Stemness and hybrid epithelial-mesenchymal profiles guide peritoneal dissemination of malignant mesothelioma and pseudomyxoma peritonei.

Intrabdominal dissemination of malignant mesothelioma (MM) and pseudomyxoma peritonei (PMP) is poorly characterized with respect to the stemness window which malignant cells activate during their reshaping on the epithelial-mesenchymal (E/M) axis. To gain insights into stemness properties and their prognostic significance in these rarer forms of peritoneal metastases (PM), primary tumor cultures from 55 patients selected for cytoreductive surgery with hyperthermic intraperitoneal chemotherapy were analyzed for cancer stem cells (CSC) by aldehyde dehydrogenase 1 (ALDH1) and spheroid formation assays, and for expression of a set of plasticity-related genes to measure E/M transition (EMT) score. Intratumor heterogeneity was also analyzed. Samples from PM of colorectal cancer were included for comparison. Molecular data were confirmed using principal component and cluster analyses. Associations with survival were evaluated using Kaplan-Meier and Cox regression models. The activity of acetylsalicylic acid (ASA), a stemness modifier, was tested in five cultures. Significantly increased amounts of ALDH1bright-cells identified high-grade PMP, and discriminated solid masses from ascitic/mucin-embedded tumor cells in both forms of PM. Epithelial/early hybrid EMT scores and an early hybrid expression pattern correlated with pluripotency factors were significantly associated with early peritoneal progression (p = .0343 and p = .0339, respectively, log-rank test) in multivariable models. ASA impaired spheroid formation and increased cisplatin sensitivity in all five cultures. These data suggest that CSC subpopulations and hybrid E/M states may guide peritoneal spread of MM and PMP. Stemness could be exploited as targetable vulnerability to increase chemosensitivity and improve patient outcomes. Additional research is needed to confirm these preliminary data.

The genetic profile and molecular subtypes of human pseudomyxoma peritonei and appendiceal mucinous neoplasms: a systematic review.

Pseudomyxoma peritonei (PMP) is a rare, progressive, slowly growing neoplastic condition which is poorly understood, with a 5-year progression-free survival rate as low as 48%. PMP is most commonly caused by appendiceal mucinous neoplasms (AMN), and understanding their genetic biology and pathogenicity may allow for the development of better novel systemic treatments to target key deleterious mutations and the implicated pathways. The primary aim of this systematic review was to identify the genetic profile of histologically confirmed human PMP or AMN samples. The secondary aim was to identify whether genetic marks could be used to predict patient survival. Ovid EMBASE, Ovid MEDLINE, PubMed, and Web of Science were searched to identify studies investigating the genetic profile of histologically-confirmed human PMP or AMN samples. We review findings of 46 studies totalling 2181 tumour samples. The most frequently identified somatic gene mutations in patients with PMP included KRAS (38-100%), GNAS (17-100%), and TP53 (5-23%); however, there were conflicting results of their effect on survival. Three studies identified molecular subtypes based on gene expression profiles classifying patients into oncogene-enriched, immune-enriched, and mixed molecular subtypes with prognostic value. This review summarises the current literature surrounding genetic aberrations in PMP and AMNs and their potential utility for targeted therapy. Given the recent advances in clinical trials to directly target KRAS and GNAS mutations in other cancers, we propose a rationale to explore these mutations in future pre-clinical studies in PMP with a view for a future clinical trial.

Breaking the Mucin Barrier: A New Affinity Chromatography-Mass Spectrometry Approach to Unveil Potential Cell Markers and Pathways Altered in Pseudomyxoma Peritonei.

