Carcinomatosis Of Colorectal Cancer Research Articles

Expression of pH-Sensitive GPCRs in Peritoneal Carcinomatosis of Colorectal Cancer—First Results

Solid tumors have an altered metabolism with a so-called inside-out pH gradient (decreased pHe < increased pHi). This also signals back to tumor cells via proton-sensitive ion channels or G protein-coupled receptors (pH-GPCRs) to alter migration and proliferation. Nothing, however, is known about the expression of pH-GPCRs in the rare form of peritoneal carcinomatosis. Paraffin-embedded tissue samples of a series of 10 patients with peritoneal carcinomatosis of colorectal (including appendix) origin were used for immunohistochemistry to study the expression of GPR4, GPR65, GPR68, GPR132, and GPR151. GPR4 was just expressed weakly in 30% of samples and expression was significantly reduced as compared to GPR56, GPR132, and GPR151. Furthermore, GPR68 was only expressed in 60% of tumors and showed significantly reduced expression as compared to GPR65 and GPR151. This is the first study on pH-GPCRs in peritoneal carcinomatosis, which shows lower expression of GPR4 and GPR68 as compared to other pH-GPCRs in this type of cancer. It may give rise to future therapies targeting either the TME or these GPCRs directly.

Adipocytic Glutamine Synthetase Upregulation via Altered Histone Methylation Promotes 5FU Chemoresistance in Peritoneal Carcinomatosis of Colorectal Cancer.

The development of resistance to 5-fluorouracil (5FU) chemotherapy is a major handicap for sustained effective treatment in peritoneal carcinomatosis (PC) of colorectal cancer (CRC). Metabolic reprogramming of adipocytes, a component of the tumor microenvironment and the main composition of peritoneum, plays a significant role in drug resistance of PC, with the mechanisms being not fully understood. By performing metabolomics analysis, we identified glutamine (Gln), an important amino acid, inducing resistance to 5FU-triggered tumor suppression of CRC-PC through activating mTOR pathway. Noteworthily, genetic overexpression of glutamine synthetase (GS) in adipocytes increased chemoresistance to 5FU in vitro and in vivo while this effect was reversed by pharmacological blockage of GS. Next, we showed that methionine metabolism were enhanced in amino acid omitted from CRC-PC of GS transgenic (TgGS) mice, increasing intracellular levels of S-carboxymethy-L-cys. Moreover, loss of dimethylation at lysine 4 of histone H3 (H3k4me2) was found in adipocytes in vitro, which may lead to increased expression of GS. Furthermore, biochemical inhibition of lysine specific demethylase 1 (LSD1) restored H3k4me2, thereby reducing GS-induced chemoresistance to 5FU. Our findings indicate that GS upregulation-induced excessive of Gln in adipocytes via altered histone methylation is potential mediator of resistance to 5FU chemotherapy in patients with CRC-PC.

MANEJO DE LA CARCINOMATOSIS PERITONEAL DE ORIGEN COLORRECTAL Y REALIDAD EN PANAMÁ

RESUMEN &#x0D; Antecedentes &#x0D; El término carcinomatosis peritoneal fue utilizado por primera vez por Sampson en 1931 para describir la diseminación peritoneal de una neoplasia avanzada de ovario. Hoy el término carcinomatosis peritoneal incluye toda diseminación tumoral, local o masiva, que compromete la serosa peritoneal y las estructuras anatómicas vecinas. Un 30% a 40% de pacientes con carcinoma colorrectal van a desarrollar en algún momento metástasis, es decir 90 pacientes, de hecho la carcinomatosis peritoneal es la segunda presentación más común de la metástasis a distancia del cáncer de colon.&#x0D; Objetivo: Presentar la evidencia publicada sobre el abordaje y tratamiento quirúrgico de la carcinomatosis peritoneal de cáncer colorrectal en otras latitudes e impulsar el estudio, manejo y difusión de los conocimientos de la metástasis peritoneal principalmente a nivel nacional.&#x0D; Diseño: Se utilizaron artículos científicos indexados entre 2010 y 2020, que fueron seleccionados por su relevancia, validez y calidad de contenido, como aquellos disponibles en National Center for Biotechnology Information, Surgical Oncology Clinics of North America, Annals of Surgical Oncology, World Journal of Surgical Oncology obtenidas a través de diversas bibliotecas virtuales.&#x0D; Conclusión: La cirugía citorreductora en combinación con quimioterapia intraperitoneal hipertérmica ha mejorado la sobrevida global a los 5 años de 40 a 51% dando resultados prometedores en pacientes con carcinomatosis peritoneal de origen colorrectal altamente seleccionados e incluso se considera el único tratamiento potencialmente curativo.&#x0D; Palabras claves: carcinomatosis peritoneal, cáncer colorrectal, Cirugía citorreductora (CRS), quimioterapia intraperitoneal hipertérmica (HIPEC).

