Expert Consensus | Expert Consensus on the Comprehensive Diagnosis and Treatment of Peritoneal Metastasis from Appendiceal Epithelial Tumors (2025 Edition)

Cite this article

Chinese Anti-Cancer Association, Peritoneal Tumor Integrated Rehabilitation Specialist Committee. Expert Consensus on the Comprehensive Diagnosis and Treatment of Peritoneal Metastasis from Appendiceal Epithelial Tumors (2025 Edition) [J]. Chinese Journal of Gastrointestinal Surgery, 2025, 28(11): 1223-1231.

DOI: 10.3760/cma.j.cn441530-20250718-00271

Corresponding author

Sun Lifeng, Email: sunlifeng@zju.edu.cn, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou 310009; Wang Hui, Email: wanghuislh@hotmail.com, The Sixth Affiliated Hospital of Sun Yat-sen University, Guangzhou 510655; Cai Guoxiang, Email: gxcai@fudan.edu.cn, Fudan University Shanghai Cancer Center, Shanghai 200032; Pang Minghui, Email: mhpang@uestc.edu.cn, Sichuan Academy of Medical Sciences—Sichuan Provincial People’s Hospital (Affiliated Hospital of University of Electronic Science and Technology of China), Chengdu 610072

Abstract

Appendiceal epithelial tumors refer to neoplastic lesions originating from the mucosal epithelium of the appendix. These tumors exhibit high heterogeneity in their pathological features and biological behavior. Due to their unique structural and biological characteristics, they have a relatively high propensity for peritoneal metastasis. Currently, there is limited evidence-based medical evidence regarding the prevention and treatment of appendiceal epithelial tumors and peritoneal metastasis, and clinical diagnosis and treatment still lack unified guidelines. To address this gap, the Specialist Committee on Integrated Rehabilitation for Peritoneal Tumors of the Chinese Anti-Cancer Association has brought together multidisciplinary experts to integrate the technical expertise of relevant specialties around key aspects such as pathological classification and clinical staging of appendiceal epithelial tumors, indications for extended resection following local excision, surgical strategies for managing concurrent peritoneal metastasis, perioperative rehabilitation, and personalized treatment approaches. At the same time, Clinical application of standardized perioperative management for cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (HIPEC) in the treatment of abdominal tumors, as well as a prehabilitation system, to enhance practical operability. Ultimately, the “Expert Consensus on the Comprehensive Diagnosis and Treatment of Peritoneal Metastasis from Appendiceal Epithelial Tumors (2025 Edition)” was developed, with the aim of... Further standardize the systematic diagnostic and therapeutic workflow for appendiceal epithelial tumors to reduce the risk of recurrence, improve patient outcomes, and promote standardization and homogenization of the diagnosis and treatment of peritoneal metastasis.

Preface

Appendiceal epithelial tumors mainly include three major categories: mucinous tumors, non-mucinous tumors, and neuroendocrine tumors. In 2020, a domestic report indicated approximately 35,000 newly diagnosed cases of appendiceal tumor peritoneal metastasis. Although the overall incidence rate is relatively low, appendiceal mucinous tumors, due to anatomical features such as the narrow lumen of the appendix and the tendency for mucus to accumulate, are prone to rupture and perforation, leading to peritoneal dissemination and metastasis, which can subsequently result in pseudomyxoma peritonei. Pseudomyxoma peritonei (PMP) PMP is a clinical syndrome characterized by malignant biological features such as mucinous ascites, peritoneal implantation lesions, omental cake-like thickening, and ovarian involvement. According to statistics, approximately 94% of PMP cases originate from rupture and perforation of appendiceal mucinous tumors; only a very small number arise from mucinous lesions in organs such as the ovary, colon, ureter, or pancreas. It is important to note that non-mucinous adenocarcinoma and signet-ring cell carcinoma of the appendix can also cause peritoneal metastasis; however, PMP exhibits a unique dissemination mechanism: tumor cells can “redistribute” along with the ascitic fluid, selectively depositing in low-lying areas such as the pelvic cavity or paracolic gutters, where they form solid implantation lesions. Moreover, PMP rarely involves isolated loops of the small intestine, which serves as an important diagnostic criterion distinguishing it from other types of peritoneal metastatic cancers.

To standardize the systematic diagnostic and therapeutic approach for appendiceal epithelial tumors and their associated peritoneal metastases, the Specialist Committee on Integrated Rehabilitation for Peritoneal Tumors of the Chinese Anti-Cancer Association has organized a multidisciplinary team of experts to develop the “Expert Consensus on the Comprehensive Diagnosis and Treatment of Appendiceal Epithelial Tumor with Peritoneal Metastasis (2025 Edition).” This consensus aims to reduce the risk of recurrence and improve patient outcomes. Based on evidence-based medical evidence from both domestic and international sources, this consensus places particular emphasis on the following aspects: (1) Precision in pathological classification (e.g., distinguishing between mucinous and non-mucinous types, as well as low-grade and high-grade tumors); (2) Cytoreductive surgery (CRS) +Intraperitoneal Hyperthermic Perfusion Chemotherapy Hyperthermic intraperitoneal chemotherapy, HIPEC (1) Perioperative management strategies, particularly key technical details such as intraoperative organ function protection; (2) The integration of a prehabilitation system, including lifestyle adjustments, standardized nutritional support therapy, physical training, and psychological interventions, to optimize treatment outcomes and the quality of postoperative recovery. At the same time, we advocate for multidisciplinary collaboration. multi-disciplinary treatment (MDT) Throughout the entire diagnostic and therapeutic process, we aim to promote standardization and homogenization of treatment protocols for appendiceal tumors and their peritoneal metastases. This consensus has been registered on the International Practice Guidelines Registry Platform. (Registration No.: PREPARE-2025CN1608).

