Colorectal Origin Research Articles

Controversies around the treatment of peritoneal metastases of colorectal cancer.

In this editorial we examine the article by Wu et al published in the World Journal of Gastrointestinal Oncology. Surgical resection for peritoneal metastases from colorectal cancer (CRC) has been gradually accepted in the medical oncology community. A randomized trial (PRODIGE 7) on cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) failed to prove any benefit of oxaliplatin in the overall survival of patients with peritoneal metastases from colorectal origin. Nevertheless, isolated systemic chemotherapy for CRC stage IV has demonstrated a reduced response in peritoneal metastases than that obtained in other metastatic sites such as the liver. Another tool is required in those patients to achieve more local control of the disease. Surgical groups in peritoneal surgery continue to use HIPEC in their procedures, using other agents than oxaliplatin for peritoneal cavity infusion, such as mitomycin C. These patients present with complex surgical issues to manage, and consequently a large burden of complications has to be anticipated. Therefore, identifying patients who will benefit from CRS with or without HIPEC would be of great interest.

Prognostic Value of Immune Scoring System for Colorectal Cancer Patients with Peritoneal Metastasis.

Background and Objectives: There is no reliable immune scoring system that can help us predict the postoperative outcomes of colorectal cancer patients with peritoneal metastases after cytoreductive surgery. In this cohort, the aims were (1) to evaluate the postoperative morbidity, mortality and surgical oncological outcomes in colorectal cancer patients with peritoneal metastasis; (2) to compare oncological and postoperative outcomes of colon cancer patients with peritoneal metastasis and rectal cancer patients with peritoneal metastasis; and (3) to assess the prognostic value of the modified Glasgow Prognostic Score (mGPS) and the CRP-albumin ratio (CAR). Materials and Methods: A prospectively maintained database of 258 patients who underwent cytoreductive surgery for peritoneal metastases of colorectal origin between 2007 and 2024 was analyzed. According to the anatomical location of the primary tumor, two different groups were created: rectum cancer patients with peritoneal metastasis (Group A) and colon cancer patients with peritoneal metastasis (Group B). All standard clinico-pathological characteristics, operative findings, morbi-mortality results, and final oncologic outcomes were compared between Groups A and B. We evaluated whether CAR and mGPS could predict postoperative morbi-mortality and overall survival in the two groups or not. Results: No significant difference was detected between Groups A and B in terms of clinical-demographic characteristics. In both groups, the preoperative mGPS and CAR values were statistically significantly higher in those who developed postoperative high-grade complications (C-D grade III/IV) (p < 0.001) and those who died perioperatively (p = 0.001 and p = 0.002). Conclusions: In multivariate Cox analysis, the CAR was found to be an independent prognostic factor for overall survival in this cohort. CAR and mGPS predicted high-grade complications and postoperative mortality in both groups.

Correlation between the histopathological growth patterns of pulmonary and liver metastases of colorectal origins

Correlation between the histopathological growth patterns of pulmonary and liver metastases of colorectal origins

Peritoneal Cell-Free DNA, and microRNAs, for Personalized Treatment in Peritoneal Carcinomatosis of Colorectal Origin: A Multicentric Study Proposal

Peritoneal Cell-Free DNA, and microRNAs, for Personalized Treatment in Peritoneal Carcinomatosis of Colorectal Origin: A Multicentric Study Proposal

EPID-27. THE INCIDENCE OF BRAIN METASTASIS IN GASTROINTESTINAL CANCER ACCORDING TO PRIMARY SITE AND STAGE: A 15-YEAR SINGLE INSTITUTIONAL ANALYSIS