Cytoreductive surgery and HIPEC for malignant ascites from colorectal cancer - a randomized study.

Introduction:The efficacy of different timings of cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) in controlling malignant ascites caused by peritoneal carcinomatosis of colorectal cancer (CRC) is not well defined. The study aims to investigate the clinical efficacy and safety of different timings of CRS with HIPEC for malignant ascites caused by peritoneal carcinomatosis from CRC.Materials and Methods:This was a preliminary randomized controlled study performed at the Intracelom Hyperthermic Perfusion Therapy Center of the Cancer Hospital of Guangzhou Medical University (China) from December 2008 to December 2016. The patients were randomized to: CRS, followed by HIPEC (CRS+HIPEC; n = 14), and ultrasound-guided HIPEC, followed by CRS 1 to 2 weeks later (HIPEC+ delayed cytoreductive surgery (dCRS) group, n = 14). The endpoints were complete remission rate of ascites, successful complete CRS rate, and overall survival.Results:Malignant ascites in all patients showed complete remission; the total effective rate was 100%. Complete CRS was not feasible in any patient. The median follow-up of the 2 groups was 41.9 and 42.3 months in the CRS+HIPEC and HIPEC+dCRS groups, respectively. Overall survival was 14.5 (95%CI: 7–19 months) and 14.3 months (95%CI: 4–21 months) (P > .05). The adverse effects of HIPEC were manageable.Conclusions:CRS+HIPEC and HIPEC+dCRS have the same efficacy in controlling malignant ascites caused by CRC and peritoneal carcinomatosis. The timing of CRS and HIPEC does not prolong the survival of patients with peritoneal carcinomatosis from CRC, even when a complete CRS is not feasible.

Development and Validation of an Image-based Deep Learning Algorithm for Detection of Synchronous Peritoneal Carcinomatosis in Colorectal Cancer.

The aim of this study was to build a SVM classifier using ResNet-3D algorithm by artificial intelligence for prediction of synchronous PC. Adequate detection and staging of PC from CRC remain difficult. The primary tumors in synchronous PC were delineated on preoperative contrast-enhanced computed tomography (CT) images. The features of adjacent peritoneum were extracted to build a ResNet3D + SVM classifier. The performance of ResNet3D + SVM classifier was evaluated in the test set and was compared to routine CT which was evaluated by radiologists. The training set consisted of 19,814 images from 54 patients with PC and 76 patients without PC. The test set consisted of 7837 images from 40 test patients. The ResNet-3D spent only 34 seconds to analyze the test images. To increase the accuracy of PC detection, we have built a SVM classifier by integrating ResNet-3D features with twelve PC-specific features (P < 0.05). The ResNet3D + SVM classifier showed accuracy of 94.11% with AUC of 0.922 (0.912-0.944), sensitivity of 93.75%, specificity of 94.44%, positive predictive value (PPV) of 93.75%, and negative predictive value (NPV) of 94.44% in the test set. The performance was superior to routine contrast-enhanced CT (AUC: 0.791). The ResNet3D + SVM classifier based on deep learning algorithm using ResNet-3D framework has shown great potential in prediction of synchronous PC in CRC.

Indications for hyperthermic intraperitoneal chemotherapy with cytoreductive surgery: a clinical practice guideline.

