Impact of obesity after cytoreductive surgery and intraperitoneal hyperthermic chemotherapy for rare peritoneal malignancies: Paradox of obesity or poor prognostic factor?

BACKGROUND: Obesity is a public health concern with an increasing occurrence worldwide. Literature regarding impact of obesity on results after management of peritoneal carcinomatosis is poor. Our aim was to compare postoperative and oncological outcomes after cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for rare peritoneal malignancies according to the body mass index. METHODS: All the patients managed by cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for rare peritoneal malignancies (including mainly pseudomyxoma peritonei and peritoneal mesothelioma), between 1995 and 2020, were retrospectively included from the French national registry of rare peritoneal tumors. RESULTS: 1450 patients were retrospectively included (63.5 % female, mean age 54 ± 13 years). Patients were divided into two groups according to their body mass index: non-obese (n = 1248, 86 %) and obese (n = 202, 14 %). Overall morbidity was significantly lower in non-obese patients in comparison with obese patients (n = 532/1248, 43 % vs n = 106/202, 53 %, p = 0.009). Medical and surgical morbidities were significantly lower in non-obese patients in comparison with obese patients (423/1258, 34 % vs n = 86/202, 43 %, p = 0.02 and n = 321/1248, 26 % vs n = 67/202, 33 %, p = 0.003, respectively). One-, 5- and 10-year overall survivals were similar between non-obese and obese patients (95 %, 82 % and 70 % vs 94 %, 76 % and 63 %; p = 0.1). One-, 5- and 10-year disease free survivals were similar between non-obese and obese patients (84 %, 67 % and 61 % vs 79 %, 62 % and 56 %, p = 0.1). CONCLUSION: Obese patients have to be carefully managed after cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for rare peritoneal malignancies. Some perioperative prophylactic treatments could be specifically implemented to reduce thromboembolic events, metabolic and wound complications.

Long-term outcomes and survival analysis of cytoreductive surgery combined with hyperthermic intraperitoneal chemotherapy in patients with pseudomyxoma peritonei at a newly established peritoneal malignancy centre in Japan.

Background: Cytoreductive surgery (CRS) combined with hyperthermic intraperitoneal chemotherapy (HIPEC) is established in the management of pseudomyxoma peritonei (PMP), selected cases of peritoneal mesothelioma, and resectable colorectal or ovarian peritoneal metastases in Western countries. However, the efficacy and feasibility of these techniques are not well established in the Asian population, and little has been reported on long-term survival outcomes for surgically resected PMP patients. Materials and Methods: Retrospective analysis of a prospective database of short- and longer-term outcomes of consecutive patients who underwent CRS and HIPEC for PMP in a newly established peritoneal malignancy unit in Japan between 2010 and 2016. Results: A total of 105 patients underwent CRS and HIPEC and 57 maximal tumor debulking (MTD) for pseudomyxoma peritonei. In the CRS group, the primary tumor was appendiceal in 94 patients (90%) followed by ovarian and colorectal. Major postoperative complications occurred in 22/105 patients (21%) with one in-hospital mortality (0.9%). The 5-year overall and disease-free survival rates for the CRS group were 74.2% and 50.1%, respectively. Multivariate analysis revealed unfavorable histology to be the significant predictor of reduced overall and disease-free survival. Completeness of cytoreduction, CA19-9, and CA125 were also associated with disease-free survival. Conclusions: This is the first report on long-term outcomes and survival analysis of CRS and HIPEC for PMP in the Asian population. CRS and HIPEC can be conducted with reasonable safety and favorable survival in a new center. Complete tumor removal and histological type are the strongest prognostic factors for both overall and disease-free survival.

Mesenteric lymph nodes: a critical site for the up-regulatory effect of hUC-MSCs on Treg cells by producing TGF-ß1 in colitis treatment.

BACKGROUND: Mesenchymal stem cells (MSCs) demonstrate a wide range of therapeutic capabilities in the treatment of inflammatory bowel disease (IBD). The intraperitoneal injection of MSCs has exhibited superior therapeutic efficacy on IBD than intravenous injection. Nevertheless, the precise in vivo distribution of MSCs and their biological consequences following intraperitoneal injection remain inadequately understood. Additional studies are required to explore the correlation between MSCs distribution and their biological effects. METHODS: First, the distribution of human umbilical cord MSCs (hUC-MSCs) and the numbers of Treg and Th17 cells in mesenteric lymph nodes (MLNs) were analyzed after intraperitoneal injection of hUC-MSCs. Subsequently, the investigation focused on the levels of transforming growth factor beta1 (TGF-ß1), a key cytokine to the biology of both Treg and Th17 cells, in tissues of mice with colitis, particularly in MLNs. The study also delved into the impact of hUC-MSCs therapy on Treg cell counts in MLNs, as well as the consequence of TGFB1 knockdown hUC-MSCs on the differentiation of Treg cells and the treatment of IBD. RESULTS: The therapeutic effectiveness of intraperitoneally administered hUC-MSCs in the treatment of colitis was found to be significant, which was closely related to their quick migration to MLNs and secretion of TGF-ß1. The abundance of hUC-MSCs in MLNs of colitis mice is much higher than that in other organs even the inflamed sites of colon. Intraperitoneal injection of hUC-MSCs led to a significant increase in the number of Treg cells and a decrease in Th17 cells especially in MLNs. Furthermore, the concentration of TGF-ß1, the key cytokine for Treg differentiation, were also found to be significantly elevated in MLNs after hUC-MSCs treatment. Knockdown of TGFB1 in hUC-MSCs resulted in a noticeable reduction of Treg cells in MLNs and the eventually failure of hUC-MSCs therapy in colitis. CONCLUSIONS: MLNs may be a critical site for the regulatory effect of hUC-MSCs on Treg/Th17 cells and the therapeutic effect on colitis. TGF-ß1 derived from hUC-MSCs promotes local Treg differentiation in MLNs. This study will provide new ideas for the development of MSC-based therapeutic strategies in IBD patients.

