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.

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.

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.

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.

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.

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.

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.

Intestinal and xxtraintestinal neoplasia in patents with inflammatory bowel diisease 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. .

Contexto O desenvolvimento de neoplasias se constitui em preocupação constante em pacientes com doenças inflamatórias intestinais (DII), especialmente o câncer colorretal (CCR). Objetivos Determinar a incidência de neoplasias intestinais e extra-intestinais entre pacientes com DII. Métodos Foram obtidas informações de 1607 pacientes, quanto a dados demográficos, duração e extensão da doença, relação temporal entre diagnóstico das DII e neoplasia, evolução clínica e fatores de risco para neoplasia. Resultados Doença de Crohn (DC) foi mais frequente entre as mulheres (P = 0.0018). A incidência de neoplasia foi maior nos doentes com retocolite ulcerativa (RCU) em relação aos com DC (P = 0.0003). Oito (0.99%) pacientes desenvolveram neoplasia entre 804 com DC: quatro tumores colorretais, dois linfomas, um carcinóide de apêndice e um câncer de mama. Trinta (3.7%) pacientes desenvolveram neoplasia entre os 803 RCU: 13 CCR, 2 linfomas e 15 tumores extra-intestinais. Enquanto a incidência de CCR não diferiu entre RCU e DC (1.7% vs 0.5%; P = 0.2953), a incidência de neoplasias extraintestinais foi maior na RCU (2.1% vs 0.5%, P = 0.0009). Dez (26.3%) pacientes de um total de 38 com neoplasia, evoluíram a óbito durante o seguimento. Conclusões A incidência de CCR foi baixa e similar em ambas as doenças inflamatórias. Observou-se incidência maior de neoplasia extra-intestinal na RCU quando comparada à DC. Neoplasias em doenças inflamatórias se desenvolveram em idade mais precoce do que a esperada para a população geral. A mortalidade associada a neoplasias é significativa, afetando 1/4 dos pacientes. .

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.

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.

Appendiceal carcinoid and mucinous cystadenoma in renal transplant recipients: case reports.

There is an increased incidence of tumors among renal transplant patients, which are associated with immunosuppression. Carcinoids are rare neuroendocrine tumors that arise from the enterochromaffin cells. Although appendiceal carcinoid tumors are the commonest malignant neoplasms affecting the appendix, and mucinous cystadenoma is the commonest benign appendiceal neoplasm, they have not been reported in immunosuppressed patients. We present two renal transplant recipients who developed combined appendiceal carcinoid and mucinous cystadenoma.

Appendiceal mucinous cystadenoma is a neoplastic complication of IBD: case-control study of primary appendiceal neoplasms.

BACKGROUND: IBD is a risk factor for development of colorectal neoplasia. Although IBD frequently involves the appendix microscopically, it is uncertain whether it also predisposes to appendiceal neoplasia. METHODS: We performed a retrospective case-control study of incidental appendiceal neoplasms in colectomy specimens of adults with and without IBD (cases and controls, respectively) based on surgical pathology records spanning 54 months. To minimize referral bias, patients were excluded if they had preoperative clinical evidence or a principal pathologic diagnosis of appendiceal disease. The pathologic diagnoses were confirmed retrospectively. RESULTS: Eleven appendiceal cystadenomas and 6 appendiceal carcinoid tumors were identified among 705 IBD cases (377 ulcerative colitis, 317 Crohn's disease, 11 indeterminate colitis) and 498 non-IBD controls meeting our inclusion criteria. There was no significant difference in prevalence of cyst adenomas between the cases and controls (9/705 [1.3%] versus 2/498 [0.4%], respectively, OR 3.2 [95% CI 0.7-14.9]). However, cyst adenomas were 15-fold more prevalent among cases with synchronous colorectal neoplasia compared with controls (4/69 [5.8%] versus 2/498 [0.4%], OR 15.3 [95% CI 2.7-85]) and 8-fold higher compared with cases without synchronous neoplasia (4/69 [5.8%] versus 5/636 [0.8%], OR 7.8 [95% CI 2.0-29.6]). Appendiceal carcinoids were equally prevalent in cases and controls (4/705 [0.6%] versus 2/498 [0.4%], OR 1.4 [95% CI 0.3-7.8]), cases with synchronous neoplasia and controls (1/69 [1.4%] versus 2/498 [0.4%], OR 3.6 [95% CI 0.3-40.8]), and cases with and without synchronous colorectal neoplasia (1/69 [1.4%] versus 3/636 [0.5%], OR 3.1 [95% CI 0.3-30.2]). CONCLUSIONS: IBD with synchronous colorectal dysplasia or cancer is a risk factor for development of appendiceal cystadenomas, implicating this tumor as a neoplastic complication of IBD. IBD does not predispose to the development of appendiceal carcinoids.

Concomitant carcinoid tumor and papillary urothelial neoplasm of low malignant potential in a patient with Crohn's disease: a case report.

Patients with a long-term history of inflammatory bowel diseases show an increased risk of developing colorectal cancers. In the case of Crohn's disease, such an increased risk is also associated with other malignant tumors. The report presents a very rare case of a concomitant carcinoid tumor and papillary urothelial neoplasm of low malignant potential in a 35-year-old patient with diagnosed Crohn's disease complicated by an enterovesical fistula. The carcinoid tumor and papillary urothelial neoplasm of low malignant potential were diagnosed by postoperative histopathology. In patients with Crohn's disease, concomitant occurrence of various malignancies may be observed even earlier in life.

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.