BACKGROUND: Pseudomyxoma peritonei (PMP) is a rare peritoneal mucinous carcinomatosis with largely unknown underlying molecular mechanisms. Cytoreductive surgery combined with hyperthermic intraperitoneal chemotherapy is the only therapeutic option; however, despite its use, recurrence with a fatal outcome is common. The lack of molecular characterisation of PMP and other mucinous tumours is mainly due to the physicochemical properties of mucin. RESULTS: This manuscript describes the first protocol capable of breaking the mucin barrier and isolating proteins from mucinous tumours. Briefly, mucinous tumour samples were homogenised and subjected to liquid chromatography using two specific columns to reduce mainly glycoproteins, albumins and immunoglobulin G. The protein fractions were then subjected to mass spectrometry analysis and the proteomic profile obtained was analysed using various bioinformatic tools. Thus, we present here the first proteome analysed in PMP and identified a distinct mucin isoform profile in soft compared to hard mucin tumour tissues as well as key biological processes/pathways altered in mucinous tumours. Importantly, this protocol also allowed us to identify MUC13 as a potential tumour cell marker in PMP. CONCLUSIONS: In sum, our results demonstrate that this protein isolation protocol from mucin will have a high impact, allowing the oncology research community to more rapidly advance in the knowledge of PMP and other mucinous neoplasms, as well as develop new and effective therapeutic strategies.

The 2022 PSOGI International Consensus on HIPEC Regimens for Peritoneal Malignancies: Pseudomyxoma Peritonei.

BACKGROUND: The combination of cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) constitutes the established standard of care for pseudomyxoma peritonei patients. However, the role of HIPEC lacks validation through randomized trials, leading to diverse proposed treatment protocols. This consensus seeks to standardize HIPEC regimens and identify research priorities for enhanced clarity. METHODS: The steering committee applied the patient, intervention, comparator, and outcome method to formulate crucial clinical questions. Evaluation of evidence followed the Grading of Recommendations, Assessment, Development, and Evaluation system. Consensus on HIPEC regimens and research priorities was sought through a two-round Delphi process involving international experts. RESULTS: Out of 90 eligible panelists, 71 (79%) participated in both Delphi rounds, resulting in a consensus on six out of seven questions related to HIPEC regimens. An overwhelming 84% positive consensus favored combining HIPEC with CRS, while a 70% weak positive consensus supported HIPEC after incomplete CRS. Specific HIPEC regimens also gained consensus, with 53% supporting Oxaliplatin 200 mg/m2 and 51% favoring the combination of cisplatin (CDDP) associated with mitomycin-C (MMC). High-dose MMC regimens received an 89% positive recommendation. In terms of research priorities, 61% of panelists highlighted the importance of studies comparing HIPEC regimens post CRS. The preferred regimens for such studies were the combination of CDDP/MMC and high-dose MMC. CONCLUSIONS: The consensus recommends the application of HIPEC following CRS based on the available evidence. The combination of CDDP/MMC and high-dose MMC regimens are endorsed for both current clinical practice and future research efforts.

Selective Gastrectomy with Knowledge of Gastric Anatomy and Blood Supply are Key to Complete Tumour Removal in Advanced Pseudomyxoma: Single-Centre Experience with 120 Gastrectomies Over 20 Years.

BACKGROUND: The role of gastrectomy to achieve complete cytoreduction (CCR) for pseudomyxoma peritonei (PMP) is controversial due to uncertain risk/benefit ratio. The outcomes of patients who gastrectomy over a twenty-year period in a high-volume unit are reported. METHODS: All patients requiring gastrectomy to achieve CCR for appendiceal PMP between 2000 and 2020 were reviewed. Demographics, disease, operative, complication, and survival data were analysed. The first and second decades were compared. RESULTS: A total of 2148 patients underwent CRS and HIPEC, of which 78% had CCR. Gastrectomy was performed in 7.1%. Median age was 55 years, and 52% were female. Among gastrectomy patients, 94.2% had ≥1 elevated tumour marker, and 18% had high-grade disease. Median PCI was 30, and 30% required subtotal colectomy. Clavien-Dindo III-IV complications occurred in 32%, and 90-day mortality was 1.75%. Median survival was 104 months, and 10-year OS was 47%. Comparing the two decades, total CRS cases almost tripled, with a greater proportion achieving CCR (82.2% vs. 67.8%) but fewer requiring gastrectomy (5.3% vs. 13.5%). In those who had gastrectomy, disease was more advanced (higher PCI, more high-grade disease, more colectomies) in the later period. However, on multivariable analysis, there was no difference in survival between decades. High-grade histology was the only predictor of survival. CONCLUSIONS: Gastrectomy can achieve good long-term survival with low mortality and acceptable morbidity and should not deter surgeons from achieving CCR. However, increasing experience shows CCR can be achieved, preserving the stomach in the majority of cases through careful consideration of the anatomy and gastric blood supply.

