Cancer Carcinomatosis Research Articles

HIPEC application potential in the treatment of extensive carcinomatosis in ovarian cancer (retrospective study)

Background. The high prevalence of advanced forms of cancer currently requires new treatment approaches. Only modern high-tech surgical procedures can provide means for improving the results of treatment.The aim. To study the results of treatment of patients with ovarian cancer with symptoms of peritoneal carcinomatosis using the HIPEC (Hyperthermic IntraPEritoneal Chemotherapy) method.Materials and methods. The study was conducted in Irkutsk Regional Cancer Center and included 88 patients. They were divided into 2 groups: group 1 – primary cytoreductive surgery (CRS) with the HIPEC method (41 patients); group 2 – primary cytoreductive surgery (47 patients). The most important criterion was the peritoneal cancer index (PCI). If the PCI was ≤ 14, we chose cytoreductive surgery with or without HIPEC.Results. PCI analysis showed differences in its values between the study groups (CRS – 10.17 ± 0.952; CRS + HIPEC – 12.93 ± 0.744; p = 0.002). There was an increase in length of stay in patients who underwent major surgeries in combination with HIPEC (21.8 ± 0.9 days versus 14.5 ± 0.6 days in the CRS group; p = 0.001). The CRS + HIPEC group had a longer duration of surgery (394.88 ± 19.935 min vs. 172.98 ± 11.514 min in the CRS group; p = 0.001). There was an increase in the overall percentage of postoperative complications in the CRS + HIPEC group – up to 26.8 % without statistically significant differences with the CRS group – 8.5 % (p = 0.082). The median time of relapse onset in the CRS + HIPEC group was 26 ± 4.3 months, while in the CRS group it was 18 ± 2.6 months.Conclusion. Using HIPEC method has proven its significance in increasing diseasefree survival.

Radiation-based immunogenic vaccine combined with a macrophage “checkpoint inhibitor” for boosting innate and adaptive immunity against metastatic colon cancers

Immunogenic dying tumor cells hold promising prospects as cancer vaccines to activate systemic immunity against both primary and metastatic tumors. Especially, X-ray- induced dying tumor cells are rich in highly immunogenic tumor-associated antigens and self-generated dsDNA as potent adjuvants. However, we found that the X-ray induction process can result in the excessive exposure of phosphatidylserine in cancer vaccines, which can specifically bind with the MerTK receptor on macrophages, acting as a “checkpoint” to facilitate immune silence in the tumor microenvironment. Therefore, we developed a novel strategy combining X-ray-induced cancer vaccines with UNC2250, a macrophage MerTK “checkpoint inhibitor,” for treating peritoneal carcinomatosis in colon cancer. By incorporating UNC2250 into the treatment regimen, immunosuppressive efferocytosis of macrophages, which relies on MerTK-directed recognition of phosphatidylserine on vaccines, was effectively blocked. Consequently, the immune analysis revealed that this combination strategy promoted the maturation of dendritic cells and M1-like repolarization of macrophages, thereby simultaneously eliciting robust adaptive and innate immunity. This innovative approach utilizing X-ray-induced vaccines combined with a checkpoint inhibitor may provide valuable insights for developing effective cancer vaccines and immunotherapies targeting colon cancer.

A Hangover Under 177 Lu-PSMA-617 Therapy : A Red Flag for Brain 68 Ga-PSMA-11 PET/MRI?

Leptomeningeal carcinomatosis in prostate cancer is extremely rare. Because of the low overall penetration of drugs into the brain and the prolonged survival of castration-resistant prostate cancer (CRPC) patients, a special attention should be paid to the appearance of neurological symptoms in long-term CRPC survivors. A patient suffering from a CRPC with bone metastases underwent 4 cycles of 177 Lu-PSMA (prostate-specific membrane antigen)-617. Starting from the third cycle, he reported an increasing feeling of a permanent hangover. A 68 Ga-PSMA-11 brain PET/MRI was carried out after the fourth cycle. It revealed intraparenchymatous brain metastases with intense uptake and evidences of leptomeningeal carcinomatosis.

Regional Immunotherapy for Peritoneal Carcinomatosis in Gastroesophageal Cancer: Emerging Strategies to Re-Condition a Maladaptive Tumor Environment.

