Search

Background: Prediction of open-close and long-term outcome is challenging in patients undergoing cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC). Prognostic scores often include factors not known at baseline. Therefore, we aimed to analyze whether patterns of preoperative tumor markers could aid in prediction of open-close surgery and outcome in patients with pseudomyxoma peritonei (PMP) or colorectal peritoneal metastases (PM)., Patients and Methods: All patients accepted for CRS and HIPEC for PMP or colorectal PM at Uppsala University Hospital in 2013-2021 were included. The tumor markers CEA, CA19-9, CA125, CA72-4, and CA15-3 were clustered using the k-means algorithm; the average silhouette width determined the optimal numbers of clusters., Results: Clustering of patients with PMP (n = 138) and colorectal PM (n = 213) resulted in two clusters each. PMPCluster-1 (n = 124) had a 5-year overall survival (OS) of 77% (95% CI 69-85%), 11 (9%) open-close surgeries, and a median peritoneal cancer index (PCI) of 17. PMPCluster-2 (n = 14) patients had poorer prognosis (36%, 95% CI 15-85%, p = 0.003), more often open-close (n = 6, 43%, p = 0.002), and higher PCI (median 36, p < 0.001). ColorectalCluster-1 (n = 191) had a 5-year OS of 28% (95% CI 21-37%), median PCI of 11, and 38 (20%) open-close surgeries. ColorectalCluster-2 (n = 22) had poorer prognosis (10%, 95% CI 3-36%, p = 0.02), higher PCI (median 26, p < 0.001), higher completeness of cytoreduction score (p = 0.005), but no difference in open-close surgery (n = 6, 27%, p = 0.411). PMPCluster-2 and ColorectalCluster-2 were characterized by markedly elevated tumor markers. Open-close surgery was unusual in cases of normal CA72-4., Conclusions: Elevation of several preoperative tumor markers is associated with poor prognosis and increased risk of open-close. CA72-4 deserves increased attention., Competing Interests: Disclosures: The authors declare no conflicts of interest. The study was funded by research grants from Uppsala University Hospital for M.E., the Bengt Ihre Research Fellowship, and the Lion’s Research Foundation in Uppsala., (© 2025. The Author(s).)

Background: The treatment for patients with colorectal cancer with metastases to the peritoneum is complex and may involve both surgery and chemotherapy. Circulating tumor cells (CTCs) have been poorly investigated in peritoneal metastatic colorectal cancer. The aim of the study is to examine the role of CTCs as a biomarker for monitoring disease progression, treatment response, and residual disease using CellMate - a new promising in vitro diagnostic platform technology., Materials and Methods: The authors prospectively followed the clinical outcomes of 46 patients treated with cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for colorectal cancer with peritoneal metastases and examined whether CTCs were present the week of surgery. The CTC measurements were made with the CellMate technology, which is a platform technology to detect CTCs based on the difference in biomechanical properties compared to blood resident cells. The study was registered online (ClinicalTrials.gov)., Results: CTCs were detected in 17 (37%) patients. The presence of CTCs was associated with shorter recurrence-free survival and overall survival after cytoreductive surgery and hyperthermic intraperitoneal chemotherapy. Both recurrence-free survival (HR 4.00, 95% CI: 1.15-13.9; P =0.029) and overall survival (HR 5.91; 95% CI: 1.18-29.7; P =0.03) were significantly worse if CTCs were detected after neoadjuvant treatment. In the subgroup of patients with CTCs detected, adjuvant therapy tended to improve the prognosis while in CTC negative patients it did not., Conclusions: Pending a prospective multicenter trial to validate these findings, CTCs may in the future be used as a dynamic personalized biomarker for prognostication, predicting response to therapy, and for monitoring disease progression in colorectal cancer with metastases to the peritoneum., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

