Fragmentation of Care in Patients with Peritoneal Metastases Undergoing Cytoreductive Surgery.

BACKGROUND: The delivery of multimodal treatment at a high-volume center is known to optimize the outcomes of gastrointestinal malignancies. However, patients undergoing cytoreductive surgery (CRS) for peritoneal metastases often must 'fragment' their surgical and systemic therapeutic care between different institutions. We hypothesized that this adversely affects outcomes. PATIENTS AND METHODS: Adults undergoing CRS for colorectal or appendiceal adenocarcinoma at our institution between 2016 and 2022 were identified retrospectively and grouped by care network: 'coordinated care' patients received exclusively in-network systemic therapy, while 'fragmented care' patients received some systemic therapy from outside-network providers. Factors associated with fragmented care were also ascertained. Overall survival (OS) from CRS and systemic therapy-related serious adverse events (SAEs) were compared across the groups. RESULTS: Among 85 (80%) patients, 47 (55%) had colorectal primaries and 51 (60%) received fragmented care. Greater travel distance [OR 1.01 (CI 1.00-1.02), p = 0.02] and educational status [OR 1.04 (CI 1.01-1.07), p = 0.01] were associated with receiving fragmented care. OS was comparable between patients who received fragmented and coordinated care in the colorectal [32.5 months versus 40.8 months, HR 0.95 (CI 0.43-2.10), p = 0.89] and appendiceal [31.0 months versus 27.4 months, HR 1.17 (CI 0.37-3.74), p = 0.55] subgroups. The frequency of SAEs (7.8% versus 17.6%, p = 0.19) was also similar. CONCLUSIONS: There were no significant differences in survival or SAEs based on the networks of systemic therapy delivery. This suggests that patients undergoing CRS at a high-volume center may safely receive systemic therapy at outside-network facilities with comparable outcomes.

Extent of Resection and Long-Term Outcomes for Appendiceal Adenocarcinoma: a SEER Database Analysis of Mucinous and non-Mucinous Histologies.

BACKGROUND: Mucinous appendiceal adenocarcinomas (MAA) and non-mucinous appendiceal adenocarcinomas (NMAA) demonstrate differences in rates and patterns of recurrence, which may inform the appropriate extent of surgical resection (i.e., appendectomy versus colectomy). The impact of extent of resection on disease-specific survival (DSS) for each histologic subtype was assessed. PATIENTS AND METHODS: Patients with resected, non-metastatic MAA and NMAA were identified in the Surveillance, Epidemiology, and End Results database (2000-2020). Multivariable models were created to examine predictors of colectomy for each histologic subtype. DSS was calculated using Kaplan-Meier estimates and examined using Cox proportional hazards modeling. RESULTS: Among 4674 patients (MAA: n = 1990, 42.6%; NMAA: n = 2684, 57.4%), the majority (67.8%) underwent colectomy. Among colectomy patients, the rate of nodal positivity increased with higher T-stage (MAA: T1: 4.6%, T2: 4.0%, T3: 17.1%, T4: 21.6%, p < 0.001; NMAA: T1: 6.8%, T2: 11.4%, T3: 25.6%, T4: 43.8%, p < 0.001) and higher tumor grade (MAA: well differentiated: 7.7%, moderately differentiated: 19.2%, and poorly differentiated: 31.3%; NMAA: well differentiated: 9.0%, moderately differentiated: 20.5%, and 44.4%; p < 0.001). Nodal positivity was more frequently observed in NMAA (27.6% versus 16.4%, p < 0.001). Utilization of colectomy was associated with improved DSS for NMAA patients with T2 (log rank p = 0.095) and T3 (log rank p = 0.018) tumors as well as moderately differentiated histology (log rank p = 0.006). Utilization of colectomy was not associated with improved DSS for MAA patients, which was confirmed in a multivariable model for T-stage, grade, and use of adjuvant chemotherapy [hazard ratio (HR) 1.00, 95% confidence interval (CI) 0.81-1.22]. CONCLUSIONS: Colectomy was associated with improved DSS for patients with NMAA but not MAA. Colectomy for MAA may not be required.

Appendiceal Neuroendocrine Neoplasms: an Update for 2023.

PURPOSE OF REVIEW: To summarize the literature from the last 5 years on treatment of appendiceal neuroendocrine neoplasms (aNEN). Furthermore, to evaluate the prognostic significance of lymph node metastases, indications for adjuvant treatment, and challenges of the current follow-up regimen. RECENT FINDINGS: Simple appendectomy is sufficient in tumors < 1 cm while extended surgery is indicated in tumors > 2 cm. In a multicenter study of aNENs measuring 1-2 cm, extended surgery offered no significant prognostic advantage and is now limited to incomplete tumor resection or high-grade G2 or G3 aNEN. Follow-up remains debatable, as the use of imaging and biomarkers lacks validation. While surgical procedure is well established in aNEN tumors < 1 cm and > 2 cm, the need for extended surgery in aNEN tumors 1-2 cm is questionable. Future studies should address the prognostic impact of lymph node metastases and the optimal design and duration of follow-up.