Decision Regret in Patients with Appendiceal Cancer Undergoing Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy.

BACKGROUND: Decision regret is an emerging patient reported outcome. The aim of this study was to assess the incidence of regret in patients with appendiceal cancer (AC) who underwent cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS-HIPEC). PATIENTS AND METHODS: An anonymous survey was distributed to patients through the Appendix Cancer and Pseudomyxoma Peritonei (ACPMP) Research Foundation. The Decision Regret Scale (DRS) was employed, with DRS > 25 signifying regret. Patient demographics, tumor characteristics, postoperative outcomes, symptoms (FACT-C), and PROMIS-29 quality of life (QoL) scores were compared between patients who regretted or did not regret (NO-REG) the procedure. RESULTS: A total of 122 patients were analyzed. The vast majority had no regret about undergoing CRS-HIPEC (85.2%); 18 patients expressed regret (14.8%). Patients with higher regret had: income ≤ $74,062 (72.2% vs 44.2% NO-REG; p = 0.028), major complications within 30 days of surgery (55.6% vs 15.4% NO-REG; p < 0.001), > 30 days hospital stay (38.9% vs 4.8% NO-REG; p < 0.001), a new ostomy (27.8% vs 7.7% NO-REG; p = 0.03), >1 CRS-HIPEC procedure (56.3% vs 12.6% NO-REG; p < 0.001). Patients with worse FACT-C scores had more regret (p < 0.001). PROMIS-29 QOL scores were universally worse in patients with regret. Multivariable analysis demonstrated > 30 days in the hospital, new ostomy and worse gastrointestinal symptom scores were significantly associated with regret. CONCLUSIONS: The majority of patients with AC undergoing CRS-HIPEC do not regret undergoing the procedure. Lower income, postoperative complications, an ostomy, undergoing > 1 procedure, and with worse long-term gastrointestinal symptoms were associated with increased regret. Targeted perioperative psychological support and symptom management may assist to ameliorate regret.

Genome-Wide Analysis of DNA Methylation in Pseudomyxoma Peritonei Originated from Appendiceal Neoplasms.

INTRODUCTION: Pseudomyxoma peritonei (PMP) is a disease characterized by progressive accumulation of intraperitoneal mucinous ascites produced by neoplasms in the abdominal cavity. Since the prognosis of patients with PMP remains unsatisfactory, the development of effective therapeutic drug(s) is a matter of pressing concern. Genetic analyses of PMP have clarified the frequent activation of GNAS and/or KRAS. However, the involvement of global epigenetic alterations in PMPs has not been reported. METHODS: To clarify the genetic background of the 15 PMP tumors, we performed genetic analysis using AmpliSeq Cancer HotSpot Panel v2. We further investigated global DNA methylation in the 15 tumors and eight noncancerous colonic epithelial tissues using MethylationEPIC array BeadChip (Infinium 850k) containing a total of 865,918 probes. RESULTS: This is the first report of comprehensive DNA methylation profiles of PMPs in the world. We clarified that the 15 PMPs could be classified into at least two epigenotypes, unique methylation epigenotype (UME) and normal-like methylation epigenotype (NLME), and that genes associated with neuronal development and synaptic signaling may be involved in the development of PMPs. In addition, we identified a set of hypermethylation marker genes such as HOXD1 and TSPYL5 in the 15 PMPs. CONCLUSIONS: These findings may help the understanding of the molecular mechanism(s) of PMP and contribute to the development of therapeutic strategies for this life-threatening disease.