Introduction: Appendiceal adenocarcinoma represents a diagnostic and therapeutic challenge since it is prone to early lymphatic and peritoneal spread. We aimed to analyze the proportion of lymph node metastases in completion right hemicolectomy specimens, risk factors for peritoneal metastases (PM), and prognosis after definitive treatment., Methods: Ninety-three patients with appendiceal adenocarcinoma scheduled for cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS + HIPEC) in Uppsala 2004-2020 were identified from a prospectively maintained registry. Risk factors for PM were assessed based on the presence (CT + group, n = 55) or absence (CT - group, n = 37) of visible PM at baseline CT scan. Prognostic factors were analyzed based on the actual presence (PM group, n = 66) or absence (no PM group, n = 27) of PM., Results: The median age was 60 (26-78). Forty-eight patients were women. Resection of PM at initial surgery indicated an 80 % risk of finding PM at a follow-up exploration. R1 appendectomy and perforated appendix had a similar risk for PM (24 %,26 %) which increased to 38 % if both were present. Regional lymph node metastases occurred in 31 % in the CT + group vs. 14 % in the CT - group (p = 0.005) and was associated with poor survival HR 5.16 (1.49-17.81). The 5-year OS and DFS rates were 54 % and 29 % in the PM group., Conclusions: Patients with certain risk factors have a high likelihood of PM despite a normal CT scan, which justifies selective exploration at a HIPEC center. Regional lymph node spread supports the current practice of completion right hemicolectomy and is a significant prognostic factor., Competing Interests: Declaration of competing interest We declare that this manuscript is original, has not been published before and is not currently being considered for publication elsewhere. We know of no conflicts of interest associated with this publication, and there has been no significant financial support for this work that could have influenced its outcome. As Corresponding Author, I confirm that the manuscript has been read and approved for submission by all the named authors., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Appendiceal tumors are uncommon and, at times, discovered incidentally during histological examination. The histopathological classification of the disease is complex and has generated some controversy. The analysis of circulating tumor cells can be used for the early detection of metastatic potential. The aim of the present study was to examine the prognostic value of circulating tumor cells in patients with appendiceal tumors and peritoneal metastases. To our knowledge, this is the first study to examine CTCs in appendiceal tumors. We performed a prospective cohort study of consecutive patients treated with cytoreductive surgery and hyperthermic intraperitoneal chemotherapy between 2015 and 2019 at a HIPEC referral center. In total, 31 patients were included in the analysis, and circulating tumor cells were detected in 15 patients (48%). CTC positivity was not associated with overall or recurrence-free survival, nor was it correlated with PCI score or histopathological grading. Surprisingly, however, CTCs were found in almost half the patients. The presence or quantities of these cells did not, on their own, predict systemic metastatic potential during the observed time, and they did not appear to significantly correlate with the oncological outcomes recorded.

Background: Careful macroscopic assessment of surgical scars is needed to avoid routine scar resection during cytoreductive surgery (CRS) for peritoneal metastases (PM). This study aimed to analyze the correlation between macroscopically suspected and microscopically confirmed scar metastases (SMs), and to analyze the prognostic impact of not undergoing routine scar resection., Method: All patients with previous surgery, treated with CRS and hyperthermic intraperitoneal chemotherapy, for colorectal PM or pseudomyxoma peritonei (PMP), at Uppsala University Hospital in 2013-2021, were included. Macroscopic SMs in surgical reports were compared with histopathological analyses., Results: In total, 227 patients were included. Among colorectal PM patients (n = 156), SM was macroscopically suspected in 41 (26%) patients, and 63 (40%) underwent scar resection. SM was confirmed in 19 (30%). Among patients with macroscopic suspicion, 45% had confirmed SM (positive predictive value, PPV). A total of 1 of 23 (4%) patients with no macroscopic suspicion had SM (negative predictive value, NPV = 96%). Among the PMP patients (n = 71), SM was macroscopically suspected in 13 (18%), and 28 (39%) underwent scar resection, of whom 12 (43%) had SM. The PPV was 77%. Occult SM was found in 1 of 14 (NPV = 93%). Not undergoing routine scar resection did not affect recurrence-free survival (RFS, p = 0.2) or overall survival (OS, p = 0.1) in colorectal PM patients or PMP patients (RFS p = 0.7, OS p = 0.7)., Conclusion: Occult SM is uncommon and scar resection does not affect RFS or OS. Therefore, macroscopically benign-appearing scars can be left without resection, though resection should be performed upon suspicion or uncertainty.

