Risk factors for appendiceal neoplasm and malignancy among patients with acute appendicitis.

PURPOSE: Non-operative management of acute uncomplicated appendicitis has shown promising results but might carry the risk of delayed diagnosis of premalignant or malignant appendiceal tumors found by chance in 0.7-2.5% of appendiceal specimen after appendectomy. Purpose of this study was to analyze whether appendiceal tumors are associated with a complicated appendicitis and to determine risk factors for appendiceal neoplasm and malignancy in patients with acute appendicitis. METHODS: We performed a retrospective analysis of 1033 adult patients, who underwent appendectomy for acute appendicitis from 2010 to 2016 at the University hospital Erlangen. Data included patients' demographics; comorbidities; pre-, intra- and postoperative findings; and histopathological results. Complicated appendicitis was defined in the presence of perforation or abscess. RESULTS: Appendiceal neoplasm respectively malignancy rate was 2.8% respectively 1.5%. Using univariate analysis, we identified seven risk factors at least for appendiceal neoplasm or malignancy: age, ASA, C-reactive protein, appendiceal diameter, perforation, intraoperative perithyphilitic abscess, and complicated appendicitis. Risk for appendiceal neoplasm or malignancy was 4.4% respectively 2.7% in complicated acute appendicitis compared to 2.0% respectively 1.0% in uncomplicated appendicitis (p = 0.043 respectively p = 0.060). In multivariate analysis, age ≥ 50 years and a diameter of the appendix in the sonography ≥ 13 mm were independent risk factors predicting the presence of appendiceal neoplasm and malignancy. CONCLUSION: Among patients with appendicitis, there are relevant risk factors predicting appendiceal tumors, especially age and appendiceal diameter in sonography. But the identified risk factors have a low sensitivity and specificity, so obtaining a confident preoperative diagnosis is challenging.

Challenging the Current Risk Factors of Appendiceal Neuroendocrine Neoplasms: Can They Accurately Predict Local Lymph Nodal Invasion? Results from a Large Case Series.

BACKGROUND: Appendiceal neuroendocrine neoplasms (ANEN) are uncommon entities, which run mostly an indolent course. Appendicectomy alone is usually curative, except for in a selected group of patients that are deemed to be at risk of loco-regional metastases, in whom a completion right hemicolectomy (RHC) is recommended. The current "Guidelines" criteria for the latter have been controversial, and may result in overtreatment, which is concerning for a young patient population. OBJECTIVE: The aim of this study is to evaluate the prognostic value of the current criteria in identifying more accurately those at-risk patients. METHODS: This was a retrospective study of the 263 cases of ANEN referred for advice or management to a tertiary referral unit over a 10-year period. Seventy-two patients underwent RHC, based on criteria, suggested by International Guidelines. Each one of those was assessed to identify whether it correlated with lymph node invasion (LNI) at the RHC surgical specimen. RESULTS: Tumour grade (p < 0.001), vascular (p = 0.044) and lymph vessel invasion (p < 0.001) were all found to be statistically significant independent risk factors for LNI identified following RHC, whilst tumour size (p = 0.375) and mesoappendiceal invasion (MAI) (p = 0.317) were not statistically significant. However, deep MAI and tumour size >2 cm showed a correlation with each other on LNI positive subgroup analysis. Location in appendiceal base made LNI more likely but again was not significant (p = 0.133). CONCLUSIONS: Higher tumour grade and lymphovascular invasion should be considered as the most important risk prognosticators. Surprisingly, tumour size was not found to be significant in our cohort. Further international multicentre studies with large numbers of patients are needed to fully validate those data.

Appendiceal neoplasm risk associated with complicated acute appendicitis-a population based study.