This consensus refers to the GRADE Collaboration’s recommended system for assessing, developing, and evaluating evidence. (grading recommendations assessment, development and evaluation, GRADE) Grading criteria are used to classify the quality of evidence and the strength of recommendations. The levels of evidence quality are categorized as “A, B, C, and D,” while the strength of recommendations is classified as “strong recommendation” and “weak recommendation.”

It should be specifically noted that this consensus does not include an economic analysis. Clinical application should involve individualized decision-making based on each patient’s specific circumstances; therefore, this consensus does not assume any legal liability for the actual outcomes of its implementation.

One

Histological Classification and Clinical Staging of Appendiceal Epithelial Tumors

(1) Histological Classification

Appendiceal epithelial tumors are classified according to the 5th edition of the World Health Organization (WHO) Classification of Tumors of the Digestive System.

1. Serrated Lesions: (1) Crypts are straight, with serrations confined to the luminal surface of the crypts and hyperplastic polyps lacking cellular atypia; (2) Crypts are distorted, with serrations and crypt dilation extending to the base of the crypts, and serrated lesions exhibiting cellular atypia but without dysplasia; (3) Serrated lesions with cellular atypia accompanied by dysplasia.

2. Appendiceal Mucinous Tumors: These are appendiceal tumors characterized by mucinous epithelial hyperplasia accompanied by extracellular mucin and pushing tumor margins. They include low-grade appendiceal mucinous neoplasms (LAMNs), which feature mildly atypical epithelium, and high-grade appendiceal mucinous neoplasms (HAMNs), which exhibit high-grade histological features and cellular characteristics. Since 2022, the WHO has reclassified LAMNs and HAMNs from borderline tumors to malignant tumors, with ICD-O biological behavior codes now being 8480/1 and 8480/2, respectively. Appendiceal mucinous tumors with peritoneal metastasis are coded as 8480/3. The prognosis of these tumors is highly dependent on staging: when the tumor remains confined to the appendix, the prognosis is favorable; however, when peritoneal dissemination occurs, leading to peritoneal mucinous pseudomyxoma (PMP), the prognosis becomes closely linked to the biological behavior of the peritoneal mucinous epithelium, the extent of dissemination, and the effectiveness of available treatments.

3. Appendiceal Adenocarcinoma: A malignant epithelial tumor characterized by invasive growth, morphologically resembling colorectal adenocarcinoma. Unless otherwise specified (NOS), there are three histological subtypes: signet-ring cell adenocarcinoma, mucinous adenocarcinoma, and undifferentiated carcinoma NOS. Signet-ring cell adenocarcinoma is predominantly composed of signet-ring cells (>50%), and may exhibit mucinous lakes; mucinous adenocarcinoma is characterized by an extracellular mucin content exceeding 50%; appendiceal undifferentiated carcinoma is rare, and its histological features closely resemble those of colorectal undifferentiated carcinoma.

4. Appendiceal goblet cell adenocarcinoma (GCA): This is a dual-secretory tumor composed of goblet cell-like mucous cells, varying numbers of endocrine cells, and Paneth cell-like cells. The tumor cells are arranged in small tubular structures resembling intestinal crypts. When the tumor loses its tubular or nest-like growth pattern, it is classified as high-grade. Based on the proportion of low-grade versus high-grade components, GCA can be further subdivided into three grades (G1, G2, and G3). The disease’s grade correlates with prognosis; high-grade tumors are more likely to develop distant metastases.

5. Neuroendocrine Tumors: These include (1) neuroendocrine tumors (NETs); (2) neuroendocrine carcinomas (NECs), which encompass small-cell and large-cell types; and (3) mixed neuroendocrine-non-neuroendocrine neoplasms (MiNENs). A MiNEN is diagnosed only when both neuroendocrine and non-neuroendocrine components each account for at least 30%. Previously, these tumors were referred to as mixed adenocarcinoma-neuroendocrine carcinomas. NECs and mixed adenocarcinoma-large/small-cell neuroendocrine carcinomas are high-grade malignancies with a poor prognosis.

(2) Clinical Staging

The 9th edition of the American Joint Committee on Cancer (AJCC) TNM staging system for appendiceal adenocarcinoma applies to LAMN and HAMN, adenocarcinoma, poorly differentiated NEC, MiNEN, and GCA. Appendiceal neuroendocrine tumors have a separate staging system. The staging of appendiceal mucinous neoplasms is unique due to the classification of LAMN and HAMN as well as the grading of PMP.

