Single-cell sequencing of the vermiform appendix during development identifies transcriptional relationships with appendicitis in preschool children.

BACKGROUND: The development of the human vermiform appendix at the cellular level, as well as its function, is not well understood. Appendicitis in preschool children, although uncommon, is associated with a high perforation rate and increased morbidity. METHODS: We performed single-cell RNA sequencing (scRNA-seq) on the human appendix during fetal and pediatric stages as well as preschool-age inflammatory appendices. Transcriptional features of each cell compartment were discussed in the developing appendix. Cellular interactions and differentiation trajectories were also investigated. We compared scRNA-seq profiles from preschool appendicitis to those of matched healthy controls to reveal disease-associated changes. Bulk transcriptomic data, immunohistochemistry, and real-time quantitative PCR were used to validate the findings. RESULTS: Our analysis identified 76 cell types in total and described the cellular atlas of the developing appendix. We discovered the potential role of the BMP signaling pathway in appendiceal epithelium development and identified HOXC8 and PITX2 as the specific regulons of appendix goblet cells. Higher pericyte coverage, endothelial angiogenesis, and goblet mucus scores together with lower epithelial and endothelial tight junction scores were found in the preschool appendix, which possibly contribute to the clinical features of preschool appendicitis. Preschool appendicitis scRNA-seq profiles revealed that the interleukin-17 signaling pathway may participate in the inflammation process. CONCLUSIONS: Our study provides new insights into the development of the appendix and deepens the understanding of appendicitis in preschool children.

Clinical Effectiveness of Preoperative 18F-FDG PET/CT in Predicting Pathological Tumor Grade in Patients with Pseudomyxoma Peritonei Originating from Appendix: A Retrospective Cohort Study.

BACKGROUND: Cytoreductive surgery combined with hyperthermic intraperitoneal chemotherapy is the standard treatment for patients with pseudomyxoma peritonei (PMP). In some malignancies, the standard uptake value of positron emission tomography with 2-deoxy-2-18F-fluoro-D-glucose integrated with computed tomography (18F-FDG PET/CT) is now accepted as a reliable indicator of neoplastic behavior. This study aimed to evaluate the association between the maximum standardized uptake value (SUVmax) and pathological grade in patients with PMP and to investigate the significance of SUVmax in the preoperative assessment of these patients. PATIENTS AND METHODS: In this retrospective single-center study, consecutively enrolled patients diagnosed with PMP of appendiceal origin underwent preoperative 18F-FDG PET/CT. SUVmax was calculated as the highest SUVmax value in the abdomen excluding the primary site. SUVmax was compared with the pathological grade (low or high grade) of PMP tumors according to the World Health Organization classification and further analyzed with respect to the estimated cutoff point, sensitivity, specificity, and receiver operating characteristic. RESULTS: In total, 160 patients were included. CRS was successfully performed in 93 patients and palliative debulking surgery in 67 patients. The pathological grade was high in 45 patients and low in 115. High-grade patients had a higher median SUVmax on 18F-FDG PET/CT than did low-grade patients (3.83 versus 2.34, p < 0.001). The highest area under the curve was 0.81, with a sensitivity of 77.8%, specificity of 72.3%, and cutoff point of 2.63. CONCLUSION: This study suggests that the SUVmax of preoperative 18F-FDG PET/CT is associated with the pathological grade in patients with PMP.

Sufficient Regional Lymph Node Examination for Staging Adenocarcinoma of the Appendix.

