Analysis of causes and prognostic impact of tube occlusion during hyperthermic intraperitoneal chemotherapy for appendiceal pseudomyxoma peritonei.

BACKGROUND: Appendiceal pseudomyxoma peritonei (PMP), a rare tumor from mucinous appendiceal origins, is treated with Cytoreductive Surgery (CRS) and Hyperthermic Intraperitoneal Chemotherapy (HIPEC). However, tubing blockages during HIPEC treatment pose a common challenge, impeding the smooth progression of therapy. Few studies to date have explored the incidence and risk factors of tube occlusion during HIPEC in patients with appendiceal PMP, as well as its adverse impact on postoperative complications. METHODS: From October 2017 to June 2023, a total of 80 patients with appendiceal PMP undergoing combined CRS and HIPEC were included in this study. Tubing blockage events were strictly defined, with patients experiencing blockages during HIPEC treatment allocated to the study group, while those with unobstructed perfusion were assigned to the control group. A comparative analysis was conducted between the two groups regarding post-HIPEC health assessments and occurrence of complications. Risk factors for luminal occlusion during closed HIPEC procedures were identified through univariate and multivariate analysis of data from 303 HIPEC treatments. RESULTS: Tubing blockages occurred in 41 patients (51.3%). The study group experienced prolonged gastrointestinal decompression time (4.1 ± 3.0 vs. 2.5 ± 1.7 days, P = 0.003) and prolonged time to bowel movement (6.1 ± 2.3 vs. 5.1 ± 1.8 days, P = 0.022) compared to the control group. There was no significant difference in the incidence of complications between the two groups. The 1-year survival rate postoperatively was 97%, and the 3-year survival rate was 81%, with no association found between tubing blockage and poorer survival. Additionally, In 303 instances of HIPEC treatment among these 80 patients, tube occlusion occurred in 89 cases (89/303, 29.4%). Multivariable logistic regression analysis revealed age, diabetes, hypertension, and pathology as independent risk factors for tube occlusion. CONCLUSION: Tubing blockages are a common occurrence during HIPEC treatment, leading to prolonged postoperative gastrointestinal functional recovery time. When patients are elderly and have concomitant hypertension and diabetes, along with a histological type of low-grade mucinous tumor, the risk of tube occlusion increases. However, this study did not find a significant correlation between tubing blockage and the incidence of postoperative complications or overall patient survival.

Transhepatic Bromelain and Acetylcysteine for Treatment of Posterior Gastric Pseudomyxoma Peritonei: A Case Report.

BACKGROUND/AIM: Pseudomyxoma peritonei (PMP) is a rare condition characterized by diffuse spread of mucinous tumors within the peritoneal cavity. Traditional treatment modalities, such as cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) are challenging in cases of recurrent disease, owing to anatomical complexities and increasing morbidity and mortality risk. BromAc® has emerged as a novel, targeted therapy for PMP with evidence for intra-tumoral administration to break down mucin deposits. CASE REPORT: We present a 70-year-old female with confirmed diagnosis of symptomatic appendiceal PMP situated behind the stomach, refractory to prior CRS and HIPEC. Transhepatic intra-tumor injection of BromAc® was performed, guided by imaging, with catheter placement into the posterior gastric mucinous tumor. The procedure was well-tolerated, and post-treatment imaging revealed a significant 40% reduction in tumor burden. The patient had fever on cycle days two and three, which self-resolved and septic screen performed was negative. Following BromAc® administration, the patient demonstrated improvement in symptoms and quality of life. CONCLUSION: This case highlights the potential efficacy and safety of transhepatic administration of BromAc® for the treatment of recurrent PMP behind the stomach. The targeted delivery of BromAc® directly into a mucinous tumor via the transhepatic route offers a minimally invasive alternative for cases where traditional surgical interventions pose challenges. However, further research and clinical trials are warranted to validate the broader applicability of this novel approach, assess long-term outcomes, and optimize procedural parameters for enhanced therapeutic outcomes in PMP treatment.

