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Background and Aims: Pseudomyxoma peritonei (PMP) is a rare disease characterized by progressive build-up of mucinous deposits inside the abdominal cavity. The aim of this study was to investigate the effect of disease recurrence on overall survival in patients with PMP after cytoreductive surgery (CRS) combined with hyperthermic intraperitoneal chemotherapy (HIPEC)., Methods: One-hundred thirty-two consecutive PMP patients treated with CRS + HIPEC at Helsinki University Hospital between 2008 and 2017 were included. The impact of clinicopathological and treatment-related characteristics on recurrence and overall survival was evaluated., Results: The median follow-up time in the study was 5.04 (range = 0.05-11.60) years. In 121 (91.7%) patients, the disease was classified as low grade and 11 (8.3%) had high-grade disease. In the low-grade group, 26 (21.5%) patients developed a recurrence during follow-up compared to 6 (54.5%) patients in the high-grade group. In the low-grade group, cumulative survival was 98.2%, 91.4%, and 91.4% at 3, 6, and 8 years, respectively. In the high-grade group, cumulative survival was 90.0% and 78.8% at 3 and 6 years, respectively. In patients with recurrent disease, the cumulative survival was 100%, 84.6%, and 84.6% at 3, 6, and 8 years in the low-grade category and 80.0% and 60.0% at 3 and 6 years in the high-grade category, respectively. In the low-grade group, a statistically significant correlation with recurrence but not with overall survival was identified with peritoneal cancer index (PCI), carcinoembryonic antigen (CEA), and the number of affected regions., Conclusion: The recurrence of low-grade PMP does not significantly affect overall survival of patients. Disease extent may not be a prognostic indicator after curative CRS and HIPEC in low-grade PMP., Competing Interests: Declaration of conflicting interestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: A.Y. has nothing to declare. L.K. declares grants from Mary and Georg Ehrnrooth’s Foundation and Cancer Foundation Finland (Syöpäsäätiö), outside the submitted work. C.H. and A.L. have nothing to declare.

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., (© 2021 Wiley Periodicals LLC.)

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., (Copyright © 2021 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Purpose: Pseudomyxoma peritonei is treated with cytoreductive surgery (CRS) combined and hyperthermic intraoperative intraperitoneal chemotherapy (HIPEC). The purpose of this study was to report the20-year experience of one surgical team inCRS and HIPEC for PMP of appendiceal origin., Methods: Retrospective study of the files of patients with PMP of appendiceal origin that underwent CRS+HIPEC. Morbidity and hospital mortality were recorded. Clinical and histopathologic variables were correlated to survival and recurrence., Results: The files of 41 patients with PMP of appendiceal origin that underwent CRS+HIPEC from 1999-2018 were retrieved. The mortality and the morbidity rates were 2.4% and 29.3%, respectively. The 5- and 8-year survival rate was 68.3%. The completeness of cytoreduction, and the extent of previous surgery were identified as the prognostic indicators of survival. The recurrence rate was 32.5% with the completeness of cytoreduction, the histologic type of the tumor being the prognostic indicator., Conclusions: CRS in combination with perioperative intraperitoneal chemotherapy is a safe and effective treatment in the management of PMP of appendiceal origin.

Importance: Studies on the prognostic role of hyperthermic intraperitoneal chemotherapy (HIPEC) in pseudomyxoma peritonei (PMP) are currently not available., Objectives: To evaluate outcomes after cytoreductive surgery (CRS) and HIPEC compared with CRS alone in patients with PMP., Design, Setting, and Participants: This cohort study analyzed data from the Peritoneal Surface Oncology Group International (PSOGI) registry, including 1924 patients with histologically confirmed PMP due to an appendiceal mucinous neoplasm. Eligible patients were treated with CRS with or without HIPEC from February 1, 1993, to December 31, 2017, and had complete information on the main prognostic factors and intraperitoneal treatments. Inverse probability treatment weights based on the propensity score for HIPEC treatment containing the main prognostic factors were applied to all models to balance comparisons between the CRS-HIPEC vs CRS-alone groups in the entire series and in the following subsets: optimal cytoreduction, suboptimal cytoreduction, high- and low-grade histologic findings, and different HIPEC drug regimens. Data were analyzed from March 1 to June 1, 2018., Interventions: HIPEC including oxaliplatin plus combined fluorouracil-leucovorin, cisplatin plus mitomycin, mitomycin, and other oxaliplatin-based regimens., Main Outcomes and Measures: Overall survival, severe morbidity (determined using the National Cancer Institute Common Terminology for Adverse Events, version 3.0), return to operating room, and 30- and 90-day mortality. Differences in overall survival were compared using weighted Kaplan-Meier curves, log-rank tests, and Cox proportional hazards multivariable models. A sensitivity analysis was based on the E-value from the results of the main Cox proportional hazards model. Differences in surgical outcomes were compared using weighted multivariable logistic models., Results: Of the 1924 patients included in the analysis (997 [51.8%] men; median age, 56 [interquartile range extremes (IQRE), 45-65] years), 376 were in the CRS-alone group and 1548 in the CRS-HIPEC group. Patients with CRS alone were older (median age, 60 [IQRE, 48-70] vs 54 [IQRE, 44-63] years), had less lymph node involvement (14 [3.7%] vs 119 [7.7%]), received more preoperative systemic chemotherapy (198 [52.7%] vs 529 [34.2%]), and had higher proportions of high-grade disease (179 [47.6%] vs 492 [31.8%]) and suboptimal cytoreduction residual disease (grade 3, 175 [46.5%] vs 117 [7.6%]). HIPEC was not associated with a higher risk of worse surgical outcomes except with mitomycin, with higher odds of morbidity (1.99; 95% CI, 1.25-3.19; P = .004). HIPEC was associated with a significantly better overall survival in all subsets (adjusted hazard ratios [HRs], 0.60-0.68, with 95% CIs not crossing 1.00). The weighted 5-year overall survival was 57.8% (95% CI, 50.8%-65.7%) vs 46.2% (95% CI, 40.3%-52.8%) for CRS-HIPEC and CRS alone, respectively (weighted HR, 0.65; 95% CI, 0.50-0.83; P < .001; E-value, 2.03). Such prognostic advantage was associated with oxaliplatin plus fluorouracil-leucovorin (HR, 0.42; 95% CI, 0.19-0.93; P = .03) and cisplatin plus mitomycin (HR, 0.57; 95% CI, 0.42-0.78; P = .001) schedules., Conclusions and Relevance: In this cohort study, HIPEC was associated with better overall survival when performed after CRS in PMP, generally without adverse effects on surgical outcomes.

Pseudomyxoma peritonei (PMP) is a rare condition characterized by the intraperitoneal accumulation of mucus derived mostly by appendiceal mucinous neoplasm. Cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) can offer a favourable overall survival. In this study, we report a single-institute outcomes following CRS and HIPEC in patients with this condition. This is a review of prospectively collected data from 32 patients (11 men and 21 women) affected by PMP of appendiceal origin who underwent CRS and HIPEC from 2008 to 2016 in our Surgical Unit of General and Esophagogastric Surgery. The median age of the patients was 53 years (range 25-77 years). After CRS, all patients underwent HIPEC (mytomicin C 3.3 mg/m 2 /L and cisplatin 25 mg/m 2 /L at 41 °C for 60 min) with closed abdomen technique. The median (range) follow-up time for surviving patients was 43 (18-119) months. The median peritoneal cancer index (PCI) was 17. Complete cytoreductive surgery (CC0) was achieved in in 22 patients (69%). The majority of patients (88%) had grade I-II complications, 3 (9%) had grade III complications, and 1 (3%) patient had a grade IV complication. There were no perioperative mortalities. The median hospital stay was 9.5 (range 9-24) days. One year and 5-year overall survival (OS) were 90% and 58%, respectively. Regardless of histotype, disease-free survival was 95% at 1 year and 46% at 5 years. CRS in combination with HIPEC is a feasible treatment strategy and can achieve a satisfactory outcome in patients with PMP of appendiceal origin.

Background: The aim of study was to develop and validate nomograms for predicting overall survival (OS) and cancer-specific survival (CSS) of patients with pseudomyxoma peritonei (PMP) and compare the predictive accuracy with the American Joint Committee on Cancer (AJCC) staging system., Methods: Data of 4959 PMP patients who underwent surgical resection were collected between 2004 and 2015 from the Surveillance Epidemiology and End Results (SEER) database. All included patients were divided into training (n = 3307) and validation (n = 1652) cohorts. The Kaplan-Meier method and Cox proportional hazard model were applied. Nomograms were validated by discrimination and calibration. Finally, concordance index (C-index) was used to compare the predictive performance of nomograms with that of the AJCC staging system., Results: According to the univariate and multivariate analyses of training sets, both nomograms for predicting OS and CSS combining age, grade, location, N stage, M stage, and chemotherapy were identified. Nomograms predicting OS also incorporated T stage and the number of lymph nodes removed (LNR). The calibration curves showed good consistency between predicted and actual observed survival. Moreover, C-index values demonstrated that the nomograms predicting both OS and CSS were superior to the AJCC staging system in both cohorts., Conclusion: We successfully developed and validated prognostic nomograms for predicting OS and CSS in PMP patients. Two nomograms were more accurate and applicable than the AJCC staging system for predicting patient survival, which may help clinicians stratify patients into different risk groups, tailor individualized treatment, and accurately predict patient survival in PMP.