Omental metastases in patients with pseudomyxoma peritonei or colorectal peritoneal metastases - is routine omentectomy justified?

BACKGROUND: The greater omentum is routinely resected during cytoreductive surgery (CRS), but few studies have analyzed the rationale behind this. This study aimed to assess the prevalence of omental metastases (OM) and the correlation between macroscopically suspected and microscopically confirmed OM, in patients with pseudomyxoma peritonei (PMP) or colorectal peritoneal metastases (PM). METHOD: All patients without previous omentectomy, treated with initial CRS and hyperthermic intraperitoneal chemotherapy for PMP or colorectal PM, at Uppsala University Hospital in 2013-2021, were included. Macroscopic OM in surgical reports was compared with histopathological analyses. RESULTS: In all, 276 patients were included. In those with PMP, 112 (98%) underwent omentectomy and 67 (59%) had macroscopic suspicion of OM. In 5 (4%) patients, the surgeon was uncertain. Histopathology confirmed OM in 81 (72%). In patients with macroscopic suspicion, 96% had confirmed OM (positive predictive value, PPV). In patients with no suspicion, 24% had occult OM (negative predictive value, NPV = 76%). In patients with colorectal PM, 156 (96%) underwent omentectomy and 97 (60%) had macroscopic suspicion. For 5 (3%) patients, the surgeon was uncertain. OM was microscopically confirmed in 90 (58%). PPV was 85% and NPV was 89%. The presence of OM was a univariate risk factor for death in PMP (HR 3.62, 95%CI 1.08-12.1) and colorectal PM (HR 1.67, 95%CI 1.07-2.60), but not in multivariate analyses. CONCLUSION: OM was common and there was a high risk of missing occult OM in both PMP and colorectal PM. These results support the practice of routine omentectomy during CRS.

Appendiceal adenocarcinoma: Current concepts & challenges.

Appendiceal adenocarcinoma (ApAC) is a rare malignancy, comprising less than 1 % of all gastrointestinal tumors. The current World Health Organization classifies ApAC as mucinous or nonmucinous. Mucinous ApAC are composed of pools of mucin lined by cells with low- and high-grade cytology and areas of infiltrative invasion. Nonmucinous ApAC histologically resemble conventional colorectal adenocarcinomas and have a worse prognosis than their mucinous counterpart. Unfortunately, the nomenclature and histologic classification of ApAC, specifically the mucinous subtype, has changed several times throughout the years, contributing to diagnostic confusion for pathologists. The treatment for mucinous ApAC differs from that of other appendiceal mucinous neoplasms, thus accurate diagnosis is key to patient management and outcome. This review discusses the current classification and staging of ApAC with a particular emphasis on the mucinous subtype and peritoneal disease, as these areas are the most challenging for practicing surgical pathologists.

Optimal peritoneal cancer index cutoff point for predicting surgical resectability of pseudomyxoma peritonei in treatment-naive patients.

BACKGROUND: The peritoneal cancer index (PCI) has been used to predict surgical outcomes for pseudomyxoma peritonei (PMP). The present study aimed to establish the optimal cutoff point for PCI to predict surgical resectability of PMP. METHODS: A total of 366 PMP patients were included. The patients were divided into low-grade and high-grade groups. Based on the completeness of the cytoreduction (CC) score, both low-grade and high-grade PMP patients were further divided into complete cytoreductive surgery (CRS) and maximal tumor debulking (MTD) subgroups. The ability to predict surgical resectability of total and selected PCI (regions 2 + 9 to 12) was analyzed through receiver operating characteristic (ROC) curves. RESULTS: Both total and selected PCI demonstrated excellent discriminative ability in predicting surgical resectability for low-grade PMP patients (n = 266), with the ROC-AUC of 0.940 (95% CI: 0.904-0.965) and 0.927 (95% CI: 0.889-0.955). The corresponding optimal cutoff point was 21 and 5, respectively. For high-grade PMP patients (n = 100), both total and selected PCI exhibited good performance in predicting surgical resectability, with the ROC-AUC of 0.894 (95% CI: 0.816-0.946) and 0.888 (95% CI: 0.810-0.943); correspondingly, the optimal cutoff point was 25 and 8, respectively. The discriminative ability between total and selected PCI in predicting surgical resectability did not show a statistical difference. CONCLUSIONS: Both total and selected PCI exhibited good performance and similarity in predicting complete surgical resection for both low-grade and high-grade PMP patients. However, the selected PCI was simpler and time-saving in clinical practice. In the future, new imaging techniques or predictive models may be developed to better predict PCI preoperatively, which might assist in confirming whether complete surgical resection can be achieved.