Establishment and characterization of NCC-PMP2-C1: a novel patient-derived cell line of pseudomyxoma peritonei with signet ring cells.

Pseudomyxoma peritonei (PMP) is a rare phenomenon, characterized by accumulation of mucus in the abdominal cavity due to a mucinous neoplasm. Histologically, PMP is divided into three prognostic classes, namely low-grade mucinous carcinoma peritonei (LGMCP), high-grade mucinous carcinoma peritonei (HGMCP), and high-grade mucinous carcinoma peritonei with signet ring cells (HGMCP-S); HGMCP-S exhibits the worst prognosis. Complete cytoreductive surgery and hyperthermic intraperitoneal chemotherapy have been established as the standard therapy for PMP. However, 50% of patients with PMP experience a recurrence, and 30-40% are unable to receive the standard treatment due to invasive diseases. Therefore, novel therapies are required for their treatment. Although patient-derived cell lines are important tools for basic and pre-clinical research, PMP cell lines derived from patients with HGMCP-S have never been reported. Thus, we established a novel PMP cell line NCC-PMP2-C1, using surgically resected tumor tissue from a patient with HGMCP-S. NCC-PMP2-C1 cells were maintained for more than five months and passaged 30 times under culture conditions. NCC-PMP2-C1 cells exhibited multiple deletions and somatic mutations, slow growth, histological features, and dissemination of tumor cells in nude mice. Screening for the anti-proliferative effects of anti-cancer drugs on cells revealed that bortezomib, mubritinib, and romidepsin had a significant response against NCC-PMP2-C1 cells. Thus, the NCC-PMP2-C1 cell line is the first PMP cell line harboring signet ring cells and will be a valuable resource for basic and preclinical studies of HGMCP-S.

Health related quality of life is excellent and sustained at two decades after cytoreductive surgery and hyperthermic intraperitoneal chemotherapy in survivors of pseudomyxoma peritonei of appendiceal origin.

INTRODUCTION: Optimal management of pseudomyxoma peritonei (PMP) is by cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC), which can achieve 20-year disease-free, and overall survival. There is limited information on the health-related quality of life (HRQOL) of PMP survivors beyond five years. We report longitudinal HRQOL in patients with PMP of appendiceal origin up to 17-years after their CRS and HIPEC in 2003-2004. METHODS: Patients had HRQOL assessed with EORTC QLQ-C30 questionnaires pre-operatively, and at 1-, 10- and 17-years post-operatively. Comparisons in global health-related QOL (global-HRQOL) measures were made with (1) an age- and sex-matched normal European population, (2) between patients who underwent complete cytoreduction (CRS CC0/1) versus maximal tumor debulking (MTD), and (3) between those with and without peritoneal recurrence. RESULTS: Forty-six patients underwent CRS & HIPEC for appendiceal PMP. One patient withdrew from the study. Of the 45 patients, 23 patients were alive at ten and 15 patients at 17-years post-operatively. 21/23 (91%) and 14/15 patients (93%) completed questionnaires respectively. Pre-operatively, patients had significantly lower global-HRQOL compared with the reference population. Over follow-up, patients experienced improvements in their global-HRQOL. By post-operative year-10 and -17, there was no difference between the global-HRQOL of patients and reference population. As expected, patients with CC0/1 and without peritoneal tumor recurrence had better global-HRQOL at ten- and 17-years post-operatively compared with those with MTD or recurrence. CONCLUSIONS: Optimal CRS and HIPEC is an effective treatment for appendiceal PMP that can achieve long-term survival. HRQOL is excellent and maintained, in those who have CC0/1 without recurrence.

Targeted Next-Generation Sequencing Improves the Prognostication of Patients with Disseminated Appendiceal Mucinous Neoplasms (Pseudomyxoma Peritonei).

