Tumor markers are used routinely for surveillance in patients treated for colorectal cancer (CRC). However, the prognostic implications of elevated preoperative tumor markers in patients treated for CRC and peritoneal metastases (PM) has not been well defined. The utility of carcinoembryonic antigen (CEA), carbohydrate antigen 19-9 (CA19-9) and cancer antigen 125 (CA125) to predict outcome for these patients is reported.

Clinical and histologic features plus preoperative tumor markers were recorded within 1 week prior to CRS. Impact on overall survival of these factors was analyzed by univariate and multivariate analysis.

Two hundred and four patients were in our database and 140 patients (75.3 %) had at least a single elevated preoperative tumor marker. In an analysis of clinical and histologic parameters preoperatively, a poorly differentiated tumor, signet ring morphology, a peritoneal cancer index (PCI) of ≥16 and an incomplete cytoreduction had a negative impact on median survival. In a multivariate analysis of clinical and histologic features together with tumor markers, an elevated CA19-9 and CA125 was independently associated with reduced overall survival (HR 2.7, p < 0.0001 and HR 2.2, p = 0.005), respectively. Quantitative assessment of CEA (HR 0.5, p = 0.0094) and CA19-9 (HR 4.9, p < 0.001) greater than x10 ULN showed reduced survival.

Preoperative assessment of symptoms and histopathology, PCI and a complete CRS combined with tumor markers CEA, CA19-9 and CA125 are independent prognostic indicators for selection by the multidisciplinary team of CRC PM patients for CRS and HIPEC. All three tumor markers are needed for a meaningful assessment.

DW-MRI is a non-invasive way to determine the peritoneal cancer index (PCI) in colorectal cancer (CRC) patients with peritoneal metastases (PM). However, like surgeons during surgery, radiologists struggle to differentiate between PM and fibrosis. This study aimed to investigate the agreement between the PCI as determined by MRI (mriPCI), during surgery (sPCI) and histopathology examination (pPCI) in CRC patients undergoing cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS-HIPEC).

This was a single-centre, retrospective study of CRC patients with PM who were staged with DW-MRI and underwent subsequent CRS-HIPEC. All initial patients' radiological, surgical and histopathology reports were reviewed for the PCI. Histopathology was the reference standard. Primary outcome was the correlation and agreement between mriPCI and pPCI.

Eighty-seven patients were included. All patients had a complete macroscopic resection. Median (interquartile range) PCI for MRI, surgery, and histopathology were respectively 6.0 (2.5-9.0), 6.0 (4.0-11.0) and 6.0 (2.5-9.5). The intraclass correlation coefficient between the sPCI and pPCI was excellent 0.87 (p <0.001), and good between mriPCI and pPCI 0.77 (p <0.001) and between sPCI and mriPCI 0.70 (p <0.001).

MRI is a promising non-invasive tool to assess the PCI rather accurately.

Treatment guidelines provided by PRODIGE-7 recommend perioperative systemic chemotherapy before cytoreductive surgery (CRS) for colorectal cancer peritoneal metastases (CRPM). Toxicity with multimodal treatment needs to be better defined. Chemotherapy response and impact on survival have not been reported. We assessed CRPM patients who received systemic oxaliplatin/irinotecan before CRS (preoperative) with Mitomycin C (35 mg/m2, 90 min) or Oxaliplatin (368 mg/m2, 30 min) heated intraperitoneal chemotherapy (HIPEC). Secondary analysis was performed from a prospective database. Overall survival (OS) in chemotherapy responders (R) and nonresponders (NR) was compared. Toxicity was assessed by rate of adverse events (AEs). From April 2005 to April 2021, 436 patients underwent CRS + HIPEC; 125 (29%) received preoperative chemotherapy. The 112 (90%) received oxaliplatin (64, 57%) or irinotecan (48, 43%). R, defined as complete (CR) or partial response on preoperative imaging and/or postoperative histology, was seen in 71, 63% (53.8-72.3); 16, 14% (8.4-22.2) had CR. Median OS in R versus NR was 43.7 months (37.9-49.4) versus 23.9 (16.3-31.4) p = 0.007, HR 0.51 (0.31-0.84). OS multivariable analysis showed HR 0.48 (0.25-0.95), p = 0.03 for chemotherapy response corrected by peritoneal cancer index, completeness of cytoreduction score. CRS led to 21% grade 3-4 AEs versus 4% for preoperative chemotherapy. HIPEC grade 3-4 AEs were 0.5%. Preoperative chemotherapy response is an independent predictor for OS in CRPM.

The primary objective of this study is to develop a prediction model for peritoneal metastasis (PM) in colorectal cancer by integrating the genomic features of primary colorectal cancer, along with clinicopathological features. Concurrently, we aim to identify potential target implicated in the peritoneal dissemination of colorectal cancer through bioinformatics exploration and experimental validation. By analyzing the genomic landscape of primary colorectal cancer and clinicopathological features from 363 metastatic colorectal cancer patients, we identified 22 differently distributed variables, which were used for subsequent LASSO regression to construct a PM prediction model. The integrated model established by LASSO regression, which incorporated two clinicopathological variables and seven genomic variables, precisely discriminated PM cases (AUC 0.899; 95% CI 0.860-0.937) with good calibration (Hosmer-Lemeshow test p = .147). Model validation yielded AUCs of 0.898 (95% CI 0.896-0.899) and 0.704 (95% CI 0.622-0.787) internally and externally, respectively. Additionally, the peritoneal metastasis-related genomic signature (PGS), which was composed of the seven genes in the integrated model, has prognostic stratification capability for colorectal cancer. The divergent genomic landscape drives the driver genes of PM. Bioinformatic analysis concerning these driver genes indicated SERINC1 may be associated with PM. Subsequent experiments indicate that knocking down of SERINC1 functionally suppresses peritoneal dissemination, emphasizing its importance in CRCPM. In summary, the genomic landscape of primary cancer in colorectal cancer defines peritoneal metastatic pattern and reveals the potential target of SERINC1 for PM in colorectal cancer.

Treatment of peritoneal surface malignancies makes physicians face demanding and new-fangled problems, as there are many uncertain aspects considering the outcomes of affected patients' prognoses. Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) are associated with favorable long-term outcomes in carefully selected patients with peritoneal metastases (PM). We aim to summarize the current results about the initial malignancies and their peritoneal spreads. The current literature has been scrutinized, and studies between 2016 and 2022 were included wherein long-term, progression-free (PFS), and overall survival (OS) data were considered relevant information. Medline, Embase, and Google Scholar have been the main sources. Hereby, we cover all the primer malignancies: gastric, ovarian, and colorectal cancers with peritoneal metastases (PM), malignant peritoneal mesothelioma, and pseudomyxoma peritonei. Examining the advances in the current peer-reviewed literature about the indications of cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC), target groups, risk factors, and other influencing elements, we intend to provide a complex state-of-the-art report, establishing the relevant aspects of that emerging treatment method.

Multimodal treatment of colorectal (CRC) peritoneal metastases (PM) includes systemic chemotherapy (SC) and surgical cytoreduction (CRS), eventually with hyperthermic intraperitoneal chemotherapy (HIPEC), in select patients. Considering lack of clear guidelines, this study was designed to analyze the role of chemotherapy and its timing in patients treated with CRS-HIPEC.