Abstract Gastrointestinal (GI) cancers are a diverse group of cancers including pancreatic, gastric/gastroesophageal junction/esophageal (G/GEJ/E), colorectal (CRC), hepatocellular (HCC), biliary tract (BT), and anal origin cancers. The risk of developing brain metastasis (BrM) is not well characterized. The aim was to determine the incidence of BrM among all GI cancer patients at Princess Margaret Hospital (PM). We included patients diagnosed with GI cancer presenting from 2005-2020, captured prospectively in our institutional registry. These patients were cross-referenced with our radiotherapy database, where radiotherapy for brain metastases (BrM) was used as a proxy for the brain metastases development. Cumulative incidences (CI) of BrM diagnoses were calculated using death as a competing risk. Overall survival (OS) was estimated using the Kaplan Meier method. The registry accounted for 22,188 patients. The median age of the cohort was 64. Most common primary sites are CRC adenocarcinoma, pancreatic adenocarcinoma, G/GEJ/E adenocarcinoma were 31.52%/11.71%/10.25%. The 15-year CI for BrM for the entire cohort was 1.65%, and for CRC, small bowel, anal, pancreatic, G/GEJ/E, HCC, and BT cancers were 2.69%/2.49%/1.30%/0.5%/3.52%/ 0.05% /0.4% (p &amp;lt; 0.001) and Stage I-IV disease were 0.39%/0.81%/1.2%/3.1%, respectively (p &amp;lt; 0.001). 5 year CI for HER2 positive G/GEJ/E patients was 19.5%. Median OS from initial presentation for those with BrM was 25.13 months. On univariable analysis, chemotherapy receipt [HR 1.916, p &amp;lt; 0.001], Stage IV at presentation [HR 3.991, p &amp;lt; 0.001], and G/GEJ/E primary [HR 1.357, p &amp;lt; 0.001] predicted for higher risk of BrM. Multivariable analysis confirmed that receipt of chemotherapy and Stage IV disease predicted a higher risk for BrM and pancreatic, HCC, and BT cancers predicted for lower BrM. We observed that among patients diagnosed with GI cancers, Stage IV disease predicted higher risk for developing BrM and were more likely to receive chemotherapy.

Pressurized Intraperitoneal Aerosol Chemotherapy for Peritoneal Carcinomatosis in Colorectal Cancer Patients: A Systematic Review of the Evidence.

Pressurized intraperitoneal aerosol chemotherapy (PIPAC) consists of the administration of aerosolized chemotherapy into the abdominal cavity of patients suffering from peritoneal carcinomatosis. Our aim was to review the evidence supporting PIPAC in patients with peritoneal carcinomatosis from colorectal cancer. A systematic review was performed in accordance with the 2020 PRISMA guideline. MEDLINE and CENTRAL were searched using combinations of terms including "Peritoneal carcinomatosis", "Peritoneal metastasis", "PIPAC", "Pressurized intraperitoneal aerosol chemotherapy" and "Colorectal cancer". Original studies, in English, including patients treated with PIPAC for colorectal peritoneal carcinomatosis, were considered eligible. Case reports, non-English or French language articles and secondary analyses were excluded. A total of 385 articles were screened and 374 articles were excluded, leaving 11 publications for inclusion in the qualitative analysis. The included studies totalized 949 patients who received PIPAC for peritoneal carcinomatosis due to colorectal cancer. The median peritoneal carcinomatosis index (PCI) ranged from 10 to 31. In all studies, the complete PIPAC protocol was achieved with an average of two to three 3 PIPAC sessions per patient. Oxaliplatin (OX) was used as a chemotherapeutic agent in all studies and could be associated with intravenous 5-FU and leucovorin. Most post-operative adverse events were recorded as mild to moderate with no intraoperative complications. Only four studies reported a decrease in the average PCI score for 50% of the patients. Median overall survival ranged from 8 to 37.8 months. Quality of life indicators were stable between PIPAC-OX cycles with a small but not statistically significant trend of improvement of most functional scales. PIPAC for peritoneal carcinomatosis from colorectal origin is feasible, safe and tolerable. Its impact on survival outcomes or quality of life remains to be demonstrated by randomized trials.

Results of complete cytoreductive strategy in patients with peritoneal metastases of colorectal origin with or without extraperitoneal metastases: A bicentric analysis