Incidental finding of Psuedomyxoma Peritonei in Malignant Peripheral Nerve Sheath Tumour.

Psuedomyxoma peritonei is an infrequent clinical entity characterised by intraperitoneal mucinous/gelatinous ascites produced by the cancerous cells. It has been associated with gastrointestinal, gynaecological, lung and breast tumours. It is commonly asymptomatic and is most often detected incidentally on abdominopelvic imaging or laparoscopy. Higher histological grade of the tumour shows increased metabolic activity on 18F-Fluorodeoxyglucose (FDG) positron-emission tomography (PET) computed tomography (CT). It has been rarely reported in patients with sarcoma. We hereby present an interesting case of incidentally diagnosed pseudomyxoma peritonei on 18FDG PET-CT scan of a patient with soft tissue sarcoma of peripheral nerve sheath.

Serum and ascites tumor markers in the diagnostic and prognostic prediction for appendiceal pseudomyxoma peritonei.

BACKGROUND: To investigate the expression of carcinoembryonic antigen (CEA), cancer antigen 199 (CA199) and CA125 in serum and ascites of appendiceal pseudomyxoma peritonei (PMP) patients relative to their diagnostic and predictive value. METHODS: The study comprised 183 patients with pathologically confirmed appendiceal PMP, enrolled from May 2012 to June 2020, in Aerospace Center Hospital. Serum and ascites tumor markers were obtained, and their diagnostic values were compared by receiver operating characteristic (ROC) curves. The prognostic factors of appendiceal PMP with different pathologic subgroups were calculated by univariate and multivariate Cox proportional hazard regression models. RESULTS: There were significant differences between the numbers of patients with positive CEA and CA199 in serum vs. ascites: p = 0.034 in CEA and p = 0.006 in CA199, respectively. The sensitivities with optimal cut-off values for ascites markers of CEA, CA199 and CA125 were 83.5%, 88.9% and 72.6%, respectively. CEA in ascites showed significant difference in the diagnosis of appendiceal PMP (p = 0.000); the areas under the ROC curves (AUROCs) and specificity were 0.725, 70.7%, respectively. Univariate analysis showed that the higher the ascites tumor markers, the poorer the survival (p = 0.014). Multivariate analysis indicated that completeness of cytoreduction (CCR), ascites CEA and pathological grade were independent risk factors for overall survival (OS). CONCLUSION: CEA in ascites can be used to help specify the origin of PMP. Furthermore, elevation of ascites CEA, high pathological grade and incomplete cytoreduction predicted poor prognosis of appendiceal PMP.

Combined ultrasonography and CT for prognosis and predicting clinical outcomes of patients with pseudomyxoma peritonei.