BACKGROUND: The presence of lymph node (LN) metastasis is a known negative prognostic factor in appendix cancer (AC) patients. However, currently the minimum number of LNs required to adequately determine LN negativity is extrapolated from colorectal studies and data specific to AC is lacking. We aimed to define the lowest number of LNs required to adequately stage AC and assess its impact on oncologic outcomes. METHODS: Patients with stage II-III AC from the National Cancer Database (NCDB 2004-2019) undergoing surgical resection with complete information about LN examination were included. Multivariable logistic regression assessed the odds of LN positive (LNP) disease for different numbers of LNs examined. Multivariable Cox regressions were performed by LN status subgroups, adjusted by prognostic factors, including grade, histologic subtype, surgical approach, and documented adjuvant systemic chemotherapy. RESULTS: Overall, 3,602 patients were included, from which 1,026 (28.5%) were LNP. Harvesting ten LNs was the minimum number required without decreased odds of LNP compared with the reference category (≥ 20 LNs). Total LNs examined were < 10 in 466 (12.9%) patients. Median follow-up from diagnosis was 75.4 months. Failing to evaluate at least ten LNs was an independent negative prognostic factor for overall survival (adjusted hazard ratio 1.39, p < 0.01). CONCLUSIONS: In appendix adenocarcinoma, examining a minimum of ten LNs was necessary to minimize the risk of missing LNP disease and was associated with improved overall survival rates. To mitigate the risk of misclassification, an adequate number of regional LNs must be assessed to determine LN status.

Predictive factors for recurrent acute appendicitis after conservative treatment.

INTRODUCTION: Conservative treatment of acute appendicitis is gaining popularity, and identifying patients with a higher risk of recurrence is becoming increasingly important. Previous studies have suggested that older age, male sex, diabetes, appendicolith and abscess formation may be contributing factors, however, results from the adult population are inconsistent. AIM: This study aims to identify predictive factors for recurrent appendicitis after conservative treatment. METHODS: This retrospective study included patients with conservatively treated acute appendicitis at Skåne University Hospital, Sweden during 2012-2019. Information on patient demographics at index admission and follow-up data were retrieved from medical charts and radiologic images. Uni -and multivariable logistic regression analysis were performed using Stata Statistical Software. RESULTS: In total, 379 patients with conservatively treated acute appendicitis were identified, of which 78 (20.6%) had recurrence. All patients were followed-up for a minimum of 41 months after the first diagnosis of acute appendicitis unless appendectomy after successful conservative treatment or death occurred during follow-up. The median time to recurrence was 6.5 (1-17.8) months. After multivariable logistic regression analysis, external appendix diameter >10 mm [OR 2.4 (CI 1.37-4.21), p = .002] and intra-abdominal abscess [OR 2.05 (CI 1.18-3.56), p = .011] on computed tomography were significant independent risk factors for recurrent appendicitis. Appendicolith was not associated with an increased risk of recurrence. CONCLUSION: This study suggests abscess formation and appendix distension of >10 mm to be potential risk factors for recurrent acute appendicitis after initial successful conservative treatment.

Predictive model for identification of gangrenous or perforated appendicitis in adults: a multicenter retrospective study.

BACKGROUND: Gangrene and perforation are severe complications of acute appendicitis, associated with a higher mortality rate compared to uncomplicated appendicitis. Accurate preoperative identification of Gangrenous or perforated appendicitis (GPA) is crucial for timely surgical intervention. METHODS: This retrospective multicenter study includes 796 patients who underwent appendectomy. Univariate and multivariate logistic regression analyses are used to develop a nomogram model for predicting GPA based on laboratory tests and computed tomography (CT) findings. The model is validated using an external dataset. RESULTS: Seven independent predictors were included in the nomogram: white blood cell count, lymphocyte count, D-dimer, serum glucose, albumin, maximum outer diameter of the appendix, and presence of appendiceal fecalith. The nomogram achieved good discrimination and calibration in both the training and testing sets. In the training set, the AUC was 0.806 (95%CI: 0.763-0.849), and the sensitivity and specificity were 82.1% and 66.9%, respectively. The Hosmer-Lemeshow test showed good calibration (P = 0.7378). In the testing set, the AUC was 0.799 (95%CI: 0.741-0.856), and the sensitivity and specificity were 70.5% and 75.3%, respectively. Decision curve analysis (DCA) confirmed the clinical utility of the nomogram. CONCLUSION: The laboratory test-CT nomogram model can effectively identify GPA patients, aiding in surgical decision-making and improving patient outcomes.

An FUO patient diagnosed as appendicitis: a case report.