Peritoneal carcinomatosis originating from gastric/gastroesophageal junction cancer (GC-PC) occurs in a defined subset of gastric cancer patients with unique clinical, pathologic, molecular and immunologic characteristics that create significant obstacles to effective treatment with modern therapy. Although systemic chemo- and immuno- therapy have yielded disappointing results in GC-PC, recent advances in the characterization of GC-PC and peritoneal immune biology present new opportunities for targeted therapeutics. In this review article, we discuss the distinct properties of GC-PC and the peritoneal immune environment as they pertain to current and investigative treatment strategies. We discuss pre-clinical studies and clinical trials relevant to the modulation of the peritoneal environment as a therapeutic intervention in GC-PC. Finally, we present a road map for future combinatorial strategies based on the conception of the peritoneal cavity as a bioreactor. Within this isolated compartment, prevailing immunosuppressive conditions can be altered through regional interventions toward an adaptive phenotype that would support the effectiveness of regionally delivered cellular therapy products. It is hoped that novel combination strategies would promote efficacy not only in the sequestered peritoneal environment, but also via migration into the circulation of tumor-reactive lymphocytes to produce durable systemic disease control, thereby improving oncologic outcome and quality of life in patients with GC-PC.

Radiologically enlarged cardiophrenic lymph nodes and CA-125 in relation to diaphragmatic carcinomatosis, surgical outcome, and overall survival in advanced ovarian cancer

Background We primarily aimed to determine whether the presence of enlarged cardiophrenic lymph nodes (CPLNs), visualized by computed tomography (CT), and CA-125 can be used to assess diaphragmatic carcinomatosis and residual disease (RD) in advanced ovarian cancer (AOC) patients treated with upfront surgery. The secondary aim was to determine the prognostic role of CT-CPLNs in overall survival (OS). Material and methods A single-center, retrospective, population-based study was conducted of patients who underwent surgery for AOC from January 1, 2014-December 31, 2018. Suspicious CT-CPLNs were defined as having a short axis ≥5 mm. The median survival and rate of survival were calculated with the Kaplan–Meier method using multivariate Cox regression analyses, including comparisons of complete cytoreductive surgery (CCS; defined as the complete removal of all intra-abdominal tumor) versus noncomplete cytoreductive surgery (non-CCS) and analyses related to CT-CPLN status and preoperative CA-125 values. Results We included 208 patients. CT-CPLNs correlated with both diaphragmatic carcinomatosis (OR 3.59, 95% CI 1.81–7.16, p < 0.01) and RD (OR 2.54, 95% CI 1.38–4.6, p = 0.003). When CCS was achieved, no differences in survival between patients with suspicious or nonsuspicious CT-CPLNs were found. The relationships between CA-125 ≥ 500 U/ml and diaphragmatic carcinomatosis (OR 3.51, 95% CI 1.86–6.64, p < 0.01) and RD (OR 2.41, 95% CI 1.33–4.38, p = 0.004) were positive. All data were adjusted for age and ECOG performance status. Survival analyses were also adjusted for RD. Conclusion Enlarged CPLNs on CT scans and CA-125 levels correlate with diaphragmatic carcinomatosis and RD at the end of the surgery. The strongest prognostic factor for OS remains CCS, regardless of the CT-CPLN status.

Abstract 5604: Circulating tumor DNA for predicting peritoneal only disease recurrence in colon cancer