BACKGROUND: Appendiceal mucinous neoplasms (AMNs) with disseminated disease (pseudomyxoma peritonei) are heterogeneous tumors with variable clinicopathologic behavior. Despite the development of prognostic systems, objective biomarkers are needed to stratify patients. With the advent of next-generation sequencing (NGS), it remains unclear if molecular testing can improve the evaluation of disseminated AMN patients. METHODS: Targeted NGS was performed for 183 patients and correlated with clinicopathologic features to include American Joint Committee on Cancer/World Health Organization (AJCC/WHO) histologic grade, peritoneal cancer index (PCI), completeness of cytoreduction (CC) score, and overall survival (OS). RESULTS: Genomic alterations were identified for 179 (98%) disseminated AMNs. Excluding mitogen-activated protein kinase genes and GNAS due to their ubiquitous nature, collective genomic alterations in TP53, SMAD4, CDKN2A, and the mTOR genes were associated with older mean age, higher AJCC/WHO histologic grade, lymphovascular invasion, perineural invasion, regional lymph node metastasis, and lower mean PCI (p < 0.040). Patients harboring TP53, SMAD4, ATM, CDKN2A, and/or mTOR gene alterations were found to have lower OS rates of 55% at 5 years and 14% at 10 years, compared with 88% at 5 years and 88% at 10 years for patients without the aforementioned alterations (p < 0.001). Based on univariate and multivariate analyses, genomic alterations in TP53, SMAD4, ATM, CDKN2A, and/or the mTOR genes in disseminated AMNs were a negative prognostic factor for OS and independent of AJCC/WHO histologic grade, PCI, CC score, and hyperthermic intraperitoneal chemotherapy treatment (p = 0.006). CONCLUSIONS: Targeted NGS improves the prognostic assessment of patients with disseminated AMNs and identifies patients who may require increased surveillance and/or aggressive management.

[Incidental finding of appendiceal mucinous neoplasms]. / Zufallsbefund muzinöse Neoplasie der Appendix.

Low-grade appendiceal mucinous neoplasms (LAMN) are rare and are diagnosed in at least 0.13% of appendectomies in Germany, although significant underreporting is likely. Perforation of the tumors can result in abdominal mucinous collections, so-called pseudomyxoma peritonei (PMP). The challenge in the treatment of LAMN is the adequate approach to the incidental finding of these tumors. If a mucinous neoplasm is preoperatively suspected in cases of an acute condition, usually appendicitis, it must be weighed up whether a conservative approach is justifiable or whether immediate appendectomy is necessary. If this is the case, an intraoperative perforation of the appendix must be avoided and the complete abdominal cavity must be inspected for mucin deposits. If conservative treatment is possible, further treatment should take place at a specialized center. If the neoplasm is first found incidentally during surgery, perforation of the appendix should also be avoided and the entire abdominal cavity should be inspected for a PMP. If a PMP is present cytoreduction and hyperthermic intraperitoneal chemotherapy (HIPEC) should be performed in a specialized center. If LAMN are found during the postoperative histological work-up, it should be evaluated whether a perforation was present and mucin collections are noted in the surgical report. In the case of LAMN without evidence of a PMP, appendectomy is the adequate treatment. In cases of intra-abdominal mucinous collections, samples should be taken and further treatment should be performed at a center with sufficient expertise. An ileocecal resection or oncological hemicolectomy is not indicated. After adequate treatment, all patients should receive a follow-up using cross-sectional imaging (preferably magnetic resonance imaging, MRI) and determination of the tumor markers CEA, CA 19-9 and CA 125.

Development and Validation of Nomograms to Predict Survival in Patients Undergoing Complete Cytoreduction and Hyperthermic Intraperitoneal Chemotherapy for Pseudomyxoma Peritonei of Appendiceal Origin.