Data from 13 Italian centers with PM expertise were collected by a collaborative group of the Italian Society of Surgical Oncology (SICO). Clinicopathological variables, SC use, and timing of administration were correlated with overall survival (OS), disease-free survival (DFS), and local (peritoneal) DFS (LDFS) after propensity-score (PS) weighting to reduce confounding factors.

A total of 367 patients treated with CRS-HIPEC were included in the propensity-score weighting. Of the total patients, 19.9% did not receive chemotherapy within 6 months of surgery, 32.4% received chemotherapy before surgery (pregroup), 28.9% after (post), and 18.8% received both pre- and post-CRS-HIPEC treatment (peri). SC was preferentially administered to younger (p = 0.02) and node-positive (p = 0.010) patients. Preoperative SC is associated with increased rate of major complications (26.9 vs. 11.3%, p = 0.0009). After PS weighting, there were no differences in OS, DFS, or LDFS (p = 0.56, 0.50, and 0.17) between chemotherapy-treated and untreated patients. Considering SC timing, the post CRS-HIPEC group had a longer DFS and LDFS than the pre-group (median DFS 15.4 vs. 9.8 m, p = 0.003; median LDFS 26.3 vs. 15.8 m, p = 0.026).

In patients with CRC-PM treated with CRS-HIPEC, systemic chemotherapy was not associated with overall survival benefit. The adjuvant schedule was related to prolonged disease-free intervals. Additional, randomized studies are required to clarify the role and timing of systemic chemotherapy in this patient subset.

Pathological response is a critical factor in predicting long-term survival of patients with esophageal cancer after preoperative therapy. However, the validity of using pathological response as a surrogate for overall survival (OS) for esophageal cancer has not yet been established. In this study, a literature-based meta-analysis was conducted to evaluate pathological response as a proxy endpoint for survival in esophageal cancer.

Three databases were systematically searched to identify relevant studies investigating neoadjuvant treatment for esophageal cancer. The correlation between pathological complete response (pCR) and OS were assessed using a weighted multiple regression analysis at the trial level, and the coefficient of determination (R2) was calculated. The research design and histological subtypes were considered in the performance of subgroup analysis.

In this meta-analysis, a total of 40 trials, comprising 43 comparisons and 55,344 patients were qualified. The surrogacy between pCR and OS was moderate (R2 = 0.238 in direct comparison, R2 = 0.500 for pCR reciprocals, R2 = 0.541 in log settings). pCR could not serve as an ideal surrogate endpoint in randomized controlled trials (RCTs) (R2 = 0.511 in direct comparison, R2 = 0.460 for pCR reciprocals, R2 = 0.523 in log settings). A strong correlation was observed in studies comparing neoadjuvant chemoradiotherapy and neoadjuvant chemotherapy (R2 = 0.595 in direct comparison, R2 = 0.840 for pCR reciprocals, R2 = 0.800 in log settings).

A lack of surrogacy of pathological response for long-term survival at trial level is established in this study. Hence, caution should be exercised when using pCR as the primary endpoint in neoadjuvant studies for esophageal cancer.

Currently, patients with a limited extent of peritoneal metastases from colon and rectal cancer are treated by cytoreductive surgery combined with perioperative chemotherapy performed at experienced centers.

To statistically evaluate features that may impact survival of ≥5 years. These data are used in the risk/benefit analyses performed by the multidisciplinary team.

This was a retrospective review of a prospective database.

This single-institution study was conducted at an academic center.

All patients who had biopsy-proven colon or rectal peritoneal metastases treated by systemic chemotherapy, complete cytoreductive surgery, and perioperative surgery were included.

The primary outcomes measured were the clinical-, histologic-, and treatment-related features that had an impact on 5-year survival.

From 131 patients who had complete cytoreduction, 35 patients (26.7%) were identified as 5-year survivors. The median survival time was 27 months. The median age was 50.5 (range, 25-80) years. By univariant analysis, an absence of lymph node involvement at the time of primary colorectal cancer resection (HR 1.899 [95% CI, 1.064-3.388]; p = 0.03), complete or near-complete response to neoadjuvant chemotherapy (HR 0.251 [95% CI, 0.092-0.684]; p = 0.007), peritoneal cancer index ≤17 (HR 0.509 [95% CI, 0.329-0.788]; p = 0.002), complete visible resection of disease indicated by the completeness of cytoreduction score of 0 (HR 0.412 [95% CI, 0.224-0.756]; p = 0.004), and well-differentiated tumor (HR 0.34 [95% CI, 0.157-0.737]; p = 0.006) were significantly associated with ≥5 years survival.

Limitations include its retrospective nature, unmeasured confounders, and data from a single institution.

The tumor biology as revealed by lymph node status and tumor differentiation plus extent of disease as measured by the response to neoadjuvant chemotherapy, peritoneal cancer index, and no visible residual disease indicated a favorable outcome. See Video Abstract at http://links.lww.com/DCR/C62 .

ANTECEDENTES:Actualmente, los pacientes con extensión limitada de metástasis peritoneales de orígen colorectal son tratados mediante cirugía citorreductora asociada con una quimioterapia peri-peratoria realizadas en centros experimentados.OBJETIVO:Estúdio y evaluación estadística de las características que puedan impactar en la sobrevida de los pacientes a 5 años o más. Se utilizaron estos datos en el análisis de riesgo /beneficio realizados por un equipo multidisciplinario.DISEÑO:Revisión retrospectiva de una base de datos prospectiva.AJUSTES:Estudio realizado en una sola institución académica.PACIENTES:Todos aquellos que presentaban metástasis peritoneales de orígen colorectal, comprobadas por biopsia y tratadas con quimioterapia sistémica, cirugía peri-operatoria y citorreductora completas.MEDIDAS DE RESULTADO PRINCIPALES:Las medidads de resultados primarios fueron las características clínicas, histológicas y relacionadas con el tratamiento que tuvieron un impacto en la sobrevida a 5 años.RESULTADOS:De 131 pacientes que tuvieron una cirugía de citorreducción completa, 35 pacientes (26, 7%) fueron identificados como sobrevivientes a 5 años. La mediana de sobrevida fué de 27 meses. Se identificarion 16 varones. La mediana de edad fue de 50, 5 años con un rango de 25 a 80 años. Según análisis univariante, la ausencia de compromiso de los ganglios linfáticos en el momento de la resección del cáncer colorrectal primario (HR 1,899 (1,064, 3,388) p = 0,03), la respuesta completa o casi completa al tratamiento neoadyuvante con quimioterapia (HR 0,251 (0,092, 0,684) p = 0,007), el índice de cáncer peritoneal ≤17 (HR 0,509 (0,329, 0,788) p = 0,002), la resección completa y visible de la enfermedad indicada por la puntuación de citorreducción de 0 (HR 0,412 (0,224), 0,756) p = 0,004) y los tumores bien diferenciados (HR 0,34 (0,157, 0,737) p = 0,006) se asociaron significativamente con 5 o más años de sobrevida.LIMITACIONES:El estudio se encontró limitado por su naturaleza retrospectiva, por la no medida de factores de confusión y por los datos provenientes de una sola institución.CONCLUSIONES:La biología tumoral demostrada según el estado de los ganglios linfáticos y la diferenciación tumoral, agregada a la extensión de la enfermedad medida por la respuesta a la quimioterapia neoadyuvante, el índice de cáncer peritoneal y la ausencia visible de enfermedad residual, demostraron un resultado favorable. Consulte Video Resumen en http://links.lww.com/DCR/C62(Traducción-Dr. Xavier Delgadillo ).