Enhanced recovery after surgery (ERAS) implementation in cytoreductive surgery (CRS) and hyperthermic IntraPEritoneal chemotherapy (HIPEC): Insights from Italian peritoneal surface malignancies expert centers.

BACKGROUND: Cytoreductive surgery (CRS) combined with Hyperthermic Intraperitoneal Chemotherapy (HIPEC) is a complex procedure that involves extensive peritoneal and visceral resections followed by intraperitoneal chemotherapy. The Enhanced Recovery After Surgery (ERAS) program aims to achieve faster recovery by maintaining pre-operative organ function and reducing the stress response following surgery. A recent publication introduced dedicated ERAS guidelines for CRS and HIPEC with the aim of extending the benefits to patients with peritoneal surface malignancies. METHODS: A survey was conducted among 21 Italian centers specializing in peritoneal surface malignancies (PSM) treatment to assess adherence to ERAS guidelines. The survey covered pre/intraoperative and postoperative ERAS items and explored attitudes towards ERAS implementation. RESULTS: All centers completed the survey, demonstrating expertise in PSM treatment. However, less than 30 % of centers adopted ERAS protocols despite being aware of dedicated guidelines. Preoperative optimization was common, with variations in bowel preparation methods and fasting periods. Intraoperative normothermia control was consistent, but fluid management practices varied. Postoperative practices, including routine abdominal drain placement and NGT management, varied greatly among centers. The majority of respondents expressed an intention to implement ERAS, citing concerns about feasibility and organizational challenges. CONCLUSIONS: The study concludes that Italian centers specialized in PSM treatment have limited adoption of ERAS protocols for CRS ± HIPEC, despite being aware of guidelines. The variability in practice highlights the need for standardized approaches and further evaluation of ERAS applicability in this complex surgical setting to optimize patient care.

Systemic immune responses do not affect significant immune responses in the skin.

Fish skin plays an important role in defending against pathogens in water, primarily through the secretion of skin mucus containing various immune-related factors. Local immune responses in the skin activate systemic immune responses by inflammatory cytokines. However, it remains unclear whether immune responses in the skin occur after systemic immune responses caused by pathogen invasion into the fish body. This study aimed to clarify the relationship between systemic immune responses and skin responses after intraperitoneal injection of formalin-killed cells (FKC) of Vibrio anguillarum. Although systemic inflammatory responses were observed in the spleen after injection, expression changes in the skin did not show significant differences. In contrast, expression of hemoglobin subunit genes significantly increased in the skin after FKC injection, suggesting that erythrocytes infiltrate extravascularly.

Clinical Significance of Circulating Tumor Cells in Epithelial Appendiceal Neoplasms with Peritoneal Metastases.

Appendiceal tumors are uncommon and, at times, discovered incidentally during histological examination. The histopathological classification of the disease is complex and has generated some controversy. The analysis of circulating tumor cells can be used for the early detection of metastatic potential. The aim of the present study was to examine the prognostic value of circulating tumor cells in patients with appendiceal tumors and peritoneal metastases. To our knowledge, this is the first study to examine CTCs in appendiceal tumors. We performed a prospective cohort study of consecutive patients treated with cytoreductive surgery and hyperthermic intraperitoneal chemotherapy between 2015 and 2019 at a HIPEC referral center. In total, 31 patients were included in the analysis, and circulating tumor cells were detected in 15 patients (48%). CTC positivity was not associated with overall or recurrence-free survival, nor was it correlated with PCI score or histopathological grading. Surprisingly, however, CTCs were found in almost half the patients. The presence or quantities of these cells did not, on their own, predict systemic metastatic potential during the observed time, and they did not appear to significantly correlate with the oncological outcomes recorded.

The role of multimodality imaging in the selection and management of patients treated with cytoreductive surgery and HIPEC.

Cytoreductive surgery (CRS) with or without hyperthermic intraperitoneal chemotherapy (HIPEC) is the mainstay of potentially curative surgical treatment for malignancies that have spread to peritoneal surfaces. This surgical procedure is however associated with high morbidity and appropriate patient selection and planning is therefore essential. Available multimodality imaging techniques include CT with oral and intravenous contrast, MRI including use of dedicated peritoneal protocol and FDG-PET/CT. These used with the correct technique, read by specialist radiologists and discussed under the auspices of a dedicated multidisciplinary team, can help to improve outcomes. We demonstrate that imaging not only provides information about peritoneal disease burden but more importantly want to shift the reader's focus to disease distribution. Our examples highlight how imaging helps avoid futile surgery by identifying patients with disease in unfavourable sites and show the strength and limitations of the various imaging modalities. We share how MR imaging can help identify multifocal and often occult sites including widespread miliary disease. Our examples provide a comprehensive overview demonstrating how imaging can help plan surgery by identifying patients who may need splenic vaccinations, counselling for stoma, egg harvesting and input from surgeons with other specialist expertise greatly increasing likelihood of achieving complete cytoreduction.