BACKGROUND: The diagnosis and management of fever of unknown origin pose significant challenges in the field of infectious diseases, as it is influenced by various factors. Infectious diseases have long been recognized as the primary etiology of fever of unknown origin. However, not all infectious diseases can definitively identify the causative pathogen and infection sites. CASE PRESENTATION: we present a case report of an individual with fever, nausea, and anorexia but did not report any abdominal pain. Physical examination revealed no signs of abdominal tenderness. Repeated imaging studies including enhanced CT and color US of the appendix, only one color US suggested the possibility of appendicitis. Despite effective anti-infective treatment, the patient continued to experience low-grade fever, leading to the decision for laparoscopic exploration and subsequent appendectomy. Pathological findings confirmed the presence of appendicitis. After the surgical procedure, the patient's temperature and infectious markers returned to within normal range, ultimately leading to a diagnosis of appendicitis. CONCLUSIONS: The atypical symptoms and signs, along with the negative imaging results, contribute to the under diagnosis of appendicitis and the progression of fever of unknown origin, thereby exacerbating the physical, mental, and economic burden on patients. Consequently, there are valuable insights to be gained regarding the management of both appendicitis and fever of unknown origin.

Beyond a vestigial organ: effects of the appendix on gut microbiome and colorectal cancer.

The role of appendectomy in the pathogenesis of colorectal cancer (CRC) is a recent topic of contention. Given that appendectomy remains one of the most commonly performed operations and a first-line management strategy of acute appendicitis, it is inherently crucial to elucidate the association between prior appendectomy and subsequent development of CRC, as there may be long-term health repercussions. In this review, we summarize the data behind the relationship of CRC in post-appendectomy patients, discuss the role of the microbiome in relation to appendectomy and CRC pathogenesis, and provide an appraisal of our current understanding of the function of the appendix. We seek to piece together the current landscape surrounding the microbiome and immunological changes in the colon post-appendectomy and suggest a direction for future research involving molecular, transcriptomic, and immunologic analysis to complement our current understanding of the alterations in gut microbiome.

Significance of retrograde flow with antegrade continence enemas in children with fecal incontinence and constipation.

BACKGROUND: For children with constipation and fecal incontinence treated with antegrade continence enemas (ACE), a fluoroscopic study with contrast administered via appendicostomy/cecostomy can define the anatomy of the colon and simulate the flush to investigate associated symptoms or inadequate response. These studies can at times show retrograde flow into the small intestine. Our objective was to investigate the significance of this finding. METHODS: We reviewed studies at our institution with contrast administered via appendicostomy/cecostomy in children treated with ACE, identifying those demonstrating retrograde flow of contrast. We recorded demographics, medical history, interventions, and outcomes. RESULTS: We identified 162 studies (52% male, median age 10.7 years) with contrast via appendicostomy (76%) or cecostomy (24%). Diagnoses included anorectal malformation (38%), spinal cord anomaly (26%), functional constipation (24%), colonic dysmotility (18%), and Hirschsprung disease (12%). Fifty-nine (36%) studies showed retrograde flow: 28/59 children (48%) were not responding adequately and 21/59 (36%) had symptoms with ACE. Children with retrograde flow were more likely to have symptoms with ACE than those without (36% vs. 15%, p < 0.01). Fourteen children underwent interventions for this finding, including administering flushes more distally (4/8 responded), changing positioning of the child during flush administration, (1/2 responded), and slowing administration (1/1 responded). Retrograde flow was associated with younger age (p < 0.01), not sex or underlying diagnosis. CONCLUSION: Identifying retrograde flow during studies with contrast administered via appendicostomy/cecostomy can be useful for children with a poor response or symptoms associated with ACE, as adjustments to the mechanics of the flush can alleviate those symptoms. LEVEL OF EVIDENCE: Prognostic study, Level III.

The role of advanced endoscopy in appendiceal polyp management and outcomes.