OBJECTIVES: This study aimed to identify the diagnostic accuracy of combined ultrasonography (US) and computed tomography (CT) in evaluating the tumor burden of pseudomyxoma peritonei (PMP). Besides, we assessed the ability of this combination to predict the likelihood of complete resection. METHODS: This retrospective study involved 504 patients diagnosed with PMP and scheduled for cytoreduction surgery. We compared tumor burden-quantified as peritoneal cancer index (PCI) by preoperative US and CT (US-CT-PCI)-with surgical findings. Next, we assessed the prognostic value of US-CT PCI and imaging features in determining the completeness of cytoreduction (CCR) score using multivariate analysis. RESULTS: US-CT PCI demonstrated a high PCI evaluation accuracy under moderate tumor burden. Higher US-CT PCI could predict incomplete resection. In addition, we identified imaging features such as mesenteric involvement as an independent predictor of incomplete resection (hazard ratio (HR) = 2.006; p = 0.007). CONCLUSIONS: US-CT PCI allowed us to predict the completeness of cytoreductive surgery in patients with PMP. Moreover, the combined US and CT imaging detected several features indicating incomplete cytoreduction. KEY POINTS: • Ultrasonography (US) can act as a complementary diagnostic modality in peritoneal cancer index (PCI) evaluation by combining CT in the small bowel area and US in the abdominal area. • A modified peritoneal cancer index (US-CT PCI) helps preoperatively evaluate tumor burden with high accuracy and allows to predict incomplete resection. • US-CT PCI of 20 or above and the involvement of particular structures such as mesentery, independently indicate incomplete resection.

Total abdominal colectomy to facilitate complete cytoreduction in 56 patients with mucinous appendiceal neoplasms with peritoneal metastases.

BACKGROUND: Cytoreductive surgery (CRS) and perioperative intraperitoneal chemotherapy are currently the standard of care for management of appendiceal mucinous neoplasms with peritoneal metastases. The goal of the CRS is complete removal of all visible disease through the use of peritonectomy procedures and visceral resections. One of the major resections that may be required is total abdominal colectomy (TAC). METHODS: From a database and secured files of patients having a complete CRS, all patients who had TAC were identified. The clinical and histologic variables associated with these patients were identified and assessed for their impact on overall survival. RESULTS: The 450 complete CRS with low-grade appendiceal mucinous neoplasms had 26 TAC (5.8%) with a 16.0-year median survival. The mucinous adenocarcinoma (MACA)-Intermediate (MACA-Int) group consisted of 37 patients with 8 patients (21.6%) having TAC that resulted in a median survival of 11.5 years. The 159 complete CRS with MACA had 22 TAC (13.8%) with a median survival of 7.5 years. There was a single mortality with a class 4 adverse event in 5 patients (10.7%). With a class 4 adverse event, survival decreased significantly (p = 0.0006, hazard ratio: 6.2). CONCLUSION: Complete CRS required TAC in 56 of 646 patients (8.7%) with appendiceal mucinous neoplasms. With TAC, median survival was 12.0 years. A class 4 adverse event markedly reduced survival.

Palliation of mucinous appendiceal neoplasms with peritoneal metastases with total abdominal colectomy.

BACKGROUND: Incomplete cytoreduction for mucinous appendiceal neoplasms is often required to temporarily alleviate symptoms. The surgical technology for this intervention may be complex and result in extensive morbidity and even mortality. Knowledgeable patient selection for this surgery is mandatory. METHODS: A database was used to identify patients who had palliative surgery that included total abdominal colectomy (TAC). Clinical- and treatment-related variables were assessed for their impact on overall survival. RESULTS: Seventy-eight patients had an incomplete cytoreductive surgery (CRS) that included a TAC. The median survival was 2.5 years and the median follow-up was 2 years. Patients with symptoms of abdominal distention and ascites showed a reduced prognosis (p = 0.0254). The low-grade appendiceal mucinous neoplasms (LAMN) and mucinous appendiceal adenocarcinoma intermediate type (MACA-Int) grouped together showed a prolonged survival (p = 0.0003). MACA with positive lymph nodes showed a reduced survival (p = 0.0009) when compared to MACA patients without positive lymph nodes. A peritoneal cancer index of 1-30 versus >30 and completeness of cytoreduction score of 2 versus 3 were not significant. CONCLUSION: TAC with end ileostomy was used as a treatment option to provide palliation of patients having an incomplete CRS for appendiceal mucinous neoplasms. With LAMN or MACA-Int, median survival was 5.0 years. The surgery can be performed with a morbidity of 9.0% and mortality of 2.6%. Although not considered a palliative option in the past, these data suggest TAC may be used with acceptable results in this group of patients.