The impact of Paclitaxel-based hyperthermic intraperitoneal chemotherapy in advanced high-grade serous ovarian cancer patients - interim analysis of safety and immediate efficacy of a randomized control trial (C-HOC trial).

OBJECTIVE: This study evaluates the potential superiority of combining paclitaxel-based hyperthermic intraperitoneal chemotherapy (HIPEC) with sequential intravenous neoadjuvant chemotherapy over intravenous neoadjuvant chemotherapy alone in Chinese patients with Federation of Gynecology and Obstetrics (FIGO) stage IIIC, IVA and IVB high-grade serous ovarian/fallopian tube carcinoma (HGSOC). This interim analysis focuses on the safety and immediate efficacy of both regimens to determine the feasibility of the planned trial (C-HOC Trial). METHODS: In a single-center, open-label, randomized control trial, FIGO stage IIIC, IVA, and IVB HGSOC patients (FAGOTTI score ≥ 8 during laparoscopic exploration) unsuitable for optimal cytoreduction in primary debulking surgery (PDS) were randomized 2:1 during laparoscopic exploration. The Experiment Group (HIPEC Group) received one cycle of intraperitoneal neoadjuvant laparoscopic hyperthermic intraperitoneal chemotherapy (paclitaxel) followed by three cycles of intravenous chemotherapy (paclitaxel plus carboplatin), while the Control Group received only three cycles of intravenous chemotherapy. Both groups subsequently underwent interval debulking surgery (IDS). The adverse effects of chemotherapy, postoperative complications, and pathological chemotherapy response scores (CRS) after IDS were compared. RESULTS: Among 65 enrolled patients, 39 HIPEC Group and 21 Control Group patients underwent IDS. Grade 3-4 chemotherapy-related adverse effects were primarily hematological with no significant differences between the two groups. The HIPEC Group exhibited a higher proportion of CRS 3 (20.5% vs. 4.8%; P = 0.000). R0 resection rates in IDS were 69.2% (HIPEC Group) and 66.7% (Control Group). R2 resection occurred in 2.6% (HIPEC Group) and 14.3% (Control Group) cases. No reoperations or postoperative deaths were reported, and complications were managed conservatively. CONCLUSIONS: Combining HIPEC with IV NACT in treating ovarian cancer demonstrated safety and feasibility, with no increased chemotherapy-related adverse effects or postoperative complications. HIPEC improved tumor response to neoadjuvant chemotherapy, potentially enhancing progression-free survival (PFS). However, the final overall survival results are pending, determining if HIPEC combined with IV NACT is superior to IV NACT alone.

Nephrotoxicity Associated with Cytoreductive Surgery Combined with Cisplatin-Based Hyperthermic Intraperitoneal Chemotherapy for Peritoneal Malignant Disease: A Systematic Review and Meta-Analysis.

Background: Cisplatin is employed in hyperthermic intraperitoneal chemotherapy (HIPEC) after cytoreductive surgery (CRS) for peritoneal surface malignancies (PSMs). The main concern regarding intraperitoneal cisplatin administration is nephrotoxicity. Numerous reports in this context are available. Our objective was to conduct a systematic review and meta-analysis to assess cisplatin-based HIPEC-related nephrotoxicity (CHRN). Methods: A systematic literature review on CHRN after CRS for the treatment of PSMs was performed. The literature search was carried out using Medline, Cochrane, and Embase. The last day of the search was 23 October 2023. PRISMA guidelines were used. A meta-analysis was then conducted. The main endpoint was the incidence of acute and chronic renal impairment after CHRN. Secondary endpoints included the potential impact of several clinical variables on the primary endpoint and a critical appraisal of the different renal impairment scales employed. Results: Our study included 26 articles with a total sample of 1473 patients. The incidence of acute kidney injury (AKI) was 18.6% (95% CI: 13.6-25%, range of true effects 3-59%). For chronic kidney disease, it was 7% (95% CI: 3-15.3%, range of true effects 1-53%). The variables that statistically influenced these results were the scale used to measure renal insufficiency, the use of nephroprotective agents, and the presence of pre-existing renal disease. Conclusions: The reported incidence of renal impairment following cisplatin-based HIPEC is highly variable. The incidence of renal failure obtained in this meta-analysis should be used as a reference for subsequent reports on this topic. Further prospective studies are warranted to establish optimal and standardized management.

Intraperitoneal drug delivery systems for peritoneal carcinomatosis: Bridging the gap between research and clinical implementation.

Several abdominal-located cancers develop metastasis within the peritoneum, what is called peritoneal carcinomatosis (PC), constituting a clinical challenge in their therapeutical management, often leading to poor prognoses. Current multidisciplinary strategies, including cytoreductive surgery (CRS), hyperthermic intraperitoneal chemotherapy (HIPEC), and pressurized intraperitoneal aerosol chemotherapy (PIPAC), demonstrate efficacy but have limitations. In response, alternative strategies are explored in the drug delivery field for intraperitoneal chemotherapy. Controlled drug delivery offers a promising avenue, maintaining localized drug concentrations for optimal PC management. Drug delivery systems (DDS), including hydrogels, implants, nanoparticles, and hybrid systems, show potential for sustained and region-specific drug release. The present review aims to offer an overview of the advances and current designs of DDS for PC chemotherapy administration, focusing on their composition, main characteristics, and principal experimental outcomes, highlighting the importance of biomaterial rationale design and in vitro/vivo models for their testing. Moreover, since clinical data for human subjects are scarce, we offer a critical discussion of the gap between bench and bedside in DDS translation, emphasizing the need for further research.

