Pathologic Analysis of Twenty-one Appendices From Children With Multisystem Inflammatory Syndrome Compared to Specimens of Acute Appendicitis: A Cross-sectional Study.

BACKGROUND: Multisystem inflammatory syndrome in children (MIS-C) is a rare, severe complication of coronavirus disease 2019, commonly involving the gastrointestinal tract. Some children with MIS-C undergo appendectomy before the final diagnosis. There are several hypotheses explaining the pathomechanism of MIS-C, including the central role of the viral antigen persistence in the gut, associated with lymphocyte exhaustion. We aimed to examine appendectomy specimens from MIS-C patients and assess their pathologic features, as well as the presence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antigens. METHODS: In this cross-sectional study we included 21 children with MIS-C who underwent appendectomy. The control group included 21 sex- and age-matched children with acute appendicitis (AA) unrelated to SARS-CoV-2 infection. Histologic evaluation of appendiceal specimens included hematoxylin and eosin staining and immunohistochemical identification of lymphocyte subpopulations, programmed cell death protein-1 (PD-1) and SARS-CoV-2 nucleocapsid antigen. RESULTS: Appendices of MIS-C patients lacked neutrophilic infiltrate of muscularis propria typical for AA (14% vs. 95%, P < 0.001). The proportion of CD20+ to CD5+ cells was higher in patients with MIS-C (P = 0.04), as was the proportion of CD4+ to CD8+ (P < 0.001). We found no proof of SARS-CoV-2 antigen presence, nor lymphocyte exhaustion, in the appendices of MIS-C patients. CONCLUSIONS: The appendiceal muscularis of patients with MIS-C lack edema and neutrophilic infiltration typical for AA. SARS-CoV-2 antigens and PD-1 are absent in the appendices of children with MIS-C. These findings argue against the central role of SARS-CoV-2 persistence in the gut and lymphocyte exhaustion as the major triggers of MIS-C.

Pathological Assessment of the Appendix in Appendectomies Performed in Children.

BACKGROUND: Acute appendicitis is known as the most common diagnosis of acute abdomen leading to surgery. Therefore, timely diagnosis is of special importance. This study was conducted with the aim of pathological assessment of the appendix in appendectomies performed in children to determine the rate of negative appendectomies and the predictors of negative appendectomy and to evaluate the paraclinical tools used in the diagnosis of acute appendicitis. METHODS: This is a cross-sectional descriptive study. All children who underwent appendectomy at Shahid Motahari Hospital in Urmia from March 2021 to March 2022 were examined. The required data including demographic, paraclinical, and final pathology characteristics were collected and recorded. The investigated cases were classified into positive and negative appendectomy categories for comparison. RESULTS: Among 234 pathology samples of the appendix, 22 cases were related to accidental appendectomy. In addition, 11.3% of cases were negative appendectomy and 88.7% were positive appendectomy. The age range of 8 to 14 years and male gender were associated with a lower negative appendectomy rate (both P<0.001). Inflammatory (49.5%) and gangrenous appendicitis (30.2%) were the most commonly reported histopathologies. Sonography had a sensitivity of 84%, a specificity of 79%, and an overall diagnostic accuracy of 83%. CONCLUSION: A relatively significant number of accidental and negative appendectomies are performed. More careful investigation and the use of expectant and medical treatment instead of surgery, especially in females and young children, can be effective in improving diagnostic accuracy and preventing negative appendectomies.

Nodular image in the appendix observed on ultrasound: endometriosis or neuroendocrine neoplasia?

Objective: To evaluate the association between clinical and imaging with surgical and pathological findings in patients with suspected neuroendocrine tumor of appendix and/or appendix endometriosis. Methods: Retrospective descriptive study conducted at the Teaching and Research Institute of Hospital Israelita Albert Einstein, in which medical records and databases of patients with suspected neuroendocrine tumor of appendix and/or endometriosis of appendix were analyzed by imaging. Results: Twenty-eight patients were included, all of which had some type of appendix alteration on the ultrasound examination. The pathological outcome of the appendix found 25 (89.3%) lesions compatible with endometriosis and three (10.7%) neuroendocrine tumors. The clinical findings of imaging and surgery were compared with the result of pathological anatomy by means of relative frequency. Conclusion: It was possible to observe a higher prevalence of appendix endometriosis when the patient presented more intense pain symptoms. The image observed on ultrasound obtained a high positive predictive value for appendicular endometriosis.