PURPOSE: Appendiceal tumors are rare, but high neoplasm rates have been reported at interval appendectomy after periappendicular abscess. Non-operative management of uncomplicated acute appendicitis has shown promising results. The data on appendiceal tumor incidence and presentation among acute appendicitis patients is limited, especially in patient cohorts differentiating between uncomplicated and complicated acute appendicitis. Objective was to assess appendiceal tumor incidence and tumor association to appendicitis in patients with uncomplicated and complicated acute appendicitis. METHODS: This nationwide population-based registry study was conducted from 2007 to 2013. The Finnish Cancer Registry and the National Institute for Health Registry were used to combine data on all appendiceal tumors and acute appendicitis diagnosis with medical reports evaluated at eight study hospitals. RESULTS: Altogether, 840 appendiceal tumors were identified, and out of these, 504 patient reports were reviewed, including 472 patients in this study. Tumor was diagnosed at appendectomy for suspected acute appendicitis in 276 patients (58%). In the whole study, histologically acute appendicitis and tumor were both present in 53% (n = 250), and out of these, 41% (n = 102) were complicated and 59% (n = 148) uncomplicated acute appendicitis. The associated tumor risk was significantly higher in complicated acute appendicitis compared with uncomplicated cases (3.24% vs. 0.87%, p < 0.001). Overall tumor prevalence among acute appendicitis patients was 1.24%. CONCLUSIONS: Appendiceal tumor prevalence in acute appendicitis was low. Tumor risk was significantly higher in complicated acute appendicitis compared with uncomplicated acute appendicitis. The risk of missed appendiceal tumors related to antibiotic therapy of uncomplicated acute appendicitis is very low.

Impact of nonappendiceal cancer-specific death on overall survival: a competing risk analysis.

Aim: The occurrence of nonappendiceal cancer-specific death (non-ACSD) and its impact on overall survival are unclear. Methods: Patients were extracted from the Surveillance, Epidemiology, and End Results. Results: Nearly 33.2 and 24.0% patients suffered ACSD and non-ACSD. In a Cox proportional-hazards model, unmarried patients were at greater risk of mortality than were married patients. In a competing risk model, unmarried patients were at greater risk of non-ACSD than were married patients, but the risk of ACSD did not differ significantly according to marriage status. Conclusion: The overall survival of patients with appendiceal cancer was reduced by non-ACSD. A competing risk model was more predictive of the prognosis than was a Cox proportional hazards model.

Guidelines for the management of gastroenteropancreatic neuroendocrine (including carcinoid) tumours (NETs).

These guidelines update previous guidance published in 2005. They have been revised by a group who are members of the UK and Ireland Neuroendocrine Tumour Society with endorsement from the clinical committees of the British Society of Gastroenterology, the Society for Endocrinology, the Association of Surgeons of Great Britain and Ireland (and its Surgical Specialty Associations), the British Society of Gastrointestinal and Abdominal Radiology and others. The authorship represents leaders of the various groups in the UK and Ireland Neuroendocrine Tumour Society, but a large amount of work has been carried out by other specialists, many of whom attended a guidelines conference in May 2009. We have attempted to represent this work in the acknowledgements section. Over the past few years, there have been advances in the management of neuroendocrine tumours, which have included clearer characterisation, more specific and therapeutically relevant diagnosis, and improved treatments. However, there remain few randomised trials in the field and the disease is uncommon, hence all evidence must be considered weak in comparison with other more common cancers.

Risk of appendiceal malignancy in conservatively treated acute appendicitis.

BACKGROUND AND AIMS: Appendectomy has historically been the standard treatment of acute appendicitis, but lately, conservative treatment of uncomplicated acute appendicitis with antibiotics has successfully been used in selected patients. Complicated acute appendicitis is often treated conservatively initially, but may benefit from interval appendectomy due to the higher risk of appendiceal malignancy and recurrence. Recommendations for follow-up after conservatively treated appendicitis vary. Furthermore, the risk of underlying malignancy and the necessity of routine interval appendectomy are unclear. This study aims to evaluate follow-up status, recurrence, and underlying appendiceal malignancy in conservatively treated uncomplicated and complicated acute appendicitis. METHODS: This study included patients with conservatively treated acute appendicitis at Skåne University Hospital, Sweden during 2012-2019. Information on patient demographics at index admission and data on follow-up, recurrence, number of appendectomies after initial conservative treatment, and underlying malignancy were retrieved from medical charts. RESULTS: The study cohort included 391 patients, 152 with uncomplicated and 239 with complicated acute appendicitis. Median time of study follow-up was 52 months. The recurrence risk was 23 (15.1%) after uncomplicated and 58 (24.3%) after complicated acute appendicitis (p = 0.030). During follow-up, 55 (23%) patients with complicated acute appendicitis underwent appendectomy. Appendiceal malignancies were found in 12 (5%) patients with previous complicated acute appendicitis versus no appendiceal malignancies after uncomplicated acute appendicitis (p = 0.002). CONCLUSION: The risk of appendiceal malignancy and recurrent appendicitis was significantly higher in patients with complicated acute appendicitis compared with uncomplicated acute appendicitis.