Importance: Pseudomyxoma peritoni, a rare condition characterized by mucinous ascites and peritoneal deposits, mainly originates from a ruptured mucinous appendix tumor and is considered an indolent disease but can progress and become fatal. Optimal treatment to improve cure and survival rates involves complete cytoreductive surgery (CCRS) and hyperthermic intraperitoneal chemotherapy (HIPEC). Accurate predictive models are useful in supporting and informing treatment strategies and stratifying patient follow-up. Objective: To evaluate the prognostic significance of clinically important variables and generate validated nomograms to predict overall (OS) and disease-free survival (DFS) following CCRS and hyperthermic intraperitoneal HIPEC for pseudomyxoma peritonei (PMP) of appendiceal origin. Design, Setting, and Participants: This retrospective study used prospectively collected data on patients who had cytoreductive surgery (CRS) and HIPEC in a single institution between 1994 and 2018. The cohort was randomly allocated into development (70%) and validation (30%) sets. Univariate and multivariate analyses were performed with Cox proportional hazards regression. Main Outcomes and Measures: A prediction model was developed with significant prognostic factors identified by multivariate analysis. The model's prognostic performance was evaluated with the concordance index (C index). The nomogram was calibrated by comparing the predicted and observed probabilities. Results: Of 2637 CRS and HIPEC operations, 1102 patients (female, 64.4%; median age [IQR], 57.0 [48.0-66.0] years) (41.8%) had CCRS for PMP of appendiceal origin. Elevated tumor markers, peritoneal carcinomatosis index, gastrectomy, and tumor grade were independent predictive factors for DFS. Gender, age, elevated tumor makers, peritoneal carcinomatosis index, and tumor grade influenced OS. The nomograms were generated with respective prognostic factors. The nomograms showed good performance in predicting survival. Median OS of the cohort was 16.5 years (95% CI, 13.7-19.2) with a 5-year probability of survival of 80.2%. The median DFS was 10.3 years (95% CI, 7.2- 13.3) and the 5-year probability of recurrence-free survival was 60.5%. Conclusions and Relevance: Clinically important independent predictors for survival and recurrence were selected to develop the nomograms for OS and DFS. These 2 nomograms are user friendly and useful tools for patient management with clinical trial design applications.

Which classification system defines best prognosis of mucinous neoplasms of the appendix with peritoneal dissemination: TNM vs PSOGI?

AIMS: Several classification systems are used for pseudomyxoma peritonei. The four-tiered classification system proposed by Peritoneal Surface Oncology Group International (PSOGI) and the two-tiered proposed by the eighth edition of the American Joint Committee on Cancer (AJCC) result from evolution in terminology and pathological insight. The aim is to evaluate the impact of PSOGI and eighth edition of the AJCC classifications on survival. METHODS: Pathological slides were reviewed from a prospectively maintained database including patients treated with cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for an appendiceal mucinous neoplasm with peritoneal dissemination between January 2009 and December 2019. Patients were reclassified according to PSOGI and AJCC eighth edition criteria. Survival analysis evaluated the impact of each classification system on overall survival (OS) and disease-free survival (DFS) while the concordance-index evaluated their predictive power. RESULTS: 95 patients were identified; 21.1% were reclassified as acellular mucin, 55.8% as low-grade mucinous carcinoma peritonei, 8.4% as high-grade MCP (HGMCP) and 14 as HGMCP with signet ring cells. Median OS was not reached, 5-year OS and DFS were 86.1% and 51.5%, respectively. Multivariate analysis revealed significant associations with OS (PSOGI: HR 10.2, p=0.039; AJCC: HR 7.7, p=0.002) and DFS (PSOGI: HR 12.7, p=0.001; AJCC: HR 3.7, p<0.001). The predictive capacity of both classification systems was unacceptable for OS and DFS (concordance-index values <0.7). CONCLUSIONS: Both classification systems behaved similarly when stratifying our series into prognostic groups. The PSOGI classification provides better histopathological description, but histology alone is insufficient for adequate patient prognostication.

The Impact of Low Skeletal Muscle Mass on Short- and Long-Term Outcomes After Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy.