Survival Difference of Endometrial Cancer Patients with Peritoneal Metastasis Receiving Cytoreductive Surgery (CRS) with and without Hyperthermic Intraperitoneal Chemotherapy (HIPEC): A Systematic Review and Meta-Analysis.

Although several studies have been completed to investigate the effect of cytoreductive surgery (CRS) with or without hyperthermic intraperitoneal chemotherapy (HIPEC) in endometrial cancer with peritoneal metastasis (ECPM), a direct comparison was not performed previously. A meta-analysis was performed to investigate the suspected additional survival benefits of CRS plus HIPEC over CRS only. Twenty-one and ten studies with a total number of 1116 and 152 cases investigating CRS only and CRS plus HIPEC were identified, respectively. When all articles were analyzed, the 1-year survival rate was 17.60% higher for CRS plus HIPEC (82.28% vs. 64.68%; p = 0.0102). The same tendency was observed for the 2-year (56.07% vs. 36.95%; difference: 19.12%; p = 0.0014), but not for the 5-year (21.88% vs. 16.45%; difference: 5.43%; p = 0.3918) survival rates. The same clinical significance, but statistically less strong observations, could be made if only the studies published after 2010 were investigated (1-year survival rate: 12.08% and p = 0.0648; 2-year survival rate: 10.90% and p = 0.0988). CRS remains one of the core elements of ECPM treatment, but the addition of HIPEC to CRS can increase the positive clinical outcome, especially in the first 2 years.

Intraperitoneal administration of doxorubicin-encapsulated Brucea javanica oil nanoemulsion against malignant ascites.

Malignant ascites is a common complication of advanced cancers, which reduces survival rates and diminishes patients' quality of life. Intraperitoneal chemotherapy is a conventional method for treating cancer-related ascites, but the poor drug retention of conventional drugs requires frequent administration to maintain sustained anti-tumor effects. In this study, we encapsulated doxorubicin (DOX) into Brucea javanica oil (BJO) to develop a water-in-oil (W/O) nanoemulsion called BJO@DOX for the treatment of malignant ascites through in-situ intraperitoneal administration. BJO significantly induced apoptosis of S180 cells by upregulating the expression of p53 and caspase-3 (cleaved). Additionally, BJO notably downregulated the expression of Bcl-2, further promoting apoptosis of S180 cells. Cell apoptosis significantly inhibited ascites formation and tumor cell proliferation in a mouse model. The combination of DOX and BJO exhibited satisfactory synergistic effects, consequently prolonging the survival period of mice. Histological examination of major organs indicated that the nanoemulsion had excellent biosafety in vivo. The BJO@DOX nanoemulsion represents a promising platform for in-situ chemotherapy of malignant ascites.

The 2022 PSOGI International Consensus on HIPEC Regimens for Peritoneal Malignancies: HIPEC Technologies.

This manuscript reports the results of an international consensus on technologies of hyperthermic intraperitoneal perioperative chemotherapy (HIPEC) performed with the following goals: To provide recommendations for the technological parameters to perform HIPEC. To identify the role of heat and its application forms in treating peritoneal metastases. To provide recommendations regarding the correct dosimetry of intraperitoneal chemotherapy drugs and their carrier solutions. To identify for each intraperitoneal chemotherapy regimen the best dosimetry and fractionation. To identify areas of future research pertaining to HIPEC technology and regimens. This consensus was performed by the Delphi technique and comprised two rounds of voting. In total, 96 of 102 eligible panelists replied to both Delphi rounds (94.1%) with a consensus of 39/51 questions on HIPEC technical aspects. Among the recommendations that met with the strongest consensus were those concerning the dose of HIPEC drug established in mg/m2, a target temperature of at least 42°C, and the use of at least three temperature probes to pursue hyperthermia. Ninety minutes as the ideal HIPEC duration seemed to make consensus. These results should be considered when designing new clinical trials in patients with peritoneal surface malignancies.

Outcome of patients with peritoneal metastasis from ovarian cancer treated with Pressurized IntraPeritoneal Aerosol Chemotherapy (PIPAC).

Objectives: There are few data on Pressurized IntraPeritoneal Aerosol Chemotherapy with cisplatin and doxorubicin (PIPAC C/D) in women with primary unresectable or recurrent platinum-resistant peritoneal metastasis (PM) from ovarian cancer (OC). We evaluated survival, histological and cytological response, Quality of Life (QoL) and toxicity after PIPAC C/D in these patients. Methods: Retrospective analysis of patients from the prospective PIPAC-OPC1 and -OPC2 studies. The histological response was evaluated by the Peritoneal Regression Grading Score (PRGS). QoL questionnaires were collected at baseline and after third PIPAC or 60 days. Adverse events were collected until 30 days after the last PIPAC. Demographic and survival data were analysed based on intention to treat. Response, QoL and toxicity were analysed per protocol (≥1 PIPAC). Results: Twenty-nine patients were included. Five patients (17 %) were non-accessible at PIPAC 1. One patient was excluded due to liver metastases at PIPAC 1. Thus, 23 patients had 76 PIPACs (median 2, range 1-12). Median overall survival was 8.2 months (95 % CI 4.4-10.3) from PIPAC 1. Biopsy data were available for 22 patients, and seven (32 %) patients had a major/complete histological response (PRGS≤2) at PIPAC 3. No cytological conversions were registered. Symptoms and function scores worsened, while emotional scores improved. Three patients had severe adverse reactions (two ileus, one pulmonary embolism); no life-threatening reactions or treatment-related mortality was observed. Conclusions: PIPAC C/D was feasible and induced histological regression in a substantial proportion of patients with platinum-resistant PM from OC. Larger studies are needed to evaluate impact on survival.