Abstract Background: Peritoneal Carcinomatosis in Colon Cancer (PCCC) is a major cause of morbidity. Early detection of PCCC is important for early intervention like systemic chemotherapy and cytoreductive surgery (CRS) +/- hyperthermic intraperitoneal chemotherapy (HIPEC). Circulating tumor DNA (ctDNA) testing is a promising method to assess recurrence not detectable yet on imaging, identifying 87.5% of recurrences in Stage I-III CRC with a mean lead-time of 8.7 months. It is unclear if ctDNA testing is sensitive in detection of recurrent PCCC ahead of clinical/radiological presentation. We report data from 6 CRC patients with PCCC who underwent complete CRS and were followed with serial ctDNA testing. Methods: In this single institution study, patients with PCCC were included from our prospectively enrolled GI cancer patient cohort (GIMER: IRB #201202743). Peritoneal carcinomatosis at CRS was determined using the Peritoneal Cancer Index. ctDNA concentration in mean tumor molecules/mL of plasma was assessed using a commercially available tumor-informed, personalized ctDNA assay (Signatera™, Natera, Inc.) that uses patient-specific somatic single-nucleotide variants. Plasma samples for ctDNA analysis were collected before surgery, 1, 2, 4, 6 months post-surgery, then every 3 months until a positive ctDNA test triggered CT imaging. Patients also had routine CT imaging every 6 months after surgery. Results: 5 of 6 patients met endpoint with median time of 35 days from positive ctDNA to recurrence on imaging. In 4 patients, positive ctDNA prompted CT imaging which was negative, but follow-up PET scan was positive. Patient 6 was ctDNA negative and recurrence-free at last follow-up. Conclusions: This analysis demonstrated the potential of longitudinal ctDNA monitoring for early detection of PCCC recurrence by prompting early imaging. PET was more sensitive in detecting recurrence than CT, and should be considered when determining PCCC recurrence. Enrollment and further analysis of ctDNA continues. Table 1. Patient Pre-op Chemo Post-chemo, pre-op ctDNA Peritoneal Cancer Index Post-op (1m) ctDNA 2m ctDNA 4m ctDNA 6m ctDNA 9m ctDNA 12m ctDNA 15m ctDNA Recurrence Days between ctDNA positivity and positive imaging Imaging Findings 1 Yes 0 5 0 0 0 0 0.48 - - Yes 6 CT CAP Positive 2 Yes 0 4 0 0 0 0.04 - - - Yes 54 CT CAP Negative; PET Positive 3 Yes 0.28 18 0 0 0 0 0.09 - - Yes 25 CT CAP Negative; PET Positive 4 Yes 0 0 0 0 0 0 0 0 0.18 Yes 35 CT CAP Negative; PET Positive 5 Yes 0.61 5 0 0 0.17 0 0.32 0.12 - Yes 274 CT CAP Negative; PET Positive 6 Yes 0 5 0 - 0 0 - - - No NA CT CAP Negative to date Citation Format: Kevin C. Chang, Daniel Berg, Chandrika Chandrasekharan, Kelsey Steckly, Saima Sharif, Carlos H. Chan. Circulating tumor DNA for predicting peritoneal only disease recurrence in colon cancer. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 5604.

Perspectives of pressurized intraperitoneal aerosol chemotherapy in terms of primary ovarian cancer with peritoneal carcinomatosis treatment

The relevance of the problem of increasing the effectiveness of standard treatment of ovarian cancer is determined by the following characteristics of the disease: high one‑year mortality, high recurrence rate and unsatisfactory results of their treatment. Peritoneal carcinomatosis in ovarian cancer occurs in 65–70 % of cases. The standard modern approach to the treatment of ovarian cancer is a combination of surgical treatment and systemic intravenous chemotherapy. At the same time, more than 70 % of ovarian cancer cases are first diagnosed at stages III–IV. However, despite the successes in the field of surgery and drug treatment, the five‑year survival rate is no more than 24 % at the III and 4.6 % at the IV stage of the disease. One of the frontiers of ovarian cancer resistance to therapy is peritoneal carcinomatosis. Its resistance to therapy is due to the low bioavailability of cytostatics in metastases on the peritoneum to almost zero. In order to increase bioavailability, various forms of intra‑abdominal chemotherapy are used. The technique of pressurized intraperitoneal aerosol chemotherapy (PIPAC) has a number of advantages over other methods of intra‑abdominal antitumor treatment. These advantages include the uniform distribution of cytostatics over the peritoneum, the absence of penetration of cytostatics beyond the peritoneum, which allows PIPAC to be combined with systemic chemotherapy, low trauma and good tolerability of the procedure. PIPAC was implemented into clinical practice in 2011, and since then has been widely used in a number of foreign and domestic clinics. The conducted studies confirm the safety of the technique and its effectiveness against peritoneal carcinomatosis. The data of multicenter studies and the analysis of available literature data, as well as the successful own experience of PIPAC use create prerequisites for investigating the effectiveness of intra‑abdominal aerosol chemotherapy under pressure in relation to peritoneal carcinomatosis in ovarian cancer.

Dynamic assessment of intraperitoneal aerosol chemotherapy under pressure impact on peritoneal carcinomatosis in ovarian cancer (immediate results)