BACKGROUND: Cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) is a potentially curative treatment for peritoneal metastases from colorectal cancer (CRC) or pseudomyxoma peritonei (PMP). Because of the considerable morbidity of this treatment, optimal patient selection is key. This study aimed to assess the impact of low skeletal muscle mass (SMM) on outcomes after CRS-HIPEC. METHODS: Patients who underwent CRS-HIPEC between 2014 and 2020 at a tertiary center were included. SMM was measured on computed tomography by means of the L3 muscle index. Postoperative complications and survival outcomes were compared between groups by use of logistic regression and Kaplan-Meier survival analyses. RESULTS: Of 284 included patients, 149 had low SMM. Occurrence of severe postoperative complications did not differ between groups (28.9% for patients with low vs. 34.1% for patients with normal SMM). Low SMM was not associated with postoperative complications (p = 0.344). For CRC patients, no significant differences were observed in disease-free (DFS) or overall survival (OS) between patients with low (median DFS 7 months [IQR 4-14], median OS 33 months [IQR 14-NR]) and patients with normal SMM (median DFS 8 months [IQR 5-20], median OS 35 months [IQR 18-NR]). Regarding PMP, survival outcomes did not significantly differ between groups (3-year DFS 47.3% for patients with low SMM vs. 54.5% for patients with normal SMM, p = 0.676; 3-year OS 70.8% vs. 90.9% respectively, p = 0.172). CONCLUSIONS: Low SMM could not be identified as a predictor of severe complications or survival outcomes after CRS-HIPEC.

The Role of Microorganisms in Appendiceal Pseudomyxoma Peritonei: A Review.

Pseudomyxoma peritonei (PMP) is a rare clinical syndrome. It originates from neoplasms of the appendix and leads to the formation of peritoneal implants and the accumulation of mucinous ascites. PMP represents a spectrum of low to high-grade disease. Despite aggressive management, many PMP patients recur, leading to debilitating symptoms and few treatment options. Therefore, scientists have continued to look for ways to improve treatment and further understand disease pathogenesis. Microorganisms were previously hypothesized to play a role in PMP progression and development. Hence, antibacterial treatment was suggested by some authors, but the data were limited. In this paper, we review the current data on the role of bacteria in PMP, discuss the significance, and suggest possible solutions to the inherent challenges in these studies. Given the limitations of the discussed studies, we remain skeptical about introducing novel antibacterial treatment into clinical practice at this time; however, the available data are valuable and indicate that more research into the molecular mechanisms of PMP is needed.

Comprehensive Understanding and Evolutional Therapeutic Schemes for Pseudomyxoma Peritonei: A Literature Review.

Pseudomyxoma peritonei is an infrequent solid tumor in clinical practice. The low morbidity and deficient understanding of this mucus-secreting malignant disease increase the risks of delayed identification or uncontrollable deterioration. In quite a lot cases, patients go through complete cytoreduction surgery and hyperthermic intraperitoneal chemotherapy could receive a long time survival over 5 years. But the recurrence rate is also hard to overlook. Unlike other types of cancer, the standard treatment for this considerable groups has not been confirmed yet. With the advanced medical progression, studies have been carrying out based on pathogenesis, biological characters, and mutated gene location. All but a few get statistical survival benefits, let alone the breaking progress on research or therapeutic practice in the field. We try to give a comprehensive exposition of pseudomyxoma peritonei around the epidemiology, radiologic features, clinical manifestation, present treatment and promising schemes, hoping to arise much attention and reflection on the feasible solutions, especially for the recrudescent part.

Diagnostic performance of positron emission tomography in the staging of pseudomyxoma peritonei.

