Is Systemic Chemotherapy Useful in Patients Treated with Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy (HIPEC) for Colorectal Peritoneal Metastases? A Propensity-Score Analysis.

PURPOSE: Multimodal treatment of colorectal (CRC) peritoneal metastases (PM) includes systemic chemotherapy (SC) and surgical cytoreduction (CRS), eventually with hyperthermic intraperitoneal chemotherapy (HIPEC), in select patients. Considering lack of clear guidelines, this study was designed to analyze the role of chemotherapy and its timing in patients treated with CRS-HIPEC. METHODS: Data from 13 Italian centers with PM expertise were collected by a collaborative group of the Italian Society of Surgical Oncology (SICO). Clinicopathological variables, SC use, and timing of administration were correlated with overall survival (OS), disease-free survival (DFS), and local (peritoneal) DFS (LDFS) after propensity-score (PS) weighting to reduce confounding factors. RESULTS: A total of 367 patients treated with CRS-HIPEC were included in the propensity-score weighting. Of the total patients, 19.9% did not receive chemotherapy within 6 months of surgery, 32.4% received chemotherapy before surgery (pregroup), 28.9% after (post), and 18.8% received both pre- and post-CRS-HIPEC treatment (peri). SC was preferentially administered to younger (p = 0.02) and node-positive (p = 0.010) patients. Preoperative SC is associated with increased rate of major complications (26.9 vs. 11.3%, p = 0.0009). After PS weighting, there were no differences in OS, DFS, or LDFS (p = 0.56, 0.50, and 0.17) between chemotherapy-treated and untreated patients. Considering SC timing, the post CRS-HIPEC group had a longer DFS and LDFS than the pre-group (median DFS 15.4 vs. 9.8 m, p = 0.003; median LDFS 26.3 vs. 15.8 m, p = 0.026). CONCLUSIONS: In patients with CRC-PM treated with CRS-HIPEC, systemic chemotherapy was not associated with overall survival benefit. The adjuvant schedule was related to prolonged disease-free intervals. Additional, randomized studies are required to clarify the role and timing of systemic chemotherapy in this patient subset.

Microsatellite and RAS/RAF Mutational Status as Prognostic Factors in Colorectal Peritoneal Metastases Treated with Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy (HIPEC).

BACKGROUND: Cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) leads to prolonged survival for selected patients with colorectal (CRC) peritoneal metastases (PM). This study aimed to analyze the prognostic role of micro-satellite (MS) status and RAS/RAF mutations for patients treated with CRS. METHODS: Data were collected from 13 Italian centers with PM expertise within a collaborative group of the Italian Society of Surgical Oncology. Clinical and pathologic variables and KRAS/NRAS/BRAF mutational and MS status were correlated with overall survival (OS) and disease-free survival (DFS). RESULTS: The study enrolled 437 patients treated with CRS-HIPEC. The median OS was 42.3 months [95% confidence interval (CI), 33.4-51.2 months], and the median DFS was 13.6 months (95% CI, 12.3-14.9 months). The local (peritoneal) DFS was 20.5 months (95% CI, 16.4-24.6 months). In addition to the known clinical factors, KRAS mutations (p = 0.005), BRAF mutations (p = 0.01), and MS status (p = 0.04) were related to survival. The KRAS- and BRAF-mutated patients had a shorter survival than the wild-type (WT) patients (5-year OS, 29.4% and 26.8% vs 51.5%, respectively). The patients with micro-satellite instability (MSI) had a longer survival than the patients with micro-satellite stability (MSS) (5-year OS, 58.3% vs 36.7%). The MSI/WT patients had the best prognosis. The MSS/WT and MSI/mutated patients had similar survivals, whereas the MSS/mutated patients showed the worst prognosis (5-year OS, 70.6%, 48.1%, 23.4%; p = 0.0001). In the multivariable analysis, OS was related to the Peritoneal Cancer Index [hazard ratio (HR), 1.05 per point], completeness of cytoreduction (CC) score (HR, 2.8), N status (HR, 1.6), signet-ring (HR, 2.4), MSI/WT (HR, 0.5), and MSS/WT-MSI/mutation (HR, 0.4). Similar results were obtained for DFS. CONCLUSION: For patients affected by CRC-PM who are eligible for CRS, clinical and pathologic criteria need to be integrated with molecular features (KRAS/BRAF mutation). Micro-satellite status should be strongly considered because MSI confers a survival advantage over MSS, even for mutated patients.

Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy for Gastric Cancer with Synchronous Peritoneal Metastases: Multicenter Study of 'Italian Peritoneal Surface Malignancies Oncoteam-S.I.C.O.'

BACKGROUND: The development of multimodality treatment, including cytoreductive surgery (CRS) with heated intraperitoneal chemotherapy (HIPEC), has led to promising results in selected patients with peritoneal disease of gastric origin. The aim of this study was to investigate the short- and long-term outcomes of CRS/HIPEC in the treatment of synchronous peritoneal metastasis in gastric cancer. METHODS: The Italian Peritoneal Surface Malignancies Oncoteam-S.I.C.O. retrospective registry included patients with synchronous peritoneal malignancy from gastric cancer submitted to gastrectomy with CRS and HIPEC between 2005 and 2018 from 11 high-volume, specialized centers. RESULTS: A total of 91 patients with a median age of 58 years (range 26-75) were enrolled. The median overall survival (OS) time for the whole group of patients was 20.2 months (95% confidence interval [CI] 11.8-28.5] and the median recurrence-free survival (RFS) was 7.3 months (95% CI 4-10.6). The completeness of cytoreduction score (CCS) of 0 and Peritoneal Cancer Index (PCI) score of ≤ 6 groups showed a significantly better long-term survival (median OS 40.7 and 44.3 months, respectively) compared with the incomplete resected groups (median OS 10.7 months, p = 0.003) and PCI score of > 6 group (median OS 13.4 months, p = 0.005). A significant difference was observed in the survival rate according to neoadjuvant treatment (untreated patients: 10.7 months, 95% CI 5.1-16.2; treated patients: 35.3 months, 95% CI 2.8-67.8; p = 0.022). CONCLUSIONS: In referral centers, CRS and HIPEC after neoadjuvant treatment significantly improved survival in selected patients. Patients with a PCI score ≤ 6, complete cytoreduction, negative nodal involvements, and negative cytology had encouraging results, showing a clinically meaningful survival.

Upfront debulking surgery versus interval debulking surgery for advanced tubo-ovarian high-grade serous carcinoma and diffuse peritoneal metastases treated with peritonectomy procedures plus HIPEC.

BACKGROUND: Whether patients with advanced tubo-ovarian high-grade serous cancer (HGSC) fare better after upfront debulking surgery (UDS) or neoadjuvant chemotherapy with interval debulking surgery (NACT-IDS) remains controversial. METHODS: We studied patients with HGSC who underwent UDS or NACT-IDS between July 2000 and December 2015, with peritonectomy procedures combined with hyperthermic intraperitoneal chemotherapy (HIPEC). Clinical reports were included peritoneal cancer index (PCI), NACT responses, surgical complexity score (SCS), completeness of cytoreduction (CC), complete follow-up with timing, site, and treatment of recurrence. Outcome measures were morbidity, progression-free survival (PFS), PFS2, and overall survival during a mean 5-year follow-up. RESULTS: A total of 34 patients (23.6%) underwent UDS and 110 (76.4%) NACT-IDS both combined with HIPEC. At a median 66.3-month follow-up, patients who underwent UDS or NACT-IDS had similar outcomes. NACT subgroup responses correlated with PCI, SCS, morbidity, and CC. Patients who underwent UDS had lower recurrence rates than those who responded partly or poorly to NACT (PFS, P < .04; PFS2, P < .01). Despite HIPEC, the peritoneal disease recurred in 42.5% of the overall patients. CONCLUSION: In patients with primary HGSC who undergo UDS or NACT-IDS, despite similar outcomes, peritonectomy procedures combined with HIPEC seem unable to prevent peritoneal recurrence.