BACKGROUND: Appendiceal orifice lesions are often managed operatively with limited or oncologic resections. The aim is to report the management of appendiceal orifice mucosal neoplasms using advanced endoscopic interventions. METHODS: Patients with appendiceal orifice mucosal neoplasms who underwent advanced endoscopic resections between 2011 and 2021 with either endoscopic mucosal resection (EMR), endoscopic mucosal dissection (ESD), hybrid ESD, or combined endoscopic laparoscopic surgery (CELS) were included from a prospectively collected dataset. Patient and lesion details and procedure outcomes are reported. RESULTS: Out of 1005 lesions resected with advanced endoscopic techniques, 41 patients (4%) underwent appendiceal orifice mucosal neoplasm resection, including 39% by hybrid ESD, 34% by ESD, 15% by EMR, and 12% by CELS. The median age was 65, and 54% were male. The median lesion size was 20 mm. The dissection was completed piecemeal in 49% of patients. Post-procedure, one patient had a complication within 30 days and was admitted with post-polypectomy abdominal pain treated with observation for 2 days with no intervention. Pathology revealed 49% sessile-serrated lesions, 24% tubular adenomas, and 15% tubulovillous adenomas. Patients were followed up for a median of 8 (0-48) months. One patient with a sessile-serrated lesion experienced a recurrence after EMR which was re-resected with EMR. CONCLUSION: Advanced endoscopic interventions for appendiceal orifice mucosal neoplasms can be performed with a low rate of complications and early recurrence. While conventionally lesions at the appendiceal orifice are often treated with surgical resection, advanced endoscopic interventions are an alternative approach with promising results which allow for cecal preservation.

Expression of Calretinin in the Cecal Muscularis Interna: Observation and Hypothetical Relevance to Appendicitis.

BACKGROUND: The unexpected observation of calretinin immunoreactivity in smooth muscle cells in the muscularis propria of the cecum led to a more detailed examination of calretinin expression and its possible relationship to propulsive contractile activity around the vermiform appendix. METHODS: Immunohistochemistry and RNA in situ hybridization were performed to analyze calretinin expression in intestinal samples from 33 patients at ages ranging from mid-gestation fetuses to adults, as well as in some potentially relevant animal models. Dual immunolabeling was done to compare calretinin localization with markers of smooth muscle and interstitial cells of Cajal. RESULTS: Calretinin expression was observed consistently in the innermost smooth muscle layers of the muscularis interna in the human cecum, appendiceal base, and proximal ascending colon, but not elsewhere in the intestinal tract. Calretinin-positive smooth muscle cells did not co-express markers located in adjacent interstitial cells of Cajal. Muscular calretinin immunoreactivity was not detected in the ceca of mice or macaques, species which lack appendices, nor in the rabbit cecum or appendix. CONCLUSIONS: Localized expression of calretinin in cecal smooth muscle cells may reduce the likelihood of retrograde, calcium-mediated propulsive contractions from the proximal colon and suppress pro-inflammatory fecal stasis in the appendix.

Occult appendix pathology in patients undergoing colorectal cancer resection and prophylactic appendectomy.

BACKGROUND: The risk-benefit balance of prophylactic appendectomy in patients undergoing left colorectal cancer resection is unclear. The aim of this report is to assess the proportion of histologically abnormal appendices in patients undergoing colorectal cancer resection in a unit where standard of care is appendectomy, with consent, when left-sided resection is performed. METHODS: A retrospective study on a prospectively collected database was conducted in a single tertiary-care center. Overall, 717 consecutive patients undergoing colorectal cancer resection between January 2015 and June 2021 were analyzed. The primary outcome was the proportion of histologically abnormal appendix specimens at prophylactic appendectomy. The secondary outcome was complications from prophylactic appendectomy. RESULTS: Overall, 576/717 (80%) patients had appendectomy at colorectal cancer surgery. In total, 234/576 (41%) had a right-/extended-right hemicolectomy or subtotal colectomy which incorporates appendectomy, and 342/576 (59%) had left-sided resection (left-hemicolectomy, anterior resection or abdominoperineal excision) with prophylactic appendectomy. At definitive histology, 534/576 (92.7%) had a normal appendix. The remaining 42/576 (7.3%) showed abnormal findings, including: 14/576 (2.4%) inflammatory appendix pathology, 2/576 (0.3%) endometriosis, 8/576 (1.4%) hyperplastic polyp, and 18/576 (3.1%) appendix tumors, which encompassed six low-grade appendiceal mucinous neoplasms (LAMNs), three carcinoids, and nine serrated polyps. In the 342 patients who had prophylactic appendectomy, 10 (2.9%) had a neoplasm (two LAMN, three carcinoids, and five serrated polyps). There were no complications attributable to appendectomy. CONCLUSION: Occult appendix pathology in patients undergoing colorectal cancer resection is uncommon when prophylactic appendectomy was performed. However, approximately 3% of patients had a synchronous appendix neoplasm.