Effect of standardized fluid management on cardiac function after CRS + HIPEC in patients with PMP: a single-center case-control study.

OBJECTIVE: To investigate the effects of standardized fluid management (SFM) on cardiac function in patients with pseudomyxoma peritonei (PMP) after cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC). METHOD: Patients with PMP who underwent CRS + HIPEC at our center were retrospectively analyzed. The patients were divided into control and study groups according to whether SFM was applied after CRS + HIPEC. We compared the preoperative and postoperative cardiac and renal function parameters, daily fluid volume three days after CRS, and cardiovascular-related adverse events. Univariate and multivariate analyses were performed to identify the indicators affecting clinical prognosis. RESULT: Among the 104 patients, 42 (40.4%) were in the control group and 62 (59.6%) in the study group. There were no statistically significant differences between the two groups in the main clinicopathological characteristics, preoperative cardiac and renal function parameters, and CRS + HIPEC-related indicators. The incidences of cardiac troponin I (CTNI) > upper limit of normal (ULN), >2 × ULN, >3 × ULN, serum creatinine > ULN, and blood urea nitrogen > ULN were higher in the control group than in the study group (p < 0.05). The median daily fluid volume of the control group was higher than that of the study group 3 days after CRS (p < 0.05). Postoperative CTNI > 2 × ULN was an independent risk factor for serious circulatory adverse events. Survival analysis revealed pathological grading, completeness of cytoreduction score, and postoperative CTNI > ULN as independent prognostic factors. CONCLUSIONS: SFM after CRS + HIPEC in patients with PMP may reduce cardiovascular adverse events risk and improve clinical outcomes.

Long-term survival in patients with PMP: a single-institutional retrospective study from China.

BACKGROUND: As the standard treatment for pseudomyxoma peritonei (PMP), cytoreductive surgery (CRS) plus hyperthermic intraperitoneal chemotherapy (HIPEC) can significantly prolong the survival of PMP patients, and some patients can even achieve long-term survival (LTS) or clinical cure. The purpose of this study was to analyze the clinicopathological and treatment features of PMP patients with LTS and to explore the survival benefit factors of PMP patients. METHODS: The clinicopathological and prognostic data of PMP patients who received CRS + HIPEC at our center from December 2004 to May 2023 were retrospectively analyzed. PMP patients were divided into LTS group (≥ 10 years) and short-term survival (STS) group (< 5 years) according to the length of natural history. Univariate and multivariate analyses were performed to explore the beneficial factors of PMP patients with LTS. RESULTS: A total of 609 patients with PMP received CRS + HIPEC treatment at our center. Two-hundred one patients with PMP were included in the study after screening, including 39 patients (19.4%) in the LTS group and 162 patients (80.6%) in the STS group. In STS group and LTS group, median overall survival based on natural history was 29.2 (2.4-59.9) vs. 138.9 (120.3-416.7) months. Univariate analysis revealed 8 factors (P < 0.05) with statistically significant differences between the two groups: gender, chemotherapy history, previous surgical score, Karnofsky Performance Status score, pathological diagnosis, lymphatic metastasis, peritoneal cancer index, and completeness of cytoreduction (CC). Multivariate analysis identified only two factors independently associated with LTS of PMP patients: CC and pathological diagnosis. CONCLUSION: Complete CRS and pathological features are two key factors affecting LTS in PMP patients.

Low-grade appendiceal mucinous neoplasm encountered during risk-reducing salpingo-oophorectomy: A case of laparoscopic surgery.

Low-grade appendiceal mucinous neoplasm (LAMN) is a rare epithelial malignancy of the appendix. If it perforates the abdominal cavity, it can cause a serious clinical syndrome called pseudomyxoma peritonei. In the present case, we laparoscopically removed a LAMN encountered during risk-reducing salpingo-oophorectomy (RRSO). The patient was a 53-year-old woman who was diagnosed with hereditary breast and ovarian cancer syndrome. RRSO was planned, and magnetic resonance imaging revealed a large cystic tumor in the right lower abdomen. We expected an ovarian cyst; however, it was a primary tumor of the appendix. Partial cecal resection was performed laparoscopically by a surgical oncologist. The pathological diagnosis was LAMN. Gynecologists may encounter this disease incidentally. Mucinous appendiceal neoplasm (MAN) may be encountered during RRSO. If a right lower abdominal mass is found near a normal ovary preoperatively, gynecologists should consider MAN as well as paraovarian cyst.