Background: Secondary treatment of recurrent colorectal peritoneal metastases after previous cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) is poorly investigated., Objectives: To evaluate the overall survival outcome of secondary (repeat) CRS + HIPEC compared to palliative treatment in recurrent peritoneal disease., Methods: Patients with colorectal peritoneal metastases treated with an index CRS + HIPEC and subsequently having recurrent peritoneal disease were identified from the prospective Swedish national HIPEC registry. Patients were divided into interventional group (secondary CRS + HIPEC) or palliative group. Multivariable logistic regression, propensity-score matching, and survival outcomes were calculated., Results: Among 575 patients who underwent complete CRS between 2010 and 2021, 208 (36 %) were diagnosed with a subsequent recurrent peritoneal disease. Forty-two patients (20 %) were offered secondary CRS + HIPEC. Propensity-score matching of secondary interventional cases with palliative cases succeeded in 88 % ( n  = 37) in which female sex, lower peritoneal cancer index at index surgery, longer disease-free interval, and absence of extra-peritoneal metastases were identified as the most relevant matching covariates. Median OS from date of recurrence was 38 months (95%CI 30-58) in the interventional group and 19 months (95%CI: 15-24) in the palliative group (HR 0.35 95%CI: 0.20-0.63, p  = 0.0004). Sensitivity analyses confirmed the results. As reference, the median OS from index CRS + HIPEC in the whole colorectal registry ( n  = 575) was 41 months (95%CI: 38-45)., Conclusion: After matching for relevant factors, the hazard ratio for death was significantly reduced in patients who were offered a secondary CRS + HIPEC procedure for recurrent peritoneal disease. Selection bias is inherent, but survival outcomes were comparable to those achieved after the initial procedure., Competing Interests: The authors have no relevant financial disclosures., (© 2024 The Authors.)

Standard treatment for patient with peritoneal metastases from colorectal cancer is cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC). In recent years, the efficacy of oxaliplatin-based HIPEC has been challenged. An intensified HIPEC (oxaliplatin+irinotecan) in combination with early postoperative intraperitoneal chemotherapy (EPIC) has shown increased recurrence-free survival in retrospective studies. The aim of this trial is to develop a new HIPEC/EPIC regimen and evaluate its effect on morbidity, oncological outcome, and quality-of-life (QoL). This study is designed as a combined phase I/III multicenter randomized trial (RCT) of patients with peritoneal metastases from colorectal cancer eligible for CRS-HIPEC. An initial phase I dose escalation study, designed as a 3+3 stepwise escalation, will determine the maximum tolerable dose of 5-Fluorouracil (5-FU) as 1-day EPIC, enrolling a total of 15-30 patients in 5 dose levels. In the phase III efficacy study, patients are randomly assigned intraoperatively to either the standard treatment with oxaliplatin HIPEC (control arm) or oxaliplatin/irinotecan-HIPEC in combination with single dose of 1-day 5-FU EPIC (experimental arm). 5-FU is administered intraoperatively after CRS-HIPEC and closure of the abdomen. The primary endpoint is 12-month recurrence-free survival. Secondary endpoints include 5-year overall survival, 5-year recurrence-free survival (registry based), postoperative complications, and QoL up to 3 years after study treatment. This phase I/III trial aims to identify a more effective treatment of colorectal peritoneal metastases by combination of HIPEC and EPIC., Competing Interests: No authors have competing interests., (Copyright: © 2024 Ghanipour et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Peritoneal metastases (PM) are observed in approximately 8% of patients diagnosed with colorectal cancer, either synchronously or metachronously during follow-up. PM often manifests as the sole site of metastasis. PM is associated with a poor prognosis and typically shows resistance to systemic chemotherapy. Consequently, there has been a search for alternative treatment strategies. This review focuses on the global evolution of the combined approach involving cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) for the management of PM. It encompasses accepted clinical guidelines, principles for patient selection, surgical and physiological considerations, biomarkers, pharmacological protocols, and treatment outcomes. Additionally, it integrates the relevant literature and findings from previous studies. The role of CRS and HIPEC, in conjunction with other therapies such as neoadjuvant and adjuvant chemotherapy, is discussed, along with the management of patients presenting with oligometastatic disease. Furthermore, potential avenues for future development in this field are explored.

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

Background: National lead time goals have been implemented across Sweden to standardize and improve cancer patient care. However, the prognostic impact of lead times has not yet been studied in patients with colorectal cancer and peritoneal metastases scheduled for cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS + HIPEC)., Aim: To study the correlation between lead times and overall survival and operability., Methods: One hundred forty-eight patients with peritoneal metastases originating from colorectal cancer and scheduled for CRS + HIPEC from June 2012 to December 2019 were identified using a HIPEC register at Uppsala University Hospital. Data were collected from medical records concerning operability, overall survival, recurrence and time from diagnosis, and decision to operate to the date of surgery. Patients who had neoadjuvant therapy or no malignant cells in the resected specimens were excluded. Statistical calculations were made with the chi-squared test, Cox regression analysis, and log-rank test., Results: The median age was 66 years (27-82). Ninety-five were women and 53 were men. One hundred six underwent CRS + HIPEC, 13 CRS only, and 29 were inoperable (open-close). No difference in overall survival was seen when comparing patients with lead times ≤ 34 days and ≥ 35 days from the decision to operate at the multidisciplinary conference to the surgery but there was a higher frequency of open-close (p = 0.023) in the group with longer lead time. Factors that impacted overall survival were open-close (p < 0.001), liver metastases (p = 0.003), and peritoneal cancer index score ≥ 20 (p < 0.001)., Conclusion: A long lead time from multidisciplinary conference to surgery has no direct impact on overall survival but can result in more cases of inoperability. In a larger cohort, this might translate into decreased survival, and efforts should therefore be made to complete preoperative work up as soon as possible and reduce overall time span. Important factors for survival are related to patient selection and extent of disease., (© 2022. The Author(s).)