LAMN does not have T1 or T2 staging. Its pTis tumor is confined to the appendix and is defined as involving non-cellular mucin or mucinous epithelium that has not breached the muscularis propria. The pT3 stage refers to non-cellular mucin or tumor-mucinous epithelium extending into the subserosal layer or within the mesoappendix. The pT4a stage is characterized by tumor penetration of the visceral peritoneum, including mucinous peritoneal tumors or non-cellular mucin involvement of the serosa of the appendix or mesoappendix. The pT4b stage denotes direct invasion of adjacent organs by the tumor.

HAMN classifies tumors according to the T and N stages of appendiceal adenocarcinoma. In the M stage, M1a refers to peritoneal involvement without cellular mucin; M1b indicates peritoneal metastasis with mucinous epithelial components. At this stage, a three-tier grading system is applied based on the histological features of the peritoneal metastatic lesions: G1 (well-differentiated) corresponds to low-grade mucinous carcinoma of the peritoneum; G2 (moderately differentiated) corresponds to high-grade mucinous carcinoma of the peritoneum; and G3 (poorly differentiated) corresponds to high-grade mucinous carcinoma of the peritoneum accompanied by signet-ring cells. M1c denotes non-peritoneal metastasis (distinct from M1c in tumors such as colorectal cancer). In clinical staging, Stage IVA encompasses either M1a or M1b (G1); Stage IVB corresponds to M1b (G2, G3, and Gx); and Stage IVC, corresponding to M1c, carries the worst prognosis. This staging system, which integrates tissue differentiation and the extent of metastasis, provides a basis for precision clinical treatment. Appendiceal neuroendocrine tumors and other rare non-epithelial appendiceal tumors—including gastrointestinal stromal tumors, lymphomas, and neurogenic proliferations—fall outside the scope of this consensus and should be managed according to the respective disease-specific diagnostic and therapeutic guidelines.

Two

Diagnosis and Assessment of Appendiceal Epithelial Tumors and Peritoneal Metastasis

The diagnosis of appendiceal tumors and peritoneal metastases should be based on a comprehensive assessment incorporating multiple factors, including medical history, clinical manifestations, physical examination findings, imaging studies, tumor markers, and endoscopic examinations. For patients with high clinical suspicion, laparoscopic exploration may be performed to confirm the nature of the lesion. It is crucial to differentiate these conditions from other sources of peritoneal metastatic cancers, such as those originating from the ovary, gastrointestinal tract, or peritoneal mesothelioma, as well as from benign conditions like appendiceal abscesses and peritoneal tuberculosis.

1. Clinical Symptoms: In the early stages, when the appendiceal tumor is localized or has a small burden, it often presents with nonspecific symptoms or manifests as right lower quadrant pain similar to that seen in appendicitis. As the tumor spreads within the abdominal cavity and progresses, typical symptoms of peritoneal cancer—such as abdominal distension, abdominal pain, and weight loss—may emerge. In some patients, inguinal hernia may be the initial presenting symptom.

2. Digital Rectal Examination and Abdominal Palpation: For lesions involving the vesicorectal or uterovaginal pouches, digital rectal examination is a simple and effective physical examination method that can help identify pelvic masses. Abdominal palpation can also detect nodules in the abdominal wall or masses in the abdominal cavity. (Evidence Level: A; Strong Recommendation)

3. Imaging Studies: Enhanced CT of the abdomen and pelvis is the preferred imaging modality for evaluating peritoneal metastasis from appendiceal tumors, staging the disease, and follow-up after surgery. It offers advantages such as low cost, ease of operation, and straightforward image interpretation. However, it has lower sensitivity (11%–28%) in detecting lesions smaller than 1 cm and is less effective in identifying small bowel or mesenteric lesions. (Evidence Level: B; Strong Recommendation)

MRI has significant advantages in soft-tissue contrast and can detect smaller metastatic lesions. Moreover, MRI outperforms CT in assessing the peritoneal cancer index (PCI) score and can serve as a complementary imaging modality to enhanced CT. (Evidence level: B; Strong recommendation)

Fibroblast activation protein inhibitor (FAPI)-PET imaging is highly sensitive to small lesions and peritoneal metastases, but shows poor sensitivity for mucinous lesions. It outperforms conventional 18F-FDG (fluorodeoxyglucose) PET in detecting peritoneal metastases. (Evidence level: B; weak recommendation)

4. Blood tumor markers—carcinoembryonic antigen (CEA), carbohydrate antigen 19-9 (CA19-9), and carbohydrate antigen 125 (CA125)—have well-established clinical value in the diagnosis and management of colorectal cancer, hepatobiliary and pancreatic cancers, and ovarian cancer. They also play an important role in the diagnosis of peritoneal metastasis from appendiceal tumors, as well as in predicting recurrence and assessing prognosis. This consensus recommends regular monitoring of CEA, CA19-9, and CA125 levels during treatment and follow-up. (Evidence level: B; Strong recommendation)

In addition, circulating tumor DNA (ctDNA) in plasma can detect minimal residual disease (MRD) through mutation or methylation analysis, and has demonstrated remarkable efficacy in the early diagnosis of colorectal cancer, monitoring treatment response, and predicting prognosis. Similarly, ctDNA plays a positive role in monitoring recurrence after CCR-0 surgery for appendiceal tumors. It is recommended that institutions with appropriate resources should initiate and conduct further research in this area. (Evidence level: B; weak recommendation)