BackgroundIncreased survival can be achieved in patients with colorectal cancer peritoneal metastases (CRPM) treated with cytoreductive surgery. The benefit of this strategy remains uncertain when CRPM are associated with extraperitoneal metastases (EPM). The aim of this study was to compare short- and long-term outcomes of patients treated with CRS for CRPM, with or without EPM. MethodsThis study included 413 consecutive patients who underwent CRS for CRPM: 120 with EPM (EPM+) and 293 without (EPM-). Patients with isolated ovarian metastases were included in EPM-group (n = 83). ResultsEPM were mainly located to the liver (66 %,n = 79), retroperitoneal lymph nodes (33 %,n = 40); less frequently to the spleen (9 %,n = 12), lung (9 %,n = 10) or pleura (1 %,n = 1). Ovarian metastases were present in 126 patients (83 in EMP-, 43 in EPM+). Peritoneal carcinomatosis index (PCI) was similar in EPM- (8 [4–14]) and EPM+ (8 [3–13],p = 0.335) groups, as postoperative mortality (3 % vs 3 %,p = 1) and major morbidity rates (28 % vs 35 %,p = 0.223). Median overall survival (mOS) and disease-free survival were significantly higher in the EPM-group (58m vs 39m, and 16m vs 10m,p = 0.003). We highlighted 3 prognostic groups 1) EPM-with PCI<10 (mOS 93m), 2) EPM+ with PCI<10 (mOS 57m), 3) EPM-with 10<PCI<15 (mOS 35m) or EPM+ with 10<PCI<15 (mOS 31m) or PCI>15 regardless EPM (mOS 26m, p < 0.001). ConclusionComplete cytoreductive surgery seems to be feasible in patients with EPM, without increase in postoperative morbidity and mortality compared to patients without EPM. This strategy provides prolonged survival in selected patients with limited peritoneal metastases from colorectal cancer.

PIPAC Pharmacologic and Clinical Data.

Pressurized intraperitoneal aerosol chemotherapy (PIPAC) emerged as an innovative intraperitoneal chemotherapy delivery system to overcome the issue of limited efficacy of systemic therapies to induce response in peritoneal malignancies. Promising results for patients with mesothelioma peritonei and peritoneal metastasis from gastric, ovarian, colorectal, pancreatic, and hepatobiliary tumors origin are changing the landscape for patients otherwise just facing palliative treatment. Ongoing trials will shed more light on the actual benefits of PIPAC.

Utility of SATB2 and MOC-31 Immunostains to Distinguish Between Poorly Differentiated Rectal Adenocarcinoma and Anal Squamous Cell Carcinoma.

Colorectal adenocarcinoma and squamous cell carcinoma (SCC) can arise in the anorectum and present a significant diagnostic challenge when poorly differentiated. Accurate diagnosis can significantly influence management, as the treatments for these conditions involve distinct neoadjuvant chemoradiotherapy regimens. MOC-31 and SATB2 have been utilized as specific markers of glandular differentiation and colorectal origin, respectively, but studies have shown that they may be positive in squamous cell carcinoma of other sites. This raises the concern that MOC-31 and SATB2 may be positive in squamous cell carcinoma of the anorectum, and overreliance on these stains may be a potential diagnostic pitfall in differentiating rectal poorly differentiated adenocarcinoma (PDA) from anal nonkeratinizing SCC. We identified biopsies from 10 rectal PDA and 17 anorectal nonkeratinizing SCC cases and stained them for MOC-31 and SATB2. We found that MOC-31 was highly sensitive, being positive in 10/10 cases of rectal PDA, but not specific, as it was also positive in 11/17 SCC cases. In contrast, SATB2 was both sensitive, with positive staining in 10/10 rectal PDA cases, and specific, with negative staining in 17/17 SCC cases. This includes equivocal staining in 4 of these negative SCC cases. MOC-31 had a sensitivity of 100% and specificity of 35.3%, while SATB2 had a sensitivity of 100% and specificity of 100%. Unlike squamous mucosa of the head and neck, and esophagus, SCC of the anus does not frequently stain positively for SATB2. These data suggest that SATB2 is a reliable marker in distinguishing rectal PDA from anorectal nonkeratinizing SCC, whereas MOC-31 is commonly positive in SCC of the anus. It is also important to note that equivocal SATB2 staining may be seen in SCC.

Pelvic Exenteration in Advanced, Recurrent or Synchronous Cancers-Last Resort or Therapeutic Option?