Ultrasound Assessment in Children With Suspected Appendicitis: Time to Revise Diagnostic Criteria: A Prospective Cohort Study.

Background: Although ultrasound is considered the gold standard for the evaluation of children with suspected appendicitis, there is still much debate about the most accurate ultrasound findings. The purpose of this study was to define the best ultrasound signs that could ultimately improve the diagnostic accuracy of ultrasound for diagnosing pediatric acute appendicitis, and to differentiate between simple appendicitis and complicated appendicitis. Patients and Methods: After approval by our Institutional Review Board, a prospective study was carried out from January 1, 2022, to July 31, 2023, in a pediatric emergency department. We included all patients aged under 14 years with suspected appendicitis and ultrasound-visualized appendix. Results: A total of 550 patients presented with suspected appendicitis during the study period. Of these children, 411 had an ultrasound-visualized appendix. Our patients' mean age was 9.4 years. The best positive predictive value of ultrasound was found for appendiceal diameter ≥7.5 mm. The combination of an appendiceal diameter <6 mm and the lack of peri-appendiceal free fluid on ultrasound rules out the diagnosis of appendicitis. The best diagnostic accuracy of ultrasound, which was 92%, was achieved for appendix diameters ≥6.5 mm. The sonographic sign giving the best ultrasound accuracy for diagnosing complicated appendicitis was an appendix diameter ≥9 mm. Conclusions: In conclusion, our present study demonstrated that appendiceal diameter ≥6.5 mm is the gold standard for diagnosing appendicitis in pediatric patients. The combination of an appendiceal diameter <6 mm and the lack of peri-appendiceal free fluid on ultrasound would rule out appendicitis.

The microbiome of the appendix differs in patients with and without appendicitis: A prospective cohort study.

BACKGROUND: Appendicitis seems to be a disease of infectious origin, but the detailed pathogenesis is unknown. We aimed to investigate the microbiome of the appendix lumen in patients with and without appendicitis, including a comparison of the subgroups of complicated versus uncomplicated appendicitis. METHODS: This prospective observational cohort study included adult patients undergoing laparoscopic appendectomy for suspected appendicitis. According to histopathologic findings, the investigated groups consisted of patients with and without appendicitis, including subgroups of complicated versus uncomplicated appendicitis based on the surgical report. A swab of the appendix lumen was analyzed for genetic material from bacteria with shotgun metagenomics, and outcomes included analyses of microbiome diversity and differential abundance of bacteria. RESULTS: A total of 53 swabs from patients with suspected appendicitis were analyzed: 42 with appendicitis (16 complicated) and 11 without appendicitis. When comparing patients with and without appendicitis, they were equally rich in bacteria (alpha diversity), but the microbiome composition was dissimilar between these groups (beta diversity) (P < .01). No consistent bacterial species were detected in all patients with appendicitis, but a least 3 genera (Blautia, Faecalibacterium, and Fusicatenibacter) and 2 species, Blautia faecis and Blautia wexlerae, were more abundant in patients without appendicitis. For the subgroups complicated versus uncomplicated appendicitis, both measures for microbiome diversity were similar. CONCLUSION: The appendix microbiome composition of genetic material from bacteria in adult patients with and without appendicitis differed, but the microbiome was similar for patients with complicated versus uncomplicated appendicitis. Trial registration NCT03349814.

Acute diverticulitis of the appendix.

Acute diverticulitis of the appendix (ADA), though uncommon, often presents similarly to acute appendicitis but carries a higher risk of complications such as perforation and malignancy. We report the case of a male patient in his 50s with acute right iliac fossa abdominal pain, diagnosed via CT scan with ADA. Urgent laparoscopic appendicectomy was performed, and the patient was discharged without further issues. This case highlights the importance of promptly identifying and managing such conditions to minimise complications and improve outcomes. Despite the overlap in symptoms between appendiceal diverticulitis and acute appendicitis, accurate diagnosis is crucial for appropriate treatment. Healthcare providers should maintain a high index of suspicion, particularly in older patients presenting with an acute appendicitis, like clinical picture to ensure timely intervention and optimal patient care.

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.