Diagnostic Accuracy of Ileocolic Artery and Vein Diameter for Acute Appendicitis.

BACKGROUND Regional inflammation-induced local vasodilation may exist in cases of appendicitis. In this study, the diameters of the ileocolic artery (ICA) and ileocolic vein (ICV) were measured using contrast-enhanced abdominal computed tomography (CT) scans in acute appendicitis cases. The study aimed to measure the diagnostic value of these measurements in the diagnosis of acute appendicitis. MATERIAL AND METHODS A total of 508 patients, including those with a diagnosis of acute appendicitis and a control group without appendicitis, were systematically evaluated. In all cases, the appendix was analyzed simultaneously on axial and coronal CT sections, and all measurement procedures were conducted with an electronic ruler after the actual images were magnified. Measurements of the ICA and ICV diameters were taken from the proximal 2-cm segments of the superior mesenteric artery and superior mesenteric vein in the axial plane. Demographic information, sex distribution, and ICA and ICV diameters were collected. RESULTS Of the 508 patients, 53.74% were men, and 46.26% were women. ICA and ICV diameters were significantly increased in the appendicitis group (P<0.001). Binomial logistic regression confirmed the independent predictive value of ICA and ICV diameters. Receiver operating characteristic curve analysis determined optimal cut-off values for distinguishing between the non-appendicitis and appendicitis groups (ICA: 2.475 mm, ICV: 3.885 mm) with high sensitivity and specificity. CONCLUSIONS ICA and ICV diameter measurements, in conjunction with major radiological findings, can enhance diagnostic accuracy in acute appendicitis cases. The use of ICA and ICV diameter measurements in diagnosing acute appendicitis offers a novel perspective in clinical practice.

A practical guide to serrated appendiceal lesions.

Several neoplastic and non-neoplastic proliferations of the appendix can show varying degrees of serrated epithelial architecture. Of these, diffuse mucosal hyperplasia is most common, followed in frequency by low-grade mucinous and serrated neoplasms. It is important to distinguish serrated appendiceal neoplasms from their potential mimics because these entities may be managed differently. Diffuse mucosal hyperplasia is a non-neoplastic change that usually develops in the setting of resolving appendicitis and requires no further therapy or surveillance, and serrated neoplasms confined to the mucosa are adequately treated by appendectomy alone. On the other hand, low-grade appendiceal mucinous neoplasms may require surveillance, and those with extra-appendiceal spread differ from adenocarcinomas arising from serrated neoplasms with respect to both treatment and prognosis. Low-grade mucinous neoplasms in the peritoneum are frequently amenable to peritoneum-directed therapies alone, while adenocarcinomas derived from serrated neoplasms often spread to both regional lymph nodes and the peritoneum, potentially requiring right colectomy and systemic chemotherapy. The purpose of this review is to summarize the literature regarding the clinical and pathologic features of appendiceal lesions that show epithelial serration and provide the reader with helpful tips to distinguish serrated neoplasms from their mimics.

Well-differentiated neuroendocrine tumors of the appendix: Diagnosis, differentials, and disease progression.