Mucocele of the appendix. Two case reports.

The authors present two cases of mucocele of the appendix and discuss them in relation to the literature and the clinical features of this disease. They clarify the definition of mucocele as an intraluminal accumulation of mucus in the appendix, and concentrate on the observable pathological processes, agreeing on the higher frequency of mucinous cystadenoma and the possibility that mucocele can develop into peritoneal pseudomyxoma or degenerate into cystadenocarcinoma. They also note that most diagnoses are made intra-operatively during appendectomy, and that, in cases suspected preoperatively, thorough investigation with imaging techniques is very important in order to plan the best treatment.

Molecular Characterization of Appendiceal Goblet Cell Carcinoid.

Goblet cell carcinoid (GCC) is a distinct subtype of appendiceal neoplasm that exhibits unique clinical and pathologic features. We aimed to reveal the molecular profiles of GCC compared with other appendiceal tumors, such as adenocarcinomas and neuroendocrine tumors. A total of 495 appendiceal tumor samples (53 GCCs, 428 adenocarcinomas, and 14 neuroendocrine tumors) were tested with next-generation sequencing (NGS) on a 592-gene panel and IHC. Microsatellite instability (MSI)/mismatch repair (MMR) status was tested with a combination of NGS, IHC, and fragment analyses. Tumor mutational burden (TMB) was evaluated by NGS, and PD-L1 expression was tested by IHC (SP142). The most prevalent mutated genes within GCCs were TP53 (24.0%), ARID1A (15.4%), SMAD4 (9.4%), and KRAS (7.5%). Pathway-specific alterations were dominantly observed in cell cycle, MAPK, epigenetic, and TGFß signaling pathways. GCCs as compared with adenocarcinomas exhibited significantly lower mutation rates in KRAS, GNAS, and APC, and significantly higher mutation rates in CDH1, CHEK2, CDC73, ERCC2, and FGFR2 GCCs as compared with neuroendocrine tumors showed significantly lower mutation rates in KRAS, APC, BRCA2, and FANCA In GCCs, MSI high/MMR deficient, TMB high (≥17 mutations/Mb), and PD-L1 expression were seen in 0.0%, 0.0%, and 2.0% of tumors, respectively. No significant differences were observed in any immunotherapy-related markers examined when compared with adenocarcinomas and neuroendocrine tumors. In conclusion, GCCs had considerably distinct mutational profiles compared with appendiceal adenocarcinomas and neuroendocrine tumors. Understanding these molecular characteristics may be critical for the development of novel and more effective treatment strategies for GCC.

Neurofibromatosis type 1 and masses of the appendix: a case report.

BACKGROUND: Neurofibromatosis type 1 is an autosomal dominant disease with high penetrance, affecting 1:3,000 pregnancies. Meningiomas and other benign central nervous system tumors, such as ependymomas, are common features. CASE: A patient with neurofibromatosis underwent cesarean section due to intrauterine growth restriction and nonreassuring fetal heart rate patterns. Examination of the abdominal cavity and intestines revealed a large (diameter, 12 cm), rubbery, fibrin-coated appendicular mass. The appendix was removed, and pathologic analysis confirmed the diagnosis of neuroma of the appendix. CONCLUSION: The case stresses the importance of careful inspection and evaluation of the abdominal cavity during surgery on patients with neurofibromatosis for the detection of possible associated masses.

Carcinoid tumors of appendix: treatment and outcome.