Purpose of the study. Dynamic assessment of the direct impact of pressurized intraperitoneal aerosol chemotherapy (PIPAC) on peritoneal carcinomatosis in ovarian cancer.Patients and methods. The study involved 164 people with visually detectable and morphologically verified ovarian cancer with peritoneal carcinomatosis of the peritoneum (IIIb-IIIc stages of ovarian cancer). All patients underwent combined treatment of ovarian cancer, which included primary cytoreduction and 6 courses of сhemotherapy according to the TC scheme. In the main group, the standard treatment was supplemented with 3 sessions of PIPAC. Statistical processing was carried out by analyzing the exact criterion of the Wilcoxon-Mann-Whitney sums, the distribution of patients in groups by age and peritoneal lesion was estimated. It was found that the distribution of the analyzed parameters was random. The distribution in the groups by stages of the disease was homogeneous, which is justified by the use of the Barnard criterion. The dynamics of the parameters of the study was evaluated by the methods of basic statistics. Used software packages: MedCals, Statistica.Results. The results obtained demonstrate a distinct positive dynamics in the group of patients receiving PIPAC in addition to standard treatment of newly diagnosed ovarian cancer: a significant decrease in the peritoneal cancer index, therapeutic pathomorphosis in peritoneal samples during treatment, reduction of ascites.Conclusion. The team of authors managed to establish that PIPAC simultaneously with standard combined treatment for newly diagnosed ovarian cancer with peritoneal carcinomatosis makes it possible to achieve a dynamic regression effect of peritoneal carcinomatosis of the peritoneum, morphological regression of carcinomatosis and complete resorption of ascites in the vast majority of treated patients. The revealed therapeutic effect was prolonged and persistent with an objective assessment 6 months after the end of treatment.

Effect of the MiR-99b and MiR-135b on peritoneal carcinomatosis and liver metastasis in colorectal cancer

AimThis study aimed to evaluate the expression levels of miR-99b and miR-135b in peritoneal carcinoma and liver metastases associated with Colorectal Cancer (CRC), assess their association with the intracellular signaling pathway proteins Kirsten Rat Sarcoma Virus (KRAS) and Akt, and investigate their effects on survival. Materials and methodsChanges in the KRAS gene and Akt proteins, expression levels of miR-99b and miR-135b, and factors affecting survival were compared between colorectal cancer-associated peritoneal carcinomatosis and liver metastasis. ResultsThe expression levels of miR-99b and miR-135b and the immunohistochemical grade classification score of Akt were higher in colorectal cancer, peritoneal carcinomatosis, and liver metastasis than in normal tissues (p < 0.05). MiR-99b expression was highest in CRC, whereas miR-135b expression was highest in peritoneal carcinomatosis (p < 0.05). The expression level of miR-99b decreased and that of miR-135b increased in peritoneal and liver metastases compared with that in the tumor tissue. MiR-99b, Akt, and recurrence were risk factors that affected the overall survival rate in the model of clinical predictions (p = 0.045, p = 0.006, and p = 0.012, respectively). ConclusionWhile the expression of miR-99b was highest in the primary tumor, its decrease in liver metastasis and peritoneal carcinomatosis suggests that miR-99b has a protective effect against liver metastasis and peritoneal carcinomatosis. However, the detection of miR-135b expression was highest in peritoneal carcinomatosis and liver metastasis compared with that in the colorectal cancer tissues suggesting that it facilitates peritoneal carcinomatosis and liver metastasis. Furthermore, miR-99b, KRAS mutations, and Akt are risk factors for the overall survival of colorectal cancer.

Лептоменингеальный канцероматоз при BRCA1-ассоциированном раке яичников

Leptomeningeal carcinomatosis (LMC) in ovarian cancer is a rare complication of malignant gynecological disease, which is characterized by the spread of tumor cells through the cerebrospinal fluid to the membranes surrounding the brain and spinal cord. The cause of rare involvement of central nervous system (CNS) meninges in ovarian cancer is unclear. To date, there are no clinical guidelines for the management of this category of patients, and treatment of LMC in ovarian cancer is based on treatment protocols for meningeal carcinomatosis in other nosologies and on selected clinical observations presented in the world literature and personal experience. This article presents a clinical case of a patient with BRCA1-associated ovarian cancer and lesions of CNS meninges and parenchyma and our own experience in the treatment of this pathology. The treatment consisted of systemic anti-cancer therapy in combination with radiation therapy. Survival time after diagnosis of CNS metastases and treatment was 8 months. Key words: ovarian cancer, meningeal carcinomatosis, brain metastases, cytological examination, cerebrospinal fluid

Can a morphological description of the peritoneal carcinomatosis in advanced ovarian cancer add prognostic information? Analysis of 1686 patients of the tumor bank ovarian cancer.