5. Other ancillary examinations: Preoperative colonoscopy can be used to evaluate the appendiceal orifice and to determine whether there are any associated colorectal lesions. Although it lacks sufficient sensitivity for detecting lesions located in the distal portion of the appendix, when combined with imaging studies, it still holds significant diagnostic value. (Evidence level: B; Strong recommendation)

Laparoscopic exploration is currently one of the most effective diagnostic methods for malignant peritoneal lesions. It allows for assessment of lesion extent, prediction of resectability, and acquisition of pathological samples. However, it’s important to note that laparoscopy may miss lesions in occult areas. (Evidence level: C; Strong recommendation)

Peritoneal nodule puncture biopsy and cytological examination of ascitic fluid can help clarify the origin of peritoneal lesions. When suggesting PMP or peritoneal metastasis, these procedures have certain diagnostic value; however, the overall positive rate is relatively low, and the puncture procedure carries risks of rupture, bleeding, and perforation. Therefore, indications for the procedure should be rigorously evaluated, and the procedure should be performed with caution. (Evidence level: C; weak recommendation)

Three

Intraoperative management of appendiceal epithelial tumors

Principles for Unexpected Findings and Additional Surgical Interventions After Surgery

(1) Principles for Managing Intraoperative Accidental Findings

1. Findings during other abdominal surgeries: During other abdominal surgical procedures, if an abnormal appendix is incidentally discovered—such as luminal dilation, irregular serosal surface, or a mass—a laparoscopic appendectomy or an appendectomy combined with partial cecum resection should be performed, and the specimen should be sent for pathological examination. (Evidence level: C; Strong recommendation)

2. Management after incidental intraoperative findings: When an appendiceal tumor or mucinous material in the peritoneal cavity is incidentally discovered during surgery, suggesting PMP, clinicians must be highly vigilant regarding the tumor’s biological behavior and the risk of dissemination. After appendectomy, if conditions permit, rapid intraoperative pathological examination can be performed to provide a preliminary assessment of the tumor’s nature. Particular attention should be paid to ensuring complete tumor resection and adopting a tumor-free surgical technique to avoid intraoperative perforation and spillage of tumor contents. If the surgical center is unable to perform HIPEC, the primary goals should be to establish a definitive diagnosis and manage the acute condition effectively, avoiding unnecessary procedures and minimizing the risk of peritoneal contamination and tumor dissemination.

In cases where the pathological condition is not yet clearly defined or in emergency settings, radical right hemicolectomy or CRS+HIPEC is not recommended as a first-line approach. Instead, surgical intervention should be limited to minimal procedures targeting the primary appendiceal lesion and peritoneal involvement. (Evidence level: C; Strong recommendation)

(2) Principles for Managing Additional Surgery Following Initial Surgery

For patients who have received a definitive pathological diagnosis following their initial surgery, the decision to proceed with additional surgery or treatment should take into account, in a comprehensive manner, the tumor’s histological type, extent of invasion, degree of peritoneal dissemination, the patient’s overall general condition, and relevant risk factors. In addition, for appendiceal neuroendocrine tumors, please refer to the relevant professional consensus guidelines for implementation. The specific treatment流程 is shown in Figure 1.

Figure 1 Flowchart of Treatment for Appendiceal Epithelial Tumors (Drawn by Zhu Akao, Sun Lifeng, and Xu Jinghong)

Note: ^a If the lesion extends beyond the appendix, partial cecectomy or ileocecal resection may be considered. For all pathological types staged as pTisN0M0 or earlier, appendectomy (R) is indicated. ₀ Simply remove it; ^b "Non-resectable" refers to cases where cytoreductive surgery is not expected to achieve CCR-0 or CCR-1. For low-grade appendiceal mucinous neoplasms (LAMN), staged or fractional cytoreductive surgery may be considered. If the LAMN involves only the appendiceal mesentery (T3N0M0), a right hemicolectomy with ileocecal resection may suffice. ^c Indications for adjuvant chemotherapy refer to colorectal adenocarcinoma; PCI stands for Peritoneal Cancer Index; RHC refers to right hemicolectomy; CRS denotes Cytoreductive Surgery; and HIPEC is Hyperthermic Intraperitoneal Chemotherapy.

1. Adenomas, serrated lesions, and polyps: In the absence of cellular atypia, appendectomy alone is sufficient. However, if the lesion diameter exceeds 1 cm or high-grade dysplasia is detected, extended resection involving ileocecal resection or even right hemicolectomy is recommended (lymph node dissection is not routinely indicated).