BACKGROUND: The aim of this study is to evaluate the clinical and histopathological features and the treatment of carcinoid tumors of the appendix. METHODS: A retrospective review of medical records and pathology specimens of patients with carcinoid tumor of the appendix has been done. The data derived from this study has been evaluated by descriptive statistical methods (mean, SD, frequency). RESULTS: The histopathological examination of the appendices revealed carcinoid tumor in 11 out of 6777 (0.16%) patients operated for acute appendicitis. Six (54.54%) patients were male, 5 (45.45%) were female and the mean age was 20.2+/-6.7 years (13-35). The tumor was localized in the distal 1/3 region in 10 patients and in the proximal 1/3 region in 1 patient. The mean tumor diameter was 0.73+/-0.36 cm (0.3-1.5). Ten patients had classical type carcinoid tumor whereas goblet cell carcinoid tumor was only seen in one patient. None of the patients underwent an expanded resection. The mean follow up of the patients is 28.5+/-15.2 months (6-48), and no recurrences were seen. CONCLUSION: In tumors with a diameter of 1 to 2 cm, appendectomy is the treatment of choice. No recurrence was detected with tumors smaller than 2 cm with simple appendectomy.

Pseudomyxoma peritonei diagnosed 19 years after appendicectomy.

Pseudomyxoma peritonei (PMP) is an uncommon clinical finding describing the intraperitoneal accumulation of abundant mucinous, jelly-like material. This entity may represent a spectrum of diseases ranging from mucinous ascites, commonly associated with ruptured epithelial tumours of the appendix, to frank mucinous carcinomatosis. In cases of appendiceal origin, the patient may present with signs and symptoms of acute appendicitis, and thus careful diagnosis must be made in order to correctly and appropriately guide management. This may include a combination of surgical debulking with or without intraperitoneal or systemic chemotherapy. We present a 52-year-old woman with a 4-month history of abdominal pain and distension with a previous appendicectomy 19 years earlier. Radiological and pathological investigations diagnosed a probable PMP secondary to ruptured appendicitis many years ago. We describe her unique case, with emphasis on length of time to diagnosis and clinical management by surgical cytoreduction alone.

Cancer of appendix as a presenting feature of Crohn's disease.

Appendiceal neoplasms are rare. Colonic malignancies, including appendiceal carcinomas, have been rarely reported in Crohn's disease patients. The involvement of the appendix in Crohn's disease is not often seen. We report an interesting case in which a caecal Crohn's disease patient presented for the first time with an appendiceal adenocarcinoma.

Human immunodeficiency virus-related Kaposi's sarcoma of the appendix and acute appendicitis. Report of a case and review of the literature.

We describe a case of acute appendicitis precipitated by human immunodeficiency virus-related Kaposi's sarcoma of the appendix. This presentation in an otherwise asymptomatic homosexual man led to the establishment of a diagnosis of acquired immunodeficiency syndrome. Immediate follow-up revealed multicentric gastrointestinal involvement by Kaposi's sarcoma, and skin involvement ensued in 2 months. Salient features of this case and two other similar reports in the literature are highlighted.

Appendiceal tumour--retrospective clinicopathological analysis.

Appendiceal tumours are rare and often discovered unexpectedly in an acute situation in which decision-making is difficult. We report the spectrum of appendiuar tumours seen in our institution over a period of more than 10 years, and discuss the clinicopathological behaviour, investigations, surgical procedures and outcomes in these patients. We have also reviewed the literature with regard to appendiceal tumours. Appendicular tumours were identified from the database of 1646 appendictomies (18% in children) performed in single centre and case notes were reviewed. Clinical presentation, investigations, histopathology, surgical procedures and outcome were analysed. Twelve patients with appendiceal tumours were identified (0.72%): 8 carcinoid, 2 mucinous (mucocele) and 2 adenocarcinoma. All the patients with a carcinoid tumour presented with features suggestive of acute appendicitis and were diagnosed postoperatively following appendicectomy and formal histology. No further surgical intervention was required as these lesions were less than 1cm away from the base of the appendix. One of the patient with mucinous cystadenoma presented acutely and underwent an appendicectomy; in the other patient with chronic pain, apreoperative MRI suggested the diagnosis leading to a planned hemicolectomy as the lesion was close to the base of the appendix. While one of the patient with an adenocarcinoma localized to the appendix did well following a right hemicolectomy, the other patient with disseminated disease succumbed within a year. Carcinoid tumours are the commonest appendiceal tumours, which present often as acute appendicitis. While appendicectomy would be adequate in most of these patients, in patients with a cystadenoma close to the base of the appendix or in case of a carcinoma, a right hemicolectomy is the appropriate option. While the prognosis is good in patients with carcinoid tumour and cystadenoma, it remains dismal in patients with disseminated malignant disease.