The safety of intraperitoneally administrated paclitaxel (op PTX) was demonstrated in the phase I trial of ip PTX combined with conventional systemic chemotherapy for colorectal cancer with peritoneal carcinomatosis. Moreover, the median survival time was 29.3 months, which was longer than that observed in previous studies. Here, we planned the phase II trial of ip PTX: the iPac-02 trial.

This multicenter, open-label, single assignment interventional clinical study includes patients with colorectal cancer with unresectable peritoneal carcinomatosis. FOLFOX-bevacizumab or CAPOX-bevacizumab is administered concomitantly as systemic chemotherapy. PTX 20 mg/m2 is administered weekly through the peritoneal access port in addition to these conventional systemic chemotherapies. The response rate is the primary endpoint. Progression-free survival, overall survival, peritoneal cancer index improvement rate, rate of negative peritoneal lavage cytology, safety, and response rate to peritoneal metastases are the secondary endpoints. A total of 38 patients are included in the study. In the interim analysis, the study will continue to the second stage if at least 4 of the first 14 patients respond to the study treatment. The study has been registered at the Japan Registry of Clinical Trials (jRCT2031220110).

We previously conducted phase I trial of ip PTX combined with conventional systemic chemotherapy for colorectal cancer with peritoneal carcinomatosis [1]. In the study, three patients underwent mFOLFOX, bevacizumab, and weekly ip PTX, and the other three patients underwent CAPOX, bevacizumab, and weekly ip PTX treatment. The dose of PTX was 20 mg/m [2]. The primary endpoint was the safety of the chemotherapy, and secondary endpoints were response rate, peritoneal cancer index improvement rate, rate of negative peritoneal lavage cytology, progression-free survival, and overall survival. Dose limiting toxicity was not observed, and the adverse events of ip PTX combined with oxaliplatin-based systemic chemotherapy were similar to those described in previous studies using systemic chemotherapy alone [3, 4]. The response rate was 25%, peritoneal cancer index improvement rate was 50%, and cytology in peritoneal lavage turned negative in all the cases. The progression-free survival was 8.8 months (range, 6.8-12 months), and median survival time was 29.3 months [5], which was longer than that observed in previous studies.

Here, we planned the phase II trial of ip paclitaxel combined with conventional chemotherapy for colorectal cancer with peritoneal carcinomatosis: the iPac-02 trial.

To maximize the results of treatments for peritoneal metastases for rare abdominal or pelvic tumors, selection of patients with a possibility for long-term success is necessary. Because these malignancies are rare, data from which these selection factors can be extracted do not exist. In order to facilitate knowledgeable patient selection for treatment, the well established clinical and histopathologic features of the common malignancies treated for peritoneal metastases were reviewed. The potential application of selection factors for common diagnoses was explored in an attempt to provide selection factors for rare tumors. The histopathologic grade, the lymph node status, the Ki-67 proliferation index, prior surgical score (PSS), preoperative radiologic imaging, preoperative laparoscopic assessment, response to neoadjuvant chemotherapy, peritoneal cancer index (PCI), and completeness of cytoreduction score were all included in this search for relevant selection factors for a rare disease. To facilitate the use of selection factors from common peritoneal metastases diagnoses, these diseases were divided into four groups. Placement of the rare cause of peritoneal metastases into one of these four groups will allow knowledgeable selection for treatment. Rare diseases with a natural history resembling low-grade appendiceal neoplasms are in group 1, diseases resembling lymph node negative colorectal cancer are in group 2, diseases resembling lymph node positive colorectal peritoneal metastases in group 3, and diseases resembling gastric cancer in group 4.

Multimodal treatment for patients with peritoneal metastases (PM) from colorectal cancer (CRC), including perioperative chemotherapy (CT) plus complete resection, is associated with prolonged survival. The oncologic impact of therapeutic delays is unknown.

The aim of this study was to assess the survival impact of delaying surgery and CT.

Medical records from the national BIG RENAPE network database of patients with complete cytoreductive (CC0-1) surgery of synchronous PM from CRC who received at least one neoadjuvant CT cycle plus one adjuvant CT cycle were retrospectively reviewed. The optimal interval between the end of neoadjuvant CT to surgery, surgery to adjuvant CT, and total interval without systemic CT were estimated using Contal and O'Quigley's method plus restricted cubic spline methods.

From 2007 to 2019, 227 patients were identified. After a median follow-up of 45.7 months, the median overall survival (OS) and progression-free survival (PFS) was 47.6 and 10.9 months, respectively. The best cut-off period was 42 days in the preoperative interval, no cut-off period was optimal in the postoperative interval, and the best cut-off period in the total interval without CT was 102 days. In multivariate analysis, age, biologic agent use, high peritoneal cancer index, primary T4 or N2 staging, and delay to surgery of more than 42 days (median OS 63 vs. 32.9 months; p = 0.032) were significantly associated with worse OS. Preoperative delay of surgery was also significantly associated with PFS, but only in univariate analysis.

In selected patients undergoing complete resection plus perioperative CT, a period of more than 6 weeks from completion of neoadjuvant CT to cytoreductive surgery was independently associated with worse OS.

The histological responses (HRs) after systemic chemotherapy should be used to determine the optimal management of patients with peritoneal and liver metastasis from colorectal cancer (cPM, cLM), in curative intent. We aimed to compare HRs of cPM and cLM in metastatic mice model after chemotherapy.

Colon carcinoma CT26-luc cells were transplanted into syngeneic BALB/c mice by intraperitoneal (leading to cPM), intrasplenic (leading to cLM), or intraperitoneal + intrasplenic (leading to cPM cLM) injections and follow up using bioluminescence during 21 days. Bi-chemotherapeutic treatment (5-fluorouracil at D11, D17, and D20, and oxaliplatin at D13 and D19) was administered. The peritoneal cancer index (PCI) and HRs using Peritoneal Regression Grading Score (PRGS) and Tumor Regression Grade (TRG) classifications were analyzed at day 21.

Unlike bioluminescence rate, PCI was reduced after chemotherapy in all treated groups with cPM comparatively to controls (33 ± 9.5 vs. 19.8 ± 5, p = 0.002 for cPM groups; 37.7 ± 3.6 vs. 25.2 ± 10.8, p = 0.0003 for the cPM + cLM groups). The complete or major HR rates were higher in all treated groups compared to the non-treated mice (cPM, 2.29 ± 0.55 vs. 3.56 ± 1.01; cLM, 2.43 ± 1.89 vs. 4.86 ± 0.378; cPM + cLM, 2.73 ± 1.03 and 2.2 ± 0.65 vs. 3.79 ± 0.75 and 4.36 ± 0.43). The complete or major HR rates after chemotherapy were similar across the metastatic sites in 60% for cPM + cLM group.

The efficacy of chemotherapeutic treatment did not differ between the metastatic sites. Murine models are suitable in histological analyses to study tumor development and regression but clinical study will be performed to confirm these results.

Limited success in the management of mucinous appendiceal adenocarcinoma (MACA) has been reported.

Cytoreductive surgery with perioperative intraperitoneal chemotherapy was used to treat a cohort of patients with peritoneal dissemination of MACA. The clinical and histopathologic variables were assessed for their impact on overall survival.