Well-differentiated neuroendocrine tumors are the most common neoplasm of the appendix. They are graded and staged using World Health Organization and American Joint Committee on Cancer criteria, respectively. They may be invisible grossly or form rounded yellow nodules, sometimes in the appendiceal tip. They show classic neuroendocrine tumor features microscopically, forming nests and cords of monotonous cells with salt-and-pepper chromatin and amphophilic cytoplasm. They are positive for neuroendocrine markers by immunohistochemistry, but their molecular characteristics are not well defined. pT-category staging relies primarily on tumor size, though higher-stage cases may involve the subserosa or mesoappendix. Few entities enter the differential diagnosis, but lesions such as goblet cell adenocarcinoma, poorly differentiated neuroendocrine carcinoma, and mixed neuroendocrine-non-neuroendocrine neoplasm may be considered. Appendiceal neuroendocrine tumors may metastasize to regional lymph nodes, but farther spread is rare. The most consistently proven risk factor for such spread is tumor size, though different studies have proposed different cutoffs. Other potential risk factors include lymphovascular invasion and margin positivity. Tumors smaller than 1 cm can be treated by appendectomy, while hemicolectomy is recommended for tumors larger than 2 cm. Proper treatment for cases measuring 1-2 cm remains a matter of debate.

Endometriosis of the appendix: prevalence, associated lesions, and proposal of pathogenetic hypotheses. A retrospective cohort study with prospectively collected data.

OBJECTIVE: To assess the prevalence of endometriosis of the appendix and the association with other pelvic localizations of the disease and to provide pathogenesis hypotheses. METHODS: Monocentric, observational, retrospective, cohort study. Patients undergoing laparoscopic endometriosis surgery in our tertiary referral center were consecutively enrolled. The prevalence of the different localizations of pelvic endometriosis including appendix involvement detected during surgery was collected. Included patients were divided into two groups based on the presence of appendiceal endometriosis. Women with a history of appendectomy were excluded. MEASUREMENTS AND MAIN RESULTS: Four hundred-sixty patients were included for data analysis. The prevalence of appendiceal endometriosis was 2.8%. In patients affected by endometriosis of the appendix, concomitant ovarian and/or bladder endometriosis were more frequently encountered, with prevalence of 53.9% (vs 21.0% in non-appendiceal endometriosis group, p = 0.005) and 38.4% (vs 11.4%, p = 0.003), respectively. Isolated ovarian endometriosis was significantly associated to appendiceal disease compared to isolated uterosacral ligament (USL) endometriosis or USL and ovarian endometriosis combined (46.2% vs 15.4% vs 7.7%, p < 0.001). Poisson regression analysis revealed a 4.1-fold and 4.4-fold higher risk of ovarian and bladder endometriosis, respectively, and a 0.1-fold risk of concomitant USL endometriosis in patients with appendiceal involvement. CONCLUSION: Involvement of the appendix is not uncommon among patients undergoing endometriosis surgery. Significant association was detected between appendiceal, ovarian, and bladder endometriosis that may be explained by disease dissemination coming from endometrioma fluid shedding. Given the prevalence of appendiceal involvement, counseling regarding the potential need for appendectomy during endometriosis surgery should be considered.

Robotic-assisted laparoscopic modified ureteroplasty using lingual mucosa grafts or appendiceal flaps for the management of complex ureteral strictures: a retrospective cohort study.

OBJECTIVE: To evaluate the feasibility, safety and efficacy of robot-assisted laparoscopic modified ureteroplasty using a lingual mucosa graft (LMG) or an appendiceal flap (AF) for complex ureteral strictures and summarize our experience. METHODS: A total of 16 patients with complex ureteral strictures (range: 1.5-5 cm) who underwent robotic-assisted laparoscopic-modified ureteroplasty and were admitted to our hospital from May 2022-October 2023 were retrospectively analyzed. We used modified presuture methods in patients who needed the posteriorly augmented anastomotic technique to reduce anastomotic tension. Perioperative variables and outcomes were recorded for each patient. RESULTS: The operation under robot-assisted laparoscopy was successfully performed in all sixteen patients (12 with LMG ureteroplasty and 4 with AF ureteroplasty) without conversion to open surgery. The mean length of the ureteral structure was 2.90 ± 0.90 cm (range: 1.5-5 cm), the mean operation duration was 209.69 ± 26.74 min (range: 170-255 min), the median estimated blood loss was 75 (62.5) ml (range: 50-200 ml), and the duration of postoperative hospitalization was 10.44 ± 2.10 d (range: 7-14 d). The follow-up time in this group was 6 ~ 21 months. The success rate of the surgery was 100%. CONCLUSION: Robot-assisted laparoscopic modified ureteroplasty using AF or LMG is a safe and feasible operation for complex ureteral strictures and deserves to be popularized.