Background: Few studies on long-term survival have been published since the new updated pseudomyxoma peritonei (PMP) classification was published in 2016. The aim was to investigate long-term survival according to the Peritoneal Surface Oncology Group International (PSOGI) classification and compare prognostic factors., Methods: From Uppsala University Hospital, consecutive patients referred for cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) from 2004 to 2017 with peritoneal disease from non-carcinoid mucinous epithelial appendiceal neoplasms were included in the study. The peritoneal disease was divided into four groups: mucin only, low-grade mucinous carcinoma peritonei (MCP-1), high-grade (MCP-2), and high-grade with signet ring cells (MCP-3). Survival curves were rendered, and prognostic factors were compared., Results: The study included 223 patients: 36 with mucin only, 112 with MCP-1, 70 with MCP-2, and 5 with MCP-3. Thirty-eight patients had a palliative debulking or open/close procedure. The 5- and 10-year overall survival was 97% and 97% for mucin only, 83% and 70% for MCP-1, 69% and 49% for MCP-2, with no patients still under follow-up after 5 years in the MCP-3 group. In a multivariable analysis, completeness of cytoreduction (CC) score 2-3 and PSOGI class MCP-3 were significantly associated with lower survival. The 5-year overall survival in the palliative setting was 40% vs. 44% (MCP-1 vs. MCP-2, P>0.05) with median survival 51 vs. 53 months, respectively., Conclusions: The PSOGI classification of PMP provides a solid differentiation of prognostic groups after CRS/HIPEC treatment, but not in the palliative setting., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://jgo.amegroups.com/article/view/10.21037/jgo-21-581/coif). PHC reports unrestricted funding from the Bengt Ihre Fellowship fund which has paid for processing charges and provided time for article drafting. The other authors have no conflicts of interest to declare., (2022 Journal of Gastrointestinal Oncology. All rights reserved.)

Background: Long-term survival for selected patients with peritoneal metastases (PM) from colorectal cancer (CRC) is possible when treated with cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC). The objective of this study was to compare three different oxaliplatin-based (OX)-HIPEC regimens. Primary end-point was disease-free survival (DFS), and secondary endpoints, morbidity and overall survival (OS)., Methods: This is a retrospective study of all patients with colorectal PM treated with CRS and HIPEC between 2004 and 2015 from the prospectively maintained Uppsala HIPEC database. One hundred and thirty-three patients were identified. Three HIPEC regimens were included: OX-HIPEC, OX-HIPEC + post-operative intraperitoneal chemotherapy (EPIC) with 5-fluorouracil (5-FU), and oxaliplatin-irinotecan-based (OXIRI)-HIPEC. Multivariable Cox regression for DFS was performed., Results: Sixty-one patients received OX-HIPEC, 24 patients received OX-HIPEC + 5-FU EPIC, and 48 patients received OXIRI-HIPEC. The DFS for the OX-HIPEC group was 10.5 months, OX-HIPEC + EPIC 11.9 months, and OXIRI-HIPEC 13.4 months (OX-HIPEC vs. OXIRI HIPEC, P=0.049). The morbidity and OS did not differ between the groups. In the multivariable analysis, low peritoneal cancer index (PCI), absence of liver metastases, low completeness of cytoreduction (CC) score, and multiple drug (EPIC or OXIRI) HIPEC regimen were independent prognostic factors for DFS., Conclusions: This study showed improved DFS with an intensification of HIPEC by adding irinotecan or EPIC compared to oxaliplatin alone without an increase in morbidity or mortality., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at http://dx.doi.org/10.21037/jgo-20-494). The authors have no conflicts of interest to declare., (2021 Journal of Gastrointestinal Oncology. All rights reserved.)