Background: Pseudomyxoma peritonei (PMP) is a rare malignancy, and there is insufficient evidence about systemic chemotherapy for this disease., Methods: We retrospectively evaluated the efficacy and safety of a chemotherapeutic regimen with 5-fluorouracil and oxaliplatin (modified FOLFOX6, mFOLFOX6) for patients with unresectable pseudomyxoma peritonei. Patients who received the therapy between April 2000 and February 2019 at the Department of Medical Oncology, Tohoku University Hospital, were enrolled in this study., Results: Eight patients were treated with mFOLFOX6. The sites of primary tumor were appendix in six patients, ovary in a patient, and urachus in a patient. Six patients received surgery. Seven patients had histologically high-grade PMP, and one patient had low-grade PMP. The median follow-up duration was 27.2 months. All the patients had non-measurable regions as the targets of tumor response. Non-complete response or non-progressive disease was observed in seven patients, with a disease control rate of 87.5%. The median progression-free survival and overall survival were 13.0 months and 27.9 months, respectively. An obvious reduction in the symptoms was observed in two patients. Five patients experienced decline in the serum tumor markers, CEA or CA19-9. The grade 3/4 toxicity that was observed was grade 4 neutropenia in one patient and grade 3 neutropenia in two patients., Conclusions: mFOLFOX6 might be an effective and tolerable treatment option for patients with unresectable PMP. To our knowledge, this is the first case series of mFOLFOX6 in patients with unresectable PMP and the first case series of systemic chemotherapy for Asian patients with unresectable PMP.

Background: Pseudomyxoma peritonei (PMP) is an extremely rare malignancy, characterized by extensive peritoneal implantation and colloidal ascites. This study was to explore the pathological prognostic factors of PMP., Methods: Specimens from 155 PMP patients were analyzed by H&E and immunohistochemistry. Parameters included primary tumor location, histological grade, lymph node metastasis, tumor emboli in the blood and lymph vessels, perineural invasion, Ki67 labeling index, p53, mismatch repair (MMR) gene mutations, MUC1, MUC2, MUC5AC, and MUC6. Clinicopathological and follow-up data were subjected to univariate and multivariate analyses., Results: The patients included 63.2% (n = 98) low-grade mucinous carcinoma peritonei, 31.6% (n = 49) high-grade mucinous carcinoma peritonei and 5.2% (n = 8) high-grade mucinous carcinoma peritonei with signet ring cells. There were 9.7% (n = 15) with lymph node metastasis; 11.6% (n = 18) with angiolymphatic invasion; 6.3% (n = 8) with defective MMR (dMMR); 35.5% (n = 55) with Ki67 labeling index ≥ 50%; 36.1% (n = 56) with p53 mutation. For PMP from appendiceal origin (n = 140), univariate analysis identified 10 potential prognostic factors. But Multivariate analysis identified only histologic grade was the independent prognostic factor for OS. Mortality risk of high-grade peritoneal mucinous carcinoma or high-grade peritoneal mucinous carcinoma with signet ring cells was 7.056 times (P < .0001, 95% CI: 2.701-18.435) or 27.224 times (P < .0001, 95% CI: 6.207-119.408), respectively, higher than low-grade., Conclusions: For PMP from the appendiceal origin, histological grade could be the only independent prognostic factor., (Copyright © 2020 The Author(s). Published by Elsevier Inc. All rights reserved.)

Pseudomyxoma peritonei (PMP) is a rare cancer commonly originating from appendiceal neoplasms that presents with mucinous tumor spread in the peritoneal cavity. Patients with PMP are treated with curative intent by cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC). The value of adding HIPEC to CRS has not been proven in randomized trials, and the objective of this study was to investigate the efficacy of intraperitoneal mitomycin C (MMC) and regional hyperthermia as components of this complex treatment. Xenograft tissue established from a patient with histologically high-grade PMP with signet ring cell differentiation was implanted intraperitoneally in 65 athymic nude male rats and the animals were stratified into three treatment groups; the cytoreductive surgery group (CRSG, CRS only), the normothermic group (NG, CRS and intraperitoneal chemotherapy perfusion (IPEC) with MMC at 35 ºC), and the hyperthermic group (HG, CRS and IPEC at 41 ºC). The main endpoints were survival and tumor weight at autopsy. Adequate imitation of the clinical setting and treatment approach was achieved. The median survival was 31 days in the CRSG, 60 days in NG and 67 days in HG. The median tumor weights at autopsy were 34 g in CRSG, 23 g NG and 20 g in HG. In conclusion, the addition of IPEC with MMC after CRS doubled the survival time and reduced tumor growth compared to CRS alone. Adding regional hyperthermia resulted in a modest improvement of treatment outcome.

Objectives: The peritoneal cancer index (PCI) is widely used for assessing pseudomyxoma peritonei (PMP) in surgery. The aim of this study was to evaluate the utility of a modified PCI using 18F-fluorodeoxyglucose (18F-FDG)-PET/CT (PET-PCI) for predicting pathologic grade and progression-free survival (PFS) in patients with PMP., Methods: Thirty-five patients who underwent 18F-FDG-PET/CT before cytoreductive surgery and/or hyperthermic intraperitoneal chemotherapy were enrolled. PET-PCI was determined by summing up the visually scored 18F-FDG uptake of PMP lesions in 13 specific abdominal-pelvic regions. Uptake score was defined as 0, no lesion or lesion without uptake; 1, slight uptake less than or equivalent to mediastinal blood pool; 2, moderate uptake above mediastinal but below or equal to liver; and 3, intense uptake moderately to markedly higher than liver. SUVmax of the lesion was also evaluated., Results: Pathologic diagnosis revealed 19 patients with low-grade PMP and 16 patients with high-grade PMP. Patients with high-grade PMP showed significantly higher PET-PCI and SUVmax than patients with low-grade PMP (PET-PCI 14.8 vs. 8.7, p = 0.007; SUVmax 3.6 vs. 2.6, p = 0.013). Using a cutoff PET-PCI of 12, Kaplan-Meier analyses showed a significant difference in PFS between patients with high and low PET-PCI (p < 0.001; hazard ratio (HR), 12.4). For SUVmax, the optimal cutoff was 2.7 and the correlation with PFS was also significant (p = 0.008; HR, 4.7). In multivariate Cox proportional-hazards regression, PET-PCI was independently and significantly correlated with PFS., Conclusions: PET-PCI can reflect histopathologic features and appears useful for predicting recurrence in patients with PMP., Key Points: • Peritoneal cancer index using 18F-FDG-PET/CT (PET-PCI) has great potential for predicting progression-free survival in patients with pseudomyxoma peritonei. • PET-PCI provides higher prognostic performance than maximum standardized uptake value (SUVmax). • PET-PCI shows high correlation with histopathologic grade of pseudomyxoma peritonei.

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.

Introduction: The optimal treatment for pseudomyxoma peritonei (PMP) combines complete cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC). Yet, achieving CRS is challenging in the case of extensive involvement of the peritoneal cavity and the survival benefit in this setting remains uncertain. The present study evaluated the surgical outcomes according to the peritoneal extent., Methods: Between 1992 and 2014, 245 patients underwent CRS and HIPEC for PMP in our institution. Their characteristics were reviewed using a prospective database. Extensive PMP was defined as a peritoneal cancer index (PCI) ≥ 28. Sixty-one patients with extensive PMP were compared to 184 with non-extensive PMP., Results: Severe complications were more frequent in the extensive group (46% vs. 23%, p < 0.001) but the post-operative mortality was not significantly different (8% vs. 3%, p = 0.1). The 5-year disease-free survival reached 45% in the extensive and 78% in the non-extensive group (p < 0.0001). The 5-year overall survival was 70% and 90% in the extensive and non-extensive group respectively (p < 0.021)., Conclusion: CRS with HIPEC offers prolonged survival even in the case of extensive PMP. Because of the high rate of surgical morbidity in the extensive group, patients should be carefully selected., (Copyright © 2019. Published by Elsevier Ltd.)