The study analyzed 196 patients during a median follow-up period of 8 years. The patients had a median age was 46 years, a median survival of 12 years, and a mean survival of 12.4 years. Preoperative systemic chemotherapy and a high prior surgical score had a negative impact on prognosis. Survival was better for 37 patients (18.9%) with mucinous appendiceal adenocarcinoma-Intermediate (MACA-Int) histology than for 159 patients (81.1%) with MACA grade 1, 2, or 3, or signet ring cells (S) (p = 0.0004). Although MACA-1 and MACA-2 versus MACA-3 and MACA-S had a difference in survival of 63.9 versus 43.2 years at 5 years, with long-term follow-up evaluation, the differences in survival became insignificant (p = 0.5841).

The histologic subtype of MACA-Int had a 10-year survival of 81.1%, which was markedly superior to that of MACA-1, -2, -3, or -S (32.7%). With long-term follow-up evaluation, MACA-1, -2, -3, and -S did not differ significantly in survival.

Selected patients with colorectal cancer peritoneal metastases (CRPM) could be offered a curative-intent strategy based on complete cytoreductive surgery (CRS), potentially combined with hyperthermic intraperitoneal chemotherapy (HIPEC) and perioperative systemic chemotherapy. The impact of different neoadjuvant systemic chemotherapy (NACT) regimens remains unclear due to a lack of comparative data.

Consecutive CRPM patients from a monocentric database who were treated with complete CRS after single-line NACT were included in this study. Chemotherapy regimens were tailored as a doublet drug (FOLFOX/FOLFIRI) with/without targeted therapy (anti-epidermal growth factor receptor/bevacizumab) and triplet-drug combination (FOLFIRINOX). Morphological response (MR) was assessed using the Response Evaluation Criteria in Solid Tumors criteria, and pathological response (PR) was assessed using the Peritoneal Regression Grading Score (PRGS). Long-term oncologic outcomes were compared.

The cohort comprised 388 patients, including 127, 202, and 59 patients in the doublet, doublet + targeted, and triplet groups, respectively. MR rates were higher in the triplet (68.0%) and doublet + targeted groups (64.2%) when compared with the doublet group (42.4%, p = 0.003). Complete and major PRs were observed in 13.6% and 32.0% of patients, respectively. Higher MR rates were observed after doublet + targeted or triplet regimens, while no difference was observed for PR rates. In multivariate analysis, FOLFIRINOX was independently associated with better overall survival (hazard ratio 0.49, 95% confidence interval 0.25-0.96; p = 0.037). FOLFIRINOX also resulted in a higher rate of severe postoperative complications.

In this retrospective study, a FOLFIRINOX regimen as NACT seemed to result in better long-term outcomes for CRPM patients after complete CRS/HIPEC, although with higher morbidity. Prospective studies are needed, including groups without NACT and those with FOLFIRINOX + bevacizumab.

There is a paucity of studies evaluating perioperative systemic chemotherapy in conjunction with cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) in patients with colorectal cancer peritoneal metastases (CRCPM). The aim was to evaluate neoadjuvant and/or adjuvant systemic therapy in CRCPM.

Patients with CRCPM from 39 treatment centres globally from January 1, 1991, to December 31, 2018, who underwent CRS+HIPEC were identified and stratified according to neoadjuvant/adjuvant use. Crude data analysis, propensity score matching (PSM) and Cox-proportional hazard modelling was performed.

Of 2093 patients, 1613 were included in neoadjuvant crude evaluation with 708 in the PSM cohort (354 patients/arm). In the adjuvant evaluation, 1176 patients were included in the crude cohort with 778 in the PSM cohort (389 patients/arm). The median overall survival (OS) in the PSM cohort receiving no neoadjuvant vs neoadjuvant therapy was 37.0 months (95% CI: 32.6-42.7) vs 34.7 months (95% CI: 31.2-38.8, HR 1.08 95% CI: 0.88-1.32, p = 0.46). The median OS in the PSM cohort receiving no adjuvant therapy vs adjuvant therapy was 37.0 months (95% CI: 32.9-41.8) vs 45.7 months (95% CI: 38.8-56.2, HR 0.79 95% CI: 0.64-0.97, p = 0.022). Recurrence-free survival did not differ in the neoadjuvant evaluation but differed in the adjuvant evaluation - HR 1.04 (95% CI: 0.87-1.25, p = 0.66) and 0.83 (95% CI: 0.70-0.98, p = 0.03), respectively. Multivariable Cox-proportional hazard modelling in the crude cohorts showed hazard ratio 1.08 (95% CI: 0.92-1.26, p = 0.37) for administering neoadjuvant therapy and 0.86 (95% CI: 0.72-1.03, p = 0.095) for administering adjuvant therapy.

Neoadjuvant therapy did not confer a benefit to patients undergoing CRS+HIPEC for CRCPM, whereas adjuvant therapy was associated with a benefit in this retrospective setting.

None.

Appendiceal mucinous neoplasms are routinely accompanied by peritoneal metastases at the time of diagnosis of the primary appendiceal tumor. In contrast, liver metastases and lymph node metastases are unusual.

From an extensive database, patients with lymph node metastases identified at the time of primary appendiceal cancer resection were selected for special study. The clinical, treatment-related and histologic variables of this group of patients were statistically analyzed for their impact on overall survival.

From a prospectively maintained database of 685 patients with a complete cytoreduction of a mucinous appendiceal neoplasm with peritoneal dissemination, 39 patients (5.6%) had lymph node metastases at the time of primary diagnosis. The median follow-up was 5.0 years and overall median survival was 6.0 years. Histologically, 6 of these patients (15.4%) had an appendiceal mucinous neoplasm - Intermediate type (MACA-Int). In 5 patients, the involved lymph nodes were not within the ileocolic lymph node group. The 7 patients (17.9%) who had a complete or near complete response to neoadjuvant chemotherapy prior to definite cytoreductive surgery (CRS) plus hyperthermic intraperitoneal chemotherapy (HIPEC) showed prolonged survival (HR 4.8 (1.1, 20.5) p = 0.0323). A prior right colon resection required repeat resection in 87% of patients.

Long-term survival is unusual but occasionally seen in this group of patients. Response to neoadjuvant chemotherapy is an important determinant of a favorable outcome.

Peritoneal surface malignancies (PSMs) are usually associated with a poor prognosis. Nonetheless, in line with advances in the management of most abdominopelvic metastatic diseases, considerable progress has been made over the past decade. An improved understanding of disease biology has led to the more accurate prediction of neoplasia aggressiveness and the treatment response and has been reflected in the proposal of new classification systems. Achieving complete cytoreductive surgery remains the cornerstone of curative-intent treatment of PSMs. Alongside centralization in expert centres, enabling the delivery of multimodal and multidisciplinary strategies, preoperative management is a crucial step in order to select patients who are most likely to benefit from surgery. Depending on the specific PSM, the role of intraperitoneal chemotherapy and of perioperative systemic chemotherapy, in particular, in the neoadjuvant setting, is established in certain scenarios but questioned in several others, although more prospective data are required. In this Review, we describe advances in all aspects of the management of PSMs including disease biology, assessment and improvement of disease resectability, perioperative management, systemic therapy and pre-emptive management, and we speculate on future research directions.

