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.

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.

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 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.

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.

Nomogram to predict overall survival of patients with pseudomyxoma peritonei of appendiceal origin: A retrospective cohort study.

BACKGROUND: Pseudomyxoma peritonei (PMP) is a rare disease, with the rate of overall survival (OS) influenced by many factors. The present study aimed to define independent predictors and establish a nomogram for individual risk prediction in PMP patients. METHODS: One hundred forty-seven PMP patients were consecutively included between June 1, 2013, and November 22, 2019. The log-rank test was used to compare the OS rate between groups; subsequently, variables with p < .10 were subjected to multivariate Cox modeling for defining independent prediction indicators. Finally, a nomogram was established based on independent prognosticators and assessed for internal validation. RESULTS: Multivariate Cox analysis showed that D-dimer level, carbohydrate antigen (CA) 125 level, CA 19-9 level, degree of radical surgery, and histological grade were all independently associated with OS in PMP patients. A nomogram was plotted and underwent internal validation. The discrimination ability of the nomogram revealed a good predictive ability as indicated by the C-index value (0.825), and calibration plots confirmed good consistency between the predicted and observed survival probabilities. CONCLUSIONS: Five independent prognostic factors for predicting the survival of PMP patients were identified, and the nomogram based on these independent indicators showed a reasonable discrimination ability for individual risk prediction.

Mode of Presentation in 1070 Patients With Perforated Epithelial Appendiceal Tumors, Predominantly with Pseudomyxoma Peritonei.

BACKGROUND: Perforated epithelial appendiceal tumors are uncommon and can give rise to pseudomyxoma peritonei. Pseudomyxoma peritonei is rare, almost always of appendiceal origin, and presents in various ways relevant to abdominal surgeons. OBJECTIVE: The aim of this study was to report the mode of presentation of pseudomyxoma peritonei of appendiceal origin in patients treated in a high-volume UK peritoneal malignancy center. DESIGN: A retrospective observational study was conducted. SETTINGS: This was a single-center study. PATIENTS: Retrospective analysis of a prospective database of consecutive patients undergoing surgery between March 1994 and December 2016 was performed. MAIN OUTCOME MEASURES: Mode of presentation was classified into 7 categories: "histological diagnosis at abdominal surgery for presumed appendicitis," "probable pseudomyxoma peritonei" based on abnormality on cross-sectional imaging (± image-guided biopsy)," "abnormal imaging (other cause suspected) and operative finding of pseudomyxoma peritonei," "diagnostic laparoscopy," "ovarian mass," "new-onset hernia," and "miscellaneous." RESULTS: Overall, 1070 patients underwent surgery (female 61%, male 39%); median age was 57. The mode of presentation was abnormality on cross-sectional imaging in 324 of 1070 patients (30.3%), histological diagnosis at emergency surgery for presumed appendicitis in 203 of 1070 patients (19%), and abnormal imaging with eventual pseudomyxoma peritonei diagnosis in 180 of 1070 patients (16.8%); 124 of 651 women (19.2%) presented with an ovarian mass. New-onset hernia was the presenting feature in 9.9%; 83 of 1070 patients (7.7%) were diagnosed at diagnostic laparoscopy, and 32 of 1070 patients (3%) were described as "miscellaneous." Overall, 775 of 1070 patients (72.4%) had complete cytoreductive surgery with 10-year survival of 63.5%. LIMITATIONS: Results are limited by the retrospective nature of the study, radiological improvements over the study period, and the number of patients who had overlapping features at presentation. CONCLUSION: Perforated appendiceal tumors present in various ways but predominantly at cross-sectional imaging or coincidentally at laparoscopy or laparotomy. All abdominal surgeons will occasionally encounter cases, often unexpectedly, and recognition and referral to a specialized unit results in excellent outcomes in most cases. See Video Abstract at http://links.lww.com/DCR/B256. MODO DE PRESENTACIÓN EN 1070 PACIENTES CON TUMORES EPITELIALES APENDICULARES PERFORADOS, PREDOMINANTEMENTE CON PSEUDOMIXOMA PERITONEAL: Los tumores epiteliales apendiculares perforados son poco frecuentes y pueden dar lugar a Pseudomyxoma peritonei. El pseudomixoma peritoneal es raro, casi siempre de origen apendicular, y se presenta de diversas formas relevantes para los cirujanos abdominales.El objetivo fue informar el modo de presentación del Pseudomixoma peritoneal de origen apendicular en pacientes tratados en un centro de malignidad peritoneal de alto volumen en el Reino Unido.Se realizó un estudio observacional retrospectivo.Este fue un estudio de centro único.Análisis retrospectivo de una base de datos prospectiva de pacientes consecutivos sometidos a cirugía entre marzo de 1994 y diciembre de 2016.El modo de presentación se clasificó en 7 categorías: "diagnóstico histológico en la cirugía abdominal por presunta apendicitis", "probable Pseudomixoma peritoneal" basado en la anormalidad en la imagen de corte transversal (biopsia guiada por imagen +/-), "imagen anormal (se sospecha otra causa) y hallazgo quirúrgico de Pseudomixoma peritoneal", "laparoscopia diagnostica", "masa ovarica", "hernia de reciente aparicion" y "varios".En total, 1070 pacientes fueron operados (mujeres 61%, hombres 39%); edad media 57. El modo de presentación fue anormalidad en la imágen transversal en 324/1070 (30.3%), el diagnóstico histológico en cirugía de emergencia por presunta apendicitis en 203/1070 (19%), la imágen anormal con eventual diagnóstico de Pseudomixoma peritoneal en 180 / 1070 (16.8%), 124/651 (19.2%) las mujeres presentaron una masa ovárica. La hernia de reciente aparición fue la característica de presentación en 9.9%, 83/1070 (7.7%) fueron diagnosticados por laparoscopia diagnóstica y 32/1070 (3%) "misceláneos". En general, 775/1070 (72,4%) se sometió a cirugía citorreductora completa con una supervivencia a 10 años del 63,5%.Una deficiencia es que los resultados están limitados por la naturaleza retrospectiva del estudio, las mejoras radiológicas a lo largo del período de estudio, y varios pacientes tenían características superpuestas en la presentación.Los tumores apendiculares perforados se presentan de varias maneras, pero predominantemente en imágenes transversales o casualmente en laparoscopia o laparotomía. Todos los cirujanos abdominales encontrarán ocasionalmente con casos, a menudo inesperados, y el reconocimiento y la derivación a una unidad especializada da lugar a excelentes resultados en la mayoría de los casos. Consulte Video Resumen en http://links.lww.com/DCR/B256.).