Background: Pseudomyxoma peritonei (PMP) is a rare disease, most commonly of appendiceal origin. Treatment consists of cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS-HIPEC). The aim of this study was to identify prognostic factors for recurrence and survival., Methods: This was an observational study using a prospectively designed database containing consecutive patients with PMP originating from the appendix, undergoing CRS-HIPEC at a tertiary referral centre between 1996 and 2015. Histopathological slides were reassessed. Cox regression was used for multivariable analyses., Results: Of 225 patients identified, 36 (16·0 per cent) were diagnosed with acellular mucin, 149 (66·2 per cent) had disseminated peritoneal adenomucinosis (DPAM) and 40 (17·8 per cent) had peritoneal mucinous carcinomatosis (PMCA). The 5-year overall survival (OS) rates were 93, 69·8 and 55 per cent respectively. Recurrence was observed in 120 patients (53·3 per cent), 39 of whom (17·3 per cent) were treated with a second CRS-HIPEC procedure. Factors independently associated with poor disease-free survival were six or seven affected regions (hazard ratio (HR) 6·01, 95 per cent c.i. 2·04 to 17·73), incomplete cytoreduction (R2a resection: HR 1·67, 1·05 to 2·65; R2b resection: HR 2·00, 1·07 to 3·73), and more than threefold raised carcinoembryonic antigen (CEA) and/or carbohydrate antigen (CA) 19-9 level (HR 2·31, 1·30 to 4·11). Factors independently associated with poorer OS were male sex (HR 1·74, 1·09 to 2·77), incomplete cytoreduction (R2a resection: HR 1·87, 1·14 to 3·08; R2b resection: HR 2·28, 1·19 to 4·34), and more than threefold raised CEA and/or CA19-9 level (HR 2·89, 1·36 to 6·16)., Conclusion: CEA and CA19-9 levels raised more than threefold above the upper limit identify patients with PMP of appendiceal origin and poorer survival.

Background: Pseudomyxoma peritonei (PMP) is a rare disease, characterized by mucinous ascites and deposits diffusely present on the peritoneal surfaces. However, extension of PMP to the thoracic cavity is extremely rare. Although there are a few case reports on the long-term postoperative prognosis of intrathoracic lesions, whether surgical resection of these lesions can improve patient prognosis remains unclear., Methods: We reviewed 17 patients with PMP who underwent resection of intrathoracic lesions after abdominal cytoreductive surgery and examined their clinical outcome after surgery., Results: Direct extension into the pleural cavity was identified in 11 patients. Extrapleural pneumonectomy of the lesions followed by hyperthermic intrathoracic chemotherapy (HITOC) was performed in four patients, parietal pleurectomy and visceral tumor resection followed by HITOC in four patients, resection of all disseminated pleural and visceral lesions followed by HITOC in one patient, resection of a single disseminated lesion in one patient, and composite resection of basal segment with the diaphragm in one patient. Pulmonary metastases were found in six patients. Partial resection was performed in four patients, segmentectomy in one patient, and lobectomy in one patient. We could perform macroscopic resection of the tumor in all the cases. The 5-year overall survival rate after thoracic surgery for the 17 patients was 46.1% and relapse-free survival was 34.9%., Conclusions: Resection of intrathoracic lesions of PMP after abdominal cytoreductive surgery achieved 5 years survival in at least 46.1% of the patients. Aggressive tumor resection should be considered for patients with PMP extending to thoracic cavity.

Purpose: Documentation of cellularity in Pseudomyxoma peritonei (PMP) is not performed on a regular basis in everyday clinical practice, but is recommended by the PSOGI (Peritoneal Surface Oncology Group International). We investigated the impact of cellularity in PMP following cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) on recurrence-free survival., Methods: Data from 25 patients with low-grade (American Joint Committee on Cancer grade G1) PMP were retrospectively evaluated. Cellularity was categorized as acellular mucin, scant (< 2% cellularity), moderate (2-19% cellularity), or high cellularity (> 20% cellularity). Impact of cellularity, PCI, CC-score, and HIPEC regimen on recurrence-free and overall survival was primarily assessed., Results: Assessment of cellularity showed acellular mucin in ten patients (40%), scant cellularity in 11 (44%) patients, moderate cellularity in one (4%) patient, and high cellularity in three (12%) patients. Median PCI was 15 (range, 1-39). A CC-0 score was achieved in 13 (52%) patients and a CC-1 score was achieved in 12 (48%) patients. After a median follow-up of 25 (range, 2-74) months, all patients were still alive. Overall, four (16%) patients suffered from recurrent disease after a median of 38 (range, 36-60) months. PCI above 17 (p = 0.03) and moderate and high cellularity (p = 0.007) were statistically significantly associated with recurrent disease. CC-score and HIPEC compound used did not impact on recurrence-free survival., Conclusions: Recurrent disease occurs more often in patients with PCI values above 17 and with moderate and high cellularity in low-grade PMP. Pathological assessment of cellularity is crucial for identification of patients at risk for recurrence.

Background: Malnutrition is associated with increased postoperative morbidity in abdominal surgery. This study aimed to determine if sarcopenia and/or abdominal fat composition could predict postoperative outcomes for patients undergoing cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS-HIPEC) for pseudomyxoma peritonei (PMP) and peritoneal mesothelioma (PM)., Methods: All patients who underwent a complete CRS-HIPEC for PMP and PM, between January 2009 and September 2017, were retrospectively studied. Preoperative computed tomography (CT) was used to measure the cross-sectional surface of skeletal muscle mass and adipose tissue (visceral and subcutaneous), at the level of the third lumbar vertebrae, to assess for sarcopenia and abdominal fat composition., Results: Among 115 patients, 82 were treated for PMP and 33 for PM. 64 patients (55.7%) were sarcopenic on the preoperative imagery. Major postoperative complications occurred in 63 patients (54.8%), without observable difference between sarcopenic and non-sarcopenic patients (56.2% vs. 52.9%; p = 0.723). The median overall survival (OS) was 73.3 for the patients with a normal muscle mass and 57.2 months for the sarcopenic patients (p = 0.05)., Conclusion: CT measured sarcopenia is an independent predictive factor for overall survival in patients treated for PMP and PM with CRS-HIPEC, but cannot predict postoperative morbidity., (Copyright © 2018 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.)

Background: Pseudomyxoma peritonei (PMP) is a rare clinical condition characterized by mucinous ascites, typically related to appendiceal or ovarian tumours. Current standard treatment involves cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC), but recurrences occur in 20-30 per cent of patients. The aim of this study was to define the timing and patterns of recurrence to provide a basis for modifying follow-up of these patients., Methods: This observational study examined a prospectively developed multicentre national database (RENAPE working group) to identify patients with recurrence after optimal CRS and HIPEC for PMP. Postoperative complications, long-term outcomes and potential prognostic factors were evaluated., Results: Of 1411 patients with proven PMP, 948 were identified who had undergone curative CRS and HIPEC. Among these patients, 229 first recurrences (24·2 per cent) were identified: 196 (20·7 per cent) occurred within the first 5 years (early recurrence) and 30 (3·2 per cent) occurred between 5 and 10 years. Three patients developed a first recurrence more than 10 years after the original treatment. The mean(s.d.) time to first recurrence was 2·36(2·21) years. Preoperative chemotherapy and high-grade pathology were significant factors for early recurrence. Overall survival for the entire group was 77·9 and 63·1 per cent at 5 and 10 years respectively. The principal site of recurrence was the peritoneum., Conclusion: Recurrence of PMP was rare after 5 years and exceptional after 10 years.

Aim: The neutrophil-lymphocyte ratio (NLR) and other inflammation-based scores have been used as a prognostic tool to predict survival in solid tumours including pseudomyxoma peritonei (PMP). The aim was to evaluate the prognostic value of this marker and risk stratify PMP patients undergoing cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC)., Methods: Retrospective analysis was conducted of a prospectively collected database of patients with PMP who underwent CRS and HIPEC between 1994 and 2015. The NLR was calculated by dividing the pre-operative neutrophil count by lymphocyte count. Predicted overall survival (OS) and disease-free interval (DFI) were calculated using a Kaplan-Meier survival model., Results: The study included 699 patients, stratified into four groups as defined by their NLR. Group A: 200 (28.6%) patients (NLR = 0.10-2.00), Group B: 160 (22.8%) patients (NLR = 2.10-2.78), Group C: 184 (26.3%) patients (NLR = 2.79-4.31) and Group D: 155 (22.2%) patients (NLR ≥ 4.32). The median follow-up for this cohort was 36 months. The predicted DFI was 132.2, 113.1, 84.4 and 47.9 months and the OS was 141.1, 117.6, 88.7 and 51.2 months for Groups A, B, C and D, respectively. As the NLR increases, there is a reduction in long-term survival., Conclusion: The pre-operative NLR is cost effective and has equivalent prognostic value to pre-operative tumour markers for patients with PMP treated with CRS and HIPEC. The NLR is a reliable tool that may have a role in predicting outcomes following CRS and HIPEC for patients with PMP of appendiceal origin.