The purpose of the present review was to provide evidence-based guidance about the provision of cytoreductive surgery (crs) with hyperthermic intraperitoneal chemotherapy (hipec) in the treatment of peritoneal cancers. The guideline was developed by the Program in Evidence-Based Care together with the Surgical Oncology Program at Ontario Health (Cancer Care Ontario) through a systematic review of relevant literature, patient- and caregiver-specific consultation, and internal and external reviews. Recommendation 1a: For patients with newly diagnosed stage iii primary epithelial ovarian or fallopian tube carcinoma, or primary peritoneal carcinoma, hipec should be considered for those with at least stable disease after neoadjuvant chemotherapy at the time that interval crs (if complete) or optimal cytoreduction is achieved. Recommendation 1b: There is insufficient evidence to recommend the addition of hipec when primary crs is performed for patients with newly diagnosed advanced primary epithelial ovarian or fallopian tube carcinoma, or primary peritoneal carcinoma, outside of a clinical trial. Recommendation 2: There is insufficient evidence to recommend hipec with crs in patients with recurrent ovarian cancer outside the context of a clinical trial. Recommendation 3: There is insufficient evidence to recommend hipec with crs in patients with peritoneal colorectal carcinomatosis outside the context of a clinical trial. Recommendation 4: There is insufficient evidence to recommend hipec with crs for the prevention of peritoneal carcinomatosis in colorectal cancer outside the context of a clinical trial; however, hipec using oxaliplatin is not recommended. Recommendation 5: There is insufficient evidence to recommend hipec with crs for the treatment of gastric peritoneal carcinomatosis outside the context of a clinical trial. Recommendation 6: There is insufficient evidence to recommend hipec with crs for the prevention of gastric peritoneal carcinomatosis outside the context of a clinical trial. Recommendation 7: There is insufficient evidence to recommend hipec with crs as a standard of care in patients with malignant peritoneal mesothelioma; however, patients should be referred to hipec specialty centres for assessment for treatment as part of an ongoing research protocol. Recommendation 8: There is insufficient evidence to recommend hipec with crs as a standard of care in patients with disseminated mucinous neoplasm in the appendix; however, patients should be referred to hipec specialty centres for assessment for treatment as part of an ongoing research protocol.

The role of the peritoneal microenvironment in the pathogenesis of colorectal peritoneal carcinomatosis

Recent insights have implicated mesothelial-to-mesenchymal transition (MMT) as a mechanism by which mesothelial cells can transdifferentiate into cancer-associated fibroblasts (CAFs) in several cancers metastasizing to the peritoneum. However, this was not evaluated extensively in colorectal cancer. We examined the presumed mesothelial origin of CAFs in three types of colorectal carcinoma: conventional type adenocarcinoma, mucinous carcinoma and signet ring cell carcinoma. We evaluated the expression of mesothelial, mesenchymal, angiogenesis and colorectal cancer-related markers in peritoneal samples of twelve colorectal cancer patients with peritoneal carcinomatosis and four control patients by immunohistochemistry. We observed morphological and immunohistochemical changes in the vicinity of tumor implants in all studied colorectal cancer types. Mesothelial cells acquired a spindle-shaped myofibroblast-like morphology, lost expression of mesothelial markers, and gained expression of mesenchymal markers. Analysis of consecutive tissue sections and double staining for mesothelial and mesenchymal markers revealed overlap in expression of mesothelial and CAF markers. These findings are highly suggestive of a mesothelial origin of CAFs in peritoneal carcinomatosis in colorectal cancer. Interfering with the process of MMT might be a valuable approach in treating and preventing peritoneal carcinomatosis. Differences observed between colorectal cancer types suggest that one single strategy might not be applicable.

A computed tomography-based nomogram for preoperative prediction of synchronous peritoneal carcinomatosis in colorectal cancer.

14 Background: Peritoneal carcinomatosis (PC) of colorectal cancer remain poor and is considered to be the terminal stage. Early detection of PC can bring survival benefit for chances of complete cytoreductive surgery. In this study, we have developed and validated a CT-based nomogram for preoperative prediction of synchronous PC in CRC. Methods: The CT-based nomogram optimized for image classification of PC was developed and validated in a large cohort. The specific features of synchronous PC were extracted from preoperative CT arterial stage scans by radiologists. A CT-based model was constructed by Boruta algorithm and multivariate logistic regression in the training set and validated in the test set. A CT-based nomogram was then built to predict the risk value of PC. The performance and efficacy of this nomogram to discriminate PC were assessed. Results: A total of 170 eligible CRC patients with synchronous PC were randomly divided into a training set (n = 92) and a validation set (n = 78). After processing and partition, five items of PC-related features including tumor location, cT stage, distant metastasis, thickened greater omentum and pelvic nodules were enrolled into this CT-based model. In the training set, the ROC shows AUC of CT-based model was 0.929(95% CI: 0.764-0.946). The sensitivity was 73.2% and the specificity was 98.3%. The positive predictive value (PPV) was 82.26%, while the negative predictive value (NPV) was 100%. In the test set, AUC by the ROC was 0.855(95% CI: 0.764-0.946). The sensitivity of CT-based model was 72.7% and the specificity was 93.3%. The PPV was 82.35%, while the NPV was 88.89%. These results show high predicted accuracy of CT-based model in diagnosis of synchronous PC both in the training set and test set. A nomogram based on these five preoperative predictors of PC was created. This CT-based nomogram showed good diagnostic performance by calibration curve. The decision curves analysis revealed high benefit of this CT-based nomogram in clinical decision. Conclusions: The CT-based nomogram has shown great potential in the detection and diagnosis of synchronous peritoneal metastasis in colorectal cancer.