First described some 80 years ago, pelvic exenteration remain controversial interventions with variable results and ever-changing indications. The previous studies are not homogenous and have different inclusion criteria (different populations and different disease characteristics) and methodologies (including evaluation of results), making it extremely difficult to properly assess the role of pelvic exenteration in cancer treatment. This study aims to describe the indications of pelvic exenterations, the main prognostic factors of oncologic results, and the possible complications of the intervention. Methods: For this purpose, we conducted a retrospective study of 132 patients who underwent various forms of pelvic exenterations in the Institute of Oncology "Prof. Dr. Al. Trestioreanu" in Bucharest, Romania, between 2013 and 2022, collecting sociodemographic data, characteristics of patients, information on the disease treated, data about the surgical procedure, complications, additional cancer treatments, and oncologic results. Results: The study cohort consists of gynecological, colorectal, and urinary bladder malignancies (one hundred twenty-seven patients) and five patients with complex fistulas between pelvic organs. An R0 resection was possible in 76.38% of cases, while on the rest, positive margins on resection specimens were observed. The early morbidity was 40.63% and the mortality was 2.72%. Long-term outcomes included an overall survival of 43.7 months and a median recurrence-free survival of 24.3 months. The most important determinants of OS are completeness of resection, the colorectal origin of tumor, and the presence/absence of lymphovascular invasion. Conclusions: Although still associated with high morbidity rates, pelvic exenterations can deliver important improvements in oncological outcomes in the long-term and should be considered on a case-by-case basis. A good selection of patients and an experienced surgical team can facilitate optimal risks/benefits.

The immunomodulatory role of paracrine signalling factor VSIG4 in peritoneal metastases

Peritoneal metastasis (PM), the regional progression of intra-abdominal malignancies, is a common sequelae of colorectal cancer (CRC). Immunotherapy is slated to be effective in generating long-lasting anti-tumour response as it utilizes the specificity and memory of the immune system. In the tumour microenvironment, tumour associated macrophages (TAMs) are posited to create an anti-inflammatory pro-tumorigenic environment. In this paper, we aimed to identify immunomodulatory factors associated with colorectal PM (CPM). A publicly available colorectal single cell database (GSE183916) was analysed to identify possible immunological markers that are associated with the activation of macrophages in cancers. Immunohistochemical analysis for V-set and immunoglobin containing domain 4 (VSIG4) expression was performed on tumour microarrays (TMAs) of tumours of colorectal origin (n = 211). Expression of VSIG4 in cell-free ascites obtained from CPM patients (n = 39) was determined using enzyme-linked immunosorbent assay (ELISA). CD163-positive TAMs cluster expression was extracted from a publicly available single cell database and evaluated for the top 100 genes. From these macrophage-expressed genes, VSIG4, a membrane protein produced by the M2 macrophages, mediates the up-regulation of anti-inflammatory and down-regulation of pro-inflammatory macrophages, contributing to an overall anti-inflammatory state. CRC TMA IHC staining showed that low expression of VSIG4 in stromal tissues of primary CRC are associated with poor prognosis (p = 0.0226). CPM ascites also contained varying concentrations of VSIG4, which points to a possible role of VSIG4 in the ascites. The contribution of VSIG4 to CPM development can be further evaluated for its potential as an immunotherapeutic agent.

Genetic Clustering of Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy Patients of Colorectal Origin: KRAS and Not TP53 Cluster Alterations are Associated with Poor Outcomes.

The prognostic impact of genetic mutations for patients who undergo cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) of colorectal origin (CRC) is not well defined. We aimed to describe the genetic classifications in an unsupervised fashion, and the outcomes of this patient population. A retrospective, bi-institutional study was performed on patients who underwent CRS-HIPEC with targeted mutation data with a median follow-up time of 61 months. Functional link analysis was performed using STRING v11.5. Genes with similar functional significance were clustered using unsupervised k-means clustering. Chi-square, Kaplan-Meier, and the log-rank test were used for comparative statistics. Sixty-four patients with peritoneal carcinomatosis from CRC origin underwent CRS-HIPEC between 2007 and 2022 and genetic mutation data were extracted. We identified 19 unique altered genes, with KRAS (56%), TP53 (33%), and APC (22%) being the most commonly altered; 12.5% had co-altered KRAS/TP53. After creating an interactome map, k-means clustering revealed three functional clusters. Reactome Pathway analysis on three clusters showed unique pathways (1): Ras/FGFR3 signaling; (2) p53 signaling; and (3): NOTCH signaling. Seventy-one percent of patients in cluster 1 had KRAS mutations and a median overall survival of 52.3 months (p<0.05). Patients with peritoneal carcinomatosis (PC) of CRC origin who underwent CRS-HIPEC and with tumors that harbored mutations in cluster 1 (Ras/FGFR3 signaling) had worse outcomes. Pathway disruption and a cluster-centric perspective may affect prognosis more than individual genetic alterations in patients with PC of CRC origin.