RNA expression profiling of peritoneal metastasis from pancreatic cancer treated with Pressurized Intraperitoneal Aerosol Chemotherapy (PIPAC).

Objectives: Pressurized Intraperitoneal Aerosol Chemotherapy (PIPAC) is an experimental treatment option in peritoneal metastasis from pancreatic cancer (PM-PC). Aims were to examine mRNA profile of fibrosis due to response after systemic chemotherapy and PIPAC (Regression) compared to treatment-naïve PM-PC and chronic cholecystitis-related peritoneal fibrosis (Controls). Methods: Peritoneal biopsies (PBs) from PM-PC patients who had undergone systemic chemotherapy and PIPAC were evaluated with Peritoneal Regression Grading Score (PRGS). We extracted RNA from PBs with Regression (PRGS 1, n=11), treatment-naïve PM-PC (n=10), and Controls (n=10). Profiling of 800 mRNAs was performed (NanoString nCounter, PanCancer Immuno-Oncology 360 (IO-360) and 30 additional stroma-related mRNAs). Results: Regression vs. PM-PC identified six up-regulated and 197 down-regulated mRNAs (FDR≤0.05), linked to TNF-α signaling via NF-kB, G2M checkpoint, epithelial-mesenchymal transition, estrogen response, and coagulation. Regression vs. Controls identified 43 significantly up-regulated mRNAs, linked to interferon-α response, and down-regulation of 99 mRNAs, linked to TNF-α signaling via NF-kB, inflammatory response, epithelial-mesenchymal transition, KRAS signaling, and hypoxia (FDR≤0.05). Conclusions: In regressive fibrosis of PM-PC after systemic chemotherapy and PIPAC (Regression), downregulation of mRNAs related to key tumor biological pathways was identified. Regression also showed transcriptional differences from unspecific, benign fibrosis (Controls). Future studies should explore whether mRNA profiling of PBs with PM from PC or other primaries holds prognostic or predictive value.

Expert consensus: Profiling and management of advanced or metastatic epithelial ovarian cancer / Consenso de expertos basado en la evidencia: perfilamiento y manejo del carcinoma epitelial de ovario de alto grado avanzado.