Cytoreduction (Peritonectomy Procedures) Combined with Hyperthermic Intraperitoneal Chemotherapy (HIPEC) in Advanced Ovarian Cancer: Retrospective Italian Multicenter Observational Study of 511 Cases.

PURPOSE: The aim of this study was to help with the process of selecting patients with advanced ovarian cancer to undergo cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) by analyzing outcome data at distinct clinical time points reflecting the natural history of the disease. METHODS: In a retrospective Italian multicenter study investigating patients with advanced ovarian cancer who underwent CRS plus HIPEC between 1998 and 2014, we analyzed data for consecutive patients at eight treatment time points: primary debulking surgery (PDS); interval debulking surgery after partial response, after no response, and after a pathologic complete response to neoadjuvant chemotherapy; first recurrence with a progression-free interval >12, <12 months, or >12 months in patients who underwent further chemotherapy before CRS and HIPEC; and patients who underwent two or more CRS procedures and chemotherapy lines before CRS and HIPEC. RESULTS: The 511 enrolled patients underwent 3373 procedures; 72.6% achieved complete cytoreduction, with an overall major morbidity of 17.4%. At a median follow-up of 53.8 months, overall survival (OS) was 54.2 months (95% confidence interval [CI] 44-58.4) and progression-free (PFS) survival was 16.6 months (95% CI 14.7-19.1). Outcome analysis in patients in whom CRS plus HIPEC was used for primary advanced cancer or recurrent ovarian cancer showed significant differences in OS and PFS according to the time points analyzed. Multivariate analysis identified completeness of CRS, Peritoneal Cancer Index, and the times when patients underwent CRS plus HIPEC as independent prognostic factors. CONCLUSIONS: This selective information on survival should help in interpreting the findings from ongoing randomized studies focusing on CRS plus HIPEC in patients with advanced ovarian cancer.

Evaluation of cisplatin plasma levels in patients undergoing cytoreductive surgery and hyperthermic intraperitoneal chemotherapy.

Introduction Peritoneal surface malignancies have long been regarded as incurable, however, they can be treated with cytoreductive surgery in addition to hyperthermic intraperitoneal chemotherapy. This approach is associated with an increase in morbidity and mortality, unless hyperhydration is provided in a timely manner. Methods Cisplatin (CDDP) is the most widely used chemotherapeutic agent. Plasma levels of cisplatin (CDDP), a widely used chemotherapeutic agent, were measured before, during, and after the procedure. This was done in order to identify the window of highest risk as a function of drug concentrations, assuming a dose-dependent effect. Results Plasma levels of CDDP peak during perfusion. The concentration remains high until the 4th post-operative day and returns to pre-operative levels by the 7th post-operative day. Conclusions Our findings suggest that ensuring hyperhydration as well as infusing albumin and fresh frozen plasma may be of particular value for at least the first 4 days after the procedure.