The Accuracy of The Clinical Peritoneal Cancer Index in Patients with Peritoneal Carcinomatosis of Colorectal Cancer

Background: The Peritoneal Cancer Index (PCI) and completeness of cytoreduction are important prognostic factors in patients with peritoneal carcinomatosis from colorectal cancer, undergoing cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS-HIPEC). The PCI is determined during laparotomy by an experienced surgeon before the decision is made to ‘do’ or ‘do not’ proceed with CRS-HIPEC. The aim of this study is to determine the accuracy of the clinical PCI score (cPCI), by comparing the cPCI with the pathological PCI (pPCI) score.

Dedicated MR Imaging vs Surgical Staging of Peritoneal Carcinomatosis in Colorectal Cancer

Dedicated MR Imaging vs Surgical Staging of Peritoneal Carcinomatosis in Colorectal Cancer

Is ascites CEA a risk factor for peritoneal carcinomatosis in colorectal cancer?: a long-term follow-up study.

Our previous study reported that carcinoembryonic antigen (CEA) levels in peritoneal fluid were significantly correlated with the prevalence of peritoneal carcinomatosis (PC) in colorectal cancer (CRC). The purpose of this study was a long-term follow up of the author's previous study, as well as the identification of correlations with the known risk factors of PC and the comparison of the predictive power of PC in CRC. A total of 495 patients without PC who underwent CRC operations at St. Mary's Hospital, The Catholic University of Korea, from January 2006 to November 2014 were included in this study. Tumor markers of peritoneal fluid sampled at the beginning of each operation were prospectively analyzed and compared with the known risk factors for PC in CRC. Multivariate analysis of PC revealed that T4 cancer (OR 5.143, 95% CI 1.400-18.897, p = 0.014), T3 mucinous cancer (OR 17.480, 95% CI 1.577-193.714, p = 0.020), obstructed tumors (OR 6.030, 95% CI 1.627-22.343, p = 0.007), and peritoneal fluid CEA above 5 ng/dl (OR 4.073, 95% CI 1.315-12.615, p = 0.015) were significant risk factors. T4 cancer, obstructed tumors, and peritoneal fluid CEA above 5 ng/dl showed correlations with cancer-free survival. Generally, higher CEA levels in peritoneal fluid were correlated with previously known risk factors for PC in CRC. Peritoneal fluid CEA has predictive value for PC and prognostic value in CRC. Therefore, we recommend routinely performing ascites CEA analysis in colorectal cancer surgery.

586P - The accuracy of the clinical PCI score in patients with peritoneal carcinomatosis of colorectal cancer