The Association Between C-Reactive Protein Levels and Pediatric Appendicitis Score and the Severity of Appendicitis in Children.

BACKGROUND: Acute appendicitis is a common cause of abdominal pain leading to emergent abdominal surgery in children. C-reactive protein (CRP), an inflammatory marker typically elevated in acute appendicitis, and Pediatric Appendicitis Score (PAS), a clinical scoring system used for the diagnosis of appendicitis, have the potential to predict the severity of inflammation of the appendix. This may be useful in helping the physician make a treatment plan prior to surgery. OBJECTIVE: The purpose of this study was to assess whether CRP value and PAS differ with the extent of inflammation of the appendix seen on histologic examination. METHODS: This was a prospective observational study of patients diagnosed with acute appendicitis via computed tomography or ultrasound. Enrolled patients had CRP levels drawn, PAS calculated, and appendix pathology reviewed. Appendix pathology was categorized by the pathologist on the basis of the level of inflammation: simple, suppurative, gangrenous, and perforated. RESULTS: One hundred sixty-three patients were enrolled. CRP levels and PAS were statistically different (p < 0.002) among the four pathology classifications. Patients with simple appendicitis (n = 3) had a mean CRP of 2.95 mg/L and PAS of 3.9, patients with suppurative appendicitis (n = 99) had a mean CRP of 26.89 mg/L and PAS of 6.5, patients with gangrenous appendicitis (n = 56) had a mean CRP of 91.11 mg/L and PAS of 7.5, and patients with perforated appendicitis (n = 6) had a mean CRP of 154.17 mg/L and PAS of 7. The results remained statistically significant (p < 0.002) after adjusting for age, race, and sex. When combined-PAS ≥ 8 and CRP level > 40 mg/L-the specificity of complicated appendicitis was 91.2% and positive predictive value was 72.7%. CONCLUSIONS: Higher CRP levels and PAS were associated with increased histologic inflammation of the appendix. This study provides preliminary evidence that CRP and PAS could potentially assist in treatment decisions for appendicitis.

Predictive values of indirect ultrasound signs for low risk of acute appendicitis in paediatric patients without visualisation of the appendix on ultrasound.

BACKGROUND AND OBJECTIVES: The ability to rule appendicitis in or out using ultrasound is limited by studies where the appendix is not visualised. We determined whether the absence of indirect ultrasound signs can rule out appendicitis in children undergoing a radiology-performed ultrasound in which the appendix is not visualised METHODS: This was a single-centre retrospective observational study of patients aged 3-13 with a clinical suspicion of acute appendicitis evaluated in a Paediatric Emergency Department in Spain from 1 January 2013 to 31 December 2019. For those patients who had formal ultrasound, direct and indirect findings of ultrasound were abstracted from the ultrasound report. The surgical pathology report was established as the gold standard in patients who underwent an appendectomy. In those who did not, appendicitis was considered not to be present if there was no evidence in their charts that they had undergone an appendectomy or conservative therapy for appendicitis during the episode. The main outcome variable was the diagnosis of acute appendicitis. For patients undergoing ultrasound, the independent association of each indirect ultrasound sign with the diagnosis of appendicitis in patients without a visualised appendix was analysed using logistic regression. RESULTS: We included 1756 encounters from 1609 different episodes. Median age at the first visit of each episode was 10.1 years (IQR, 7.7-11.9) and 921 (57.2%) patients were men. There were 730 (41.6%) encounters with an Alvarado score ≤3, 695 (39.6%) with a score 4-6 and 331 (18.9%) with a score ≥7. Appendicitis was diagnosed in 293 (17.8%) episodes. Ultrasonography was performed in 1115 (61.6%) encounters, with a visualised appendix in 592 (53.1%).The ultrasound findings independently associated with appendicitis in patients without a visualised appendix were the presence of free intra-abdominal fluid in a small quantity (OR:5.0 (95% CI 1.7 to 14.6)) or in an abundant quantity (OR:30.9 (95% CI 3.8 to 252.7)) and inflammation of the peri-appendiceal fat (OR:7.2 (95% CI 1.4 to 38.0)). The absence of free fluid and inflammation of the peri-appendiceal fat ruled out acute appendicitis in patients with an Alvarado score <7 with a sensitivity of 84.6% (95% CI 57.8 to 95.7) and a negative predictive value of 99.4% (95% CI 97.8 to 99.8). CONCLUSIONS: Patients with an Alvarado score <7 and without a visualised appendix on ultrasound but who lack free fluid and inflammation of the peri-appendiceal fat are at very low risk of acute appendicitis.