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.

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.

Beyond acute appendicitis: a single-institution experience of unexpected pathology findings after 989 consecutive emergency appendectomy.

INTRODUCTION: Appendiceal neoplasms (ANs) are rare, with an estimated incidence of around 1%: neuroendocrine tumours (NETs) and low-grade appendiceal mucinous neoplasms (LAMNs) comprise most cases. Most tumours are cured by appendectomy alone, although some require right hemicolectomy and intra-operative chemotherapy. The aim of the present study is to evaluate our institution's experience in terms of the prevalence of AN, their histological types, treatment and outcomes in adult patients undergoing emergency appendectomy. MATERIAL AND METHODS: Single-centre retrospective cohort analysis of patients treated for acute appendicitis at a large academic medical centre. Patients with a diagnosis of acute appendicitis (AA) where further compared with patients with acute appendicitis and a histologically confirmed diagnosis of appendiceal neoplasm (AN). RESULTS: A diagnosis of acute appendicitis was made in 1200 patients. Of these, 989 patients underwent emergency appendectomy. The overall incidence of appendiceal neoplasm was 9.3% (92 patients). AN rate increased with increasing age. Patients under the age of 30 had a 3.8% (14/367 patients) rate of occult neoplasm, whereas patients between 40 and 89 years and older had a 13.0% rate of neoplasm. No difference was found in clinical presentations and type of approach while we found a lower complicated appendicitis rate in the AN group. CONCLUSION: ANs are less rare with respect to the literature; however, clinically, there are no specific signs of suspicious and simple appendicectomy appears to be curative in most cases. However, age plays an important role; older patients are at higher risk for AN. ANs still challenge the non-operative management concept introduced into the surgical literature.

Retrospective analysis of the incidence of appendiceal neoplasm and malignancy in patients treated for suspected acute appendicitis.

BACKGROUND: Nonoperative management of uncomplicated appendicitis is currently being promoted as treatment option, albeit 0.7-2.5% of appendectomies performed due to suspected acute appendicitis show histologically malignant findings. The purpose of this study was to investigate the incidence of neoplasm and malignancy of the appendix in patients presenting with suspected acute appendicitis in real world setting. METHODS: This is a retrospective single-centre investigation of 457 patients undergoing appendectomy between the years 2017-2020. The patients' demographics, symptoms and diagnosis, intraoperative findings, and histopathological results were analysed. RESULTS: In 3.7% (n = 17) histological analysis revealed neoplasms or malignancies. Median age was 48 years (20-90 years), without sex predominance. Leukocytes (11.3 ± 3.7 G/l) and C-reactive protein (54.2 ± 69.0 mg/l) were elevated. Histological analysis revealed low-grade mucinous appendiceal neoplasia (n = 3), sessile serrated adenoma of the appendix (n = 3), neuroendocrine tumours (n = 7), appendiceal adenocarcinoma of intestinal type (n = 3), and goblet cell carcinoma (n = 1). Additional treatment varied between no treatment or follow-up due to early tumour stage (n = 4), follow-up care (n = 3), additional surgical treatment (n = 8), or best supportive care (n = 2). CONCLUSIONS: Preoperative diagnosis of appendiceal tumours is difficult. Nonoperative management of patients with acute, uncomplicated appendicitis potentially prevents the correct diagnosis of malignant appendiceal pathologies. Therefore, close follow-up or surgical removal of the appendix is mandatory.

[A Case of Perforated Low-Grade Appendiceal Mucinous Neoplasm Diagnosed During Appendectomy].

A 46-year-old female presented persistent right lower abdominal pain for 4 days. Computed tomography revealed an enlarged appendix with a surrounding low-attenuation mass. The patient was diagnosed with appendiceal abscess-forming appendicitis and initially treated with antibiotics. However, owing to the manifestation of nausea as a side effect, laparoscopic appendectomy was performed 3 days after the initial consultation. Intraoperative examination revealed mucinous material on the surface of the appendix and within the abdominal cavity, leading to the decision to perform an appendectomy with partial cecum resection and excision of the omentum with mucinous deposits. Pathological examination confirmed the diagnosis of a perforating low-grade appendiceal mucinous neoplasm and pseudomyxoma peritonei. The patient was subsequently referred to a specialized center for ongoing management, and at 9 months postoperatively, surveillance is being conducted. Low-grade appendiceal mucinous neoplasms can progress to pseudomyxoma peritonei through perforation; however, an optimal treatment approach has not yet been established. In particular, patients in advanced stages of the disease often require challenging management decisions. This case is reported along with a review of the literature to provide further guidance.