BackgroundThe Peritoneal Cancer Index (PCI) and completeness of cytoreduction are important prognostic factors in patients with peritoneal carcinomatosis from colorectal cancer, undergoing cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS-HIPEC). The PCI is determined during laparotomy by an experienced surgeon before the decision is made to ‘do’ or ‘do not’ proceed with CRS-HIPEC. The aim of this study is to determine the accuracy of the clinical PCI score (cPCI), by comparing the cPCI with the pathological PCI (pPCI) score. MethodsAll consecutive patients who underwent CRS-HIPEC for peritoneal carcinomatosis from colorectal origin between February 2015 and June 2018 where identified. Relevant patient- and tumor related characteristics were collected. ResultsIn total 119 patients were included in this study; 60 males (50.4%). Median age was 64 years [IQR 55-71]. The pPCI was lower than the cPCI score in 80 patients (67.2%), the score was equal in 38 patients (31.9%), and in 1 patient (0.8%) the pPCI was higher than the cPCI. The median total cPCI 11 (IQR 6-16) was significantly higher than the median pPCI, (pPCI=8, IQR 3-13, p<0.001). In 21 patients (17.6%) the cPCI was overestimated ≥5 points. When patients were divided in different PCI categories, 0-5, 6-10, 11-15, ≥16 respectively, 39 patients (32.8%) moved to a lower pPCI category with corresponding better median survival rates. ConclusionsClinical determination of the PCI often results in overestimation of the score. Far-reaching consequences are tied to the macroscopic evaluation of the cPCI by the surgeon, but this evaluation is not very reliable. Further research is warranted to determine whether the pPCI is a better scoring method/more precise prognostic factor for oncological outcomes after CRS-HIPEC. Legal entity responsible for the studyThe authors. FundingHas not received any funding. DisclosureAll authors have declared no conflicts of interest.

Peritoneal carcinomatosis in colorectal cancer: Defining predictive factors for successful cytoreductive surgery and hyperthermic intraperitoneal chemotherapy – A pilot study

BackgroundPeritoneal carcinomatosis originating from colorectal cancer (PC-CRC) carries a dismal prognosis. Cytoreductive surgery (CRS) combined with hyperthermic intraperitoneal chemotherapy (HIPEC) have been offered to those patients with substantial health and economic burden, nevertheless not all patients are fitting this treatment modality and outcome is generally still poor. ObjectiveTo elicit predictive factors associated with the success of CRS and HIPEC in PC-CRC patients. Patients and methodsThis is a pilot study including 30 consecutive patients with PC-CRC; 20 of them (66.7%) presented with metachronous peritoneal disease. All patients were planned for CRS and HIPEC with Mitomycin-C after receiving preoperative systemic chemotherapy for 3 months. ResultsOn exploration, CRS and HIPEC were successful in 17 patients (56.6%) who had completeness of cytoreduction score 0–1 (CC-0/1), whereas failure (CC-2) was encountered in 13 patients (43.3%). The presence of ascites, extensive peritoneal disease (PCI > 20) was significantly correlated with failure to achieve CRS and HIPEC (p < 0.001); also, the primary rectal site showed a trend towards significance (p = 0.08). The cumulative overall survival (OS) and progression-free survival (PFS) at 2 years were 66.6 and 62.6%, respectively. Patients who achieved CC-0/1 had significantly prolonged OS compared to CC-2 (p < 0.001). On multivariate analysis, the CC score and the original site were independent prognostic factors for OS (p = 0.04 and 0.02, respectively). ConclusionIn patients with PC-CRC, malignant ascites and PCI > 20 are poor prognostic factors associated with failure to accomplish CRS with consequent poor survival.

Murine Models of Intraperitoneal Perfusion for Disseminated Colorectal Cancer

BackgroundReproduction of the perfusion used in therapy (hyperthermic intraperitoneal chemotherapy) procedures preclinically represents a valuable asset for investigating new therapeutic agents that may improve patient outcomes. This article provides technical descriptions of our execution of closed and open “coliseum” abdominal perfusion techniques in a mouse model of peritoneal carcinomatosis of colorectal cancer. Materials and MethodsBALB/c mice presenting with disseminated colorectal cancer (CT26-luciferin cells) underwent 30-min perfusions mimicking either the closed perfusion or the coliseum perfusion technique. Disease burden was monitored by bioluminescence signaling using an in vivo imaging system. Perfusion circuits consisted of single inflow lines with either a single or dual outflow line. ResultsTwelve mice presenting with disseminated disease underwent the closed perfusion technique. Surgical complications included perfusate leakage and organ constriction/suction into the outflow line(s). Nine mice underwent the coliseum perfusion technique with surgical debulking, using bipolar cauterization to remove tumors attached to the peritoneum. All mice survived the coliseum perfusion with limited intraoperative complications. ConclusionsFewer intraoperative complications were experienced with our coliseum perfusion technique than the closed perfusion. The methods described here can be used as a guideline for developing future perfusion murine models for investigating perfusion models useful for delivery of chemotherapy or other tumor-sensitization agents, including selective targeted agents, nanoparticles, and heat.