Investigate the Relationship Between the Presence of JCV DNA and the Immunohistochemical Expression of CK2 0, CK7, and CDX2 in Colorectal Cancer

Abstract Background: Globally, colorectal cancer (CRC) is the most common malignancy and has a high fatality rate. Early childhood the John Cunningham virus or JC virus (JCV) infection persists throughout life and has been linked through multiple routes to colorectal cancer. The expression of cytokeratins 7 (CK7), 20 (CK20), and CDX2 have been investigated in a variety of primary and metastatic carcinomas, and their patterns of expression may be used to determine the site of origin of metastatic carcinomas. Objectives: The aim is to assess the relationship between JCV DNA and tumor markers (CK7, CK20, and CDX2) in patients with colorectal cancer, this study was carried out. Materials and Methods: Ninety CRCs (45 of which were squamous cell carcinomas and 45 of which were adenocarcinomas) had their paraffin sections randomly chosen, extracted, and immunostained for CK7, CK20, CDX2, and for the detection of JCV DNA by real-time (PCR). Results: JCV DNA was detected in 22 (24.4%) of AD-CRC and 24 (26.7%) of SCC-CRC (P = 0.004). The presence of JCV was significantly correlated with tumor stages (P = 0.04) and age categories (P = 0.05). Moreover, JCV presence was significantly correlated with all studied tumor markers (P &lt; 0.05). Conclusion: JCV might play a role in the development of colorectal cancer, and CDX2, which is highly specific and sensitive as markers of colorectal origin should be helpful in the detection of intestinal adenocarcinomas.

Role of Pap Smear Cervical Cytology in the Diagnosis of Extrauterine Malignancies: Largest Study of 104 Cases from Tertiary Care Cancer Centre in India

Introduction: Extrauterine malignancies in cervical samples are rarely seen. It is important to differentiate these cells from those of primary uterine malignancies to determine appropriate line of further investigations and management. Literature on these lesions is limited largely restricted to case reports. The aim of the present study was to study the spectrum and cytomorphological features of extrauterine malignancies in cervical Pap smears. Materials and Methods: It is a retrospective and descriptive study conducted in Department of Cytopathology from January 2019 to July 2023. All cases of extrauterine malignancies with available cytology material were included in this study. All cases of primary uterine malignancies, i.e., uterine corpus or cervix confirmed by clinical, radiological, and histopathological examination were excluded. Results: 104 out of 11,674 cytology Pap smears were those of extrauterine malignancy. Diagnosis of extrauterine malignancy was given in 47.1% cases, 30.9% were reported as positive for malignancy without giving the possibility of an extrauterine origin, and 22.0% were reported as atypical glandular cells only. In 56 cases where Pap smear was the first investigation which led to the diagnosis. Most common extrauterine malignancy was adenocarcinoma principally from ovarian, colorectal, and vaginal origin. Other epithelial malignancies noted were urothelial carcinoma and invasive breast carcinoma. Among non-epithelial malignancies, we reported vaginal mucosal melanoma, cutaneous melanoma, acute leukaemia, and anaplastic large cell lymphoma. Conclusion: High index of suspicion, presence of squamous and glandular elements with no atypical features, and occasional clusters of cells with marked atypia and usually no necrosis in the background are helpful cytomorphological clues to raise suspicion for extrauterine malignancy. Correlation with serology, radiology, and immunocytochemistry can help in reaching final diagnosis.

Long-Term Outcomes following Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy for Peritoneal Carcinomatosis of Colorectal Origin.