BACKGROUND: Pseudomyxoma peritonei (PMP) is a rare clinical entity, commonly derived from a mucin-producing tumour of the appendix. International consensus is unclear on the role of positron emission tomography (PET) in preoperative staging. This study aimed to assess the ability of preoperative PET in predicting the histological grade of PMP. METHODS: All patients scheduled for cytoreductive surgery (CRS) +/- hyperthermic intraperitoneal chemotherapy (HIPEC) for PMP who underwent preoperative PET at a single centre between June 2007 and June 2020 were included. A nuclear medicine physician, blinded to patient outcomes, retrospectively reviewed imaging studies to assess for maximum tumour standardised uptake value (SUV) to mean liver SUV ratio (SUVTLR) and maximum porta hepatis SUV to mean liver SUV ratio (SUVPLR). RESULTS: Between April 2007 and December 2020, a total of 204 patients underwent surgical intervention for PMP. Of these, 124 (60.8%) met the inclusion criteria. Median peritoneal carcinomatosis index for the entire cohort was 9 and complete cytoreduction (CC0/1) was achieved in 109 (88%) patients. Patients with high-grade PMP were more likely to have diffuse peritoneal disease (p < 0.001) and higher SUVTLR (p<0.001). The area under the ROC curve (AUC) of SUVTLR in predicting high-grade pathology was 71% (p = 0.003). Patients with a SUVTLR ≤ 0.78 had improved disease-free survival (p = 0.042). CONCLUSION: Preoperative PET showed positive correlation with high-grade PMP and acceptable sensitivity and specificity as a diagnostic tool. PET should be considered a useful adjunct to standard imaging for predicting histological grade in the staging of patients with PMP.

Peritoneal metastases found in routinely resected specimens after cytoreductive surgery and heated intraperitoneal chemotherapy.

INTRODUCTION: Peritoneal metastases (PM) originating from colorectal cancer (CRC) and pseudomyxoma peritonei (PMP) can be treated with cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC). Certain sites in the peritoneal cavity are prone to contain PM and are, therefore, routinely resected. The aim of this study is to investigate the frequency of disease in CRS specimens routinely resected. Secondly, to investigate if the risk of finding PM in routinely resected specimen is associated with involvement of anatomic related peritoneal areas. MATERIALS AND METHODS: This study investigated 433 patients diagnosed with PMP (n = 119) or PM from CRC (n = 314) and operated with CRS + HIPEC between June 2006 and November 2020 at a national center. Baseline data were prospectively registered. Pathology reports were reviewed for the presence of metastases in the routinely resected umbilicus, ligamentum teres hepatis, ovaries and greater omentum. Tumor extent was estimated using the Dutch region count. RESULTS: PM was found in 14.7% of umbilical resections, in 17.4% of the resected ligamentum teres hepatis, in 48.2% of the resected ovaries and in 49.5% of the greater omentum specimens. We found an association between macroscopic disease involvement of the nearest region and risk of PM found in the related resections. Seven of 31 women with no macroscopically visible disease in the pelvis had PM diagnosed in the resected ovaries. CONCLUSIONS: A substantial proportion of routine resections held histologic verified PM. Our results may advocate for a routinely performed resection of the umbilicus, ligamentum teres hepatis, ovaries and greater omentum.

A Proposal for Modification of the PSOGI Classification According to the Ki-67 Proliferation Index in Pseudomyxoma Peritonei.

BACKGROUND: Pseudomyxoma peritonei (PMP) is a rare malignancy, classified according to the Peritoneal Surface Oncology Group International (PSOGI) classification, whose response to treatment remains highly heterogeneous within the high-grade (HG) category. Molecular profiling of PMP cases might help to better categorize patients and predict treatment responses. METHODS: We studied the Ki-67 proliferation rate and P53 overexpression in tissue samples from our historical cohort of HG-PMP patients. We established as cut-off levels the third quartile of each marker to perform univariate and multivariate Cox regression survival analyses. According to these results, the HG-PMP category was divided into subcategories and a new survival analysis was performed. RESULTS: A total of 90/117 patients with PMP undergoing cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) were selected for secondary analysis. The survival analysis of the HG-PMP category for preoperative variables showed that a proliferation index defined by Ki-67 >15% is a bad prognostic factor, with a hazard ratio (HR) of 3.20 (95% confidence interval [CI] 1.24-8.25). Accordingly, the HG-PMP group was divided using the Ki-67 15% cut-off. The new PSOGI/Ki-67 variable was an independent prognostic factor for overall survival (OS), with an HR of 3.74 (95% CI 1.88-7.47), and disease-free survival (DFS), with an HR of 4.184 (95% CI 1.79-9.75). The estimated 5-year OS rate was 100%, 70% and 24% for the LG-PMP, HG-PMP ≤15% and HG-PMP >15% groups, respectively (p = 0.0001), while the 5-year DFS rate was 90%, 44% and 0%, respectively (p = 0.0001). CONCLUSION: Division of the HG-PMP category of the PSOGI classification, according to the Ki-67 proliferation index, provides two well-defined subcategories, with significant differences in terms of OS and DFS, and hence high prognostic value.