Peritoneal carcinomatosis in ovarian cancer is frequent and generally associated with higher stage and poorer outcome. The clinical features of peritoneal carcinomatosis are diverse and their relevance for surgical and long-term outcome remains unclear. We conducted this prospective study to describe intraoperatively the different features of peritoneal carcinomatosis(PC) and correlate them with clinicopathological features, progression-free(PFS) and overall survival (OS),. We performed a systematic analysis of all patients with documented intraoperative PC and a primary diagnosis of epithelial ovarian, tubal, or peritoneal cancer from January 2001 to September 2018. All data were evaluated by using the systematic tumor bank tool. Specific PC features included texture(soft-hard), consistency(coarse-fine or both), wet vs dry(PC with ascites vs. PC without ascites), and localization(diffuse-local). PC characteristics were then evaluated for correlation with age, FIGO-stage, histology, lymph-node involvement, grade, and presence of residual tumor at primary surgery. Moreover, the influence of PC characteristics on OS and PFS was analyzed. A total of 1686 patients with PC and primary epithelial ovarian cancer were included. Majority of the patients were characterized by diffuse PC(73.9%). The majority of peritoneal nodules were fine in texture (55.3%) and hard in consistency (87.4%). Moreover, 27.6% of patients had dry PC. Diffuse PC localization was significantly associated with higher FIGO-stage (p<0.001), high-grade (p=0.003) and serous tumors (p=0.006) as well as residual tumor as compared to local PC (p<0.001). Wet PC also significantly correlated with diffuse localization (p <0.001) and residual tumor as compared to dry PC (p<0.001). Coarse PC was significantly associated with residual tumor as compared to fine PC (p=0.044). All other PC features didn´t correlate with clinicopathological features. As for survival outcomes, diffuse peritoneal localization (p<0.001), wet PC (p<0.001), and additional lymph node involvement (p<0.001) were associated with lower OS and PFS rates. Other PC features did not significantly impact survival. Diffuse localization of peritoneal carcinomatosis was significant predictor of recurrence. Lower OS and PFS were associated with diffuse peritoneal localization, wet PC, and additional lymph node involvement. Further prospective trials are warranted with the inclusion of translational research aspects to better understand the different peritoneal carcinomatosis patterns.

Usefulness of [68Ga]FAPI-04 and [18F]FDG PET/CT for the detection of primary tumour and metastatic lesions in gastrointestinal carcinoma: a comparative study.

To assess and compare the diagnostic performance of gallium-68-labelled fibroblast activation protein inhibitor ([68Ga]FAPI-04) and fluorine-18 fluorodeoxyglucose ([18F]FDG) positron emission tomography/computed tomography (PET/CT) in gastrointestinal cancer. Fifty-one patients who underwent both [18F]FDG and [68Ga]FAPI-04 PET/CT for initial staging or restaging were enrolled. Histopathological findings, typical radiological appearances, and clinical imaging follow-up were used as the reference standard. The diagnostic performance of the two tracers was calculated and compared. The maximum standardised uptake value (SUVmax), mean SUV (SUVmean), tumour-to-mediastinal blood pool ratio (TBR), and tumour-to-liver ratio (TLR) of primary and metastatic lesions were measured and compared between two imaging modalities. In patient-based analysis, [68Ga]FAPI-04 showed much better diagnostic sensitivity than [18F]FDG in detecting primary tumour (94.44% [17/18] vs. 61.11% [11/18]), postoperative recurrence and metastases (95.65% [22/23] vs. 69.57% [16/23]), and peritoneal carcinomatosis (100% [28/28] vs. 60.71% [17/28]) (all p < 0.05). In lesion-based analysis, [68Ga]FAPI-04 showed higher sensitivity than [18F]FDG for detecting lymph node metastases. In peritoneal carcinomatosis, the median SUVmax (12.12 vs. 7.18) and SUVmean (6.84 vs. 4.11) with [68Ga]FAPI-04 were significantly higher than those with [18F]FDG (all p < 0.005). The TBR and TLR of [68Ga]FAPI-04 were significantly higher than those of [18F]FDG for detecting primary tumour, lymph node, liver, and peritoneal metastases (all p < 0.005). Therapeutic management changed in 13 patients according to [68Ga]FAPI-04 PET/CT compared with conventional imaging. [68Ga]FAPI-04 is superior to [18F]FDG PET/CT for detecting primary tumour, postoperative recurrence and metastasis, and peritoneal carcinomatosis in gastrointestinal cancer. • [68Ga]FAPI-04 PET/CT showed significantly higher sensitivity than [18F]FDG PET/CT in the detection of primary tumour and postoperative recurrence and metastasis in patients with gastrointestinal carcinoma. • [68Ga]FAPI-04 PET/CT had obvious advantages over [18F]FDG PET/CT in the detection of peritoneal carcinomatosis from gastrointestinal carcinoma with a much higher FAPI uptake value, TBR, and TLR. • Although the median SUVmax and SUVmean of [68Ga]FAPI-04 were similar to those of [18F]FDG for the primary tumour, lymph node metastases, and liver metastases in gastrointestinal carcinoma, the TBR and TLR of the SUVmax and SUVmean were significantly higher on [68Ga]FAPI-04 PET/CT, causing the lesions to be displayed more clearly.