Introduction: - Early post-operative intraperitoneal chemotherapy (EPIC) can be used after cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) in patients with resectable peritoneal metastases (PM). Whether EPIC adds any benefit is debatable., Methods: - We performed a retrospective case-control analysis of patients with PM of appendiceal origin treated by CRS + HIPEC ± EPIC at Uppsala University Hospital between 2004 and 2012. The 206 patients were divided into two groups depending on if they received EPIC or not. The two groups were propensity-matched with a 1:1 ratio. The patients in the EPIC group were mostly operated in the first three years of the unit's experience., Results: - After matching, 76 patients were left in each group. The groups were similar, except for the proportion of histological subtypes (p = 0.021) and chemotherapy agents used for HIPEC (0.017). Survival outcomes were stratified by histology. The patients who received EPIC had a longer hospital and ICU length of stay (15.71 vs 14.28 days, p = 0.049), (1.45 vs 1.05 days, p = 0.002), respectively. Post-operative complications were similar in both groups. Overall Survival (OS) and recurrence-free survival (RFS) did not differ for the patients with low-grade histology. The patients with high-grade tumors who received EPIC had a significantly worse OS (p = 0.0088) while having the same RFS as the patients who did not receive EPIC., Conclusion: Our results suggest there is no benefit of EPIC in patients with advanced appendiceal tumors while increasing hospital and ICU length of stays. A suboptimal group matching might influence our results., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.)

Background: Peritoneal cancer index (PCI) >20 is often seen as a contraindication for cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) in patients with peritoneal metastases (PM) from colorectal cancer. The aim of this study was to compare the overall survival in colorectal PM patients with PCI >20 and PCI ≤20 treated with CRS and HIPEC to those having open-close/debulking procedure only., Methods: All patients with colorectal PM and intention to treat with CRS and HIPEC in Uppsala Sweden 2004-2017 were included. Patients scheduled for CRS and HIPEC were divided into three groups, PCI >20, PCI ≤20, and those not operated with CRS and HIPEC stated as open-close including those treated with palliative debulking., Results: Of 201 operations, 112 (56%) resulted in CRS and HIPEC with PCI ≤20, 45 (22%) in CRS and HIPEC with PCI >20 and 44 (22%) resulted in open-close/debulking. Median survival for CRS and HIPEC and PCI >20 was 20 months (95%CI 14-27 months) with 7% surviving longer than 5 years (n = 3). For CRS and HIPEC and PCI ≤20 the median survival was 33 months (95%CI 30-39 months) with 23% (n = 26) surviving >5years. The median survival for open-close was 9 months (95%CI 4-10 months), no one survived >5years., Conclusion: Patients with PM from colorectal cancer and PCI >20 that were treated with CRS and HIPEC experience a one year longer and doubled overall survival compared with open-close/debulking patients. In addition to PCI, more factors should be taken into account when a decision about proceeding with CRS or not is taken., Competing Interests: Declaration of competing interest The authors declare no conflicts of interest., (Copyright © 2020 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: The implications of neutropenia after cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (HIPEC) treatment have never been investigated., Aim: To evaluate the occurrence of neutropenia and its effect on the risk of increased Clavien-Dindo morbidity as well as its effect on overall or disease-free survival., Methods: All patients with colorectal peritoneal metastases (1996-2015) completing cytoreductive surgery and oxaliplatin-based HIPEC treatment from a bi-institutional database (Uppsala and Sydney) were included in the study. Clavien-Dindo grade 3-4 morbidity differences between the neutropenia group vs non-neutropenia group were calculated and Kaplan-Meier curves with log rank test were rendered. Univariate and multivariable Cox regression models for disease-free survival were implemented., Results: Two hundred and forty-six patients were identified - 32 postoperative any-grade neutropenia patients and 214 non-neutropenia patients. The neutropenia group had more combination oxaliplatin + irinotecan treatment than the non-neutropenia group (66% vs 13%, P = 0.0001). The neutropenia group was not associated with increased Clavien-Dindo grade 3-4 morbidity. Median overall survival was 53 mo vs 37 mo for the neutropenia and non-neutropenia group, P = 0.07. Median disease-free survival was 16 mo vs 11 mo, respectively, P = 0.02. Neutropenia was an independent prognostic factor for disease-free survival with hazard ratio: 0.58, 95% confidence interval: 0.36-0.95, P = 0.03., Conclusion: 13% of patients developed neutropenia which was not associated with increased Clavien-Dindo grade 3-4 morbidity. Neutropenia was an independent positive prognostic factor for disease-free survival and was associated with more intense HIPEC treatment. This is in direct contrast to the current paradigm of decreasing the treatment intensity., Competing Interests: Conflict-of-interest statement: The authors have no conflicts of interest to declare., (©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.)