Objective: To analyze the relationship between clinicopathologic characteristics of pseudomyxoma peritonei (PMP) and its prognosis. Methods: Fifty-two cases of PMP collected from 2012 to 2017 at Beijing Shijitan Hospital, Capital Medical University were reviewed using the diagnostic criteria of WHO 2010. The histopathologic features, including original location, neural invasion and calcification were observed; and the relationship with prognosis was analyzed. Immunohistochemical staining for CK7, CK20 and CDX2 was performed on all cases. ER, PR, and p16 were additionally performed on those without clear origin. Results: Patients' mean age was 52.0 years, and included 29 males and 23 females. Thirty-two cases were derived from appendix; among them, 23 were low grade and 29 were high grade. Signet ring-cells, neural invasion and calcification were detected in 15, 12 and 9 cases respectively. Neural invasion was associated with adverse prognosis ( P =0.025) and signet ring cell morphology ( P <0.01). Prognosis was not related to gender, age, original location or grade. Conclusion: Neural invasion is not uncommon in PMP and predicts a bad prognosis.

Background: Pseudomyxoma peritonei (PMP) is a rare carcinomatosis limited to the peritoneal cavity, mainly supplied by the superior mesenteric artery (SMA). The only curative treatment is cytoreductive surgery (CRS) associated with hyperthermic intraperitoneal chemotherapy. This study aimed to evaluate the ability of blood flow volume (BFV) recorded in the SMA using Doppler ultrasonography pre-operatively to predict the extent and resectability of the disease and post-operatively to assess clinical outcome., Methods: BFV was measured in the SMA of forty-nine patients before and the year following CRS. Patients were categorized in 3 groups according to clinical and surgical outcomes: group-1 (n = 22): patient with completed CRS, group-2 (n = 16): incomplete resection with slowly progressive disease (alive at 2 years without severe clinical symptoms), group-3 (n = 11): incomplete resection and with severe clinical symptoms or dead within two years., Results: Pre-operative mean SMA BFV was higher in group-2 (510 mL/min, p = 0.027) and in group-3 (572 mL/min, p = 0.004) than in group-1 (378 mL/min). After surgery, BFV dropped to normal values (203 mL/min, p = 0.001) in group-1, and to 423 mL/min (p = 0.047) in group-2. It remained elevated in group-3 (626 mL/min, p = 0.566). BFV allowed stratification of 1) resectability before CRS (group-2 and -3 vs group-1, area under the ROC curve: 0.794 [0.650-0.939]), and 2) non progression after incomplete CRS (group-3 vs group-2, area under the ROC curve: 0.827 [0.565-1.00]., Conclusions: Pre-operative BFV in the SMA correlates with extent and resectability of PMP. After incomplete surgery, post-operative BFV might aid in identifying patients who may benefit of post-operative therapy., (Copyright © 2017 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.)

Background and Objectives: Appendiceal neoplasms with extra-appendiceal spread may show different clinical patterns with pseudomyxoma peritonei (PMP) being one of them. We analyse the results in a series of patients treated in our centre., Material and Methods: Retrospective study of patients operated on for appendiceal peritoneal carcinomatosis from January 2012 to May 2015., Results: Twenty-seven consecutive patients were included. Median age 63 years (26-73); 14 were men. Peritoneal carcinomatosis index=16±8 (3-31). The suspected preoperative origins were appendix in 23, ovary in 3 and urothelial in one. Postoperative mortality in 2 patients (7.4%). The remaining 36% presented morbidity. Major morbidity (Clavien-Dindo grades 3 and 4) occurred in 3 patients (12%)., Conclusions: Mucinous adenocarcinomas with extra-appendiceal spread may present as PMP with mucinous ascites, jelly-nodular carcinomatosis without ascites, nodular or desmoplasic plates carcinomatosis without jelly mass/nodules. Histology is not correlated to clinical picture. Preoperative diagnosis of mucinous ovarian cancer in peritoneal carcinomatosis scenario may increase the doubt of their ovarian origin and force an appendiceal origin to be ruled out., (Copyright © 2017 Elsevier España, S.L.U. All rights reserved.)

Aim: Pseudomyxoma peritonei is a rare disease that affects 1-2 per million population per year. Treatment with cytoreductive surgery with heated intraperitoneal chemotherapy (CRS with IPC) has been well described. The purpose of this study was to look at the short-term outcomes following CRS with IPC for all such patients treated in Waikato., Method: Records for all patients presenting to surgery for CRS with IPC were retrospectively reviewed. CRS with IPC was performed in accordance with the techniques described by Sugarbaker. Data recorded included patient characteristics, characteristics of surgical treatment and early post-operative outcomes., Results: Sixty-eight patients underwent 72 procedures. Fourteen patients were deemed unresectable at surgery and were treated palliatively. The median age was 57 with the majority being female (59%). The median time, from the decision made for surgery to CRS with IPC, was three months. The median prior surgical score was 1 and the median peritoneal cancer index (PCI) was 19.5. The median operating time was 9.08 hours (5.43-15.20). The majority of patients (76%) had pseudomyxoma peritonei, while the remainder had a combination of other appendiceal, colorectal, ovarian, gastric and primary mesothelial primaries. The major complication rate was 24% and the 30-day mortality rate was 1.4%. The median hospital stay was 12 days., Conclusion: Short-term outcomes following CRS with IPC at Waikato are comparable to those published in the literature. Further follow-up is anticipated for the publication of survival and recurrence data., Competing Interests: Nil.

Cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) has been shown to improve quality of life and survival rates in patients suffering from pseudomyxoma peritonei. The procedure is long and associated with significant intraoperative blood loss. As such, the anaesthetic management of patients undergoing this procedure can be challenging. The aim of this paper is to describe our perioperative management of pseudomyxoma peritonei patients who received CRS and to report a retrospective audit of our outcomes and complications over a six-year period at a large tertiary centre. A total of 70 patients were included, of whom three (4.3%) had CRS alone, 42 (60.0%) had CRS with HIPEC, and 25 (35.7%) had CRS with HIPEC and early postoperative intraperitoneal chemotherapy. There were no intraoperative deaths. A total of four patients (5.7%) died during their hospital admission. At one-year follow-up, six patients (9.0%) had died, and at the end of the study 15 (22.4%) had died. No statistically significant difference in blood loss was seen between patients who received tranexamic acid (30 patients, 42.9%) and those who did not, but the incidence of deep venous thrombosis was much higher (10/30 versus 1/40). Different intravenous fluid strategies appeared not to influence the incidence of postoperative acute renal failure. Further research is required to evaluate the effects of intraoperative tranexamic acid and different intraoperative fluid strategies on outcomes in patients undergoing CRS with HIPEC.

Altered expression of carbonic anhydrase (CA) II is associated with human carcinogenesis. We analysed CA II protein expression in 89 patients with pseudomyxoma peritonei (PMP) and correlated its association against survival. We determined the expression of CA II by immunohistochemistry and then scored the staining results. The correlations of CA II expression with Peritoneal Cancer Index (PCI) and tumour grade were examined. The effect of CA II and tumour grade on survival was investigated. Positive CA II expression was found in 58 patients (65%) and absent in 31 patients (35%). High-grade (HG) morphology was associated with a loss of CA II expression (p = 0.048). The mean CA II immunostaining intensity score was 1.00 ± 1.1 (median 1, range 0-3) for HG morphology and 1.54 ± 1.1 (median 2, range 0-3) for low-grade (LG) morphology. The 5-year overall survival (OS) for those patients with CA II expression was 80% and 59% for those without (p < 0.001). The 5-year OS rates for those patients with HG morphology and positive CA II expression was 72% and 31% for those with negative CA II expression (p = 0.044). This study suggests that the expression of CA II acts as independent prognostic biomarker for survival in PMP., (© 2017 APMIS. Published by John Wiley & Sons Ltd.)