The Frontiers of Appendiceal Controversies: Mucinous Neoplasms and Pseudomyxoma Peritonei.

Appendiceal mucinous neoplasms show a range of morphologic features and biological risk. At one end of the spectrum, high-grade adenocarcinomas are cytologically malignant with infiltrative invasion, lymph node metastases, and behavior similar to that of extra-appendiceal mucinous adenocarcinomas. At the other end, mucinous neoplasms confined to the mucosa are uniformly benign. Some cases lying between these extremes have potential risk to metastasize within the abdomen despite a lack of malignant histologic features. They show "diverticulum-like," pushing invasion of mostly low-grade epithelium through the appendix with, or without, concomitant organizing intra-abdominal mucin. The latter condition, widely termed "pseudomyxoma peritonei," tends to pursue a relentless course punctuated by multiple recurrences despite cytoreductive therapy, culminating in death for many patients. The combination of bland histologic features and protracted behavior of peritoneal disease has led some authors to question whether these metastatic tumors even represent malignancies. The World Health Organization and its cadre of experts widely promote usage of "low-grade appendiceal mucinous neoplasm" as an umbrella term to encompass benign and malignant conditions, as well as those that have uncertain biological potential. Although this practice greatly simplifies tumor classification, it causes confusion and consternation among pathologists, clinical colleagues, and patients. It also increases the likelihood that at least some patients will undergo unnecessary surveillance for, and treatment of, benign neoplasms and non-neoplastic conditions. The purpose of this review is to critically evaluate the relevant literature and discuss a practical approach to classifying appendiceal mucinous neoplasms that more closely approximates their biological risk.

Overall Survival is More Closely Associated with Peritoneal than Primary Appendiceal Pathological Grade in Pseudomyxoma Peritonei with Discordant Pathology.

BACKGROUND: The WHO classification of mucinous appendix neoplasms and pseudomyxoma peritonei (PMP) describes low- and high-grade histology and is of prognostic importance. The metastatic peritoneal disease grade can occasionally be different from the primary appendix tumor. This analysis aimed to report outcomes from a high-volume center in patients with pathological discordance. METHODS: This was a retrospective analysis of prospective data of patients treated by cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) for PMP at a single institution between January 2016 and December 2020. Reporting was by pathologists with a special interest in peritoneal malignancy. Discordant pathology was classified as a low-grade primary appendix tumor with high-grade peritoneal disease, or a high-grade primary appendix tumor with low-grade peritoneal disease. Outcomes analyzed were overall and recurrence-free survival, and Kaplan-Meier survival curves and the log-rank test were used to analyze the outcomes. RESULTS: Between 2016 and 2020, 830 patients underwent CRS and HIPEC for PMP, of whom 37 (4.4%) had discordant pathology. The primary appendix tumors were low-grade in 23 patients and high-grade in 14 patients. The median Peritoneal Cancer Index (PCI) was significantly higher in patients with a low-grade primary tumor (31 vs. 16; p = 0.001), while complete cytoreduction (CC0/1) was achieved in 31/37 (83.8%) patients. The median follow-up was 19 months. Overall survival was worse in those with high-grade peritoneal disease (p = 0.029), whereas recurrence-free survival was similar in both groups (p = 0.075). CONCLUSION: In PMP with pathological discordance, the peritoneal disease grade influences prognosis and survival.