Introduction and objective: The approach to patients with advanced or metastatic high-grade epithelial ovarian cancer (EOC) has evolved over time with the advent of new therapies and multimodal strategies. The objective of this consensus of experts is to generate national recommendations for the profiling and management of advanced or metastatic high-grade OEC, defined as stages III and IV of the "The International Federation of Gynecology and Obstetrics (FIGO) classification at the time of diagnosis to base on the literature review that included international evidence-based clinical practice guidelines (CPG). Material and methods: Eleven panelists (oncologists and gynecological oncologists) answered 8 questions about the profiling and management of advanced or metastatic ovarian epithelial carcinoma. The panelists were chosen for their academic profile and influence in national health institutions. Guidelines from the "ESMO Standardized Operating Procedures Consensus Conference" were used to develop the consensus. It was agreed that the level of agreement to accept a recommendation should be ≥ 80%. The document was peer reviewed. Results: Eight general recommendations are made, which are presented into five domains. Some of these recommendations are subdivided into specific recommendations. Initial treatment Recommendation 1.1 Complete primary cytoreduction (PCS) surgery is suggested as the initial therapy of choice for patients with high-grade or metastatic EOC, which should ideally be carried out in centers with experience, followed by adjuvant therapy. 1.2 Neoadjuvant chemotherapy followed by interval cytoreduction surgery (ICS) is suggested in those who are unlikely to achieve a complete cytoreduction in PCS either due to unresectable metastatic disease or who present unresectability criteria (imaging, laparoscopic and/or by laparotomy) and that have been defined by a gynecological oncologist and patients with poor functional status and comorbidities according to the criteria of the multidisciplinary team (clinical oncology, gynecological oncology, radiology, etc.). Recommendation 2. In patients with high-grade epithelial ovarian cancer (EOC), in stage III locally advanced or metastatic, who received neoadjuvant chemotherapy and achieved a complete or partial response (cytoreduction with tumor residue < 2.5 mm), the use of Hyperthermic IntraPeritoneal Chemotherapy (HIPEC) could be considered as an alternative to standard platinum-based adjuvant intravenous chemotherapy during interval cytoreductive surgery, after discussion in a multidisciplinary tumor board, at a center experienced in treating this type of patients. Use of genetic testing. Recommendation 3. It is suggested at the time of diagnosis to offer molecular genetic testing to all patients with high-grade advanced or metastatic EOC regardless of family history. Recommendation 4. It is suggested to offer genetic counseling, by qualified personnel, to all patients with high-grade advanced or metastatic EOC who are ordered genetic testing. Recommendation 5. It is suggested that all patients with advanced or metastatic high-grade EOC undergo a germ panel that includes the Breast Cancer Susceptibility Genes 1/2 genes (BRCA 1/2) and the other susceptibility genes according to with institutional protocols and the availability of genetic testing panels; If it is negative, then somatic testing should be performed that includes the homologous recombination deficiency (HRD) status, regardless of family history. Adjuvant Therapy Recommendation 6. 6.1. It is suggested that all patients with advanced stage III/IV EOC, with PSC of (0-2), got adjuvant intravenous chemotherapy as standard treatment within six weeks after Prc. It is suggested paclitaxel/carboplatin. Recommendation 6.2. It is suggested to use standard chemotherapy base on platinum plus Bevacizumab as adjuvant chemotherapy to patients with high-risk disease (EOC stage IV or stage III with suboptimal tumor cytoreduction), following by bevacizumab as maintenance. The use of bevacizumab as maintenance therapy is not recommended if bevacizumab was not included in the first line of treatment. We suggested the dose used in GOG-0218 and ICON7 trials. Recommendation 6.3 It is suggested combined intravenous/intraperitoneal chemotherapy only for selected patients, with optimal cytoreduction (residual lesions < 1 cm), especially those without residual disease (R0) and who are evaluated in a multidisciplinary meeting. It is not considered standard treatment. Recommendation 6.4. 6.4.1 It is suggested to use Poly ADP ribose polymerase (PARP) inhibitors such as olaparib or niraparib as maintenance after receiving first-line chemotherapy in patients with stage III/IV BRCA1/2 positive EOC who received platinumbased chemotherapy and obtained complete response/partial response (CR/PR), 6.4.2 It is suggested to use olaparib alone or in combination with bevacizumab or niraparib in patients with stage III/IV BRCA1/2 positive EOC who received platinum-based chemotherapy plus bevacizumab and achieved CR/PR. 6.4.3 It is suggested to use niraparibin patients with stage III/IV BRCA1/2 negative or unknown EOC who received platinum-based chemotherapy and achieved CR/PR. 6.4.4 It is suggested to use bevacizumab or olaparib plus bevacizumab in patients with EOC stage III/IV BRCA1/2 negative or unknown (HRD positive) who received platinum-based chemotherapy plus bevacizumab and obtained CR/PR. Treatment of disease relapse Recommendation 7. Secondary cytoreductive surgery followed by chemotherapy is suggested for selected patients with high-grade advanced EOC in first relapse, platinum-sensitive (platinum-free interval ≥ 6 months), positive "Arbeitsgemeinschaft Gynäkologische Onkologie ­ AGO" score or "I-model" positive (< 4.7) with a potential resection to R0 in centers with access to optimal surgical and postoperative support. Note: Platinum-free interval and AGO score have only been developed as positive predictors of complete resection and not to exclude patients from surgery. Recommendation 8. 8.1 For patients with relapse advanced high-grade EOC platinum-sensitive, the following is suggested: Platinum-based combination chemotherapy: carboplatin/liposomal doxorubicin or carboplatin/paclitaxel or carboplatin/nab-paclitaxel or carboplatin/docetaxel or carboplatin/gemcitabine) for six cycles. If combination therapy is not tolerated, give carboplatin or cisplatin alone. Combination chemotherapy (carboplatin/gemcitabine or carboplatin/paclitaxel or carboplatin/doxorubicin liposomal) plus bevacizumab followed by bevacizumab as maintenance (until progression or toxicity). Recommendation 8.2 For patients with relapsed advanced high-grade EOC platinum-resistant, it is suggested: Sequential treatment with chemotherapy, preferably with a non-platinum single agent (weekly paclitaxel or pegylated liposomal doxorubicin or docetaxel or oral etoposide or gemcitabine or trabectidine or, topotecan). Weekly paclitaxel or pegylated liposomal doxorubicin or topotecan could be administrate with or without bevacizumab. Other agents are considered potentially active (capecitabine, cyclophosphamide, ifosfamide, irinotecan, oxaliplatin, pemetrexed, vinorelbine, cyclophosphamide) could be recommended for later lines. Hormone receptor-positive patients who do not tolerate or have no response to cytotoxic regimens may receive hormone therapy with tamoxifen or other agents, including aromatase inhibitors (anastrozole and letrozole) or leuprolide acetate, or megestrol acetate. Patients with a performance score ≥ 3 should be considered only for best supportive care. Recommendation 8.3 Maintenance therapy with PARP inhibitors: It is suggested in patients with relapse advanced high-grade EOC stage III/IV BRCA1/2 (positive, negative or unknown) who have received two or more lines of platinum-based chemotherapy and have achieved CR/PR, use olaparib, niraparib or rucaparib. Niraparib could be useful in BRCA 1/2 +/-/unknown patients, as rucaparib, however, the latter does not yet have approval from the regulatory office in Colombia. Conclusions: It is expected that the recommendations issued in this consensus will contribute to improving clinical care, oncological impact, and quality of life of these women.