Appendicular mucocele and peritoneal pseudo-myxoma. / Mucoeéle appendiculaire et pseudo-myxome péritonéal

From 2 personal cases the authors present a pathological appraisal of appendicular mucoceles. They distinguish between a benign kind with an atrophic mucous membrane and a malignant type with a hyperplasic epithelium arranged in papillary and vegetating structures; this is a neoplasm with local malignancy. This variety remains the most liable to become a peritoneal pseudo-myxoma representing the most serious complication of the appendicular mucecele. Treatment of the mucocele, which consists in an appenicectomy or a right bemi-colectomy, usually yields good results provided operative rupture can be avoided. Contrarily the peritoneal pseudo-myxoma remains a serious disease with a disappointing treatment.

[Inflammatory pseudotumor of the appendix. Apropos of a case. Review of the literature]. / Pseudo-tumeur inflammatoire de l'appendice. A propos d'un cas. Revue de la littérature.

We report one new case inflammatory pseudotumor of the appendix. The inflammatory pseudotumor of the appendix is one of these benign tumors of the ileocecal junction that mimic neoplasia and can be treated by appendicectomy.

Risk factors for appendiceal metastasis with epithelial ovarian cancer.

PURPOSE: To investigate the risk factors for appendiceal metastasis of epithelial ovarian cancer and compare findings with the previous studies. MATERIALS AND METHODS: One hundred and thirty-four patients with epithelial ovarian cancer were assessed in this study. All of them had undergone a surgical procedure including appendectomy. Of these, 21 (15.7%) patients who had appendiceal metastasis were analyzed as the case group and the patients with no metastasis were the controls, compared according to stage, grade, histology of tumor, preoperative Ca125 levels, presence of ascites, peritoneal cytology, diameter and site of tumor considered as risk factors. RESULTS: We found statistically significant differences between the groups in terms of stage, grade, right-sided tumor location, presence of ascites, diameter of tumor ≥ 10 cm and positive peritoneal cytology (p<0.05). In the logistic regression model, stage, grade, presence of ascites, right-sided location and diameter of tumor were independent risk factors. ROC curve analysis showed that stage, grade and diameter of the tumor were discriminative factors for appendiceal metastasis. CONCLUSIONS: In epithelial ovarian cancer, stage, grade, presence of ascites, right-sided location and large tumor size have importance for estimation of risk of appendiceal metastasis. As we compare our findings with previous studies, there is no definite recommendation for the risk factors of appendiceal metastasis in epithelial ovarian cancer and more studies are needed.

Intestinal and extraintestinal neoplasia in patients with inflammatory bowel disease in a tertiary care hospital.

CONTEXT: The development of neoplasia is an important concern associated with inflammatory bowel disease (IBD), especially colorectal cancer (CRC). OBJECTIVES: Our aim was to determine the incidence of intestinal and extraintestinal neoplasias among patients with inflammatory bowel disease. METHODS: There were retrieved information from 1607 patients regarding demographics, disease duration and extent, temporal relationship between IBD diagnosis and neoplasia, clinical outcomes and risk factors for neoplasia. RESULTS: Crohn's disease (CD) was more frequent among women (P=0.0018). The incidence of neoplasia was higher in ulcerative colitis (UC) when compared to CD (P=0.0003). Eight (0.99%) patients developed neoplasia among 804 with CD: 4 colorectal cancer, 2 lymphomas, 1 appendix carcinoid and 1 breast cancer. Thirty (3.7%) patients developed neoplasia among the 803 UC: 13 CRC, 2 lymphomas and 15 extraintestinal tumors. While CRC incidence was not different among UC and CD (1.7% vs 0.5%; P=0.2953), the incidence of extraintestinal neoplasias was higher among UC (2.1% vs 0.5%, P=0.0009). Ten (26.3%) patients out of 38 with neoplasia died. CONCLUSIONS: CRC incidence was low and similar in both diseases. There was a higher incidence of extraintestinal neoplasia in UC when compared to CD. Neoplasias in IBD developed at a younger age than expected for the general population. Mortality associated with malignancy is significant, affecting 1/4 of the patients with neoplasia.