Background: KRAS and BRAF mutations are prognostic and predictive tools in metastatic colorectal cancer, but little is known about their prognostic value in patients scheduled for cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC). Therefore, we analyzed the prognostic impact of KRAS and BRAF mutations in patients with peritoneal metastases scheduled for CRS and HIPEC., Patients and Methods: In a consecutive series of 399 patients scheduled for CRS and HIPEC between 2009 and 2017, 111 subjects with peritoneal metastases from primaries of the appendix, colon, or rectum were analyzed for KRAS mutation and 92 for BRAF mutation., Results: Mutation in KRAS was present in 51/111 (46%), and mutated BRAF was found in 10/92 (11%). There was no difference in overall survival between KRAS mutation tumors and KRAS wild type, whereas BRAF mutation was associated with short survival. No subject with BRAF mutation survived 2 years. On multivariate analysis, completeness of cytoreduction score (CCS, p = 0.000001), presence of signet cell differentiation (p = 0.000001), and BRAF mutation (p = 0.0021) were linked with poor prognosis., Conclusions: BRAF mutation is a marker of poor prognosis in patients with appendiceal and colorectal peritoneal metastases scheduled for CRS and HIPEC, whereas survival outcome in subjects with mutated KRAS does not differ from wild-type KRAS. This finding suggests that those with BRAF mutation should be considered for alternative treatment options.

Background: In the search for prognostic biomarkers, a significant amount of precious biobanked blood samples is needed for conventional analyses. Solid-phase proximity ligation assay (SP-PLA) is an analytic method with the ability to analyze many proteins at the same time in small amounts of plasma. The aim of this study was to explore the potential use of SP-PLA for biomarker validation in patients with colorectal cancer (CRC)., Material and Methods: Plasma samples from patients with stage I to IV CRC, with (n = 31) and without (n = 29) disease dissemination at diagnosis or later, were analyzed with SP-PLA using 35 antibodies targeting an equal number of proteins in 5-μl plasma samples. Carcinoembryonic antigen (CEA), analyzed earlier in this cohort using a different technology, was used as a reference., Results: A total of 21 of the 35 investigated proteins were detectable with SP-PLA. Patients in stage II to III with disseminated disease had lower plasma concentrations of HCC-4 (P = .025). Low plasma levels of tissue inhibitor of metalloproteinases-1 were seen in patients with disseminated disease stage II (P = .003). The level of CEA was higher in patients with disease dissemination compared with those without (P = .007)., Conclusion: SP-PLA has the ability to analyze many protein markers simultaneously in a small amount of blood. However, none of the markers selected for the present SP-PLA analyses gave better prognostic information than CEA., (Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: The importance of absent neoplastic epithelium in specimens from cytoreductive surgery (CRS) is unknown. This study aimed to investigate the prevalence and prognostic value of histopathology without neoplastic epithelium in patients treated with CRS and hyperthermic intraperitoneal chemotherapy (HIPEC)., Methods: Data were extracted from medical records and histopathology reports for patients treated with initial CRS and HIPEC at Uppsala University Hospital, Sweden, between 2004 and 2012. Patients with inoperable disease and patients undergoing palliative non-CRS surgery were excluded from the study. Patients lacking neoplastic epithelium in surgical specimens from CRS, with or without mucin, were classified as "neoplastic epithelium absent" (NEA), and patients with neoplastic epithelium were classified as "neoplastic epithelium present" (NEP)., Results: The study observed NEA in 78 of 353 patients (22 %). Mucin was found in 28 of the patients with NEA. For low-grade appendiceal mucinous neoplasms and adenomas, the 5-year overall survival rate was 100 % for NEA and 84 % for NEP, and the 5-year recurrence-free survival rate was 100 % for NEA and 59 % for NEP. For appendiceal/colorectal adenocarcinomas (including tumors of the small intestine), the 5-year overall survival rate was 61 % for NEA and 38 % for NEP, and the 5-year recurrence-free survival rate was 60 % for NEA and 14 % for NEP. Carcinoembryonic antigen level, peritoneal cancer index, and completeness of the cytoreduction score were lower in patients with NEA., Conclusions: A substantial proportion of patients undergoing CRS and HIPEC have NEA. These patients have a favorable prognosis and a decreased risk of recurrence. Differences in patient selection can affect the proportion of NEA and hence explain differences in survival rates between reported series.