The Significance of Staging Laparoscopy in Detection of Radiologically Occult Peritoneal Carcinomatosis in Gastric Cancer With Gastric Outlet Obstruction: Consideration of The Optimal Treatment Approach.

Gastric cancer with gastric outlet obstruction (GOO) is generally found at an advanced stage and with an unfavorable prognosis. This study was performed to examine the prevalence of radiologically occult peritoneal carcinomatosis in GOO and determine the optimal treatment strategy. This single-center study was a retrospective review of the clinical data of 186 patients with locally advanced gastric cancer at the distal stomach who underwent surgery from 2008 to 2016. These patients were divided into two groups according to the presence or absence of GOO due to cancer progression: With GOO (n=71) and without GOO (n=115). The incidence of peritoneal carcinomatosis [with macroscopic peritoneal deposits (P1)/positive peritoneal cytology (CY1)] detected at laparotomy/laparoscopy was significantly higher in the group with GOO than in the group without (32.4% vs. 9.6%, p<0.01). The R0 resection rate was lower in the group with GOO (62.0% vs. 87.0%, p<0.01). The 5-year overall survival rate was also lower in the group with GOO (43.9% vs. 68.5%, p<0.01). However, in the subset of patients who underwent R0 surgery, the 5-year rates were similar for the two groups (67.4% vs. 73.1%, p=0.91). The multivariable analysis showed that a type 3 tumor appearance (odds ratio=3.66) and presence of GOO (odds ratio=2.87) were predictors of peritoneal carcinomatosis. The prevalence of radiologically occult peritoneal carcinomatosis in gastric cancer with GOO exceeded 30%. Staging laparoscopy (gastrojejunal bypass, if needed) should be performed to determine the optimal treatment plan.

MDCT Detection of Omental Metastases with Peritoneal Carcinomatosis and Ascites in Prostate Cancer: An unusual metastatic site

Prostate cancer is the second most common cause of cancer related death in males. The most common sites of prostate cancer metastases include bone and regional lymph nodes followed by lung, liver and brain. Peritoneal metastasis without skeletal involvement is extremely rare, with only a few cases reported in the literature. We present herein a patient of prostate cancer with omental metastases and peritoneal carcinomatosis accompanied by ascites but without bone metastases. The importance of this case report is to keep in mind that the lack of skeletal involvement does not exclude the possibility of distant metastases in prostate cancer. Prostate cancer can present with distant metastases in unexpected sites. The presence of ascites may indicate peritoneal involvement. KYAMC Journal Vol. 13, No. 02, July 2022: 124-126

Optimal cytoreductive LIVER surgery for unresectable colorectal liver metastases: A prospective observational study.

3570 Background: Patients with multiple colorectal liver metastases (CLM) involving all the hepatic segments are currently not eligible for potentially curative liver surgery. Transplantation is a promising alternative but graft shortage and stringent selection criteria limit its accessibility. Owing to the improving efficacy of chemotherapy, the impossibility to resect all the initial metastatic sites could lead to revisit the role of optimal cytoreductive liver surgery (CLS) aiming to treat by resection ± radiofrequency, all the macroscopic residual tumors after a good response to chemotherapy. Although validated for ovarian cancer and peritoneal carcinomatosis, this strategy remains unexplored in CLM. Our objective was to evaluate the outcome of this strategy in patients with definitively unresectable CLM. Methods: Within a prospective monocentric study, we enrolled for debulking surgery, between 2017 and 2021, all consecutive patients with multinodular unresectable CLM involving all segments on initial imaging and consequently ineligible for a curative surgery either after a one or two-stage hepatectomy. These patients should have a strong response to chemotherapy ( &gt; 50 % on RECIST criteria) for at least a 3-month period and no or limited extrahepatic disease, to be included. End-points of the analysis were overall and disease-free survival at 3 years. Results: Among 26 patients considered for this strategy, optimal CLS could be achieved in 21 patients after a median interval of 10 months from CLM diagnosis. The median number of lesions was 11 (7 - 26) on initial imaging. Four patients (19%) had synchronous lung metastases. Liver-first strategy was undertaken in 19 patients (90%). Postoperative complications (Grade ≥ III) occured in 5 patients (24%). One patient died within 90-day after operation from intra-abdominal hemorrage while on anticoagulation therapy. After a median follow-up of 25 months from hepatectomy, the 3-year OS rates was 85%. Median survival was not reached at the time of the analysis. Of the 4 (19%) patients with complete pathological response on the liver specimen, 3 developed recurrence. A total of 17 patients (81%) developed recurrence after a median time of 10,5 months from hepatectomy. Among them, repeat hepatectomy could be undertaken in four patients. The survival time to surgical failure (recurrence untreatable with curative intent) was 32% and 16% at 2 and 3 years. At last follow-up, seven patients (33%) are alive and recurrence-free. Conclusions: The promising results of this prospective series suggest that CLS may be worthy in patients with diffuse CLM non curatively treatable by surgery but responding well to chemotherapy. This strategy should however be reserved to hyperselected patients, super responders, eligible for an optimal resection of all the macroscopic residual tumors, and confimed by other expert centers, to be definitively validated.