[Adult Intussusception Associated with a Low-Grade Appendiceal Mucinous Neoplasm-A Case Report].

A 52-year-old woman patient, who presented with lower abdominal pain, was suspected of having colonic intussusception. An enhanced CT examination indicated that the end of the small intestine or appendix tumor had invaginated into the transverse colon. The CT revealed no evidence of intestinal ischemia, the emergency operation was performed on the following day. After relieving a colonic intussusception, a mass of the appendix was found and we performed laparoscope-assisted ileocolic resection and D3 dissection because of a strong possibility of carcinoma. The patient was discharged 8 days after the surgery and showed no evidence of recurrence for 6 months after the surgery. In postoperative histopathological examination, appendix tumor was diagnosed as a low-grade appendiceal mucinous neoplasm(LAMN). Adult intussusception is a rare disease and most of the cases are caused by malignant lesions, and a treatment strategy for LAMN has not yet been established. We report this case , as there are very few reported cases of adult intussusception caused by LAMN, with a review of the relevant literature.

[A Case of Appendiceal Carcinoma with BRAF V600E Mutation and Microsatellite Instability-High].

A 75-year-old woman presented to our hospital with abdominal pain and melena. Colonoscopy revealed an ulcer at the appendiceal orifice. Histopathological examination of biopsy specimens revealed adenocarcinoma. Computed tomography showed an appendiceal mass of 11.8×6.7 cm in size involving the cecum and terminal ileum without any distant metastatic findings. Ileocecal resection with regional lymph node dissection to the root of the ileocolonic artery was performed. Histopathological examination of the specimen revealed appendiceal adenocarcinoma. Molecular subtype of the tumor was BRAF V600E mutation and microsatellite instability-high(MSI-H). The pathological stage was pT4bpN1bcM0, pStage ⅢC. She received 8 courses of CapeOX as adjuvant chemotherapy and no recurrence was noted 12 months following the surgery. The establishment of standard treatment strategies including surgery, chemotherapy, and immunotherapy for carcinoma of the appendix with BRAF V600E mutation and/or MSI-H is needed.

[Goblet Cell Carcinoid of the Appendix with Complicated Appendicitis-A Case Report].

A 50-year-old male was referred to our hospital for the further evaluation and treatment of abdominal pain. He was diagnosed with complicated appendicitis using computed tomography. After conservative treatment, he underwent an interval appendectomy. A histopathological examination revealed a goblet cell carcinoid(GCC)of the appendix with subserosal invasion. He underwent laparoscopic ileocecal resection with D3 lymph node dissection. Histopathological findings showed neither residual tumor nor lymph node metastasis. The patients is currently followed as an outpatient without recurrence. Here we report our experience with GCC, a rare disease.

[A Case of Goblet Cell Adenocarcinoma Incidentally Diagnosed after Appendectomy That Required Additional Bowel Resection with Lymph Nodes Dissection].

A 54-year-old male presented to the clinic, complaining of dull lower abdominal pain that started a day ago. There was a tenderness on right lower quadrant on palpation and abdominal computed tomography(CT)showed that dilated appendix with a diameter of 12 mm. The patient was diagnosed with acute appendicitis and laparoscopic appendectomy was performed on the same day. The tip of the appendix was swollen and looked purple, gangrenous appendicitis findings were identified. However, histopathology detected GCA on resected appendix with positive surgical margin and additional tumor resection was indicated. Laparoscopic ileocecal resection with D3 lymph nodes dissection was performed 24 days after the first surgery. Resected specimen showed that the stump of the appendix was palpable as a mass in the orifice of the appendix and histopathology revealed the remnant of the appendiceal GCA. No lymph nodes tumor metastasis was identified. Chromogranin A and synaptophysin were positive and Ki-67 was approximately 50%. According to the guideline of neoadjuvant chemotherapy for colon cancer, oral 5-fluorouracil therapy was performed for half a year after the second surgery and the patient remains still healthy without recurrence 1 year after the surgery. Here, we experienced a rare case of GCA of the appendix that was detected incidentally after appendectomy for acute appendicitis.

[A Case of Appendiceal Metastasis from Hilar Cholangiocarcinoma with Acute Perforated Appendicitis and Cholecystitis].