This retrospective multicenter cohort study compared the feasibility and safety of oxaliplatin-based pressurized intraperitoneal aerosol chemotherapy (PIPAC-Ox) with or without intraoperative intravenous 5-fluorouracil (5-FU) and leucovorin (L).

Our study included consecutive patients with histologically proven unresectable and isolated colorectal peritoneal metastases (cPM) treated with PIPAC-Ox in seven tertiary referral centers between January 2015 and April 2020. Toxicity events and oncological outcomes (histological response, progression-free survival, and overall survival) were compared between patients who received intraoperative intravenous 5-FU/L (PIPAC-Ox + 5-FU/L group) and patients who did not (PIPAC-Ox group).

In total, 101 patients (263 procedures) were included in the PIPAC-Ox group and 30 patients (80 procedures) were included in the PIPAC-Ox + 5-FU/L group. Common Terminology Criteria for Adverse Events v4.0 grade 2 or higher adverse events occurred in 48 of 101 (47.5%) patients in the PIPAC-Ox group and in 13 of 30 (43.3%) patients in the PIPAC-Ox + 5-FU/L group (p = 0.73). The complete histological response rates according to the peritoneal regression grading score were 27% for the PIPAC-Ox + 5-FU/L group and 18% for the PIPAC-Ox group (p = 0.74). No statistically significant differences were observed in overall or progression-free survival between the two groups.

The safety and feasibility of PIPAC-Ox + 5-FU/L appears to be similar to the safety and feasibility of PIPAC-Ox alone in patients with unresectable cPM. Oncological outcomes must be evaluated in larger studies.

In the last decades, several new therapeutic strategies have been introduced in the field of gynecologic oncology. These include neoadjuvant chemotherapy for high-grade serous tubo-ovarian carcinoma, hormonal fertility-sparing strategies for endometrial cancer, pressurized intraperitoneal aerosol chemotherapy (PIPAC) for surgically incurable peritoneal metastasis, and neoadjuvant treatments for locally advanced cervical carcinomas. All these recent advances lead to the development of novel scoring systems for the evaluation of pathological response related to specific treatments. In this regard, pathological evaluation of the morphological modifications related to these treatments and the definition of a tumor regression grading score have been introduced in clinical practice in order to achieve a more efficient prognostic stratification of patients affected by gynecological malignancies. The aim of the present paper is to provide a detailed review on the post-treatment pathological scoring systems in patients affected by gynecological malignancies.

Peritoneal metastases from colon and rectal cancer presents a new target for a regional approach to treatment. Proper patient selection requires an understanding of the natural history of the disease progression.

Data from colorectal cancer patients treated for peritoneal metastases by cytoreductive surgery (CRS) plus hyperthermic intraperitoneal chemotherapy and early postoperative intraperitoneal chemotherapy and the records from the primary colon or rectal cancer surgery were analyzed to assess their impact on survival. Data regarding the anatomic sites of colorectal peritoneal metastases was gathered at the time of a complete CRS.

A cohort of 73 patients with peritoneal metastases and lymph node metastases but no liver metastases provided the information. All patients had a complete cytoreduction. Left-sided primary cancer and a complete or near complete response to neoadjuvant chemotherapy (NAC) indicated improved survival. Tumor progression within the abdominal incision, carcinoembryonic antigen (CEA) >10, peritoneal cancer index >9 and peritoneal metastases present in the abdominopelvic regions 6 and 11 carried an especially guarded prognosis.

Reduced survival occurred with a right-sided or rectal primary cancer, a CEA >10, tumor cell entrapment, and involvement of abdominopelvic regions 6 and 11. Effective NAC showed a favorable outcome.

Patients with locally advanced or metastatic colorectal cancer (CRC) display heterogeneous responses to standard-of-care therapy. Robust preclinical models of malignancy in the form of patient-derived tumor organoids (PDTOs) have recently come to the fore in tailoring patient care to a personalized medicine level. This study aimed to review the literature systematically regarding PTDOs and gauge their impact on precision medicine in the management of CRC.

A PRISMA-compliant systematic review of the MEDLINE, EMBASE, Web of Science, and Cochrane Library databases was performed. The results were categorized based on the primary objective of the individual studies as follows: organoid use in predicting effective hyperthermic intraperitoneal chemotherapy (HIPEC), systemic chemotherapy in CRC, or neoadjuvant chemoradiotherapy in rectal cancer.

The literature search found 200 publications, 16 of which met the inclusion criteria. Organoid models of primary and metastatic CRC have been increasingly used to assess clinical responses to standard therapy. Marked heterogeneity exists, matching the responses observed in clinical practice with ex vivo drug and radiation screening. Repeated correlation between organoid and patient sensitivity to forms of HIPEC, systemic chemotherapy, and chemoradiotherapy has been observed.

Patient-derived tumor organoids are the latest tool in predictive translational research. Current organoid-based studies in precision medicine have shown their great potential for predicting the clinical response of patients to CRC therapy. Larger-scale, prospective data are required to fully support this exciting avenue in cancer care.

The standardization of surgical outcomes throughout surgical procedures is mandatory. Cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS + HIPEC) should provide proficient oncological and surgical outcomes.

The aim of this study was to identify clinically relevant quality indicators and their quality standard, and to determine their acceptable quality limit. A systematic review on cytoreductive results from 2000 to 2018 was performed focusing on clinical guidelines, consensus conferences, and publications. After the selection of quality indicators, a systematic review of indexed references was performed in order to calculate the quality standard for each indicator.

Unicentric/multicentric series, comparative studies, and clinical trials. Studies were to include outcomes after cytoreduction of colorectal origin and series with more than 50 patients. Quality indicators with at least 10 series were mandatory and objective measurements were also mandatory for inclusion.

Quality indicators selected were 1- to 5-year survival, overall disease-free survival, 1- to 5-year disease-free survival, complete surgical resection, duration of surgery, length of stay, overall morbimortality, major morbidity, re-intervention, postoperative hemorrhage, intestinal fistula, anastomotic leakage, wound infection, postoperative medical complications, overall recurrence, and failure to rescue.

The most relevant quality indicators and critical quality limits were overall disease-free survival and 5-year overall disease-free survival (14 months and <10 months, and 14% and <4%, respectively), completeness of surgical resection (89% and <80%, respectively), overall mortality (3% and >8%, respectively), overall morbidity (47% and >63%, respectively), failure to rescue (12% and <30%, respectively), reintervention (13 and <22%, respectively), anastomotic leakage (6% and <13%, respectively), and overall recurrence (60% and <74%, respectively).

This is the first study to assess quality standards in CRS + HIPEC for colorectal peritoneal metastases. The current data are of particular relevance for future studies to control the variability of this surgery.

Pathological response of colorectal peritoneal metastasis (CRPM) may affect prognosis. We investigated the relationship between oncological outcomes and pathological response to chemotherapy of CRPM following cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC).

We conducted a retrospective analysis of a prospectively maintained Peritoneal Surface Malignancies database between 2015 and 2020. Analysis included patients with CRPM who underwent a CRS/HIPEC procedure (n = 178). The cohort was divided into three groups according to the response ratio (ratio of tumor-positive specimens to the total number of specimens resected): Group A, complete response; Group B, high response ratio, and Group C, low response ratio.