Is Being Overweight a Risk Factor for Torsion of the Appendix Testis in Children?: A Paired Case-Control Study.

OBJECTIVE: This study aimed to determine whether being overweight during childhood is a risk factor for torsion of the appendix testis (TAT). METHODS: We conducted a paired case-control study with all boys surgically treated for TAT, paired by age and sex with patients who were seen in the emergency department for a reason other than acute scrotum. Age and weight were registered, and weight percentile (WP) by age was calculated and compared between groups. Weight percentile was classified into 4 groups (<25, 25-50, 50-75, >75), and a conditional logistic regression analysis was performed to establish the risk of TAT related to the WP. RESULTS: A total of 980 patients were diagnosed as having TAT in our institution, of which 118 patients (12%) were surgically treated and randomly paired with 118 controls. Mean age was the same in both groups (11.2 years, P = 0.908). Patients with TAT had a higher median of WP (79; interquartile range, 49-94) than the control group (49; interquartile range, 20-79; P < 0.0001). For each WP point increase, risk of TAT raised by 2.2% (odds ratio [OR], 1.022; 95% confidence interval [CI], 1.011-1.032; P < 0.001). Weight percentile >75 increased the risk of TAT: 6-fold compared with WP <25 (OR, 5.9; 95% CI, 2.5-14; P < 0.001), 4-fold compared with WP of 25 to 50 (OR, 4.3; 95% CI, 1.8-10.5; P = 0.001), and 3-fold compared with WP of 50 to 75 (OR, 3.3; 95% CI, 1.5-7.6; P = 0.004). CONCLUSIONS: Overweight increases the risk of being operated on because of TAT. Because obesity is a rising problem, a greater incidence of TAT remains to be proved.

Diagnostic performance of spectral Doppler in acute appendicitis with an equivocal Alvarado score.

PURPOSE: This study aims to evaluate the added value of duplex Doppler examination to the routinely graded compression grayscale ultrasound (US) for patients with suspected acute appendicitis (AA) in correlation with surgical management outcomes. METHODS: The study lasted from January 2020 to March 2021. Throughout that period, patients who had suspected appendicitis were included with a visible appendix in the grayscale US. These patients were categorized clinically based on Alvarado's score. They underwent graded compression grayscale US of the appendix and duplex Doppler study. Subsequently, they were assigned for non-contrast multislice computed tomography (MSCT) according to Alvarado's score and underwent either emergency appendicectomy or conservative clinical management afterward. A Student's t-test was used to determine if there were significant differences in the mean values between the groups. The diagnostic performance of spectral Doppler US for the diagnosis of AA was depicted. RESULTS: Eighty-four patients with visualized color flow in the appendicular Doppler US were enrolled, with 60 (71.4%) having AA, and 24 (28.6%) not having appendicitis. Spectral Doppler criterion of PSV greater than 8.6 cm/s demonstrated a high sensitivity of 91.67% and specificity of 77.78% for patients with Alvarado score ranging from 4 to 7, and appendiceal MOD ranging from 6 to 8 mm, while a discriminatory criterion of RI greater than 0.51 had a high sensitivity of 100% and a relatively lower specificity of 66.67%. CONCLUSION: The patients with AA have significantly higher point PSV and point RI values than those without AA and are especially useful in equivocal patients whose MODs and Alvarado scores are in the diagnostically equivocal ranges of 6-8 mm and 4-7, respectively, with the point PSV and RI demonstrating negative predictive value 87.5% and 100%.