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.

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.

Nonneoplastic pathology of the appendix: A review article, based on the recent literature.

OBJECTIVES: The appendix, although considered a vestigial organ, is of considerable clinical importance because acute appendicitis is a common medical problem. There are also other disease processes involving the appendix. The appendix is among the first specimens that the pathologist (and surgeon) cuts one's teeth on. Thus, there may be a tendency to underestimate the clinically and prognostically significant appendiceal pathologies. METHODS: We provide a vade mecum of the pathologic features of a wide range of nonneoplastic appendiceal pathologies, with an emphasis on developing a practical approach to grossing, microscopy, and reporting-all with clinical and therapeutic implications. Much of this is based on literature on MEDLINE with reference to years 2008 to 2023, as well as on personal experiences and interpretations. RESULTS: The appendix can harbor a myriad of nonneoplastic pathologies, including infections, inflammations of varying etiologies (including interval appendectomy), endometriosis, diverticulosis, and so on. Chronic appendicitis, Crohn disease, and clinical audit are recurring themes while COVID-19 is a new entity. CONCLUSIONS: Most importantly, all pathologists should appreciate that the appendix is not as "routine" a specimen as one would want to believe.

Transverse colon diverticulitis mimicking acute appendicitis.

Diverticulitis in a solitary transverse colon diverticulum is uncommon, with only a handful of cases documented in the literature. There are various clinical manifestations of the disease, which make clinical and radiological diagnosis rather challenging. Herein, we present a case of a premenopausal female patient in her late 40s who presented to the emergency department, complaining of right lower quadrant abdominal pain, nausea, anorexia and fever. Following clinical, biochemical and radiological tests, the patient was prepared for surgical operation, with the presumed diagnosis of acute appendicitis. An appendicectomy was planned via a McBurney incision. Notably, no inflammation of the appendix was discovered. However, on further exploration, an inflammatory mass was identified in the transverse colon, which was subsequently excised and sent for histological examination. The histology results confirmed the presence of a ruptured solitary transverse colon diverticulum, accompanied by an adjacent mesenteric abscess. The patient's postoperative recovery was uneventful.

'It's just a mucocele': a case report of a massive appendiceal mucocele presenting as a left upper quadrant mass.

Tumours of the appendix are very rare tumours that can and often present with a mucocele. This is a case report highlighting the associated pathology of appendix tumours and the management of a large mucocele. Specifically, how a right hemicolectomy is very rarely needed in these cases regardless of size and local anatomical relationships and some important considerations for the practicing surgeon in the non-tertiary centre that encounters a case like this.

Predictive Factors of Acute Appendicitis in Children With Non-Visualized Appendix on Ultrasound: A Prospective Cohort Study.

Background: Most studies have demonstrated the high accuracy of ultrasound for the diagnosis of acute appendicitis (AA) in children. However, the lack of visualization of the appendix on ultrasound is usually a challenge. The aim of this study was to identify any factors that might help the physician make the right decision when dealing with a child with suspected appendicitis and an appendix not seen on ultrasound. Patients and Methods: After receiving Institutional Review Board approval, we conducted a prospective study in a pediatric emergency department from January 1, 2022, to December 31, 2022. All children under 14 years of age with suspected AA and an appendix not visualized on ultrasound were included. Results: During the study period, 333 children presented with suspected AA. Of these patients, 106 had an appendix not seen on ultrasound. Our patients' median age was 10 years (interquartile range [IQR], 8-11 years), with 54.7% (n = 58) of children being female. Twenty-five (23.6%) were ultimately diagnosed with AA based on pathologic examination. Multivariable logistic regression analysis revealed that Alvarado score ≥6 and increased peri-appendiceal fat echogenicity were predictive for AA. The combination of these two factors provided a positive predictive value of 100%. A white blood cell (WBC) count ≤10 × 109/L and/or a C-reactive protein (CRP) level ≤6 mg/L makes the diagnosis of appendicitis unlikely. Conclusions: In conclusion, our study demonstrated that an Alvarado score at or above six and increased peri-appendiceal fat echogenicity are independent predictive factors of AA in children with non-visualized appendix on ultrasound. The combination of these two factors would confirm the diagnosis of AA in these patients.

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.

Negative appendectomy rate in the pediatric population: can we reach near-zero rates? An observational study.