The group demographics were similar, but the overall complication rate was higher in Group C (65.2%) compared with Groups A (55%) and B (42.8%) [p = 0.03]. Survival correlated to response ratio; the estimated median disease-free survival of Group C was 9.1 months (5.97-12.23), 14.9 months (4.72-25.08) for Group B, and was not reached in Group A (p = 0.001). The estimated median overall survival in Group C was 35 months (26.69-43.31), and was not reached in Groups A and B (p = 0.001).

The pathological response ratio to systemic therapy correlates with survival in patients undergoing CRS/HIPEC. This study supports the utilization of preoperative therapy for better patient selection, with a potential impact on survival.

Despite optimal patient selection and surgical effort, recurrence is seen in over 70% of patients undergoing cytoreductive surgery (CRS) for peritoneal metastases (PM). Apart from the Peritoneal Cancer Index (PCI), completeness of cytoreduction and tumour grade, there are other factors like disease distribution in the peritoneal cavity, pathological response to systemic chemotherapy (SC), lymph node metastases and morphology of PM which may have prognostic value. One reason for the underutilisation of these factors is that they are known only after surgery. Identifying clinical predictors, specifically radiological predictors, could lead to better utilisation of these factors in clinical decision making and the extent of peritoneal resection performed for different tumours. This study aims to study these factors, their impact on survival and identify clinical and radiological predictors.

There is no therapeutic intervention in the study. All patients with biopsy-proven PM from colorectal, appendiceal, gastric and ovarian cancer and peritoneal mesothelioma undergoing CRS will be included. The demographic, clinical, radiological, surgical and pathological details will be collected according to a prespecified format that includes details regarding distribution of disease, morphology of PM, regional node involvement and pathological response to SC. In addition to the absolute value of PCI, the structures bearing the largest tumour nodules and a description of the morphology in each region will be recorded. A correlation between the surgical, radiological and pathological findings will be performed and the impact of these potential prognostic factors on progression-free and overall survival determined. The practices pertaining to radiological and pathological reporting at different centres will be studied.

The study protocol has been approved by the Zydus Hospital ethics committee (27 July, 2020) and Lyon-Sud ethics committee (A15-128).

CTRI/2020/09/027709; Pre-results.

Neoadjuvant chemotherapy is widely used in treatment of peritoneal metastases from colorectal cancer, but there is little scientific evidence for this approach. This study aimed to study survival in patients treated with direct surgery with cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS-HIPEC), i.e. without neoadjuvant chemotherapy.

Patients with histopathologically confirmed peritoneal metastases from colorectal cancer that underwent first-time CRS-HIPEC with complete cytoreduction (CC0 or 1) at Karolinska University Hospital 2012-2019 were included. Patients with synchronous extraperitoneal metastases were excluded if not treated before end of follow-up. Factors associated with overall survival (OS) and disease-free survival (DFS) were evaluated using the Kaplan-Meier method and Cox regression models. The multivariable models were adjusted for sex, age, synchronous/metachronous peritoneal metastases, peritoneal carcinomatosis index (PCI), extraperitoneal metastases and the pathological tumor (T) and lymph node (N) stage of the primary tumor.

In all, 131 patients underwent complete CRS-HIPEC for peritoneal metastases without neoadjuvant chemotherapy. The median OS and DFS were 40.3 months and 12.5 months, respectively, in patients treated with direct surgery. In the multivariable model, PCI≥16 was the only variable associated with decreased OS, whereas elevated PCI, metachronous development of peritoneal metastases and synchronous extraperitoneal metastases were associated with decreased DFS. Age was not associated with an impaired prognosis.

Patients who underwent direct surgery with CRS-HIPEC had a good prognosis, with a median OS of more than 3 years. The results from this study question the need of neoadjuvant chemotherapy in all patients eligible for CRS-HIPEC.

To date, no randomized clinical trials have investigated perioperative systemic therapy relative to cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS-HIPEC) alone for resectable colorectal peritoneal metastases (CPM).

To assess the feasibility and safety of perioperative systemic therapy in patients with resectable CPM and the response of CPM to neoadjuvant treatment.

An open-label, parallel-group phase 2 randomized clinical trial in all 9 Dutch tertiary centers for the surgical treatment of CPM enrolled participants between June 15, 2017, and January 9, 2019. Participants were patients with pathologically proven isolated resectable CPM who did not receive systemic therapy within 6 months before enrollment.

Randomization to perioperative systemic therapy or CRS-HIPEC alone. Perioperative systemic therapy comprised either four 3-week neoadjuvant and adjuvant cycles of CAPOX (capecitabine and oxaliplatin), six 2-week neoadjuvant and adjuvant cycles of FOLFOX (fluorouracil, leucovorin, and oxaliplatin), or six 2-week neoadjuvant cycles of FOLFIRI (fluorouracil, leucovorin, and irinotecan) and either four 3-week adjuvant cycles of capecitabine or six 2-week adjuvant cycles of fluorouracil with leucovorin. Bevacizumab was added to the first 3 (CAPOX) or 4 (FOLFOX/FOLFIRI) neoadjuvant cycles.

Proportions of macroscopic complete CRS-HIPEC and Clavien-Dindo grade 3 or higher postoperative morbidity. Key secondary outcomes were centrally assessed rates of objective radiologic and major pathologic response of CPM to neoadjuvant treatment. Analyses were done modified intention-to-treat in patients starting neoadjuvant treatment (experimental arm) or undergoing upfront surgery (control arm).

In 79 patients included in the analysis (43 [54%] men; mean [SD] age, 62 [10] years), experimental (n = 37) and control (n = 42) arms did not differ significantly regarding the proportions of macroscopic complete CRS-HIPEC (33 of 37 [89%] vs 36 of 42 [86%] patients; risk ratio, 1.04; 95% CI, 0.88-1.23; P = .74) and Clavien-Dindo grade 3 or higher postoperative morbidity (8 of 37 [22%] vs 14 of 42 [33%] patients; risk ratio, 0.65; 95% CI, 0.31-1.37; P = .25). No treatment-related deaths occurred. Objective radiologic and major pathologic response rates of CPM to neoadjuvant treatment were 28% (9 of 32 evaluable patients) and 38% (13 of 34 evaluable patients), respectively.

In this randomized phase 2 trial in patients diagnosed with resectable CPM, perioperative systemic therapy seemed feasible, safe, and able to induce response of CPM, justifying a phase 3 trial.

ClinicalTrials.gov Identifier: NCT02758951.

In the management of peritoneal metastases from colon and rectal cancer, the most favorable results are reported with an aggressive combined treatment on patients who have a small extent of the disease. A test to detect occult peritoneal metastases would greatly facilitate the management of this component of colorectal dissemination.

Currently, the standard test by which to confirm the diagnosis of the peritoneal spread of colorectal cancer is peritoneal cytology. To study the utility of this test, we gathered information from patients with biopsy-proven peritoneal metastases. The clinical, histologic, and treatment-related features of these patients at the time of a cytoreductive surgery were statistically correlated with the results of the peritoneal cytology test.

Forty-nine patients with colorectal cancer peritoneal metastases and a peritoneal cytology determination at the time of a cytoreductive surgery were available for analysis. Twenty-eight patients (55.1%) had a positive test. Patients with a high peritoneal cancer index and mucinous histology were most likely to have positive peritoneal cytology.

Peritoneal cytology identified patients with mucinous histology and a large extent of disease but was consistently negative in patients who had a small extent of disease compatible with a favorable response to treatment.