Long-term results of laparoscopic cytoreductive surgery and HIPEC for the curative treatment of low-grade pseudomyxoma peritonei and multicystic mesothelioma.

BACKGROUND: Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) provide long-term survival for low-grade pseudomyxoma peritonei (PMP) and multicystic peritoneal mesothelioma (MM). Feasibility of laparoscopic CRS-HIPEC has been reported for selected patients but data regarding long-term outcomes are missing to assess the oncological interest. This study aimed to report long-term outcomes for low-grade PMP and MM treated by laparoscopic approach. METHODS: From a prospectively maintained CRS-HIPEC database, all patients who underwent laparoscopic CRS-HIPEC with curative intent were analyzed. Selection criteria for laparoscopic approach were low-grade PMP or MM, with pathological confirmation prior to CRS-HIPEC, ASA 2, age < 75 years, no extrap-eritoneal disease, Peritoneal Cancer Index (PCI) < 10, and a limited history of abdominal surgery. RESULTS: Between March 2009 and June 2017, 43 patients were scheduled for laparoscopic CRS and HIPEC. Laparoscopic CRS and HIPEC was completed (LSC) in 32 patients and 11 patients were converted to open surgery (CONV). Median age was 44.5 years (17.13-71.4) in the LSC group and 54.9 years (22.5-70.5) in the CONV group (p = 0.086). Median BMI was not different between groups, 21.2 and 23.9 for LSC and CONV groups, respectively (p = 0.267). There were 21 and 11 patients in the LSC group, and 8 and 3 in the CONV group, with PMP and MM, respectively (p = 0.794). Median PCI was 2.5 (0-9) and 7 (1-15) in the LSC and CONV groups, respectively (p = 0.004). There was no difference in the completeness of cytoreduction score (p = 0.256). After a median follow-up of 31.6 months (95% CI 19.3-36.4), 2 patients in the LSC group and 2 patients in the CONV group presented with peritoneal recurrence. CONCLUSION: For selected patients with low aggressive peritoneal disease, laparoscopic CRS-HIPEC provides interesting long-term outcomes.