2. Low-grade appendiceal mucinous neoplasm (LAMN): Complete resection (R ₀ ) For patients with non-penetrating LAMN (pTis–4NxM0), standardized follow-up is sufficient. If the tumor is at stage pM1a and the peritoneal cancer index (PCI) is less than 3, perform R. ₀ After mucosal resection and clearance, patients can proceed to observation and follow-up. Direct right hemicolectomy combined with CRS or HIPEC is not recommended. (Evidence level: C; weak recommendation)

Incompletely resected (R ₁ or R ₂ ) It is recommended to add cecum resection (lymph node dissection is not recommended); if the tumor invades the mesoappendiceal region, right hemicolectomy is recommended. For patients with perforated lesions or pM1a stage with a PCI > 3, multi-regional involvement, or pM1b stage, CRS or HIPEC is recommended. (Evidence level: C; Strong recommendation)

3. High-grade appendiceal mucinous neoplasms (HAMNs): For patients with pTisN0M0 disease after complete resection, follow-up observation is sufficient. For patients with cTisN+ disease, right hemicolectomy (including lymph node dissection) is recommended. For non-perforated HAMNs staged pT1–3N0M0, right hemicolectomy (including lymph node dissection) is adequate. For perforated HAMNs (pT1–4NxM0), right hemicolectomy (including lymph node dissection) combined with cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) may be considered. In cases staged pTxNxM1b, right hemicolectomy (including lymph node dissection) combined with CRS and HIPEC is strongly recommended. Although there are limited data on the prognosis of HAMNs, guidelines from organizations such as the International Society for Peritoneal Surface Malignancies and the French Society of Gastroenterology recommend that HAMNs be treated similarly to appendiceal adenocarcinomas. (Evidence level: C; Strong recommendation)

4. Appendiceal adenocarcinoma (mucinous adenocarcinoma or signet-ring cell carcinoma): For non-perforated lesions of pT1–3NxM0, right hemicolectomy (including lymph node dissection) is strongly recommended. If perforation is present, combined CRS+HIPEC may be considered. For perforated lesions (pT4a–4bNxM0) and stage pTxNxM1b, right hemicolectomy (including lymph node dissection) plus CRS+HIPEC is strongly recommended. (Evidence level: B; Strong recommendation)

5. Appendiceal Goblet Cell Adenocarcinoma (GCA): For patients with G1-type GCA, if the tumor is staged as pT1 or pT2, the lesion size is less than 20 mm, the surgical margins are negative after local resection, the appendiceal mesentery involvement is less than 3 mm, there is no vascular or neural invasion, and the Ki-67 index is less than 2%, right hemicolectomy can be avoided provided all these criteria are met. If any one of these criteria is not met, right hemicolectomy (including lymph node dissection) is recommended. (Evidence Level: B; Strong Recommendation) For non-perforated GCA cases without peritoneal involvement, CRS+HIPEC is not recommended. However, for perforated GCA cases—regardless of whether peritoneal involvement is present—adjuvant CRS+HIPEC may be considered.

6. Women who are not of childbearing age or have no reproductive needs: For example, in cases of ruptured appendiceal tumors leading to unilateral metastatic ovarian malignancy (Krukenberg tumor), given the higher likelihood of occult contralateral metastasis and the increased risk of postoperative recurrence, we recommend performing ipsilateral oophorectomy combined with prophylactic contralateral oophorectomy. (Evidence level: B; Strong recommendation)

Four

Cytoreductive Surgery (CRS) and Organ Preservation Strategies

The prognosis of patients with appendiceal epithelial tumors and PMP primarily depends on the histological type and the completeness of the cytoreductive surgery (CRS). Complete CRS (CCRS) is defined as CC0 (no visible lesions) or CC1 (residual nodules ≤2.5 mm). High-grade histological subtypes and the presence of adenocarcinoma components significantly reduce disease-free survival (DFS) and overall survival (OS). For PMP patients undergoing simple CCRS combined with adjuvant therapy, the 5-year OS ranges from 15% to 67%, and the 10-year OS ranges from 0% to 32%. In contrast, for PMP patients treated with CRS plus HIPEC, the 5-year OS can reach 74.0% to 87.4%, and the 10-year OS can reach 63.0% to 70.3%.

1. Organ-preserving strategies in CRS surgery: In CRS for appendiceal epithelial tumors and PMP, the judicious application of organ-preserving techniques is crucial. (1) When the colon is involved, partial or total colectomy can be selected based on the distribution of the tumor to achieve complete tumor removal. (2) If the serosa of the gallbladder is invaded, cholecystectomy is recommended. (3) For most implantation lesions on the peritoneal surface, the hepatic diaphragmatic surface, or the diaphragmatic surface itself, diaphragmatic surface stripping, partial diaphragmatic resection, or various physical thermal ablation techniques (such as bipolar electrocoagulation, high-frequency electrosurgery, argon plasma coagulation, or ultrasonic scalpel) can be employed. (4) When the serosa of the stomach is involved, serosal stripping or partial gastrectomy can be performed. (5) For patients with involvement of the pelvic peritoneum, thorough excision of the pelvic peritoneum is necessary to eliminate implantation lesions. (6) For multiple small implantation lesions on the peritoneal or mesenteric surfaces, high-frequency electrosurgery or argon plasma coagulation can be used for superficial electrocautery ablation. (7) For areas of the gastrointestinal tract involving local damage to the muscular layer, timely suture repair of the seromuscular layer should be performed. (Evidence level: C; Strong recommendation)