A surgical peritoneal cancer index of >20 is often used to exclude patients from cytoreductive surgery for colorectal peritoneal metastases. The pathologic peritoneal cancer index in these patients may be <20.

The purpose of this study was to compare the pathologic and surgical findings and to look at potential pathologic prognostic factors.

This is a prospective observational study including patients undergoing cytoreductive surgery.

The study was carried out at 3 peritoneal surface malignancy centers, 1 in France and 2 in India.

One-hundred patients were included from July 1, 2018, to June 30, 2019.

The pathologic peritoneal cancer index, peritoneal disease distribution, pathologic response to chemotherapy, factors affecting them and their relation with surgical findings, and potential prognostic value were explored.

Ninety percent had colonic primaries. Fifty-one percent had left-sided tumors. The median surgical peritoneal cancer index was 4 (range, 0-35). Upper regions were involved in 32% and small bowel regions in 26%, and their involvement increased with a higher peritoneal cancer index (p < 0.001). The median pathologic peritoneal cancer index was 2 (range, 0-27) and was less than the surgical peritoneal cancer index in 57%. A pathologic complete response was obtained in 25%. Patients with pathologic complete response received more antiepidermal growth factor receptor therapy (p = 0.008); more leucovorin, 5-fluorouracil, and oxaliplatin; and folinic acid, fluorouracilirin, irinotecan hydrochloride, and oxaliplatin (p < 0.001). In 7 patients with a surgical peritoneal cancer index of >20, pathologic peritoneal cancer index was <20 in 4 patients. Disease in the primary tumor/anastomotic site was found in ≈80%.

Survival outcomes are not available.

Surgical peritoneal cancer index of >20 should not be the sole factor to exclude patients from surgery, especially in responders to systemic therapies. The pathologic peritoneal cancer index, pathologic response to systemic chemotherapy, and disease distribution in the peritoneal cavity should be meticulously documented. Correlation with survival will define their future prognostic value. The primary anastomotic site is a common site for peritoneal disease and should be carefully evaluated in all patients. See Video Abstract at http://links.lww.com/DCR/B490. IMPLICACIONES DE LOS HALLAZGOS PATOLÓGICOS EN MUESTRAS DE CIRUGÍA CITORREDUCTORA EN EL TRATAMIENTO DE METÁSTASIS PERITONEALES COLORRECTALES: RESULTADOS DE UN ESTUDIO PROSPECTIVO MULTICÉNTRICO: Una ICP quirúrgica de >20 se utiliza a menudo para excluir a los pacientes de la cirugía citorreductora por metástasis peritoneales colorrectales. La PCI patológica en estos pacientes puede ser <20.Comparar los hallazgos patológicos y quirúrgicos y observar los posibles factores pronósticos patológicos.Se trata de un estudio observacional prospectivo que incluye a pacientes sometidos a cirugía citorreductora.El estudio se llevó a cabo en tres centros de malignidad de la superficie peritoneal, 1 en Francia y 2 en India.Se incluyeron 100 pacientes desde el 1 de julio de 2018 al 30 de junio de 2019.No hubo intervención terapéutica.Se exploró la ICP patológica, la distribución de la enfermedad peritoneal, la respuesta patológica a la quimioterapia, los factores que la afectan y su relación con los hallazgos quirúrgicos y el valor pronóstico potencial.El noventa por ciento tenía lesiones primarias colónicas. El 51% tenía tumores del lado izquierdo. La mediana de la ICP quirúrgica 4 [0-35]. Las regiones superiores estuvieron involucradas en el 32% y las regiones del intestino delgado en un 26% y su participación aumentó con una ICP más alta (p <0,001). La mediana de la ICP patológica fue 2 [0-27] y fue menor que la ICP quirúrgica en el 57%. Se obtuvo respuesta patológica completa en el 25%. Los pacientes con respuesta patológica completa recibieron más terapia anti-EGFR (p = 0,008) y más FOLFOX y FOLFIRINOX (p <0,001). En 7 pacientes con una ICP quirúrgica de> 20, la ICP patológica fue menor de 20 en 4 pacientes. Se encontró enfermedad en el tumor primario/anastomósis en casi el 80%.Los resultados de supervivencia no están disponibles.La ICP quirúrgica de> 20 no debería ser el único factor para excluir a los pacientes de la cirugía, especialmente en los que responden a las terapias sistémicas. La PCI patológica, la respuesta patológica a la quimioterapia sistémica y la distribución de la enfermedad en la cavidad peritoneal deben documentarse meticulosamente. La correlación con la supervivencia definirá su valor pronóstico futuro. El sitio anastomótico primario es un sitio común de enfermedad peritoneal y debe evaluarse cuidadosamente en todos los pacientes. Consulte Video Resumen en http://links.lww.com/DCR/Bxxx. (Traducción-Dr. Gonzalo Hagerman).

There is a lack of randomized or high-quality intention-to-treat cohort studies addressing the role of systemic therapy in addition to cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS-HIPEC) as part of the treatment of colorectal peritoneal metastases (PM). Therefore, the choice whether or not to treat patients with systemic therapy is currently mainly based on expert opinion. As a result, treatment with neoadjuvant and/or adjuvant systemic therapy is implemented in various ways around the world. The aim of this review was to provide an overview of recent insights with regard to the systemic treatment of PM of colorectal origin obtained from clinical studies and translational research.

The application of nanosecond pulsed electric fields (nsPEFs) could be an effective therapeutic strategy for peritoneal metastasis (PM) from colorectal cancer (CRC). The aim of this study was to evaluate in vitro the sensitivity of CT-26 CRC cells to nsPEFs in combination with chemotherapeutic agents, and to observe the subsequent in vivo histologic response.

In vitro cellular assays were performed to assess the effects of exposure to 1, 10, 100, 500 and 1000 10 ns pulses in a cuvette or bi-electrode system at 10 and 200 Hz. nsPEF treatment was applied alone or in combination with oxaliplatin and mitomycin. Cell death was detected by flow cytometry, and permeabilization and intracellular calcium levels by fluorescent confocal microscopy after treatment. A mouse model of PM was used to investigate the effects of in vivo exposure to pulses delivered using a bi-electrode system; morphological changes in mitochondria were assessed by electron microscopy. Fibrosis was measured by multiphoton microscopy, while the histological response (HR; hematoxylin-eosin-safran stain), proliferation (KI67, DAPI), and expression of immunological factors (CD3, CD4, CD8) were evaluated by classic histology.

10 ns PEFs exerted a dose-dependent effect on CT-26 cells in vitro and in vivo, by inducing cell death and altering mitochondrial morphology after plasma membrane permeabilization. In vivo results indicated a specific CD8+ T cell immune response, together with a strong HR according to the Peritoneal Regression Grading Score (PRGS).

The effects of nsPEFs on CT-26 were confirmed in a mouse model of CRC with PM.

The peritoneal cancer index (PCI) is one of the most important prognostic factors in patients with peritoneal metastases from colorectal cancer undergoing cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS-HIPEC). The PCI is determined during laparotomy by 2 experienced surgeons and plays a major role in the decision to proceed with CRS-HIPEC. The primary objective of this study was to determine the accuracy of the surgical PCI (sPCI) by comparing it with the PCI confirmed by the pathologist (pPCI).