A comprehensive review of childbearing after cytoreductive surgery and hyperthermic intraperitoneal chemotherapy.

PURPOSE: Our aim is to present a review on childbearing following CRS and HIPEC for peritoneal malignancy. METHODS: A review of the English literature, up to December 2019, was conducted, using PubMed/MEDLINE, EmBase and Google Scholar bibliographic databases, following the MOOSE guidelines. The terms "Cytoreductive Surgery", "Hyperthermic Intraperitoneal Chemotherapy", "Peritoneal Carcinomatosis", "Pregnancy", "Fertility Preservation", "Conception" were used. All study designs were eligible for inclusion in the final analysis. RESULTS: In total, 7 studies (5 case reports and 2 case series) were included in the final analysis, reporting on 14 successful pregnancies after CRS and HIPEC. The mean age of patients at the time of CRS/HIPEC was 28.8 ± 5.9 years (range 18-36), while the mean interval between CRS/HIPEC and pregnancy was 29.6 ± 20.3 months (range 9-80 months). Nine patients were treated for pseudomyxoma peritonei, four for primary peritoneal mesothelioma and one for endocrine carcinoma. Mean Peritoneal Carcinomatosis Index was 9.8 ± 7.8 (range 1-26). All patients underwent fertility-sparing CRS (preservation of at least one ovary and the uterus). In 12 cases, conception was spontaneous, whereas two pregnancies were achieved through in-vitro fertilization. One patient developed gestational hypertension, while two labors were preterm. Mean disease-free survival was 64.1 months (range 24-106 months). CONCLUSION: A successful pregnancy is feasible in selected patients, after CRS and HIPEC. Assisted reproduction techniques (IVF using frozen oocytes or frozen embryos, ovarian tissue cryopreservation, preoperative treatment with GnRH analogs) should be discussed pre-operatively with the patient, without, however, compromising overall survival or risking locoregional recurrence.

Role of Epithelial-Mesenchymal Plasticity in Pseudomyxoma Peritonei: Implications for Locoregional Treatments.

The mechanisms by which neoplastic cells disseminate from the primary tumor to metastatic sites, so-called metastatic organotropism, remain poorly understood. Epithelial-mesenchymal transition (EMT) plays a role in cancer development and progression by converting static epithelial cells into the migratory and microenvironment-interacting mesenchymal cells, and by the modulation of chemoresistance and stemness of tumor cells. Several findings highlight that pathways involved in EMT and its reverse process (mesenchymal-epithelial transition, MET), now collectively called epithelial-mesenchymal plasticity (EMP), play a role in peritoneal metastases. So far, the relevance of factors linked to EMP in a unique peritoneal malignancy such as pseudomyxoma peritonei (PMP) has not been fully elucidated. In this review, we focus on the role of epithelial-mesenchymal dynamics in the metastatic process involving mucinous neoplastic dissemination in the peritoneum. In particular, we discuss the role of expression profiles and phenotypic transitions found in PMP in light of the recent concept of EMP. A better understanding of EMP-associated mechanisms driving peritoneal metastasis will help to provide a more targeted approach for PMP patients selected for locoregional interventions involving cytoreductive surgery and hyperthermic intraperitoneal chemotherapy.

[The perioperative safety of cytoreductive surgery plus hyperthermic intraperitoneal chemotherapy for pseudomyxoma peritonei].