10 Years of Pressurized Intraperitoneal Aerosol Chemotherapy (PIPAC): A Systematic Review and Meta-Analysis.

BACKGROUND: Pressurized intraperitoneal aerosol chemotherapy (PIPAC) is a novel intraperitoneal drug delivery method of low-dose chemotherapy as a pressurized aerosol in patients affected by peritoneal cancer of primary or secondary origin. We performed a systematic review and meta-analysis with the aim of assessing the feasibility, safety, and efficacy of PIPAC. METHODS: A systematic literature search was performed using Medline and Web of Science databases from 1 January 2011, to inception, to 31 December 2021. Data were independently extracted by two authors. The Newcastle-Ottawa Scale was used to assess the quality and risk of bias of studies. Meta-analysis was performed for pathological response, radiological response, PCI variation along treatment, and for patients undergoing three or more PIPAC. Pooled analyses were performed using the Freeman-Tukey double arcsine transformation, and 95% CIs were calculated using Clopper-Pearson exact CIs in all instances. RESULTS: A total of 414 papers on PIPAC were identified, and 53 studies considering 4719 PIPAC procedure in 1990 patients were included for analysis. The non-access rate or inability to perform PIPAC pooled rate was 4% of the procedures performed. The overall proportion of patients who completed 3 or more cycles of PIPAC was 39%. Severe toxicities considering CTCAE 3-4 were 4% (0% to 38.5%). In total, 50 studies evaluated deaths within the first 30 postoperative days. In the included 1936 patients were registered 26 deaths (1.3%). The pooled analysis of all the studies reporting a pathological response was 68% (95% CI 0.61-0.73), with an acceptable heterogeneity (I2 28.41%, p = 0.09). In total, 10 papers reported data regarding the radiological response, with high heterogeneity and a weighted means of 15% (0% to 77.8%). PCI variation along PIPAC cycles were reported in 14 studies. PCI diminished, increased, or remained stable in eight, one and five studies, respectively, with high heterogeneity at pooled analysis. Regarding survival, there was high heterogeneity. The 12-month estimated survival from first PIPAC for colorectal cancer, gastric cancer, gynecological cancer and hepatobiliary/pancreatic cancer were, respectively, 53%, 25%, 59% and 37%. CONCLUSIONS: PIPAC may be a useful treatment option for selected patients with PM, with acceptable grade 3 and 4 toxicity and promising survival benefit. Meta-analysis showed high heterogeneity of data among up-to-date available studies. In a subset analysis per primary tumor origin, pathological tumor regression was documented in 68% of the studies with acceptable heterogeneity. Pathological regression seems, therefore, a reliable outcome for PIPAC activity and a potential surrogate endpoint of treatment response. We recommend uniform selection criteria for patients entering a PIPAC program and highlight the urgent need to standardize items for PIPAC reports and datasets.

Repeated Cytoreduction Combined with Hyperthermic Intraperitoneal Chemotherapy (HIPEC) in Selected Patients Affected by Peritoneal Metastases: Italian PSM Oncoteam Evidence.

The reiteration of surgical cytoreduction (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) in patients affected by recurrent peritoneal metastases is still questioned regarding safety and effectiveness. This study evaluates the safety, efficacy, and associated factors of iterative CRS combined with HIPEC. This multicentric retrospective study collected data from four surgical oncology centers, on iterative HIPEC. We gathered data on patient and cancer characteristics, the peritoneal cancer index (PCI), completeness of cytoreduction (CC), postoperative complications, and overall survival (OS). In the study period, 141 CRS-plus-HIPECs were performed on 65 patients. Nine patients underwent three iterative procedures, and one underwent five. No increased incidence of complications after the second or third procedure was observed. Furthermore, operative time and hospitalization stay were significantly shorter after the second than after the first procedure (p < 0.05). Optimal cytoreduction was achieved in more than 90% of cases in each procedure, whether first, second, or third. A five-year (5 y) OS represented 100% of the cases of diffuse malignant-peritoneal-mesotheliomas, 81.39% of pseudomyxoma peritonei, 34.67% of colorectal cancer (CRC), and 52.50% of ovarian cancer. During the second CRS combined with HIPEC, we observed a lower rate of complete cytoreduction and a non-significantly better survival in cases with complete cytoreduction (5 y-OS CC-0 56.51% vs. 37.82%, p = 0.061). Concomitant hepatic-CRC-metastasis did not compromise the CRS-plus-HIPEC safety and efficacy. This multicentric experience encourages repeated CRS-plus-HIPEC, showing promising results.

External validation of COMPASS and BIOSCOPE prognostic scores in colorectal peritoneal metastases treated with cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (HIPEC).