Background: Cytoreductive Surgery (CRS) and Hyperthermic Intraperitoneal Chemotherapy (HIPEC) are considered standard of care for pseudomyxoma peritonei (PMP) and selected patients with colorectal peritoneal metastases (CPM) or peritoneal mesothelioma. A National Peritoneal Malignancy programme was established in Ireland (population of 4.5 million) in May 2013 with mentoring and support from the Peritoneal Malignancy Institute, Basingstoke UK. This study reviews the operative and oncological outcomes for the first 50 patients who underwent CRS and HIPEC in Ireland., Methods: This is a retrospective review of all patients referred, and of the subset who underwent CRS and HIPEC, for peritoneal malignancy in Ireland between May 2013 and November 2015., Results: During the study period, 130 patients were referred and 50 patients were selected for CRS and HIPEC. Three patients were found to have unresectable disease at laparotomy. Of the remaining 47 patients, eight had major tumour debulking. In total, 39 underwent complete cytoreduction and 45 received HIPEC. After a median follow-up of 12.7 months, 12 patients had developed further metastatic disease. The rates of complete cytoreduction, major complication (Clavien-Dindo III/IV) and operative mortality were 83%, 0% and 0%, respectively. 32% of patients experienced grade I/II complications., Conclusions: We report the successful establishment of a national peritoneal malignancy programme. Mentoring from an experienced centre may have shortened the known learning curve evident by our encouraging outcomes. The follow-up period is short, however our early results are comparable with internationally reported figures., (Copyright © 2016 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.)

Background: The modified Glasgow prognostic score (incorporating C-reactive protein and albumin) predicts survival in patients with gastro-intestinal tract cancer but has not been evaluated in patients with peritoneal malignancy. The aim was to evaluate the modified Glasgow score preoperatively in patients undergoing complete cytoreductive surgery (CCRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) for pseudomyxoma peritonei (PMP) of appendiceal origin., Methods: Prospectively collected data from patients with PMP of appendiceal origin following CCRS and HIPEC between January 2007 and December 2011 were analysed. The mGPS was calculated from preoperative C-reactive protein and albumin. Predicted overall survival (OS) and disease-free survival (DFS) for each mGPS score were calculated using the Kaplan-Meier model. In a separate analysis, a comparison was made between mGPS and Tumour Markers (TM)., Results: 260 patients were included in the study. The mGPS of 0, 1, and 2 were found in 111, 130, and 19 patients respectively. The median follow-up was 48 months. For mGPS-0, -1, and -2, the predicted OS was 82.2, 73.7, and 69.2 months and the DFS was 73.5, 62.9, and 54.4 months respectively. As mGPS increases, there is a reduction in long-term survival. There was no difference between mGPS and TM., Conclusion: Preoperative mGPS may be a cost effective prognostic tool for predicting OS and DFS in patients following complete CRS-HIPEC, and performs well compared to TM for predicting patients at high risk of recurrence., (Copyright © 2016 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.)

Purpose: To evaluate the short-term outcomes of patients of pseudomyxoma peritonei (PMP) of appendiceal origin treated with cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) at two tertiary Indian centers., Methods: Data was prospectively collected from January 2011 to January 2016. Palliative procedures were excluded. HIPEC was performed by the coliseum technique using either a mitomycin or oxaliplatin-based regimen., Results: 77 procedures were performed on 71 patients. The average time interval between diagnosis and CRS was 15.3 months. Of the tumors, 22.1% were high grade, 77.9% low grade and 24.6% intermediate grade. The median peritoneal carcinomatosis index (PCI) was 26 (<25 in 70.1% and >30 in 38.9%). Completeness of cytoreduction score (CCS)-1 was achieved in 75.3% (CC-0 in 42.9%). The mean number of bowel anastomoses was 1.1 and the mean number of organs resected per patient was 3.3. Of the 77 patients, 71% had resection of 3 or more organs and 50.6% had resection of 4 or more organs. Grade 3-4 complications occurred in 42.9% of the patients and the perioperative mortality was 5.2%. The projected 5-year overall survival (OS) was 62.3% and the 3-year disease-free survival (DFS) was 71% at a median follow up of 13 months., Conclusion: CRS and HIPEC can be used to treat PMP with an acceptable morbidity and mortality in Indian patients. Lack of early referrals leads to a large portion of patients presenting with extensive disease and an inferior survival which should improve with increasing awareness about the procedure and its results.

Three patients of pseudomyxoma peritonei who were diagnozed by transumbilical endoscopic surgery (TUES) were reviewed retrospectively from September 2014 to November 2014. Three cases of ascites patients underwent TUES were diagnozed as pseudomyxoma peritonei. All operations were successful. No open surgery or laparoscopic surgery was required. The mean operative time was (45±16) min; the mean intraoperative blood loss was 510 mL; the mean hospital stay time was 3 days. During the follow up of 911 months, no obvious scar was observed. Cosmetic results appear to be excellent. All patients were treated with intraperitoneal hyperthermia and chemotherapy. The survival rate was 100%. As a novel scarless endoscopic invasive abdominal surgery, TUES has high clinical value with the advantages such as small trauma, no scars, small risk and low cost in the diagnosis of unexplained ascites.

Pseudomyxoma peritonei is a fatal clinical syndrome with mucinous tumor cells disseminated into peritoneal cavity and secreting abundant mucinous ascites. The serum tumor markers CEA, CA19-9, and CA125 are used to monitor pseudomyxoma peritonei remission, but their expression at tissue level has not been well characterized. Herein, we analyzed expression of these proteins and the adenocarcinoma marker EpCAM in 92 appendix-derived pseudomyxoma peritonei tumors by immunohistochemistry. All tumors were found to ubiquitously express CEA and EpCAM. In the majority of the tumors (94.6%), CEA showed polarized immunostaining, but in 5 aggressive high-grade tumors containing numerous signet ring cells, a nonpolarized staining was detected. We found preoperative CEA serum values to correlate with peritoneal cancer index. However, the serum values of the advanced cases with nonpolarized staining pattern were normal, and the patients died within 5 years after diagnosis. Thus, serum CEA measurements did not reflect aggressiveness of these tumors. CA19-9 showed strong immunopositivity in most of the tumors (91.3%), and mutated enzyme FUT3 was demonstrated from the cases showing negative or weak staining. CA125 was infrequently expressed by tumor cells (focal staining in 6.5% of the cases), but in most of the cases (79.3%), adjacent nonneoplastic mesothelial cells showed immunopositivity. As a conclusion, CEA and EpCAM are invariably expressed by pseudomyxoma peritonei tumor cells and could be exploited to targeted therapies against this malignancy., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Background: This study aims to evaluate the safety and efficacy of cytoreductive surgery (CRS) including total gastrectomy and total colectomy in selected pseudomyxoma peritonei (PMP) patients with entire stomach and colon covered by mucinous tumor., Methods: A total of 48 patients received this extensive treatment between January 2006 and January 2014. The main focus of this study was survival after CRS as well as perioperative morbidity and mortality., Results: Twenty-eight patients were male, and median age was 52.5 years. Median peritoneal cancer index was 33. Complete cytoreduction was achieved in all 48 patients, and 26 patients received hyperthermic intraperitoneal chemotherapy (HIPEC). Until last follow-up, the estimated median survival after CRS was 54.0 months (95% CI 36.5-71.6 months). The 1-, 2-, 3-, and 5-year survival rates were 91.7%, 81.3%, 70.1%, and 48.6%, respectively. Histology was significantly associated with survival (P = 0.020). The median disease-free survival was 32.0 (95% CI 25.7-38.3) months. HIPEC (P = 0.048) and histology (P = 0.002) was significantly associated with disease-free survival after CRS. Overall Grade 3-5 complications occurred in 18 (37.5%) patients with mortality of 2.1%. For patients who received surgery over 6 months, they could gradually have an acceptable quality-of-life similar as other patients receiving ordinary CRS and HIPEC., Conclusion: CRS including total gastrectomy and total colectomy can be performed in experienced specialized institutions as a feasible option to achieve complete cytoreduction with acceptable safety in selected PMP patients with stomach and colon covered by mucinous tumor. Perioperative management should be carried out cautiously to decrease and avoid complications., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Introduction: Pseudomyxoma peritonei is a rare disease causing peritoneal carcinomatosis. In patients with extensive carcinomatosis, curative treatment is unachievable. Palliative debulking therapy is the only treatment in relieving symptoms. We report our results from palliative debulking surgery at a national pseudomyxoma peritonei center in Denmark., Methods: From January 2007 to October 2012, we performed 27 palliative operations for pseudomyxoma peritonei with debulking at our institution. All patients were evaluated and found eligible for palliative treatment only. Patients were prospectively registered, while perioperative data were collected retrospectively from patient records., Results: The majority of patients (n = 25) received an omentectomy (93%) as the primary procedure. In total, 17 (63%) received additional surgery. Median operative time was 88 min (range: 33-160 min). Median stay at the recovery ward was 6 h (2-288 h). Median hospital stay was 8 days (4-105 days). In all, 23 (85%) patients had no in-hospital complications, whereas 4 patients experienced complications (15%). Two of the complications were mild (Clavien-Dindo grade II), and two experienced severe complications (grade III and IV). Thirty-day mortality was 0%. Median survival was 3.0 years (0.2-6.2 years)., Conclusion: Palliative debulking is a safe procedure with an acceptable morbidity and mortality offering immediate disease control., (© The Finnish Surgical Society 2015.)