Cytoreductive surgery (CRS) combined with hyperthermic intraperitoneal chemotherapy (HIPEC) is a major treatment of colorectal peritoneal carcinomatosis (CPC). The aim was to determine the disease-free survival (DFS) and overall survival (OS) of patients undergoing CRS-HIPEC for CPC and factors associated with long-term survival (LTS). consecutive CPC patients who underwent CRS-HIPEC at a HIPEC center between 2007 and 2021 were included. Actual survival was calculated, and Cox proportional hazards models were used to identify factors associated with OS, DFS and LTS. there were 125 patients with CPC who underwent primary CRS-HIPEC, with mean age of 54.5 years. Median follow-up was 31 months. Average intraoperative PCI was 11, and complete cytoreduction (CC-0) was achieved in 96.8%. Median OS was 41.6 months (6-196). The 2-year and 5-year OS were 68% and 24.8%, respectively, and the 2-year DFS was 28.8%. Factors associated with worse OS included pre-HIPEC systemic therapy, synchronous extraperitoneal metastasis, and PCI ≥ 20 (p < 0.05). Progression prior to CRS-HIPEC was associated with worse DFS (p < 0.05). Lower PCI, fewer complications, lower recurrence and longer DFS were associated with LTS (p < 0.05). CRS and HIPEC improve OS in CPC patients but they have high disease recurrence. Outcomes depend on preoperative therapy response, extraperitoneal metastasis, and peritoneal disease burden.

GATA4 is diagnostically useful for distinguishing primary ovarian mucinous carcinomas from metastatic colorectal adenocarcinomas to the ovary.

Determining the primary origin of an ovarian mucin-producing carcinoma can be challenging at times because some metastases of primary colorectal origin may exhibit gross, microscopic, and/or immunohistochemical features that overlap with those of primary ovarian mucinous carcinomas (OMCs). We hypothesized that GATA binding protein 4 (GATA4) might be a novel, useful marker for differentiating primary OMCs from metastatic colorectal adenocarcinomas to the ovary. For comparison with the usefulness of other markers (special AT-rich sequence-binding protein 2 (SATB2) and caudal type homeobox 2 (CDX2)), we elucidated the expression profiles of GATA4 in OMCs, colorectal non-mucinous adenocarcinomas (CNMACs), and colorectal mucinous adenocarcinomas (CMACs) using immunohistochemistry. We confirmed GATA4 expression (H-score ≥50 points) in 93%, SATB2 in 0%, and CDX2 in 64% of 14 OMCs. GATA4 was expressed in 13%, SATB2 in 90%, and CDX2 in 93% of 30 CNMACs. GATA4 was expressed in 20%, SATB2 in 73%, and CDX2 in 100% of 30 CMACs. The expression of GATA4 in a mucus-producing ovarian tumor strongly supports it being a primary OMC rather than a metastatic colorectal carcinoma: GATA4 expression indicates OMC and SATB2 expression indicates colorectal adenocarcinoma. However, three cases of colorectal adenocarcinoma were GATA4-positive and SATB2-negative, so the GATA4/SATB2 marker combination is not absolute for determining the primary site. Further research for more markers is necessary to find the ideal combination.

Population pharmacokinetics of intraperitoneal irinotecan and SN-38 in patients with peritoneal metastases from colorectal origin.

Peritoneal metastases (PM) are common in patients with colorectal cancer. Patients with PM have a poor prognosis, and for those who are not eligible for cytoreductive surgery (CRS) with or without hyperthermic intraperitoneal chemotherapy (HIPEC), palliative chemotherapy is currently the only option. Recently, we conducted a phase I trial (INTERACT) in which irinotecan was administered intraperitoneally (IP) to 18 patients ineligible for CRS-HIPEC. The primary objective was to evaluate covariates influencing the PK profile of irinotecan and SN-38 after IP administration. Secondly, a population PK model was developed to support the further development of IP irinotecan by improving dosing in patients with PM. Patients were treated with IP irinotecan every 2 weeks in combination with systemic FOLFOX-bevacizumab. Irinotecan and SN-38 were measured in plasma (588 samples) and SN-38 was measured in peritoneal fluid (267 samples). Concentration-Time data were log-transformed and analyzed using NONMEM version 7.5 using FOCE+I estimation. An additive error model described the residual error, with inter-individual variability in PK parameters modeled exponentially. The final structural model consisted of five compartments. Weight was identified as a covariate influencing the SN-38 plasma volume of distribution and GGT was found to influence the SN-38 plasma clearance. This population PK model adequately described the irinotecan and SN-38 in plasma after IP administration, with weight and GGT as predictive factors. Irinotecan is converted intraperitoneal to SN-38 by carboxylesterases and the plasma bioavailability of irinotecan is low. This model will be used for the further clinical development of IP irinotecan by providing dosing strategies.