INTRODUCTION: The selection of patients undergoing cytoreductive- surgery (CRS) followed by hyperthermic intraperitoneal chemotherapy (HIPEC) is crucial. BIOSCOPE and COMPASS are prognostic scores designed to stratify survival into four classes according to clinical and pathological features. The purpose of this study is to analyze the prognostic role of these scores using a large cohort of patients as an external reference. METHODS: Overall survival analysis was performed using Log-Rank and Kaplan-Meier curves for each score. The probability of survival at 12, 36, and 60 months was tested using receiver operating characteristic (ROC) curves to determine sensitivity and specificity. RESULTS: From the validation cohort of 437 patients, the analysis included 410 patients in the COMPASS group and 364 patients in the BIOSCOPE group (100% data completeness). We observed a different patient distribution between classes (high-risk for BIOSCOPE compared to COMPASS, p = 0.0001). Nevertheless, both COMPASS and BIOSCOPE effectively stratified overall survival (Log-Rank, p = 0.0001 in both cases), with a lack of discrimination between COMPASS classes II and III (p = n.s.). COMPASS at 12 m and BIOSCOPE at 60 m showed the best performance in terms of survival prediction (AUC of 0.82 and 0.81). The specificity of the two tests is good (median 81.3%), whereas sensibility is quite low (median 64.2%). CONCLUSION: Following external validation in a large population of patients with CRC-PM who are eligible for surgery, the COMPASS and BIOSCOPE scores exhibit high inter-test variability but effectively stratify cancer-related mortality risk. While the quality of the scores is similar, BIOSCOPE shows better inter-tier differentiation, suggesting that tumor molecular classification could improve test discrimination capability. More powerful stratification scores with the inclusion of novel predictors are needed.

Doppler perfusion index and colorectal hepatic metastases: personal experience and review of the literature.

BACKGROUND/AIMS: To evaluate the role of the hepatic perfusion in the assessment of the colorectal cancer. METHODOLOGY: For this research 18 patients affected by colorectal cancer were enrolled. All the patients were submitted to the evaluation of the Doppler Perfusion Index (DPI) which represents the ratio of hepatic arterial to total liver blood flow. RESULTS: The correlation between the evaluation of the Doppler Perfusion Index and the occurrence of the liver metastases did not show false negative but has highlighted 6 false positive, achieved a good sensitivity and very low specificity. CONCLUSIONS: A review of the literature and the results obtained in our study suggest that DPI may be helpful in detection of hepatic metastases.

[Coping styles in schizophrenia: study of clinical and functional variables as determinants of strategies to cope with stress]. / Strategie di coping nella schizofrenia: studio delle variabili cliniche e funzionali come determinanti delle modalità di adattamento allo stress.

AIM: The purpose of this study was to analyze the relation between coping styles, and both clinical and functional variables in a sample of patients with stable schizophrenia. METHODS: Forty-seven consecutive outpatients were enrolled in a cross-sectional study. A clinical assessment was performed and included: the Positive and Negative Syndrome Scale (PANSS), the Calgary Depression Scale for Schizophrenia (CDSS), the Scale for the Assessment of Unawareness of Mental Disorder (SUMD), the Rosenberg Self-Esteem Scale (RSES), the Quality of Life Scale (QLS) and the questionnaire Short Form Health Survey 36 (SF-36). Coping strategies were assessed with the Coping Inventory for Stressful Situations (CISS), identifying three main coping styles: task-, emotion- and avoidance-oriented. Three different multiple regression models with backward elimination were performed in order to discover contributing factors to coping styles. RESULTS: From the results of multiple regression, depressive symptoms and objective quality of life were contributing factors to task-oriented coping style, explaining about 32% of variance. Negative symptoms, subjective quality of life, self-esteem, awareness of symptomatology and attribution of symptoms to illness resulted to be contributing factors to emotion-oriented coping strategies, explaining about 60% of variance. DISCUSSION: These results suggested the role of some clinical and functional variables as contributing factors to coping styles. In this context, supportive and rehabilitative interventions and cognitive-behavioral therapy focused to manage psychotic symptoms and to decrease distress could help patients to employ more adaptive coping strategies and improve their outcomes.

Pseudomyxoma peritonei involving the canal of Nuck: The added value of magnetic resonance imaging for detection and presurgical planning.