Preoperative prognostic factors for obstructive colorectal cancer.

The aim of the study was to determine the preoperative predictive factors of overall survival, relapse-free survival, and peritoneal carcinomatosis in obstructive colorectal cancer. Data from patients undergoing emergency surgery for obstructive colorectal cancer at our center between 2004 and 2016 were extracted retrospectively from our health records. Several preoperative parameters were used to predict survival and peritoneal carcinomatosis using univariate and multivariate analysis, and ROC curves. A total of 107 patients with obstructive colorectal cancer were included. Five-year relapse-free and overall survival rates were 14% and 28%, respectively, with 15% peritoneal carcinomatosis. Univariate analysis showed that age ≥ 83years old, preoperative ASA score ≥ 3, initial hemodynamic instability, and CRP > 18.3mg/L was significantly associated with worse relapse-free and overall survival. In a multivariate analysis, only age > 83years (HR = 1.75; HR = 2.16, for relapse-free and overall survival status, respectively) and hemodynamic instability (HR = 7.29; HR = 6.55) were confirmed in the multivariate model. Global peritoneal carcinomatosis was significantly associated with synchronous liver metastases in the multivariate model (OR = 4.56), and synchronous peritoneal carcinomatosis only was significantly associated with platelet to lymphocyte ratio (PLR) > 269 and synchronous liver metastases in the multivariate model (OR = 0.003; OR = 7.26). Synchronous liver metastases are prognostic risk factor for global and synchronous peritoneal carcinomatosis whereas PLR > 269 was a significant protective factor for synchronous peritoneal carcinomatosis only for obstructive colorectal cancer. Age > 83years and initial hemodynamic instability were key preoperative prognostic risk factors for worse relapse-free and overall survival. Prognostic usefulness of blood cell ratios for mortality and peritoneal carcinomatosis warrants further investigation.

Conversion Surgery in Gastric Cancer Carcinomatosis.

BackgroundAfter the REGATTA trial, patients with stage IV gastric cancer could only benefit from chemotherapy (CHT). However, some of these patients may respond extraordinarily to palliative chemotherapy, converting their disease to a radically operable stage. We present a single centre experience in treating peritoneal carcinomatosis from gastric cancer.MethodsAll patients with stage IV gastric cancer with peritoneal metastases as a single metastatic site operated at a single centre between 2005 and 2020 were included. Cases were grouped according to the treatment received.ResultsA total of 118 patients were considered, 46 were submitted to palliative gastrectomy (11 were considered M1 because of an unsuspected positive peritoneal cytology), and 20 were submitted to Hyperthermic Intraperitoneal Chemotherapy (HIPEC) because of a <6 Peritoneal Cancer Index (PCI). The median overall survival (OS) after surgery plus HIPEC was 46.7 (95% CI 15.8–64.0). Surgery (without HIPEC) after CHT presented a median OS 14.4 (8.2–26.8) and after upfront surgery 14.7 (10.9–21.1). Patients treated with upfront surgery and considered M1 only because of a positive cytology, had a median OS of 29.2 (25.2–29.2). The OS of patients treated with surgery plus HIPEC were 60.4 months (9.2–60.4) in completely regressed cancer after chemotherapy and 31.2 (15.8–64.0) in those partially regressed (p = 0.742).ConclusionsConversion surgery for peritoneal carcinomatosis from gastric cancer was associated with long survival and it should always be taken into consideration in this group of patients.