Aim: To study the results of intraperitoneal chemoperfusion combined with cytoreductive procedure in patients with peritoneal pseudomyxoma., Material and Methods: For the period 2006--2015 seven patients with peritoneal pseudomyxoma underwent aggressive treatment using hyperthermic intraperitoneal chemoperfusion combined with cytoreductive procedure at the Department of General Oncology of N.N. Petrov Research Institute of Oncology., Results: Two patients had postoperative complications. One of them died after 12 days postoperatively. Features of postoperative complications were predominantly determined by volume of cytoreduction. Advanced tumoral process caused death in 2 patients additionally. Other patients are still alive during 4--28 months after surgery., Conclusion: Hyperthermic intraperitoneal chemoperfusion combined with cytoreductive procedure is advisable for peritoneal pseudomyxoma to improve survival. Optimal cytoreduction should be developed in researches with large number of patients to decrease incidence of complications.

Aims: Inflammation-based scores such as neutrophil-lymphocyte ratio (NLR) and Onodera nutritional index (ONI) have been identified as new prognosticators in several tumors. We conducted a prognostic analysis of these markers and performed a risk stratification of PMP patients submitted to cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC)., Methods: 226 patients from two peritoneal surface malignancies centers participated in this study. Cox proportional modeling was used to select predictors of overall survival (OS) among baseline inflammation-based scores, serum tumor markers, clinical and surgical variables. Risk stratification was done using conditional inference tree model., Results: One hundred eighty-two cases had diffuse peritoneal adenomucinosis subtype. Fifty-four cases had received previous systemic chemotherapy. The means of ONI and NLR were 51.4 (SD = 9.8) and 3.2 (SD = 2.3), respectively. Two hundred ten cases were optimally cytoreduced. Cox analysis identified completeness of cytoreduction, histological subtype, previous systemic chemotherapy, NLR, and CA 19-9 as independent prognosticators. Conditional inference tree method identified two poor prognostic subsets: NLR ≤2.7 and CA 19-9>336 (5yr-OS = 15%) and NLR >2.7 and ONI ≤42 (5yr-OS = 30%)., Conclusions: NLR, ONI, and CA 19-9 are new prognosticators that contributed to improve prediction of OS in PMP patients treated by CRS and HIPEC. These markers allowed a risk stratification that could optimize therapeutic management of PMP patients., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Pseudomyxoma peritonei (PMP) is an uncommon clinical condition that typically originates from a perforated epithelial neoplasm of the appendix. The clinical presentation is variable, often with non-specific symptoms and is associated with abdominal distension in advanced cases. Whilst traditionally considered benign, it is apparent that PMP represents a spectrum of disease and, at best, should be considered a "border-line" malignancy. The condition is characterised by the development of mucinous ascites. Tumour cells and mucin accumulate at characteristic sites within the peritoneal cavity according to the redistribution phenomenon, usually sparing the mobile small bowel. In advanced cases, high volume disease and mucinous ascites lead to compression of the gastrointestinal tract, bowel obstruction, and ultimately, starvation. Controversy still exists over the pathological classification of PMP and its prognostic value. Computed tomography remains the optimal preoperative staging investigation. Elevation of serum tumour markers correlates with a worse prognosis. Optimal treatment involves cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (HIPEC). With complete cytoreduction and HIPEC an 80% 5 year survival can be achieved in patients with low grade disease. Maximal tumour debulking can produce good palliation and long term survival in a small number of patients. Initial high morbidity and mortality is seen to decrease with increasing experience and this is likely to represent improvement in patient selection and postoperative management as well as surgical expertise.

Pseudomyxoma peritonei (PMP) is a relatively rare clinical syndrome characterized by neoplastic epithelial cells growing in the peritoneal cavity and secreting mucinous ascites. Our aim was to explore the molecular events behind this fatal but under-investigated disease. We extracted DNA from 19 appendix-derived PMP tumors and nine corresponding normal tissues, and analyzed the mutational hotspot areas of 48 cancer-related genes by amplicon-based next-generation sequencing (NGS). Further, we analyzed the protein expression of V600E mutated BRAF, MLH1, MSH2, MSH6 and p53 from a larger set of PMP tumors (n = 74) using immunohistochemistry. With NGS, we detected activating somatic KRAS mutations in all of the tumors studied. GNAS was mutated in 63% of the tumors with no marked difference between low-grade and high-grade tumors. Only one (5.3%) tumor showed oncogenic PIK3CA mutation, one showed oncogenic AKT1 mutation, three (15.8%) showed SMAD4 mutations and none showed an APC mutation. P53 protein was aberrantly expressed in higher proportion of high-grade tumors as compared with low-grade ones (31.3 vs. 7.1%, respectively; p = 0.012) and aberrant expression was an independent factor for reduced overall survival (p = 0.002). BRAF V600E mutation was only found in one (1.4%) high-grade tumor by immunohistochemistry (n = 74). All the studied tumors expressed mismatch repair proteins MLH1, MSH2 and MSH6. Our results indicate that KRAS mutations are evident in all and GNAS mutations in most of the PMPs, but BRAF V600E, PIK3CA and APC mutations are rare. Aberrantly expressed p53 is associated with high-grade histology and reduced survival., (© 2014 UICC.)

Purpose: Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) are a novel curative treatment option for selected patients with peritoneal carcinomatosis (PC). We aimed to report the mortality rate and the most frequent grade III-IV adverse events and to identify associated prognostic markers. We report oncological outcomes and major prognostic factors influencing overall survival (OS) and disease-free survival., Methods: A total of 401 CRS plus HIPEC procedures were performed on 356 patients. Mortality, grade III-IV adverse events, OS, disease-free survival, and prognostic factors were studied., Results: Based on Common Terminology Criteria for Adverse Events (CTCAE of the National Cancer Institute 2006), mortality rate was 1 % and overall rate of morbidity grade III-IV was 12.5 %. In multivariate analysis, only the number of digestive anastomoses (>1) significantly correlated with adverse events with an odds ratio of 2.8 (p = 0.032). OS was related to histological type of PC, with a median survival reaching 47.6 months for PC of ovarian cancer origin, 45.8 months for that of colorectal origin, 64.2 months for peritoneal mesothelioma, and 8.1 months for PC of gastric cancer origin. Over half the patients with pseudomyxoma are still alive. Major prognostic factors influencing survival were histological type, World Health Organization performance status (WHO PS) (hazard ratio (HR) = 3.56), operating time (HR = 0.45), previous chemotherapy (HR = 2.04), number of peritonectomies (HR = 2.03), and completeness of cytoreduction score (HR = 3.12). Disease-free survival across all groups was 16.8 months., Conclusion: The low mortality rate and 12.5 % grade III-IV morbidity of CRS and HIPEC are acceptable when weighed against overall oncologic survival. This multimodal treatment appears feasible for selected patients and trained centers.

Background: Appendiceal peritoneal carcinomatosis (PC) is rare and its long-term prognosis is poor. The aim of this study was to evaluate the results of an aggressive treatment approach used in our institution for the last eight years., Methods: Data from all patients with PC arising from the appendix were prospectively collected and analyzed. Treatment consisted of complete surgical cytoreduction (CRS), followed by hyperthermic intraperitoneal chemotherapy (HIPEC) with oxaliplatin (460 mg/m2) at 43°C over 30 minutes. Ronnett's histologic classification was used for tumor grading., Results: Between February 2003 and April 2011, 78 patients underwent laparotomy with curative intent. The mean follow-up period was 33.7 months. A total of 58 patients received HIPEC, but 11 patients could not have CRS and received no HIPEC. Nine patients with a negative second-look surgery also received no HIPEC. The five-year overall survival for the entire cohort was 66.2%; 100% for the negative second-look patients, 77% for the HIPEC patients and 9% for the unresectable patients (P<0.0001). A total of 15 patients (25.9%) had isolated peritoneal recurrence, no patient had visceral recurrence only, and five patients (8.6%) had both. In regards to the five-year disease-free survival for the HIPEC patients, histologic grade (disseminated peritoneal adenomucinosis 100%, peritoneal mucinous carcinomatosis with intermediate features 40%, peritoneal mucinous carcinomatosis 20%; p=0.0016) and completeness of cytoreduction (CCR-0 56%, CCR-1 24%; P=0.0172) were prognostic factors. There was one postoperative mortality. The major complication rate for patients treated with HIPEC was 40%, including intra-abdominal abcess (17%), hemorrhage (12%) and anastomotic leak (10%). One patient in the HIPEC group experienced temporary grade II neuropathy and grade III thrombocytopenia., Conclusions: This therapeutic approach seems both feasible and safe in selected patients. Recurrence is, however, frequent and represents a challenge.