The canal of Nuck is an abnormal patent pouch of the parietal peritoneum caused by the incomplete obliteration of the processus vaginalis in females. The most common disorders of the canal of Nuck are: hernia, hydrocele and endometriosis. Pseudomyxoma Peritonei (PMP) is a clinical condition characterized by the accumulation of mucinous material on the surfaces and in the recesses of the peritoneal cavity, resulting from the perforation of an appendiceal mucinous neoplasm. We report the case of a young woman with a clinical history of chronic pelvic pain and infertility who was referred to our center after being diagnosed with appendiceal mucinous neoplasm and PMP. MRI staging examination revealed the right canal of Nuck filled with mucinous material, which was confirmed at surgery. The involvement of canal of Nuck is extremely rare in PMP. MRI provides a sensitive imaging modality for appropriate preoperative planning of PMP and helps surgeons identify uncommon disease sites such such as the canal of Nuck in women, which, if missed, may prevent complete cytoreductive surgery.

Chemical Characterization, Antibacterial Activity, and Embryo Acute Toxicity of Rhus coriaria L. Genotype from Sicily (Italy).

This study reports a full characterization of the Sicilian sumac, Rhus coriaria L. This fruit represents a potential source of fiber (33.21 ± 1.02%) and unsaturated fatty acids, being the contents of linoleic and α-linolenic acids, 30.82 ± 1.21% and 1.85 ± 0.07%, respectively. In addition, the content of phenolic and total anthocyanin was 71.69 ± 1.23 mg/g as gallic acid equivalents, and 6.71 ± 0.12 mg/g as cyanidin-3-O-glucoside equivalents, respectively. The high content in mineral elements, consisting mainly of potassium, calcium, magnesium, and phosphorus, followed by aluminum, iron, sodium, boron, and zinc, was detected by inductively coupled plasma mass spectrometry (ICP-MS). Moreover, its antimicrobial activity was evaluated against multidrug resistant (MDR) microorganisms, represented by Escherichia coli and Klebsiella pneumoniae strains isolated from poultry. The activity of seven different sumac fruit extracts obtained using the following solvents-ethanol (SE), methanol (SM), acetone (SA), ethanol and water (SEW), methanol and water (SMW), acetone and water (SAW), water (SW)-was evaluated. The polyphenol profile of SM extract, which showed better activity, was analyzed by ultra-high performance liquid chromatography coupled with mass spectrometry (UHPLC-MS). The major component identified was gallic acid, followed by quercetin, methyl digallate, pentagalloyl-hexoside, and kaempferol 3-O-glucoside. The non-toxicity of Sicilian R. coriaria was confirmed by testing the effect of the same extract on zebrafish embryos.

Mineral and Microbiological Analysis of Spices and Aromatic Herbs.

Spices and aromatic herbs have always had great historical importance in human nutrition. Their use has been documented for centuries as a rich source of bioactive compounds; they have been used for their health benefits and also for flavoring or coloring food. However, despite the many health properties linked to the use of spices and aromatic herbs, these can represent biological hazards and can contain chemical substances of concern. Certainly, monitoring potential health hazards in spices and aromatic herbs includes microbiological safety and also the content of inorganic substances: both represent a key step. This research aims at monitoring the compliance of various spices and aromatic herbs from a non-European country market (namely: black cumin seeds, Iranian Tokhme Sharbati, clove buds, Shahjeera, Abbaszadeh saffron, organic fenugreek, whole black pepper, cinnamon, Abthul Ahmar (Asario), Ajwan seeds, whole coriander seeds, black sesame seeds, Sabja seeds) with the current European Union (EU) and WHO regulations, when available, regarding mineral and microbiological parameters. In particular, microbiological assays using rapid and conventional methods, and trace mineral determination by inductively coupled plasma mass spectrometry (ICP-MS) were performed. Results show the safety of the tested spices, given that the microbiological parameters were within the legal microbiological criteria set by the European Commission Regulation (EC) No. 2073/2005 and its amendment Regulation (EC) No. 1441/2007. With reference to potentially toxic Cd, Pb, As, Hg, these were within the limits set by the European Commission Regulation (EC) No. 1881/2006 and its amendments, Regulation (EU) No. 1317/2021 and Regulation (EU) No. 1323/2021, and WHO. According to EU regulations, for Pb content, 2 samples out of 16 showed values different from the set limits.