Introducción y objetivo: el abordaje de pacientes con cáncer epitelial de ovario (CEO) de alto grado avanzado o metastásico ha ido evolucionando a través del tiempo con el advenimiento de nuevas terapias y estrategias multimodales. El objetivo de este consenso de expertos es generar recomendaciones nacionales para el perfilamiento y manejo del CEO de alto grado avanzado o metastásico, definido como estadios III y IV de la clasificación de la Federación Internacional de Ginecología y Obstetricia (FIGO) al momento del diagnóstico, a partir de la revisión de la literatura que incluyó guías de práctica clínica (GPC) internacionales basadas en la evidencia. Materiales y métodos: once panelistas (oncólogos y ginecólogos oncólogos) respondieron ocho preguntas sobre el perfilamiento y manejo del carcinoma epitelial de ovario avanzado o metastásico. Los panelistas fueron escogidos por su perfil académico e influencia en instituciones de salud nacionales. Para el desarrollo del consenso se utilizaron los lineamientos de la "Conferencia de consenso de procedimientos operativos estandarizados de ESMO". Se definió que el nivel de acuerdo para aceptar una recomendación debía ser ≥ 80%. El documento fue revisado por pares. Resultados: Se hacen 8 recomendaciones generales, presentadas en cinco dominios; algunas de ellas se subdividen en recomendaciones específicas. Tratamiento inicial Recomendación 1 1.1. Como terapia inicial de elección para pacientes con CEO de alto grado o metastásico se sugiere la cirugía de citorreducción primaria (Cpr) completa que, idealmente, debe realizarse en centros con experiencia, seguida de terapia adyuvante. 1.2. Se sugiere quimioterapia neoadyuvante seguida de cirugía de citorreducción de intervalo (Cint) en quienes sea improbable alcanzar una citorreducción completa en la Cpr, bien sea por enfermedad metastásica no resecable o que presenten criterios de irresecabilidad (imagenológicos, laparoscópicos o por laparotomía) que hayan sido definidos por un ginecólogo oncólogo. También en pacientes con un pobre estado funcional y comorbilidades de acuerdo con el criterio del equipo multidisciplinario (oncología clínica, ginecología oncológica, radiología, etc.). Recomendación 2. En pacientes con CEO de alto grado, en estadio III localmente avanzado o metastásico, que recibieron quimioterapia neoadyuvante y alcanzaron respuesta completa o parcial (citorreducción con residuo tumoral < 2,5 mm), se podría evaluar el uso de la quimioterapia intraperitoneal hipertérmica (Hyperthermic IntraPeritoneal Chemotherapy - HIPEC) como alternativa a la quimioterapia IV adyuvante estándar basada en platinos durante la Cint, previa discusión en junta multidisciplinaria, en un centro de experiencia en este tipo de pacientes. Uso de pruebas genéticas Recomendación 3. Al momento del diagnóstico, se sugiere ofrecer testeo molecular genético a toda paciente con CEO de alto grado avanzado o metastásico, independientemente de la historia familiar. Recomendación 4. Se sugiere ofrecer asesoramiento genético, por parte de personal calificado, a toda paciente con CEO de alto grado avanzado o metastásico a quien se le ordene un testeo genético. Recomendación 5. Se sugiere que a toda paciente con CEO de alto grado avanzado o metastásico se le realice panel germinal que incluya los genes de susceptibilidad al cáncer de mama 1/2 (BRCA 1/2) y los otros genes de susceptibilidad de acuerdo con los protocolos institucionales y la disponibilidad de paneles de testeo genético; si es negativo entonces se debería realizar testeo somático que incluya el estatus de deficiencia de la recombinación homóloga (homologous recombination deficiency - HRD), independientemente de la historia familiar. Terapia adyuvante Recomendación 6 6.1. Se sugiere que a toda paciente con CEO estadios III/IV avanzado o metastásico, con estatus de desempeño (performance score care - PSC) de 0-2 se le administre como tratamiento estándar quimioterapia intravenosa (IV) adyuvante dentro de las seis semanas posteriores a la Cpr. Se sugiere administrar paclitaxel/carboplatino. 6.2. Se sugiere utilizar quimioterapia estándar basada en platino más bevacizumab como adyuvancia en pacientes con enfermedad de alto riesgo (CEO estadios IV o III con citorreducción tumoral subóptima), continuando con bevacizumab como mantenimiento. No se recomienda el uso de bevacizumab como terapia de mantenimiento si no se incluyó en la primera línea de tratamiento. Se sugiere seguir los esquemas de los estudios Gynecologic Oncology Group Study (GOG-0218) e International Collaborative Ovarian Neoplasm (ICON7). 6.3. Se sugiere la quimioterapia combinada IV/intraperitoneal (IP) solo para pacientes seleccionadas, con una citorreducción óptima (lesiones residuales < 1 cm), en especial aquellas sin enfermedad residual (R0) y que sean evaluadas en junta multidisciplinaria. La quimioterapia combinada IV/IP no se considera como tratamiento estándar. 6.4. 6.4.1. Se sugiere utilizar inhibidores de poli(ADP-ribosa) polimerasa (PARP) tales como olaparib o niraparib como mantenimiento después de recibir una primera línea de quimioterapia en pacientes con CEO estadios III/IV BRCA1/2 positivo que recibieron quimioterapia basada en platino y obtuvieron respuesta completa/respuesta parcial (RC/RP). 6.4.2. Se sugiere utilizar olaparib solo o en combinación con bevacizumab o niraparib en pacientes con CEO estadios III/IV BRCA1/2 positivo que recibieron quimioterapia basada en platino más bevacizumab y obtuvieron RC/RP. 6.4.3. Se sugiere utilizar niraparib en pacientes con CEO estadio III/IV BRCA1/2 negativo o desconocido que recibieron quimioterapia basada en platino y obtuvieron RC/RP. 6.4.4. Se sugiere utilizar bevacizumab u olaparib más bevacizumab en pacientes con CEO estadios III/IV BRCA1/2 negativo o desconocido (HRD positivo) que recibieron quimioterapia basada en platino más bevacizumab y obtuvieron RC/RP. Tratamiento de la recaída de la enfermedad Recomendación 7. Se sugiere la realización de la cirugía de citorreducción secundaria (Csec), seguida de quimioterapia, a pacientes seleccionadas con CEO de alto grado avanzado o metastásico en primera recaída, platino-sensibles (intervalo libre de platinos ≥ 6 meses), puntuación Arbeitsgemeinschaft Gynäkologische Onkologie (AGO) positiva o Integrate model (I-Model) positivo (< 4,7), y con una potencial resección a R0, en centros con acceso a soporte quirúrgico y posoperatorio óptimo. Nota: el intervalo libre de tratamiento con platinos y la puntuación AGO solo se han desarrollado como predictores positivos de resección completa y no para excluir a las pacientes de la cirugía. Recomendación 8 8.1. Para pacientes con CEO de alto grado avanzado o metastásico en recaída platino-sensibles se sugiere: Quimioterapia combinada basada en platino: carboplatino/doxorrubicina liposomal o carboplatino/paclitaxel o carboplatino/ nab-paclitaxel o carboplatino/docetaxel o carboplatino/gemcitabina, por seis ciclos. Si no se tolera la terapia combinada, dar carboplatino o cisplatino solo. Quimioterapia combinada: carboplatino/gemcitabina o carboplatino/paclitaxel o carboplatino/doxorubicina liposomal, más bevacizumab, seguida de bevacizumab como mantenimiento (hasta progresión o toxicidad). 8.2. Para pacientes con CEO de alto grado avanzado o metastásico en recaída, platino-resistentes, se sugiere: Tratamiento secuencial con quimioterapia, preferiblemente con un agente único que no sea un platino (paclitaxel semanal o doxorrubicina liposomal pegilada o docetaxel o etopósido oral o gemcitabina o trabectidina o topotecan). El paclitaxel semanal o la doxorrubicina liposomal pegilada o el topotecan pueden ser administrados con o sin bevacizumab. Existen otros agentes que se consideran potencialmente act ivos (capecitabina, ciclofosfamida, ifosfamida, irinotecán, oxaliplatino, pemetrexed, vinorelbina, ciclofosfamida), que se podrían recomendar para líneas posteriores. Las pacientes con receptores hormonales positivos que no toleran o no tienen respuesta a los regímenes citotóxicos pueden recibir terapia hormonal con tamoxifeno u otros agentes, incluidos los inhibidores de la aromatasa (anastrozol y letrozol) o acetato de leuprolide o acetato de megestrol. Pacientes con PSC ≥ 3 deberían ser consideradas solo para el mejor cuidado de soporte. 8.3. Terapia de mantenimiento con inhibidores PARP. Para pacientes con CEO de alto grado avanzado o metastásico en recaída estadios III/IV BRCA1/2 (positivo, negativo o desconocido), que hayan recibido dos o más líneas de quimioterapia basada en platino y hayan alcanzado RC/RP, se sugiere utilizar olaparib, niraparib o rucaparib. El niraparib podría ser útil en pacientes BRCA 1/2 +/-/desconocido, al igual que el rucaparib, sin embargo, este último no tiene aún aprobación del ente regulador en Colombia. Conclusiones: se espera que las recomendaciones emitidas en este consenso contribuyan a mejorar la atención clínica, el impacto oncológico y la calidad de vida de estas mujeres.