Objective: This study was to investigate the perioperative safety of cytoreductive surgery (CRS) plus hyperthermic intraperitoneal chemotherapy (HIPEC) for pseudomyxoma peritonei (PMP), and analyze the risk factors of serious adverse events (SAEs). Methods: The occurrences of perioperative SAEs were retrospectively analyzed in 254 PMP patients treated with CRS plus HIPEC. Univariate and multivariate analysis were performed to identify independent risk factors. Results: Among the 272 CRS plus HIPEC procedures for 254 PMP patients, a total of 93 (34.2%) perioperative SAEs occurred, including 26 in infection, 22 in digestive system, 17 in respiratory system, 15 in cardiovascular system, 8 in hematological system, and 4 in urinary system. In terms of severity, the vast majority was grade Ⅲ with 76 cases, followed by grade Ⅳ with 13 cases and grade Ⅴ with 4 cases. Univariate analysis revealed 3 risk factors of perioperative SAEs: HIPEC regimen (P=0.020), intraoperative red blood cell transfusion volume (P=0.004), and intraoperative blood loss volume (P=0.002). Multivariate analysis by logistic regression model analysis revealed that intraoperative red blood cell transfusion volume was an independent risk factor for perioperative SAEs (OR=1.160, P=0.001). Conclusion: In conclusion, the perioperative safety of CRS plus HIPEC was acceptable. Moreover, intraoperative blood loss volume and red blood cell transfusion volume are expected to be reduced in order to prevent SAEs for PMP patients.

Pleuropulmonary Recurrence Following Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemoperfusion for Appendiceal Pseudomyxoma Peritonei.

BACKGROUND: The aim of this study was to identify factors associated with pleuropulmonary disease recurrence following cytoreductive surgery with hyperthermic intraperitoneal chemoperfusion (CRS/HIPEC) for appendiceal pseudomyxoma peritonei (PMP) and to evaluate the oncologic impact of pleuropulmonary disease recurrence compared with isolated peritoneal recurrence. METHODS: From a prospective database, we identified patients who developed pleuropulmonary recurrence, isolated peritoneal recurrence, or no recurrence following CRS/HIPEC for appendiceal PMP. Clinicopathologic, perioperative, and oncologic data associated with the index CRS/HIPEC procedure were reviewed. The Kaplan-Meier method was used to estimate survival. Multivariate analyses identified associations with recurrence and survival. RESULTS: Of 382 patients undergoing CRS/HIPEC, 61 (16%) developed pleuropulmonary recurrence. Patients who developed a pleuropulmonary recurrence were more likely to have high-grade (American Joint Committee on Cancer [AJCC] grade 2/3) tumors (74% vs. 56%, p = 0.02) and increased operative blood loss (1651 vs. 1201 ml, p = 0.05) and were more likely to have undergone diaphragm stripping/resection (79% vs. 48%, p < 0.01) compared with patients with an abdominal recurrence. In a multivariate analysis, pleuropulmonary recurrence after CRS/HIPEC was associated with diaphragm stripping/resection, incomplete cytoreduction, and higher AJCC tumor grade. There was a trend towards reduced survival in patients with pleuropulmonary recurrence compared with patients with isolated peritoneal recurrence (median overall survival 45 vs. 53 months, p = 0.87). CONCLUSION: Pleuropulmonary recurrence of appendiceal PMP following CRS/HIPEC is common and may negatively impact survival. Formal protocols for surveillance and therapeutic intervention need to be studied and implemented to improve oncologic outcomes.

Evaluation of cytoreductive surgery and HIPEC for peritoneal surface malignancies: analysis of 384 consecutive cases.

BACKGROUND: Peritoneal surface malignancy (PSM) was historically associated with a poor survival. The adoption of cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) can now offer patients with PSM a favourable overall survival. Here, we report our single-institute outcomes following CRS and HIPEC for PSM and evaluate changes in our practice over time. METHODS: This is a retrospective review from 2009 to 2018 of all patients undergoing CRS and HIPEC for PSM at a statewide peritoneal disease centre. Cases were divided into the first half and second to compare changes in practice over time. RESULTS: Three hundred and eighty four CRS and HIPEC cases were performed during this time. The median age was 56 years with 59.6% female. The median peritoneal carcinomatosis index (PCI) was 11, with a reduction in PCI in the second cohort (9 v 15, p < 0.01). Complete cytoreduction rates were significantly higher in the second cohort (82.3% v 67.7%, p < 0.01). Overall, grade III/IV complications occurred in 101 cases (26.3%) with three (0.8%) perioperative mortalities. Median overall survival (OS) for the entire cohort was 85 months, with a 5-year survival of 52%. Median OS was 97 months for PMP, 34 months for colorectal peritoneal metastases and 27 months for other histologies. Completeness of cytoreduction, histology type, and PCI were factors independently associated with overall survival. CONCLUSION: CRS and HIPEC can offer highly favourable outcomes for PSM with low morbidity. Successful complete cytoreduction rates improved significantly with greater experience and better patient selection.