Complications and Mortality Rate of Cytoreductive Surgery with Hyperthermic Intraperitoneal Chemotherapy: Italian Peritoneal Surface Malignancies Oncoteam Results Analysis.

BACKGROUND: Cytoreductive surgery with hyperthermic intraperitoneal chemotherapy may significantly improve survival for selected patients with peritoneal surface malignancies, but it has always been criticized due to the high incidence of postoperative morbidity and mortality. METHODS: Data were collected from nine Italian centers with peritoneal surface malignancies expertise within a collaborative group of the Italian Society of Surgical Oncology. Complications and mortality rates were recorded, and multivariate Cox analysis was used to identify risk factors. RESULTS: The study included 2576 patients. The procedure was mostly performed for ovarian (27.4%) and colon cancer (22.4%). The median peritoneal cancer index was 13. Overall postoperative morbidity and mortality rates were 34% and 1.6%. A total of 232 (9%) patients required surgical reoperation. Multivariate regression logistic analysis identified the type of perfusion (p ≤ 0.0001), body mass index (p ≤ 0.0001), number of resections (p ≤ 0.0001) and colorectal resections (p ≤ 0.0001) as the strongest predictors of complications, whereas the number of resections (p ≤ 0.0001) and age (p = 0.01) were the strongest predictors of mortality. CONCLUSIONS: Cytoreductive surgery with hyperthermic intraperitoneal chemotherapy is a valuable option of treatment for selected patients with peritoneal carcinomatosis providing low postoperative morbidity and mortality rates, if performed in high-volume specialized centers.

Pressurized intraperitoneal aerosol chemotherapy (PIPAC) in multimodal therapy for patients with oligometastatic peritoneal gastric cancer: a randomized multicenter phase III trial PIPAC VEROne.

Objectives: Peritoneal carcinomatosis is the most frequent site of metastases in patients with gastric cancer. Current standard treatment is palliative systemic chemotherapy with very poor prognosis. Cytoreductive surgery (CRS) combined with hyperthermic intraperitoneal chemotherapy (HIPEC) resulted in long-term benefits in selected patients. Among patients with peritoneal carcinomatosis, a distinctive subset is oligometastatic disease which is characterized by low metastatic burden. Pressurized intraperitoneal aerosol chemotherapy (PIPAC) is a recent technique of intraperitoneal chemotherapy used in combination with systemic chemotherapy with promising results. Methods: PIPAC VER-One is a prospective, randomized, multicenter phase III clinical trial that aims to evaluate the effectiveness of the use of PIPAC in combination with systemic chemotherapy in patients with gastric cancer and synchronous positive peritoneal cytology and/or limited peritoneal metastases (peritoneal cancer index [PCI] ≤6). Patients will be randomized into two arms: arm A (control) treated with standard systemic chemotherapy and arm B (experimental) treated with a bidirectional scheme including PIPAC and systemic chemotherapy. Results: Primary endpoint is the secondary resectability rate. Secondary endpoints are: overall survival (OS), pregression-free survival (PFS), disease-free survival (DFS), histological response assessed both on primary tumor and peritoneal lesions, quality of life (QoL), complication rate (CTCAE v5), and incremental cost-effectiveness ratios (ICER). Conclusions: The role of PIPAC in multimodal treatment for oligometastatic gastric cancer will be investigated in this trial.

Corrigendum: Adenosine receptor stimulation by polydeoxyribonucleotide improves tissue repair and symptomology in experimental colitis.

[This corrects the article DOI: 10.3389/fphar.2016.00273.].