Purpose: Patients with pseudomyxoma peritonei (PMP) benefit from cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC). Reports on this modality usually have included only patients with successful HIPEC treatment, which can potentially cause biased results. We report the survival of a PMP population treated by CRS and HIPEC, including patients who were not eligible for HIPEC., Methods: The outcome of the whole population of 87 patients with PMP treated by CRS and HIPEC in Helsinki University Central Hospital between 2008 and 2011 was evaluated. The results of treatment were compared with 33 patients treated by serial debulking in our unit between 1984 and 2008., Results: Of the 87 patients in the HIPEC-era group, 56 received HIPEC, 12 were treated non-radically in an attempt at HIPEC, 9 were debulked and 10 were referred back or transferred to palliative care without surgery. The 5-year overall survival for the debulking-era group and the HIPEC-era group were 67 and 69 %, respectively. The number of patients with no evidence of disease was higher in the HIPEC-era group (47/87) than that in the debulking-era group (8/33) at the end of the follow-up. Overall survival for patients who underwent successful CRS and HIPEC at 2 and 5 years was 95 and 93 %, respectively., Conclusions: The improved survival from using the CRS and HIPEC was not apparent after 5-year follow-up, when the whole patient population was included in the analysis. Even so, patients successfully treated by CRS and HIPEC manage well.

Background: The role of systemic chemotherapy (SC) in conjunction with cytoreductive surgery (CS) with hyperthermic intraperitoneal chemotherapy (HIPEC) in appendiceal mucinous carcinoma peritonei (MCP) is unknown., Methods: A retrospective review (1999-2011) of MCP patients who had undergone CS/HIPEC with or without perioperative SC., Results: Twenty-two low-grade MCP patients treated with CS/HIPEC and SC were matched to patients who received CS/HIPEC alone. Median overall survival (OS) was 107 months for patients treated with perioperative SC compared to 72 without (P = 0.46). CS/HIPEC was performed on 109 patients with high-grade MCP: 70 were treated with perioperative SC, while 39 were not. Median OS (22.1 vs. 19.6 months, P = 0.74) and progression-free survival (PFS) (10.9 vs. 7.0 months, P = 0.47) were similar in patients treated with SC compared to CS/HIPEC alone. Progression while on pre-operative SC was seen in eight patients (17%), while four (8%) had a partial response. Treatment with post-operative SC was associated with longer PFS (13.6 months) compared to pre-operative SC (6.8 months, P < 0.01) and CS/HIPEC alone (7.0 months, P = 0.03)., Conclusions: Post-operative SC appears to improve PFS in patients with high-grade appendiceal MCP treated with CS/HIPEC. In contrast, there is no evidence to support the routine use of perioperative SC in low-grade disease., (© 2013 Wiley Periodicals, Inc.)

Background: Cytoreductive surgery (CRS) combined with Hyperthermic Intraperitoneal Chemotherapy (HIPEC) is the optimal treatment for Pseudomyxoma Peritonei (PMP). Despite treatment, disease often recurs and may not be amenable to further CRS. Clinical experience suggests a spectrum of disease which may correlate with tumour marker levels. The aim of this study was to analyse the influence of markers on recurrence and survival., Methods: The details of all patients undergoing surgery for PMP of appendiceal origin at a national centre for peritoneal malignancy were recorded in a dedicated prospective database. The data on all patients who had CRS and HIPEC between March 1994 and January 2012 was analysed and recurrence and survival correlated with pre-operative levels of CEA, CA-125 and CA19-9., Results: Overall, 519 (69%) of 752 consecutive patients, underwent complete CRS and HIPEC. The median (range) age was 56 (20-82) years with 342/519 (66%) females. The mean overall (OS) and disease free survival (DFS) in the 131/519 patients who had normal preoperative tumour markers was 168 (128-207) and 125 (114-136) months respectively, significantly higher when compared with the 109/519 (21%) who had all three tumour markers elevated (OS of 65 (42-88) and DFS of 55 (41-70) months respectively) (P = 0.002)., Conclusions: Elevated tumour markers predict an increased risk of recurrence and reduced survival after complete CRS. This may reflect cell biology in low grade tumours and is an independent prognostic feature. Further analysis may help to select patients for post-operative chemotherapy, second look procedures or stratification of follow up., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Background: Pseudomyxoma peritonei is a condition characterised by dissemination of mucin-producing neoplastic cells throughout the peritoneal cavity. There are two pathological subsets, disseminated peritoneal adenomucinosis and peritoneal mucinosis carcinomatosis. Once a lethal disease, cytoreductive surgery combined with heated intraperitoneal chemotherapy (HIPEC) is challenging debulking as the standard of care., Objective: We present the first case series detailing the postoperative morbidity, mortality and survival outcomes of patients treated for pseudomyxoma peritonei by cytoreductive surgery without heated intraperitoneal chemotherapy by a single surgeon., Design: Wellington Hospital clinical databases were retrospectively searched. Inclusion criteria were a diagnosis of pseudomyxoma peritonei with a major cytoreductive operation with the intention of complete cytoreductive clearance. Exclusion criteria were palliative debulking operations and patient records not available for analysis., Results: 25 patients underwent cytoreductive surgery between June 1999 and July 2011. Mean follow-up was 43.5 months (1.5-138). Histological classification was DPAM for 13/25 and PMCA for 12/25. Complete cytoreduction (CC-0 and CC-1) was achieved in 21/25 patients. There was no 30 day mortality following primary cytoreduction. Six patients underwent subsequent debulking/cytoreductive surgery; one patient died following repeat surgery. Clavien-Dindo grade 3 or 4 complications occurred in 7/25 patients. Combined 5-year survival was 64%, 92% for DPAM and 33% for PMCA., Conclusion: Cytoreductive surgery alone may result in comparable survival outcomes to those achieved with combined surgery and HIPEC in selected patients, especially for patients with DPAM.

Background: Selected patients with peritoneal surface malignancies (PSM) have been treated effectively by the combination of cytoreduction surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC)., Purpose: The purpose of this study is to summarize the treatment outcomes and general considerations regarding definitions and staging systems of current CRS and HIPEC modalities in malignant peritoneal mesothelioma and in secondary peritoneal malignancies such as peritoneal metastasis from appendiceal, colorectal, gastric, and epithelial ovarian cancers., Conclusion: Disease progression within the peritoneal cavity has in the past been regarded as a terminal event. Accumulating evidence underlines the therapeutic potential and the acceptable morbidity and mortality rates of CRS and HIPEC in selected patients.

The nomenclature and classification of pseudomyxoma peritonei (PMP) is confusing and controversial. Numerous classification systems have been proposed, none of which are easily reproducible or a useful guide for treatment. Patients with PMP of appendiceal origin were identified from our institution's database. Kaplan-Meier analyses were performed based on a proposed new PMP classification, a three-tiered grading system designated PMP1, PMP2, and PMP3. These results were compared with the established schemes by Ronnett and Bradley et al. There were 211 patients included in the analysis with a mean age of 51 ± 12 years at diagnosis. For PMP1, 86 patients (40.8%) included cases with abundant extracellular mucin and columnar nonstratified epithelium without dysplasia or atypia. For PMP3, 50 patients (23.7%) consisted of PMP with any percentage of signet ring cells (SRCs), For PMP2, 75 patients (35.5%) included all other patients. The mean age (± standard deviation) for PMP 1, 2, and 3 were 51 ± 12, 51 ± 12, and 51 ± 10 years, respectively (P = 0.90). The three groups had similar sex distribution (P = 0.24) and resection status (P = 0.47). Kaplan-Meier analyses showed median survivals of 120, 88, and 40 months and 5-year survival rates of 85.7, 63.05, and 32.2 per cent (P < 0.0001) for PMP 1, 2, and 3, respectively. Three distinct categories, PMP1, 2, and 3, were identified, which provide better stratification in terms of overall survival and represent differences in tumor biology that may impact treatment recommendations.