All consecutive patients who underwent CRS-HIPEC for colorectal peritoneal metastases between February 2015 and June 2018 were identified. Relevant patient- and tumor-related characteristics were collected.

In total, 119 patients were included, 60 males (50.4%). The median age was 64 (IQR 55-71). The median sPCI (sPCI = 11, IQR 6-16) was significantly higher than the median pPCI (pPCI = 8, IQR 3-13, p < 0.001). The total pPCI was lower than the total sPCI in 80 patients (67.2%). In 21 patients (17.6%), the sPCI was overestimated with ≥5 points. Small lesions are more likely to be negative. In patients that underwent resection of their primary tumor prior to CRS-HIPEC, the difference between the sPCI and pPCI was significantly larger (p < 0.05).

Surgical calculation of the PCI often results in overestimation. Far-reaching consequences are tied to the macroscopic evaluation of the sPCI, but this evaluation seems not very reliable.

The benefit of repetitive PIPAC specifically in CPM patients has yet to be demonstrated in terms of oncological and functional outcomes.

The aim of this study was to evaluate the outcome of patients with non-resectable colorectal peritoneal metastases (CPM) treated with pressurized intraperitoneal aerosol chemotherapy (PIPAC).

We conducted an analysis of a prospective single-center database of all CPM patients who underwent PIPAC with oxaliplatin 92 mg/m² body surface (PIPAC-Ox). The outcome criteria were adverse events (Common Terminology Criteria for Adverse Events version 4.0), Peritoneal Regression Grading Score (PRGS), and survival.

Overall, 102 patients with a median age of 64 years (33-88) were scheduled for PIPAC-Ox. Access to the abdominal cavity for the first application failed in 22/102 (21.6%) patients. A total of 185 PIPACs were performed, with 26/102 (25.5%), 20/102 (19.6%), 17/102 (16.7%), and 17/102 (16.7%) patients undergoing one, two, three, and four or more PIPACs, respectively. Perioperative overall morbidity/mortality Grade I-V occurred in 14 (7.6%), 29 (15.8%), 6 (3.2%), 1 (0.5%), and 1 (0.5%) patient without significant differences between each cycle. Of 27 patients who underwent three or more PIPACs, 20/102 (19.6%) had major/complete CPM regression (PRGS 1-2). In a multivariate analysis, independent predictive factors for > 12 months' survival following the first PIPAC-Ox administration were three or more PIPACs (odds ratio [OR] 4.5, 95% confidence interval [CI] 1.35-15.2; p = 0.014) and younger patient age (OR 1.058, 95% CI 1.00-1.12; p = 0.039).

Repetitive PIPAC-Ox for CPM patients, alone or combined with perioperative systemic chemotherapy, is feasible. Our data suggest that three or more consecutive PIPAC-Ox cycles for advanced CPM can improve survival.

The peritoneal cancer index (PCI) is one of the strongest prognostic factors in patients undergoing cytoreductive surgery (CRS) for colorectal peritoneal metastases. Using pathological evaluation, however, the disease extent differs in a large proportion of patients. Our aim was to study the correlation between the radiological (rPCI), surgical (sPCI) and pathological (pPCI) PCI in order to determine factors affecting the discordance between these indices and their potential therapeutic implications.

From July 2018 to December 2019, 128 patients were included in this study. The radiological, pathological and surgical findings were compared. A protocol for pathological evaluation was followed at all centres.

All patients underwent a CT scan and 102 (79.6%) had a peritoneal MRI. The rPCI was the same as the sPCI in 81 (63.2%) patients and the pPCI in 93 (72.6%). Concordance was significantly lower for moderate-volume (sPCI 13-20) and high-volume (sPCI > 20) disease than for low-volume disease (sPCI 0-12) (P < 0.001 for sPCI; P = 0.001 for pPCI). The accuracy of imaging in predicting presence/absence of disease upon pathological evaluation ranged from 63% to 97% in the different regions of the PCI. The pPCI concurred with the sPCI in 86 (68.8%) patients. Of the nine patients with sPCI > 20, the pPCI was less than 20 in six.

The rPCI and sPCI both concurred with pPCI in approximately two thirds of patients. Preoperative evaluation should focus on the range in which the sPCI lies and not its absolute value. Radiological evaluation did not overestimate sPCI in any patient with high/moderate-volume disease. The benefit of CRS in patients with a high r/sPCI (> 20) who respond to systemic therapies should be prospectively evaluated.

Patients undergoing cytoreductive surgery for colorectal peritoneal metastases who have a pathologic complete response (pCR) to neoadjuvant chemotherapy experience a significantly longer survival than those with residual disease. This response is known only after surgery. This study aimed to examine clinical and radiologic predictors of a pCR.

From July 2018 to December 2019, the study prospectively enrolled 120 patients. The clinical and radiologic findings were compared between patients with and without a pCR. A protocol for pathologic evaluation was followed.

A pCR was observed in 34 patients (28.3%). Receiver operating characteristic (ROC) curves showed that patients with a surgical Peritoneal Cancer Index (sPCI) of 3 or lower had an 80% probability of experiencing a pCR, and that patients with a radiologic PCI (rPCI) of 2 or lower had a 70% probability of experiencing a pCR. A pCR was correctly predicted for 47% of the patients by imaging and for 44.4% of the patients by surgical evaluation. The site of primary tumor, the timing of peritoneal metastasis (PM), histology, tumor marker positivity, and mutations in known poor prognostic genes (KRAS) did not differ between the patients with and those without pCR. The primary tumor showed residual disease in 23.5% and regional nodes in 26.4% of the patients with pCR.

The rPCI and sPCI concurred with a pCR in less than 50% of the patients. The patients with a lower PCI had greater concordance. An sPCI of 3 or lower was predictive of a pCR in 80% of the patients. The impact of KRAS mutations on pCR should be evaluated in a larger series. The predictors of pCR and response to systemic chemotherapy should be incorporated in prognostic scores used to select patients for surgery.

Peritoneal metastases from colorectal cancer confer the worst survival among all metastatic sites. The adoption of cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) can offer selected patients with isolated colorectal peritoneal metastases (CRPM) a favourable long-term survival. There are numerous factors postulated to influence survival in patients undergoing CRS and HIPEC. The aim of this study was to identify the key perioperative prognostic factors that influence survival in patients undergoing CRS and HIPEC for isolated CRPM.

A systematic review and meta-analysis were conducted to evaluate prognostic factors influencing survival in patients undergoing CRS and HIPEC for isolated CRPM.

Thirty-three studies fitted the inclusion criteria for the systematic review, with 25 studies included in the meta-analysis. On pooled analysis, incomplete cytoreduction, increasing peritoneal carcinoma index (PCI) and lymph node involvement were significantly associated with a worse survival. Additionally, a rectal primary [hazard ratio (HR) 1.93, 95% CI 1.10-3.37], adjuvant chemotherapy (HR 0.71, 95% CI 0.54-0.93) and perioperative grade III/IV morbidity (HR 1.59, 95% CI 1.17-2.16) were also found to significantly influence survival. Notably, tumour differentiation and signet ring cell histology did not influence survival on pooled analysis.

This meta-analysis confirms that in patients undergoing CRS and HIPEC for isolated CRPM, incomplete cytoreduction, high PCI and lymph node involvement have a negative influence on survival. In addition, a rectal primary, adjuvant chemotherapy use and grade III/IV morbidity are important factors that also significantly influence survival.