Looking for a strategy in treating peritoneal gastric cancer carcinomatosis: an Italian multicenter Gastric Cancer Research group\u2019s analysis

BackgroundThe present study provides a snapshot of Italian patients with peritoneal metastasis from gastric cancer treated by surgery in Italian centers belonging to the Italian Research Group on Gastric Cancer. Prognostic factors affecting survival in such cohort of patients were evaluated with the final aim to identify patients who may benefit from radical intent surgery.MethodsIt is a multicentric retrospective study based on a prospectively collected database including demographics, clinical, surgical, pathological, and follow-up data of patients with gastric cancer and synchronous macroscopic peritoneal metastases. Patients were surgically treated from January 2005 to January 2017. We focused on patients with macroscopic peritoneal carcinomatosis (PC) treated with upfront surgery in order to provide homogeneous evidences.ResultsOur results show that patients with peritoneal carcinomatosis cannot be considered all lost. Strictly selected cases (R0/R1 and P1 patients) could benefit from an aggressive surgical approach performing an extended lymphadenectomy and HIPEC treatment.ConclusionThe main result of the study is that GC patients with limited peritoneal involvement can have a survival benefit from a surgery with “radical oncological intent”, that means extended lymphadenectomy and R0 resection. The retrospective nature of this study is an important bias, and for this reason, we have started a prospective multicentric study including Italian stage IV patients that hopefully will give us more answers.

Slug and CD133 expression are associated with peritoneal carcinomatosis and survival in gastric cancer.

Slug is an activating transcription factor involved in epithelial-mesenchymal transition, and CD133 is a cancer stem cell marker found in various cancers, including gastric cancer (GC). We investigated the relationship between Slug and CD133 and the occurrence of peritoneal carcinomatosis and survival in patients with GC. This retrospective study included 196 patients with stage 2 or 3 GC who underwent curative surgery with D2 lymph node dissection and adjuvant chemotherapy between 2001 and 2009. We analyzed the expression of Slug, CD133, ABCG2, E-cadherin, vimentin, NEDD9, and SMAD4 in surgical tissue specimens using immunohistochemical analysis to determine their prognostic value. Among the 196 patients, expression of Slug was elevated in 157 tumors (81%) while the expression of CD133 was high in 153 tumors (81%). The expression of Slug and CD133 in combination significantly predicted peritoneal relapse (P=0.002). High Slug and high CD133 expression were significantly associated with poor peritoneal relapse-free survival [hazard ratio (HR), 7.239; P=0.007] and overall survival (HR, 1.682; P=0.027) in multivariate Cox analysis. Our study shows that a high Slug and high CD133 expression status is predictive of peritoneal recurrence in high-risk resected GC patients. They are also a poor prognostic factor for peritoneal relapse-free survival and overall survival.

Little Clinical Relevance of Ca125, Cea and Ca125/Cea Ratio for the Differential Diagnosis of Ovarian and Non- Ovarian Carcinomatosis

Background In women, peritoneal cancer is commonly associated to epithelial ovarian cancer. Ovarian peritoneal carcinomatosis patient survival appears to be better in comparison to other peritoneal Malignancies, e.g., colorectal neoplasms or mesotheliomas. Here, we aim to analyze the value of CA125, CEA, CA125/CEA ratio (CCR) tumor markers as preoperative tools for the diagnosis ovarian cancer. Material and methods: From 2005-2008, we recruit prospectively patients admitted to the Navarre Hospital Complex Gynecological service with peritoneal carcinomatosis and suspicion of ovarian cancer origins. The final diagnosis of ovarian cancer carcinomatosis or other malignancies was obtained through Biopsy or cytology. CA 125, CEA and CCR were determined from preoperative venous blood Samples. We compared the tumor markers values between groups of ovarian cancer carcinomatosis and non-ovarian cancer carcinomatosis and calculate the receiver operating curves (ROC) for CA 125, CEA and CCR. Results From 250 patients with suspicion of having ovarian peritoneal carcinomatosis, only 86.4% of the Cases were finally diagnosis of ovarian cancer. Sensitivities of CA125 &gt; 35 mg/dL, CEA &lt; 5 ngr/mL, and CCR &gt; 25 were 95.5%, 91.9%, and 93.6% with specificities of 4.6%, 40.9% and 40.0%, respectively. ROC displayed poor performance for CA125 and CEA for detecting ovarian peritoneal carcinomatosis patients (area under the curve (AUC): 0.69 and 0.63, respectively) while ROC analysis of CCR showed better results (AUC: 0.74). Conclusions: CCR is somehow useful to differentiate between ovarian and non-ovarian peritoneal carcinomatosis patients in comparison with CA125 and CEA alone, although without sufficient specificity for improving the differential diagnosis.