Prognostic Impact of Pathology, Cytoreduction, and Tumor Markers in Pseudomyxoma Peritonei.

INTRODUCTION: The pathologic classification of pseudomyxoma peritonei is controversial. This study aimed to standardize the histopathological evaluation of pseudomyxoma peritonei and identify the clinicopathological factors associated with survival. METHODS: A pathologic review was performed to systematize the pathology report and verify the relationship between clinical features and survival. Terminology was based on the World Health Organization and Peritoneal Surface Oncology Group International definitions. Preoperative serum levels of carcinoembryonic antigen, CA19-9, and CA-125 were evaluated to determine their association with overall survival (OS) and ability to predict CC0-1 cytoreduction. RESULTS: Among 109 patients with carcinomas resulting from primary appendiceal neoplasms, 72 had pseudomyxoma peritonei of appendiceal origin and underwent debulking surgery. CC0-1 cytoreduction and CC2-3 cytoreduction were achieved in 61% and 39% of patients, respectively. Patients in the CC0-1 and CC2-3 groups had an OS of 122.80 and 32.92 mo, respectively. The histologic grade was associated with CC0-1 cytoreduction; however, it did not influence OS. Patients with CC0-1 cytoreduction, acellular mucin, and low-grade lesions had better disease-free survival. Higher preoperative CA19-9 levels were associated with poor OS. Normal carcinoembryonic antigen values were associated with 100% sensitivity for predicting CC0-1. CA19-9 levels of 625 U/mL were associated with a low possibility of predicting CC0-1. CONCLUSIONS: Histologic grades are associated with disease-free survival when CC0-1 cytoreduction is achieved. Normal preoperative CA19-9 levels were associated with a better OS. CC0-1 cytoreduction is the main determinant of longer survival.

The association between appendicitis severity and patient age with appendiceal neoplasm histology-a population-based study.

PURPOSE: Recent studies have reported alarming appendiceal tumor rates associated with complicated acute appendicitis, especially in patients presenting with a periappendicular abscess. However, the data on histology of appendiceal tumors among acute appendicitis patients is limited, especially in patient cohorts differentiating between uncomplicated and complicated acute appendicitis. We have previously reported the association of increased appendiceal tumor prevalence with complicated acute appendicitis in this population-based study. The objective of this secondary analysis was to evaluate the association of both appendicitis severity and patient age with appendiceal tumor histology. METHODS: This nationwide population-based registry study (The Finnish Cancer Registry) was conducted from 2007 to 2013. All appendiceal tumors (n = 840) and available medical reports (n = 504) of these patients at eight study hospitals were previously evaluated, identifying altogether 250 patients with both acute appendicitis and appendiceal tumor. RESULTS: The severity of acute appendicitis was significantly associated with more malignant tumor histology. The risk of adenocarcinoma or pseudomyxoma was significantly higher among patients with periappendicular abscess (OR 15.05, CI 95% 6.98-32.49, p < 0.001) and patients presenting with perforated acute appendicitis (OR 4.09, CI 95% 1.69-9.90, p = 0.0018) compared to patients with uncomplicated acute appendicitis. Similarly, patient age over 40 years was significantly associated with the risk of adenocarcinoma and pseudomyxoma (OR 26.46, Cl 95% 7.95-88.09, p < 0.001). Patient sex was not associated with a more malignant appendiceal tumor histology (p = 0.67). CONCLUSION: More malignant appendiceal tumor histology of adenocarcinoma or pseudomyxoma was significantly associated with patient age over 40 years and complicated acute appendicitis, especially periappendicular abscess.