The Added Value of (18) F-FDG Positron Emission Tomography/ Computed Tomography Compared to Contrast Enhanced Computed Tomography in the Detection and Assessment of Peritoneal Deposits of Colorectal Origin.

The Added Value of (18) F-FDG Positron Emission Tomography/ Computed Tomography Compared to Contrast Enhanced Computed Tomography in the Detection and Assessment of Peritoneal Deposits of Colorectal Origin.

Cytoreductive surgery plus hyperthermic intraoperative peritoneal chemotherapy for people with peritoneal metastases from colorectal, ovarian or gastric origin: A systematic review of randomized controlled trials.

There is uncertainty in the relative benefits and harms of hyperthermic intraoperative peritoneal chemotherapy (HIPEC) when added to cytoreductive surgery (CRS) +/- systemic chemotherapy or systemic chemotherapy alone in people with peritoneal metastases from colorectal, gastric, or ovarian cancers. We searched randomized controlled trials (RCTs) in the medical literature until April 14, 2022 and applied methods used for high-quality systematic reviews. We included a total of eight RCTs (seven RCTs included in quantitative analysis as one RCT did not provide data in an analyzable format). All comparisons other than ovarian cancer contained only one trial. For gastric cancer, there is high uncertainty about the effect of CRS+HIPEC+systemic chemotherapy. For stage III or greater epithelial ovarian cancer undergoing interval cytoreductive surgery, CRS+HIPEC+systemic chemotherapy probably decreases all-cause mortality compared to CRS+systemic chemotherapy. For colorectal cancer, CRS+HIPEC+systemic chemotherapy probably results in little to no difference in all-cause mortality and may increase the serious adverse events proportions compared to CRS +/- systemic chemotherapy, but probably decreases all-cause mortality compared to fluorouracil-based systemic chemotherapy alone. The role of CRS+HIPEC in gastric peritoneal metastases is uncertain. CRS+HIPEC should be standard of care in women with stage III or greater epithelial ovarian cancer undergoing interval CRS. CRS+systemic chemotherapy should be standard of care for people with colorectal peritoneal metastases, with HIPEC given only as part of a RCT focusing on subgroups and regimes. CRD42019130504.

A Glimpse into the Role and Effectiveness of Splenectomy for Isolated Metachronous Spleen Metastasis of Colorectal Cancer Origin: Long-Term Survivals Can Be Achieved.

Background: Many papers exploring the role of resectioning metastases in colorectal cancer (CRC) have focused mainly on liver and lung sites, showing improved survival compared with non-resectional therapies. However, data about exceptional metastatic sites such as splenic metastases (SMs) are scarce. This paper aims to assess the role and effectiveness of splenectomy in the case of isolated metachronous SM of CRC origin. Methods: The patients' data were extracted after a comprehensive literature search through public databases for articles reporting patients with splenectomies for isolated metachronous SM of CRC origin. Potential predictors of survival were explored, along with demographic, diagnostic, pathology, and treatment data for each patient. Results: A total of 83 patients with splenectomies for isolated metachronous SM of CRC origin were identified. The primary CRC was at an advanced stage (Duke's C-70.3%) and on the left colon (45.5%) for most patients, while the median interval between CRC resection and SM was 24 months. The median overall survival after splenectomy was 84 months, and patients younger than 62 years presented statistically significantly worse overall survival rates than those ≥62 years old (p = 0.011). There was no significant impact on the long-term outcomes for factors including primary tumor location or adjuvant chemotherapy (p values ≥ 0.070, ns). Laparoscopic splenectomy was increasingly used in the last 20 years from 2002 (33.3% vs. 0%, p < 0.001). Conclusions: Splenectomy is the optimal treatment for patients with isolated metachronous SM of CRC, with the laparoscopic approach being increasingly used and having the potential to become a standard of care. Encouraging long-term survival rates were reported in the context of a multidisciplinary approach. Younger ages are associated with worse survival. Perioperative chemotherapy in the context of a patient diagnosed with SM of CRC origin appears to be a reasonable option, although the present study failed to show any significant impact on long-term survival.