2. Reproductive Organ Preservation Strategies for Women of Childbearing Age: For female patients of childbearing age, on the basis of ensuring the achievement of CCRS, efforts should be made to preserve uterine and ovarian function as much as possible. If removal is indeed necessary, thorough preoperative evaluation and communication are essential; when appropriate, it is recommended to consider fertility preservation options, such as oocyte or ovarian tissue cryopreservation. Although the probability of direct invasion of the uterine parenchyma by appendiceal mucinous tumors is relatively low, the incidence of ovarian dissemination is relatively high. For women of childbearing age with localized, low-grade PMP who do not have other adverse prognostic factors, cautious consideration may be given to preserving the ovaries. (Evidence Level: B; Weak Recommendation)

3. Prophylactic Ileostomy Strategy: For patients at high risk of anastomotic leakage or requiring extensive bowel resection, a prophylactic ileostomy is recommended to reduce postoperative complications. This approach is particularly suitable for patients whose tumors involve multiple segments of the colorectum or who undergo low rectal resection and anastomosis. Although an ileostomy can lower the risk of anastomotic leakage and intra-abdominal infection, it may affect the patient’s quality of life. Therefore, thorough preoperative communication is essential, and postoperative care and patient education should be strengthened. (Evidence Level: C; Strong Recommendation)

4. Cytoreductive Surgery with Limited Resection and Staged Treatment Strategies: For PMP patients who are unable to undergo complete cytoreductive surgery (CCRS) or cannot tolerate prolonged surgical procedures, maximal tumor debulking (MTD) can serve as an alternative approach. MTD can alleviate symptoms such as acute intestinal obstruction, renal failure, enterocutaneous fistula, and infection, and it can also prolong the “obstruction-free survival period,” with superior efficacy compared to simple repeated mucin clearance procedures. For patients with excessively high PCI scores or those preoperatively assessed as intolerant to prolonged surgery, a “two-stage” or “delayed” approach combining CRS and HIPEC may be considered to avoid the risks associated with a single, high-intensity surgical procedure. For PMP patients with longer recurrence intervals and good functional status, repeated or multiple cycles of CRS or HIPEC can also be considered to extend patient survival and control disease progression. (Evidence Level: C; Strong Recommendation)

5. Contraindications for CRS: Absolute contraindications include: extensive mesenteric and intestinal wall infiltration, an estimated postoperative residual small bowel length of less than 1.5 m, and tumor invasion of the proximal root of the superior mesenteric artery and vein leading to severe mesenteric contraction. (Evidence level: A; Strong recommendation)

Relative contraindications include: age >75 years, invasive histology with PCI >20 (excluding LAMN and HAMN), involvement of the hepatic hilum, pancreatic infiltration, ureteral obstruction, severe cardiopulmonary dysfunction, or coagulation abnormalities, etc. (Evidence level: A; Strong recommendation)

Five

HIPEC Treatment Principles and Drugs

1. HIPEC Technology and Timing of Treatment: There are differences in the application of HIPEC technology both domestically and internationally. In China, the closed-loop HIPEC approach is predominantly used; operational parameters and details can be referred to the “Expert Consensus on Clinical Application of Hyperthermic Intraperitoneal Chemotherapy in China (2019 Edition).” (Evidence Level: B; Strong Recommendation)

Regarding the timing of treatment, HIPEC should be initiated as early as possible, based on the patient’s postoperative recovery status and surgical safety. Studies have shown that within one week after CRS, repeating HIPEC treatment with different drugs three times every 24 hours is safe. It is recommended to administer 1 to 5 HIPEC sessions, tailored to the individual patient’s condition. (Evidence level: B; Strong recommendation)

2. Commonly Used Chemotherapeutic Agents for Hyperthermic Intraperitoneal Chemotherapy (HIPEC): The commonly used chemotherapeutic agents for HIPEC in appendiceal tumors include mitomycin C (MMC) at a dose of 20–30 mg/m², oxaliplatin at a dose of 130–200 mg/m², or raltitrexed at a dose of 2–4 mg/m². (Evidence Level: B; Strong Recommendation)

Studies have shown that oxaliplatin (200 mg/m²) and mitomycin C (total dose of 40 mg) are equally effective and safe when used in HIPEC for the treatment of appendiceal tumors. In HIPEC treatment for peritoneal metastases from colorectal cancer, a multicenter retrospective study revealed that the median overall survival (OS) in the oxaliplatin group (at the specified dose) was 47 months, significantly longer than the 39 months observed in the mitomycin C group (at the specified dose). However, to date, the optimal drug regimen remains unclear, and further clinical studies are still needed. When multiple HIPEC sessions are performed postoperatively, sequential use of different chemotherapy agents can be considered to avoid accumulation of chemotherapeutic drugs. (Evidence level: C; Strong recommendation)

3. Other intraperitoneal treatment approaches: In addition to HIPEC, other intraperitoneal chemotherapy methods include early postoperative intraperitoneal chemotherapy (enhanced peritoneal intracavity chemotherapy, EPIC). There are also reports of using intraperitoneal chemotherapy port systems for intraperitoneal infusion; however, further exploration is needed. (Evidence level: C; weak recommendation)

Existing studies have applied pressurized intraperitoneal aerosol chemotherapy (PIPAC) to the treatment of peritoneal metastasis from solid abdominal tumors and have achieved promising oncological outcomes. However, the efficacy of PIPAC in patients with peritoneal metastasis from appendiceal tumors still requires further research and exploration. (Evidence level: C; weak recommendation)