Tumor-stroma ratio as a new prognosticator for pseudomyxoma peritonei: a comprehensive clinicopathological and immunohistochemical study.

BACKGROUND: As a rare clinical tumor syndrome with an indolent clinical course and lack of pathognomonic symptoms, pseudomyxoma peritonei (PMP) is usually diagnosed at an advanced stage. In-depth pathological analysis is essential to assess tumor biological behaviors, assist treatment decision, and predict the clinical prognosis of PMP. The tumor-stroma ratio (TSR) is a promising prognostic parameter based on the tumor and stroma. This study explored the relationship between TSR and the pathological characteristics and prognosis of PMP. METHODS: PMP patients with complete data who underwent cytoreductive surgery plus hyperthermic intraperitoneal chemotherapy were enrolled. The TSR of postoperative pathological images was quantitatively analyzed by Image-Pro Plus. Then the relationship between TSR and the clinicopathological characteristics, immunohistochemical characteristics and prognosis of PMP was analyzed. RESULTS: Among the 50 PMP patients included, there were 27 males (54.0%) and 23 females (46.0%), with a median age of 55 (range: 31-76) years. 25 (50.0%) patients were diagnosed with low-grade PMP (LG-PMP), and 25 (50.0%) were diagnosed with high-grade PMP (HG-PMP). There were 4 (8.0%) patients with vascular tumor emboli, 3 (6.0%) patients with nerve invasion, and 5 (10.0%) patients with lymph node metastasis. The immunohistochemical results showed that the Ki67 label index was < 25% in 18 cases (36.0%), 25 - 50% in 18 cases (36.0%) and > 50% in 14 cases (28.0%). The range of TSR was 2 - 24% (median: 8%). The cutoff value of TSR was 10% based on the receiver operating characteristic (ROC) curve and X-Tile analysis. There were 31 (62.0%) cases with TSR < 10% and 19 (38.0%) cases with TSR ≥ 10%. The TSR was closely related to histopathological type (P < 0.001) and Ki67 label index (P < 0.001). Univariate analysis showed that preoperative carcinoembryonic antigen (CEA), preoperative carbohydrate antigen 19-9, pathological type, vascular tumor emboli and TSR influenced the prognosis of PMP patients (P < 0.05). Multivariate analysis showed that preoperative CEA, vascular tumor emboli and the TSR were independent prognostic factors. CONCLUSIONS: The TSR could be a new independent prognosticator for PMP.

Peritoneal Spread of Low-grade Appendiceal Tumours - 2 Days of Early Postoperative Intra-peritoneal Chemotherapy Are Enough.

BACKGROUND/AIM: While controversial, cytoreductive surgery (CRS) with heated intra-peritoneal chemotherapy (HIPEC) and early postoperative intra-peritoneal chemotherapy (EPIC) remains the mainstay of treatment for low grade appendiceal neoplasm with pseudomyxoma peritonei (PMP). Our study aimed to investigate the difference in survival when administering HIPEC alone vs. HIPEC + EPIC. Additionally, we examined whether the duration of EPIC affects survival. PATIENTS AND METHODS: We compared the difference in survival in 238 patients who underwent CRS + HIPEC alone vs. CRS + HIPEC/EPIC combination for low grade appendiceal cancer. We also compared short course (1-2 days) vs. long course (3-5 days) of EPIC. RESULTS: HIPEC/EPIC combination group (n=179) showed a significantly better 5-year survival of 95% compared to 71% in HIPEC alone (n=59). There was no statistically significant difference in 5-year survival between short course (n=22) and long course of EPIC (n=157). CONCLUSION: Combined use of HIPEC and EPIC improves 5-year survival in low-grade appendiceal neoplasm. Two days of EPIC are sufficient.