Background: Pseudomyxoma peritonei (PMP) is a malignancy characterized by dissemination of mucus-secreting cells throughout the peritoneum. This disease is associated with significant morbidity and mortality and despite effective treatment options for early-stage disease, patients with PMP often relapse. Thus, there is a need for additional treatment options to reduce relapse rate and increase long-term survival. A previous study identified the presence of both typed and non-culturable bacteria associated with PMP tissue and determined that increased bacterial density was associated with more severe disease. These findings highlighted the possible role for bacteria in PMP disease., Methods: To more clearly define the bacterial communities associated with PMP disease, we employed a sequenced-based analysis to profile the bacterial populations found in PMP tumor and mucin tissue in 11 patients. Sequencing data were confirmed by in situ hybridization at multiple taxonomic depths and by culturing. A pilot clinical study was initiated to determine whether the addition of antibiotic therapy affected PMP patient outcome., Main Results: We determined that the types of bacteria present are highly conserved in all PMP patients; the dominant phyla are the Proteobacteria, Actinobacteria, Firmicutes and Bacteroidetes. A core set of taxon-specific sequences were found in all 11 patients; many of these sequences were classified into taxonomic groups that also contain known human pathogens. In situ hybridization directly confirmed the presence of bacteria in PMP at multiple taxonomic depths and supported our sequence-based analysis. Furthermore, culturing of PMP tissue samples allowed us to isolate 11 different bacterial strains from eight independent patients, and in vitro analysis of subset of these isolates suggests that at least some of these strains may interact with the PMP-associated mucin MUC2. Finally, we provide evidence suggesting that targeting these bacteria with antibiotic treatment may increase the survival of PMP patients., Conclusions: Using 16S amplicon-based sequencing, direct in situ hybridization analysis and culturing methods, we have identified numerous bacterial taxa that are consistently present in all PMP patients tested. Combined with data from a pilot clinical study, these data support the hypothesis that adding antimicrobials to the standard PMP treatment could improve PMP patient survival.

Background: Incomplete cytoreduction (IC) is one of the main prognostic factor in pseudomyxoma peritonei (PMP). We evaluated the ability of preoperative Ca125, CEA, and Ca19-9 to predict IC and prognosis in PMP., Methods: One hundred fifty-six cases elected candidate to cytoreductive surgery and hyperthermic intraperitoneal chemotherapy from 1996 to 2011 were included in the study. We assessed the: (1) optimal cut-off values for circulating Tumor markers (CTM) in predicting IC (residual disease >2.5 mm) using receiver-operating characteristics (ROC); (2) discriminant power of CTM and risk prediction models for IC by calculating the area under ROC curve (AUC-ROC); (3) prognostic factors using Cox proportional-hazard model., Results: Optimal cut-offs were 125 U/ml for Ca125, 18 ng/ml for CEA, and 89 U/ml for Ca19-9. The AUCs-ROC were 0.76, 0.68, and 0.69 for Ca125, CEA, and Ca19-9, respectively. The addition of CTM to risk prediction model that considered preoperative clinicopathological factors increased marginally the AUC-ROC (0.80-0.84). Ca125 > 125 U/ml, Ca19-9 > 89 U/ml independently affected overall survival., Conclusions: Preoperative CTMs were reasonable but not perfect discriminators of IC. Moreover, Ca125 and Ca19-9, using new cut-off values, were proven to be new strong prognostic factors that overcome the value of disease extension and histological subtype., (Copyright © 2013 Wiley Periodicals, Inc.)

Background: Pseudomyxoma peritonei (PMP) is an uncommon but lethal variant of adenocarcinoma. Many recent case series have reported improved survival with the combination of cytoreductive surgery and intraperitoneal chemotherapy (IPEC) in treating PMP. The aim of this study was to analyze the published studies for improved survival with this treatment strategy., Methods: Data from all studies using IPEC in treating PMP were analyzed. We searched PubMed, MEDLINE, and the Cochrane Library (through September 2011). Studies were limited to English and PMP with appendiceal origin. Twenty-nine studies were identified, with 15 studies from different treatment centers that were specifically analyzed for differences in 5-y mortality and morbidity. Observed to expected (OE) ratios were calculated for both mortality and morbidity., Results: Mean and median 3-y, 5-y, and 10-y survival rates were 77.18%/77.85%, 76.63%/79.5%, and 57.3%/55.9%, respectively. Of the 10 studies that had sufficient data to calculate OE ratios from the 5-year mortality data, two had OE ratios lower than 1. Of the 11 studies that had data sufficient to calculate OE ratios from the morbidity data, four had OE ratios that were less than 1., Conclusions: Combining cytoreductive surgery and IPEC improves the survival of patients with PMP, regardless of treatment modality. Although this treatment strategy is associated with an increased risk of morbidity, the increase in survival may be acceptable in proposing an alternative to debulking procedures alone., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Objective: To determine whether ovaries can be preserved in selected young women with peritoneal pseudomyxoma (PMP)., Background Data: The traditional rule is to systematically perform a bilateral oophorectomy., Patients and Methods: A new policy was developed to preserve the ovaries when they are macroscopically normal in young women with PMP, strongly desiring a future pregnancy., Results: Thirty-three women younger than 41 years were selected after undergoing complete cytoreductive surgery plus hyperthermic intraperitoneal chemotherapy for PMP. A normal ovary was preserved in 6 of them, but in 6 of the 14 women who strongly desired a future pregnancy. Subsequently, ovarian preservation was only performed in cases of grade-1 PMP. Ovarian invasion was correlated with the grade (p < 0.05) and with the extent of peritoneal disease (p < 0.01). After a median follow-up of 54 months, none of the 6 women with preserved ovaries has developed an ovarian or a peritoneal recurrence. One woman became pregnant and egg harvesting and cryopreservation were performed for 4 women with a partially normal ovary., Conclusion: This new policy allowed ovarian preservation in 43% of the young women desiring a future pregnancy and has already resulted in one birth. It exclusively concerned low-grade PMP. Recurrence in the preserved ovary was 0% with our selection criteria., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Introduction: Hyperthermic intraperitoneal chemoperfusion (HIPEC) with oxaliplatin is increasingly used in patients with carcinomatosis from colorectal cancer. For reasons of chemical stability, oxaliplatin can only be administered in a dextrose (D5%) solution, and this causes peroperative glucose and electrolyte shifts. Here, we examined the influence of perfusion temperature on glucose and electrolyte transport, metabolic shifts, and surgical morbidity., Methods: Patients with carcinomatosis underwent cytoreduction and HIPEC using oxaliplatin (460 mg/m(2) in D5%, open abdomen) during 30 min at 39°-41 °C. Intraperitoneal (IP) temperature was measured at three locations using thermocouple probes. The area under the temperature versus time curve (AUCt) was calculated using the trapezoid rule. The influence of perfusion temperature on surgical outcome was assessed using linear regression models and the Mann Whitney U test where appropriate., Results: From July 2005 until March 2011, 145 procedures were performed in 139 patients with a diagnosis of CRC (70%), pseudomyxoma peritonei (11%), ovarian cancer (10%), or miscellaneous peritoneal malignancies (9%). Postoperative mortality and major morbidity were 1.4% and 26%, respectively. Higher perfusion temperature was related to more pronounced changes in serum glucose (P = 0.058), sodium (P = 0.017), and lactate (P < 0.001). The median duration of nasogastric drainage was 5 days, and this was unrelated to perfusion temperature (P = 0.76). The GI fistula rate and reoperation rate were 12.4% and 16.5% respectively; neither was related to perfusion temperature., Conclusions: In patients undergoing HIPEC with oxaliplatin, perfusion temperature exacerbates peroperative metabolic shifts but does not affect surgical outcome., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Background: Little information exists on Kras mutations and p53 overexpression in pseudomyxoma peritonei (PMP). These genetic alterations are associated with poorer prognoses in colorectal cancer. We postulated that these mutations might be more frequent in high-grade (HG) PMP (peritoneal mucinous carcinomatosis) versus low-grade (LG) PMP (disseminated peritoneal adenomucinosis/peritoneal mucinous carcinomatosis), for which survival differences are well documented., Methods: We collected data retrospectively on patients with PMP of appendiceal origin tested for Kras mutation (commercial assay) and p53 overexpression (immunohistochemistry). We used Fisher's exact test, chi-square test, and Kaplan-Meier survival curves for analysis., Results: Of 64 cases with Kras mutations, 25 were classified as LG and 39 as HG PMP. Median age at diagnosis was 53 ± 11.5 y. We detected Kras mutations in 37 of 64 patients (57.8%). In LG PMP, 15 of 25 (60%) were Kras mutant versus 22 of 39 (56.4%) in HG PMP (P=0.80). Nearly 89% of mutations were seen in codon 12. We noted overexpression of p53 in 44.3% (86 of 194) of patients overall, which was significantly different between LG PMP and HG PMP: 35.5% (37 of 104) versus 54.4% (49 of 90), respectively (P=0.009). Kras mutations did not affect prognosis. Overexpression of p53 was associated with a worse outcome., Conclusions: Kras mutation and p53 overexpression rates are comparable to those of colorectal adenomas and mucinous colorectal cancer. Codon 12 mutations may be associated with mucin production. Kras mutation status is not prognostic for overall survival. Overexpression of p53 was significantly correlated with female sex, higher-grade disease, and worse survival., (Copyright © 2013 Elsevier Inc. All rights reserved.)