Six

Perioperative management

(1) Preoperative

1. Multidisciplinary Assessment: For patients scheduled for surgical treatment of appendiceal tumors and peritoneal metastases, it is recommended that they undergo a comprehensive assessment at a center with expertise in the diagnosis and management of peritoneal tumors, followed by a multidisciplinary team discussion. (Evidence Level: A; Strong Recommendation)

2. Preoperative Medication Management: For patients undergoing preoperative chemotherapy, platinum-based drugs (such as oxaliplatin) should be discontinued for at least 14 days prior to surgery; anti-angiogenic drugs (such as bevacizumab) should be discontinued for more than 28 days prior to surgery. Other medications should be adjusted according to standard surgical protocols to reduce the risk of intraoperative complications. (Evidence Level: A; Strong Recommendation)

3. Preoperative Integrated Prehabilitation: For patients undergoing CRS ± HIPEC, we recommend implementing a multimodal prehabilitation program that includes nutritional, physical, and psychological interventions to improve overall patient condition, reduce postoperative complications, and accelerate recovery. Specific measures include: (1) Lifestyle modifications, such as smoking cessation and alcohol abstinence; (2) Individualized nutritional interventions aimed at correcting malnutrition and increasing protein intake; (3) Exercise training to enhance muscle strength and cardiopulmonary function; (4) Psychological support through cognitive behavioral therapy to alleviate anxiety and depression. (Evidence Level: A; Strong Recommendation)

4. Standardize preoperative preparation: This includes enhanced recovery after surgery (ERAS) protocols, preoperative fasting, bowel preparation and oral antibiotics, thromboprophylaxis, surgical site preparation, and optimal patient positioning to ensure surgical safety and promote recovery. (Evidence level: A; Strong recommendation)

(2) Intraoperative

1. Blood Transfusion Strategy: For patients with extensive CRS and a high risk of substantial bleeding, we recommend preoperative autologous blood storage followed by reinfusion at the completion of surgery. A liberal blood transfusion strategy should be adopted, with supplemental plasma administration. If necessary, tranexamic acid should be used intraoperatively to reduce blood loss. (Evidence Level: C; Strong Recommendation)

2. Fluid Management and Internal Environment Control: Implement goal-directed fluid therapy based on cardiac output monitoring to avoid fluid overload. During the CRS and HIPEC phases, pay close attention to changes in body temperature, intra-abdominal pressure, and the internal environment to prevent hypothermia during CRS and hyperthermia during HIPEC. (Evidence Level: B; Strong Recommendation)

(3) Prevention and Treatment of Common Complications

1. Anastomotic leakage and enterocutaneous fistula: The incidence rates are comparable to those observed in conventional colorectal surgery; standardized anastomosis techniques can help reduce the risk. For high-risk patients, a preventive ileostomy may be considered. The timing of anastomosis should be determined individually, taking into account factors such as the patient’s clinical status, surgical conditions, and tissue blood supply. (Evidence level: B; Strong recommendation)

2. Urological Complications: For high-risk patients (e.g., those with pelvic tumors or imaging findings suggesting ureteral involvement), preoperative placement of a ureteral stent is recommended. During surgery, if the ureter is injured or repaired, a ureteral stent should be implanted simultaneously. (Evidence Level: C; Strong Recommendation)

3. Incision Complications: It is recommended to use either absorbable or nonabsorbable synthetic sutures for intermittent or continuous closure of the midline incision’s fascia. After surgery, wearing an elastic abdominal binder can help reduce incision tension, relieve pain, and promote recovery. (Evidence Level: A; Strong Recommendation)

seven

Neoadjuvant chemotherapy, adjuvant chemotherapy after surgery, and therapeutic chemotherapy

1. Neoadjuvant chemotherapy and adjuvant chemotherapy after surgery are not recommended: For low-grade PMP patients who, according to preoperative assessment, are suitable for CCRS+HIPEC, neoadjuvant chemotherapy prior to surgery has no significant effect and is therefore not recommended. Similarly, for low-grade PMP patients who have already undergone CCRS+HIPEC, adjuvant chemotherapy after surgery does not improve prognosis and is also not routinely recommended. (Evidence level: B; weak recommendation)

2. Neoadjuvant chemotherapy and adjuvant chemotherapy after surgery are recommended: For patients with high-grade PMP or high-grade PMP accompanied by signet-ring cells who are assessed preoperatively as suitable for CCRS + HIPEC and who remain asymptomatic, neoadjuvant chemotherapy may be considered. For patients with high-grade PMP or signet-ring cell carcinoma who have already undergone CCRS + HIPEC, adjuvant chemotherapy after surgery is recommended. Treatment regimens should follow those used for colorectal adenocarcinoma or incorporate participation in clinical trials. (Evidence level: B; Strong recommendation)

3. Therapeutic Chemotherapy: For PMP patients who are not suitable for surgery and/or have unresectable tumors but are in good physical condition and have high-grade disease or signet-ring cell features, palliative chemotherapy may be considered. Treatment regimens should prioritize chemotherapy combinations that include anti-angiogenic agents (such as bevacizumab). (Evidence Level: C; Weak Recommendation) For advanced appendiceal malignancies, targeted therapy and immunotherapy can draw on treatment approaches used for advanced colorectal cancer; however, their efficacy still requires further clinical studies to confirm. (Evidence Level: C; Weak Recommendation)

Eight

Follow-up method

Currently, there is no globally unified guideline for the follow-up of appendiceal tumors. Follow-up protocols for patients with appendiceal adenocarcinoma often draw on guidelines developed for colorectal cancer. Given the significant differences in biological behavior among various types of appendiceal tumors, it is recommended that individualized follow-up plans be developed based on stratification according to pathological type.