Leptomeningeal Carcinomatosis in Colorectal Cancer: The Mayo Clinic Experience

BackgroundLeptomeningeal metastasis (LM) is an uncommon form of metastatic disease in many cancers. There remains a paucity of literature with regard to the course and management of LM in colorectal cancers (CRCs). The aim of this study was to estimate the incidence of LM in patients with CRC seen at our institution over a 15-year period, and to describe the clinical course and outcome of these cases. MethodsLM in CRC primary cases between 2000 and 2014 were identified in the Mayo Clinic databases. The charts were retrospectively reviewed. ResultsOf 17,095 CRC primaries, we identified 10 patients with LM (0.058%) in this 15-year period. Nine cases were included in the analysis. Four had metastatic disease at the time of their initial CRC diagnosis. Median overall survival after CRC diagnosis was 25.7 months (range, 4.7-74.8 months). Median time to diagnosis of LM after CRC diagnosis was 25.3 months (range, 0-68.1 months). All patients had magnetic resonance imaging findings consistent with LM: 3 patients with spinal LM, 5 patients with intracranial LM, and 1 with both. Neurologic symptoms correlated with site of the lesions, with headache, cranial nerve palsy, lower extremity weakness, and gait disturbance among the most frequently reported. However, not all patients had neurologic findings, with LM lesions found incidentally in 2 cases. Seven patients (78%) had palliative radiotherapy for LM. Three patients continued to receive systemic chemotherapy after diagnosis of LM. Median survival after LM diagnosis was 7 weeks (range, 2-39 weeks). ConclusionsLM is an exceedingly rare development in the natural course of CRC. It confers a poor prognosis with limited treatment options. At our institution, most patients had their disease addressed by palliative means, with many receiving radiotherapy to control their neurologic symptoms. Based on our series, supportive care remains a sensible approach to the management of LM in CRC.

Safety of intraperitoneal Mitomycin C versus intraperitoneal oxaliplatin in patients with peritoneal carcinomatosis of colorectal cancer undergoing cytoreductive surgery and HIPEC

BackgroundColorectal peritoneal carcinomatosis (PC) is commonly treated with cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC). There is an ongoing international debate about which intraperitoneal chemotherapeutic agent is preferred, Mitomycin C (MMC) or oxaliplatin. We questioned whether the type of chemotherapeutic agent influenced postoperative complication rates or short-term survival. MethodsIn this retrospective cohort study patients with colorectal PC who underwent CRS-HIPEC between January 2010 and December 2016 were included. Until March 2014 patients had preferentially been treated with MMC and thereafter with oxaliplatin in an iso-osmotic glucose/electrolyte dialysis (Dianeal®) carrier solution. Main outcomes were postoperative complications, disease free survival (DFS) and overall survival (OS). Survival analyses and multivariable analyses were performed. ResultsOne hundred four patients received MMC and 73 patients oxaliplatin. Postoperative complications did not differ between groups (44.2% (MMC) versus 43.8% (oxaliplatin); P = 0.958). Median DFS was 12.5 months (IQR 6.4–32.4) in the MMC-group and 13.1 months (IQR 6.1-NA) in the oxaliplatin-group (P = 0.669). Median OS was 37.2 months (IQR 17.2-NA) in the MMC-group and 29.4 months (IQR 17.0-NA) in the oxaliplatin-group (P = 0.764). The type of chemotherapeutic agent did not influence OS in multivariable analysis (oxaliplatin versus MMC HR 1.09 (95%CI 0.58–2.06)). The HIPEC-phase was shorter for oxaliplatin (median 32 (IQR 31–34) versus 91 min (IQR 90–92) for MMC (P < 0.001)). ConclusionIntraperitoneal oxaliplatin reduced the chemoperfusion time when compared to intraperitoneal MMC without adversely influencing complication rates or short-term survival. It may therefore be the preferential drug in CRS-HIPEC procedures for colorectal PC.

External Validation of the Prognostic Nomogram (COMPASS) for Patients with Peritoneal Carcinomatosis of Colorectal Cancer.