INTRODUCTION: Correct diagnosis of acute appendicitis may sometimes be challenging. The Negative appendectomy rate (NAR) has declined in the recent years in Europe and USA, in part due to better diagnostic imaging tools. The aim of this study was to examine the rates of negative appendectomy in our institution, investigate trends in its incidence, and identify possible predicting factors. METHODS: A retrospective cohort study, including all patients younger than 18 years of age who underwent an appendectomy between 2007 and 2021 in a single tertiary medical center. Data regarding patient's demographics, laboratory and imaging results, pathological results and clinical outcome were collected. RESULTS: Between 2007 and 2021, a total of 3937 pediatric patients underwent appendectomy due to a working diagnosis of acute appendicitis. Overall, 143 patients (3.6%) had normal appendix on pathological examination. However, in the last 5 years, the rate of normal appendix was 1.9%, together with an increased rate of pre-operative imaging (from 40% to nearly 100%). CONCLUSION: Low NAR under 2% is an achievable benchmark in the era of accessible pre-operative imaging. In unequivocal cases, a secondary survey that includes repeated physical examination, blood work and imaging is recommended and may result in near-zero rates of NAR.

Neurogenic appendicopathy: A rare differential diagnosis of acute appendicitis.

AIM OF THE STUDY: In histologically non-inflamed but clinically suspect appendices, changes described as neurogenic appendicopathy with fibrous or fibrolipomatous obliterations can be observed. The purpose of this study was to analyse the incidence of these entities of the appendix in a longitudinal patient cohort. PATIENTS AND METHODS: This is a retrospective single-centre study of 457 patients undergoing laparoscopic appendectomy from 2017 to 2020 due to suspected acute appendicitis. RESULTS: In 72 patients (15.8%) with clinically suspected acute appendicitis, the appendix showed no distinct signs of acute inflammation during the procedure. In 43 patients, histological analysis revealed neurogenic appendicopathy or fibrous and fibrolipomatous obliteration. Female gender (P=0.088), younger age (P<0.0001), longer pain duration (P<0.0001) and repetitive pain episodes were more frequent in these patients than in those with acute appendicitis. Inflammation markers were also decreased in the group of patients with neurogenic appendicopathy (leukocytes 9.8±3.5 vs. 13.0±4.5 G/L and C-reactive protein 38.7±60.7 vs. 59.4±70.5mg/L). CONCLUSION: Neurogenic appendicopathy with fibrous/fibrolipomatous obliteration is a differential diagnosis of acute appendicitis that can only be confirmed by pathology. Female gender, young age, prolonged duration with repetitive episodes of pain, and relatively low inflammatory markers are evocative of this diagnosis.

Intraoperative predictors of appendiceal abnormalities in patients with mucinous ovarian neoplasms.

OBJECTIVE: To evaluate intraoperative factors predicting appendiceal pathology during gynecologic oncology surgery for suspected mucinous ovarian neoplasms. METHODS: We conducted a retrospective study on 225 patients with mucinous ovarian neoplasms who underwent surgery for an adnexal mass with concurrent appendectomy between 2000 and 2018. Regression analyses were used to evaluate intraoperative factors, such as frozen section of the ovarian mass and surgeon's impression of the appendix in predicting appendiceal pathology. RESULTS: Most patients (77.8%) had a normal appendix on final pathology. Abnormal appendix cases (n = 26) included: metastasis from high-grade adenocarcinoma of the ovary (n = 1), neuroendocrine tumor of the appendix (n = 4), and low-grade appendiceal mucinous neoplasms (n = 26; 23 associated with a mucinous ovarian adenocarcinoma, 2 with a benign mucinous ovarian cystadenoma, and 1 with a borderline mucinous ovarian tumor). Combining normal intraoperative appearance of the appendix with benign or borderline frozen section yielded a negative predictive value of 85.1%, with 14.9% of patients being misclassified, and 6.0% having a neuroendocrine tumor or low-grade appendiceal neoplasm. CONCLUSION: Benign or borderline frozen section of an ovarian mucinous neoplasm and normal appearing appendix have limited predictive value for appendiceal pathology. Appendectomy with removal of the mesoappendix should be considered in all cases of mucinous ovarian neoplasm, regardless of intraoperative findings.

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.