1. Low-grade PMP: It is recommended to undergo chest, abdominal, and pelvic CT scans along with tumor marker tests for CEA, CA19-9, and CA125 every 6 months for the first 3 years after surgery; then once a year for the subsequent 3 years; and thereafter, follow-up every 2 years until 15 years have passed since the initial treatment.

2. High-level PMP: It is recommended to undergo chest, abdominal, and pelvic CT scans along with tumor marker tests for CEA, CA19-9, and CA125 every 3 to 6 months after surgery for a period of 3 years; thereafter, repeat the examinations every 6 months for another 2 years; and then annually thereafter, continuing until 15 years after the initial treatment. (Evidence level: B; Strong recommendation)

Discussion of the list of expert committee members (sorted by the first letter of their surnames in pinyin):

Cai Guoxiang (Fudan University Affiliated Tumor Hospital), Chen Guofeng (The Second Affiliated Hospital of Zhejiang University School of Medicine), Ding Kefeng (The Second Affiliated Hospital of Zhejiang University School of Medicine), He Jinjie (The Second Affiliated Hospital of Zhejiang University School of Medicine), Hou Nengyi (Sichuan Academy of Medical Sciences—Sichuan Provincial People’s Hospital), Hu HanGuang (The Second Affiliated Hospital of Zhejiang University School of Medicine), Hu Huabin (The Sixth Affiliated Hospital of Sun Yat-sen University), Hu Yeting (The Second Affiliated Hospital of Zhejiang University School of Medicine), Huang Feng (Fujian Provincial Tumor Hospital), Huang Chaoqun (Zhongnan Hospital of Wuhan University), Li Yan (Beijing Century Tan Hospital Affiliated to Capital Medical University/Beijing Changgeng Hospital Affiliated to Tsinghua University), Pang Minghui (Sichuan Academy of Medical Sciences—Sichuan Provincial People’s Hospital), Pei Wei (Cancer Hospital of Chinese Academy of Medical Sciences), Shen Tu Xiaoyan (The Second Affiliated Hospital of Zhejiang University School of Medicine), Song Yongchun (First Affiliated Hospital of Xi’an Jiaotong University), Sun Lifeng (The Second Affiliated Hospital of Zhejiang University School of Medicine), Sun Yongkun (Cancer Hospital of Chinese Academy of Medical Sciences), Tang Hongsheng (Tumor Hospital Affiliated to Guangzhou Medical University), Tao Kaixiong (Union Hospital Affiliated to Tongji Medical College, Huazhong University of Science and Technology), Wang Hui (The Sixth Affiliated Hospital of Sun Yat-sen University), Wang Jian (The Second Affiliated Hospital of Zhejiang University School of Medicine), Wang Jin (Tumor Hospital Affiliated to Guangzhou Medical University), Wang Wei (The First Affiliated Hospital of Guangzhou University of Chinese Medicine), Wang Huaiming (The Sixth Affiliated Hospital of Sun Yat-sen University), Wang Jinshen (Provincial Hospital Affiliated to Shandong First Medical University), Wang Junfeng (Tianjin Medical University Cancer Hospital), Wang Renjie (Fudan University Affiliated Tumor Hospital), Wang Ximo (The Third Central Hospital of Tianjin), Wang Yanli (The First Affiliated Hospital of Zhengzhou University), Wang Zhanhuai (The Second Affiliated Hospital of Zhejiang University School of Medicine), Wang Zhengwen (Hainan Provincial Tumor Hospital), Wu Chuanqing (Union Hospital Affiliated to Tongji Medical College, Huazhong University of Science and Technology), Xu Jinghong (The Second Affiliated Hospital of Zhejiang University School of Medicine), Xu Zhengwen (Suining Central Hospital of Sichuan Province), Yan Jun (Union Hospital Affiliated to Fujian Medical University), Yang XiaoJun (Zhongnan Hospital of Wuhan University), Zheng Song (The First People’s Hospital of Hangzhou Affiliated to the School of Medicine of Westlake University)

Writing Team:

Zhu Akao (The Second Affiliated Hospital of Zhejiang University School of Medicine), Chen Chao (The Second Affiliated Hospital of Zhejiang University School of Medicine), Lu Juan (Cancer Hospital of the Chinese Academy of Medical Sciences), Yang Keli (The Sixth Affiliated Hospital of Sun Yat-sen University), Yang Qi (The Second Affiliated Hospital of Zhejiang University School of Medicine), He Xue Ren (The Second People’s Hospital of Chengdu, Affiliated to Sichuan University)

Source: Chinese Journal of Gastrointestinal Surgery