A unique presentation of superinfected pseudomyxoma peritonei secondary to a low-grade appendiceal mucinous neoplasm.

BACKGROUND: Pseudomyxoma peritonei (PMP) is an uncommon condition characterized by diffuse mucinous material in the abdomen and pelvis, generally arising from a perforated epithelial neoplasm. Typically, the disease presents as suspected acute appendicitis, ovarian mass, abdominal distension, or ventral hernia. Our case represents a very rare presentation of superinfected PMP. CASE PRESENTATION: A 46-year-old female with a past medical history notable for depression, asthma, and uterine leiomyomas presented to an urgent care with 5 days of progressive abdominal pain, bloating, nausea, and subjective fevers. The patient had a diffusely tender abdomen, without peritonitis, was mildly tachycardic, and had a white blood cell count of 15 K. A CT of the abdomen/pelvis was consistent with PMP with a ruptured appendiceal mucocele versus PMP secondary to an adnexal ovarian neoplastic pathology with an infectious component. The patient initially improved on antibiotics but ultimately required two surgeries, the first of which controlled intraabdominal sepsis while the second permitted definitive management of PMP with cytoreductive surgery (CRS) and HIPEC. CONCLUSION: Superinfected PMP is a rare entity with very few documented cases. A staged approach that incorporates clearing the peritoneal infection, with or without resection of the primary tumor, followed by rehabilitation and definitive surgery appears to be a safe and effective management strategy.

[A single-center clinical analysis of 65 cases of pseudomyxoma peritonei from appendiceal origin in the early stage].

Objective: To analyze the efficacy and safety of cytoreduction surgery (CRS) combined with hyperthermic intraperitoneal chemotherapy (HIPEC) for pseudomyxoma peritonei (PMP) in the early stage. Methods: The clinical data, including pathological features, recurrence and survival of 65 PMP patients in the early stage underwent CRS combined with HIPEC in Aerospace Center Hospital from January, 2011 to December, 2018 were retrospectively analyzed. Results: 65 patients with early stage PMP underwent CRS+ HIPEC. Among these patients, 25 were males and 40 were females, and the mean age was 52.5 years. The median peritoneal cancer index was 3 (0-16). The score of completeness of cytoreduction (CC) of 63 patients (96.9%) was 0, and 2 patients (3.1%) was 1. No perioperative death occurred, the incidence of surgical complications above grade 3 was 3.1%. Three patients relapsed during the follow-up period, including 1 patient with low-grade PMP, 1 patient with high-grade PMP, and 1 patient with high-grade PMP accompanied by signet ring cell. The 5-year disease-free survival rate of the whole group was 92.4%. Conclusions: PMP patients in the early stage treated by CRS combined with HIPEC can achieve benefit and safety. A close long-term follow-up is necessary.

Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy for the Treatment of Peritoneal Carcinomatosis: Our Initial Experience.