An 88-year-old woman had been diagnosed with hilar cholangiocarcinoma for 3 years since she received metallic stents for malignant biliary obstruction, and observed without any aggressive medical treatment. She was admitted to our hospital for further investigation of her abdominal pain. Abdominal CT showed an enlarged gallbladder, fluid collection in the right paracolic gutter, and swollen appendix. Laboratory tests showed high-grade inflammation. She was diagnosed with acute perforated appendicitis with acute cholecystitis. Laparoscopic cholecystectomy and appendectomy were performed. Perforation was confirmed intraoperatively in the appendix wall and accumulation of pus was found in the right paracolic gutter. There were no macroscopic findings of metastasis and peritoneal dissemination. Microscopic examination of the resected appendix showed adenocarcinoma cells positive for CK7 and negative for CK20 and CDX2, and were predominantly infiltrated from the muscular layer to the serosa of the appendix wall, with a diagnosis of appendiceal metastasis from hilar cholangiocarcinoma. Metastatic appendiceal carcinoma is rare, and appendiceal metastasis from hilar cholangiocarcinoma is extremely rare. Herein, we report a rare case of metastatic appendiceal carcinoma from hilar bile duct cancer with acute perforated appendicitis and cholecystitis along with findings of previous literature.

[Appendix ... it's not just appendicitis: neuroendocrine tumors.] / L'appendice... non è solo appendicite: i tumori neuroendocrini.

Well-differentiated neuroendocrine tumors of the appendix (NETs) are rare in pediatric and adolescent age groups. However, they are the most common gastrointestinal epithelial tumor in this age group and the most common malignancy of the appendix in the general population. The classification of these tumors considers factors such as the proliferation index, size of the neoplasm, and the presence of perineural and/or lymphovascular invasion, which can contribute to distant metastases. Preoperative diagnosis is challenging, except in cases where patients exhibit symptoms of carcinoid syndrome or signs of metastatic disease, which are uncommon in pediatric and adolescent patients. For tumors smaller than 1 cm, appendectomy is usually curative, while larger tumors or those at risk of spreading may require right hemicolectomy with lymphadenectomy. We present a case of an adolescent with NET and provide a literature review on the diagnostic and therapeutic approaches that should be considered for this relatively rare condition.Key words. Adolescent age, appendix, neuroendocrine tumors, pediatric age.

Hyperthermic intraperitoneal chemotherapy in patients with incomplete cytoreduction for appendiceal pseudomyxoma peritonei: a 10-year treatment experience in China.

BACKGROUND: To explore the application value of hyperthermic intraperitoneal chemotherapy (HIPEC) in patients with incomplete cytoreduction for appendiceal pseudomyxoma peritonei (PMP). METHODS: We retrospectively analyzed the clinical data of 526 patients with incomplete cytoreduction for appendiceal PMP to discover its prognostic factors, and the therapeutic value of HIPEC. RESULTS: The 5-year and 10-year overall survival rates of patients after cytoreductive surgery (CRS) treated with HIPEC were significantly higher than those without HIPEC (5y-OS: 58% vs. 48%, 10y-OS: 37% vs. 16%, P = 0.032). The median progression-free survival (PFS) following CRS was 20 months, with a 20% 3-year PFS. The median PFS following CRS + HIPEC was 33 months, with a 60% 3-year PFS (P = 0.000). Univariate analysis indicated that HIPEC, gender, completeness of cytoreduction (CCR) and pathological grade had statistical difference. Multivariate analysis showed that CRS without HIPEC and high pathological grade were independent risk factors for poor prognosis and rapid tumor progression. CONCLUSIONS: HIPEC may prolong the survival in patients with incomplete cytoreduction for low-grade appendiceal PMP. High pathological grade indicates poor survival and rapid tumor progression.

What is the diagnostic accuracy of fluorescence-guided surgery for margin assessment in appendicular bone and soft tissue tumors? - A systematic review of clinical studies.

BACKGROUND: Fluorescence-guided surgery (FGS) is a novel technique to successfully assess surgical margins intraoperatively. Investigation and adoption of this technique in orthopaedic oncology remains limited. METHODS: The PRISMA guidelines were followed for this manuscript. Our study was registered on PROSPERO (380520). Studies describing the use of FGS for resection of bone and soft tissue sarcomas (STS) on humans were included. Diagnostic performance metrics (sensitivity, specificity, positive predictive value [PPV], negative predictive value [NPV] and accuracy) and margin positivity rate were the outcomes assessed. RESULTS: Critical appraisal using the Joanna Brigs Institute checklists showed significant concerns for study quality. Sensitivity of FGS ranged from 22.2 % to 100 % in three of the four studies assessing his metrics; one study in appendicular tumors in the pediatric population reported 0 % sensitivity in the three cases included. Specificity ranged from 9.38 % to 100 %. PPV ranged from 14.6 % to 70 % while NPV was between 53.3 % and 100 %. The diagnostic accuracy ranged from 21.62 % to 92.31 %. Margin positivity rate ranged from 2 % to 50 %, with six of the seven studies reporting values between 20 % and 50 %. CONCLUSIONS: FSG is a feasible technique to assess tumor margins in bone and STS. Reported performance metrics and margin positivity rates vary widely between studies due to low study quality and high heterogeneity in dying protocols. LEVEL OF EVIDENCE: Level III, diagnostic study.