To optimize outcome, selection of patients for cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) is critical. Recently, Simkens et al.7 evaluated the peritoneal surface disease severity score (PSDSS) and suggested a new prognostic nomogram, the colorectal peritoneal metastases prognostic surgical score (COMPASS) based on age, peritoneal carcinomatosis index score, locoregional lymph node status, and signet ring cell histology. This COMPASS nomogram had better discriminative ability according to the Harrell c-index than PSDSS (c=0.72 vs. 0.62). This study aimed to validate the COMPASS nomogram externally. Data were retrieved from a prospectively maintained database, and all patients who underwent surgery between May 2005 and May 2016 were included in the study. For each patient, the PSDSS and COMPASS were calculated and then divided into subgroups. The discriminative ability of both scores for overall survival were quantified using Harrell c indices. A total of 153 patients underwent CRS+HIPEC for peritoneal carcinomatosis (PC) of colorectal cancer. The median overall survival (OS) was 46months, and the mean PSDSS was 7.8±3.7. When the PSDSS was divided into subgroups, the c index was 0.67. The mean COMPASS was 55.5±25.6. When the patients were divided into four groups according to cutpoints of Simkens et al.7 a c index of 0.72 was obtained, showing its significant superiority over the discriminative ability of the PSDSS (p=0.016). External validation of the COMPASS confirms its moderate to good discriminative ability and its superiority over the PSDSS. Nevertheless, discrimination with the COMPASS score remains suboptimal, and further research on prognostic variables is essential for optimal patient selection.

Treatment of peritoneal carcinomatosis with hyperthermic intraperitoneal chemotherapy in colorectal cancer.

The peritoneum is the second most common site of metastasis after the liver and the only site of metastatic disease in approximately 25% of patients with colorectal cancer (CRC). In the past, peritoneal carcinomatosis in CRC was thought to be equivalent to distant metastasis; however, the transcoelomic spread of malignant cells is an acknowledged alternative pathway. Metastasectomy with curative intent is well accepted in patients with liver metastasis in CRC despite the paucity of randomized trials. Therefore, there is rationale for local treatment with peritonectomy to eliminate macroscopic disease, followed by hyperthermic intraperitoneal chemotherapy to destroy any residual free tumour cells within the peritoneal cavity. The aim of this paper is to summarize the current evidence for cytoreduction and hyperthermic intraperitoneal chemotherapy in the treatment of peritoneal carcinomatosis in CRC.

Preoperative intraperitoneal oxaliplatin for unresectable peritoneal carcinomatosis of colorectal origin: a pilot study.

Peritoneal carcinomatosis in colorectal cancer is an advanced stage of the disease where improved survival can be attained whenever the resection associated with hyperthermic intreperitoneal chemotherapy is possible. In unresectable cases, systemic chemotherapy is administered to obtain conversion to resectability but results have not yet been clearly evaluated. Local chemotherapy in this setting has been proven useful in several similar situations. The aim of the present pilot study was to evaluate the feasibility of pre-operative intraperitoneal chemotherapy with oxaliplatin in these patients. Six patients with unresectable peritoneal disease of colorectal origin were included in the study. An intraperitoneal implantable chamber catheter was inserted during the laparotomy that evaluated the extent of the peritoneal disease (peritoneal carcinomatosis index 25 to 39). Patients then underwent intraperitoneal chemotherapy with oxaliplatin 85 mg/m2 in combination with systemic chemotherapy (FOLFIRI or simplified LV5FU) and a targeted therapy every 2 weeks. Two catheter perfusion incidents were reported due to the abdominal wall thickness. Two patients completed the four intraperitoneal (IP) chemotherapy cycles without major toxicity. One patient developed grade 3 or 4 diarrhea requiring a short intensive care unit (ICU) stay, though it is not clear whether the event was induced by intravenous irinotecan, IP oxaliplatin or the combination of both. Grade 3 fatigue and abdominal pain were also recorded. For one patient with aggressive disease, best supportive care was initiated after the first course of chemotherapy. Our study is the first to assess intraperitoneal oxaliplatin-based chemotherapy in the preoperative setting for patients with unresectable peritoneal metastases. The tolerance was acceptable for 85 mg/m2 IP oxaliplatin combined with systemic therapy in these patients. Our results justify carrying on with a phase I/II trial to determine the recommended dose of oxaliplatin in this clinical context and its efficacy.

Peritoneal carcinomatosis of colorectal cancer is characterized by structural and functional reorganization of the tumor microenvironment inducing senescence and proliferation arrest in cancer cells

GRAPHICAL ABSTRACTIllustration 1. Overview of immune response in primary CRC and PC.