Introduction: Peritoneal carcinomatosis represents an advanced stage of tumor dissemination of abdominal cancers in general and colorectal cancer in particular. The only therapeutic methods currently available for the treatment of this pathology are systemic chemotherapy (palliative character) and cytoreductive surgery (CR) with intraperitoneal chemotherapy. After evaluation of evidence-based medical literature and current guide lines we can state that CR + HIPEC procedure is considered to be the treatment of choice in case of patients with peritoneal carcinomatosis of colorectal, ovarian and mucinous appendicular origin. Material and method: In the present study we prospectively analyzed the immediate postoperative results obtained in the first 50 patients that were treated by our team for peritoneal carcinomatosis of different origin. We described the protocol of selection, the patients characteristics that were included in our CR+HIPEC program and analyzed the complications and death rate. Results: From January 2015 till Dec 2018 we evaluated 98 patients with peritoneal carcinomatosis. From them, 51 received radical CR+HIPEC treatment, 33 were not suitable for surgery because of the exclusion criteria's and 15 had only exploratory laparotomies. In regard with the histopathological diagnosis, 30 patients had ovarian cancer and 19 had colorectal cancer or peritoneal pseudomixoma of appendicular origin. There was no 30 days postoperative mortality. The incidence of significant postoperative complications was 15%. Conclusions: Cytoreductive surgery followed by hyperthermic intraperitoneal chemotherapy is a complex technique accompanied by an acceptable rate of complications and postoperative deaths, the results being optimized by a standardized perioperative management and patient selection. The initial results obtained by our team emphasize the feasibility of this procedure, with immediate good results, as a result of a standardization protocol of patient selection and perioperative care.

Impact of Cellularity on Oncologic Outcomes Following Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemoperfusion for Pseudomyxoma Peritonei.

BACKGROUND: The Peritoneal Surface Oncology Group International (PSOGI) recommends pathologic reporting of tumor cellularity in patients with pseudomyxoma peritonei (PMP) undergoing cytoreductive surgery and hyperthermic intraperitoneal chemoperfusion (CRS-HIPEC). We investigated the prognostic significance of PMP cellularity, or lack thereof (acellular mucin), following CRS-HIPEC. METHODS: We reviewed clinical data for 310 CRS-HIPEC procedures in low-grade (American Joint Committee on Cancer grade G1) PMP with acellular mucin (n = 19), scant cellularity (n = 30), or moderate cellularity (n = 242). Kaplan-Meier survival curves and multivariate Cox regression models identified prognostic factors affecting oncologic outcomes. RESULTS: Compared with patients with acellular mucin, those with scant and moderate cellularity had higher PCI and less-frequent complete macroscopic resection. After an estimated median follow-up of 49 months, 4 patients (14%) with scant cellularity and 127 patients (56%) with moderate cellularity progressed, while none of the patients with acellular mucin progressed. While the median progression-free survival (PFS) was not reached for patients with acellular mucin or scant cellularity (estimated 5-year PFS probability of 100 and 83%, respectively), patients with moderate cellularity demonstrated a median PFS of 32 months (estimated 5-year PFS probability of 27%). In a multivariate model, degree of disease cellularity, or lack thereof (acellular mucin), was an independent predictor of PFS but not overall survival. CONCLUSIONS: Early disease progression is unlikely in patients with acellular mucin undergoing CRS-HIPEC, as opposed to a 14% recurrence rate with scant cellularity. Thorough pathologic assessment for cellularity, or lack thereof (acellular mucin), is vital for accurate prognostication of disease progression for patients with low-grade PMP undergoing CRS-HIPEC.

Validation of the Recent PSOGI Pathological Classification of Pseudomyxoma Peritonei in a Single-Center Series of 265 Patients Treated by Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy.

BACKGROUND: Controversies still persist regarding the terminology and pathologic classification of appendiceal mucinous neoplasms and associated pseudomyxoma peritonei (PMP). We assessed reproducibility and prognostic significance of the classification recently proposed by the Peritoneal Surface Oncology Group International (PSOGI). METHODS: A prospective database of 265 PMP patients uniformly treated by cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) from 1995 to 2017 was reviewed. According to the PSOGI, peritoneal disease was retrospectively classified into three categories: low-grade (LG-PMP), high-grade (HG-PMP), and signet-ring cells (SRC-PMP). Acellular mucin (AC) was classified separately. The extent of peritoneal involvement was quantified by the peritoneal cancer index (PCI). RESULTS: Twenty-six patients were diagnosed with AC (9.8%), 197 with LG-PMP (74.4%), 38 with HG-PMP (14.3%), and 4 with SRC-PMP (1.5%). In the overall series, median follow-up was 65.5 months (95% confidence interval 53.7-78.8) and 10-year overall survival was 62.9% (median 148.7 months). Operative death occurred in 10 patients (3.8%) and major complications occurred in 89 patients (33.6%). Ten-year survival was 89.6% for AC, 63.2% for LG-PMP, 40.1% for HG-PMP, and 0 for SRC-PMP. In a multivariate model, the World Health Organization (WHO) pathological classification independently correlated with survival (p = 0.028). In a separate model, the PSOGI classification did not reach statistical significance (p = 0.149). Completeness of cytoreduction and PCI > 22 correlated with prognosis in both models. CONCLUSIONS: AC and SRC-PMP pathological categories of the PSOGI classification identified two subsets of patients with favorable and exceedingly dismal prognosis, respectively. It remains unclear whether the PSOGI classification might provide better prognostic stratification than the current WHO classification. Further studies in larger prospective series are needed.

