TAPP) hernioplasty procedure was undertaken. The patient made an uninterrupted recovery. She did well postoperatively with no complications, left the hospital the same day in a stable condition, returned to complete activities, and has enjoyed good health since. Clinical Discussion: Our literature review shows that in selected cases an appendectomy may be safely avoided, eliminating appendectomy-associated morbidity, and could be considered the first-line alternative when expertise is available. Conclusion: A fully laparoscopic appendix-sparing TAPP approach seems safe and feasible to treat this entity.
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