Long-term Quality of Life After Cytoreductive Surgery and Heated Intraperitoneal Chemotherapy for Pseudomyxoma Peritonei: A Prospective Longitudinal Study.

BACKGROUND: Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) are an established treatment for pseudomyxoma peritonei (PMP), but it is a major surgical procedure and may be associated with long-term morbidity. To date, health-related quality-of-life (HRQL) data among survivors are lacking. METHODS: A two-period qualitative study investigated patients undergoing CRS-HIPEC for PMP at a national peritoneal tumor center between 2003 and 2011. First, the European Organization for Research and Treatment (EORTC)-QLQ C30 HRQL questionnaire was used longitudinally preoperatively and at postoperative months 3, 6, 9, 12, 18, and 24, then yearly thereafter. Second, it was updated in 2016 as a cross-sectional study. Both studies were compared with age- and sex-matched reference populations (one-way t tests). RESULTS: A total of 553 longitudinal HRQL questionnaires were completed for 137 patients, truncated at 60 months. In the 2016 update, 85 responses were received from 103 survivors (mean follow-up period, 8.11 years). Patients' physical, role, and social function scores were impaired until 12 months postoperatively, after which the scores did not differ significantly from those of with reference populations. Similarly, fatigue, appetite loss, insomnia, and financial difficulties worsened significantly compared with reference populations in the first 12-months and then normalized. In contrast, impaired cognitive function (82.3 vs 88.5; P = 0.017), constipation (13.7 vs 7.3; P = 0.032), and diarrheal symptoms (15.1 vs 4.9; P = 0.0006) persisted through both periods. Global health scores did not differ significantly from those of the reference population. CONCLUSIONS: Beyond 12 months postoperatively, CRS-HIPEC for PMP is associated with a good quality of life except for some cognitive functional impairment and bowel disturbances.

Prediction of Resectability in Pseudomyxoma Peritonei with a New CT Score.

BACKGROUND: Curative treatment of pseudomyxoma peritonei (PMP) is complete cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC). OBJECTIVE: The aim of this study was to build and evaluate a preoperative imaging score to predict resectability. PATIENTS AND METHODS: Between 2007 and 2014, all PMP patients in two tertiary reference centers who underwent laparotomy with intent to undergo CRS and HIPEC were included in this study retrospectively. Thickness of tumor burden was measured on preoperative multidetector-row computed tomography (MDCT) by two radiologists blinded to surgical results in five predetermined areas. Patients were divided into two cohorts with the same resectability rate (building and validation). The performances of the scores were assessed using receiver operating characteristic (ROC) curve analyses. RESULTS: Overall, 126 patients were included, with compete CRS being achieved in 91/126 patients (72.2%). Two cohorts of 63 patients matched by age, sex, burden of disease, resectability rate, and pathological grade were constituted. The MDCT score was the sum of the five measures, and was higher in unresectable disease [median 46.2 mm (range 27.9-74.6) vs. 0.0 mm (range 0.0-14.0), p < 0.001]. Area under the ROC curve was 0.863 (range 0.727-0.968) and 0.801 (range 0.676-0.914) in the building and validation cohorts, respectively. A threshold of 28 mm yielded a sensitivity, specificity, positive predictive and negative predictive value of 94, 81, 81 and 94% in the building cohort, and 80, 68, 59 and 85% in the validation cohort, respectively. Using our score, overall and disease-free survival were increased in the group classified as resectable. CONCLUSION: A simple preoperative MDCT score measuring tumor burden in the perihepatic region is able to predict resectability and survival of PMP patients.