Operative Management of Intra-abdominal Lymphatic Malformations in Children: A Single Tertiary Center Experience.

BACKGROUND: Intra-abdominal lymphatic malformations (LMs) are relatively rare congenital anomalies and can be divided into intra- and retroperitoneal subgroups. This study aims to evaluate the outcomes after surgical resection of intraperitoneal LMs in children. METHODS: The records of all patients ≤16 years of age with intraperitoneal LMs managed at our tertiary center between 2007-2022 were reviewed. Patients with retroperitoneal LMs were excluded. Our preferred approach is surgical exploration for large (>5 cm), symptomatic lesions if they are potentially resectable on imaging. RESULTS: A total of 12 patients (10 males) were diagnosed with intraperitoneal LMs located in the small bowel mesentery or omentum at a median age of 6.6 (range, 0.6-14.4) years. Ten (83%) patients presented with acute symptoms, including abdominal pain (n = 8; 67%) and vomiting (n = 3; 25%). Two (17%) intraperitoneal LMs were found on imaging performed for other reasons. Surgical exploration was performed in 11/12 (92%) cases. Intestinal volvulus around a mesenteric macrocyst had occurred in 4 (36%) patients. Complete macroscopic resection was achieved in 10/11 (91%) patients. Most lesions were localized to a short intestinal segment. One mixed type LM with an extensive mesenteric involvement was biopsied as the lesion was deemed to be unresectable in preoperative imaging and the diagnosis was initially unclear. There was one recurrence (8%) during postoperative follow-up on imaging (median 3.6 (range, 1.5-6.9) years) but the patient has remained asymptomatic and not undergone interventions. 6/8 (75%) of screened intraperitoneal LMs were positive for a somatic PIK3CA mutation. CONCLUSIONS: Most large, pedunculated macrocystic LMs in the small bowel mesentery or omental location were amenable to macroscopic resection. Intraperitoneal LMs tend to present with acute symptoms including a risk for intestinal volvulus based on anatomical location. Our results suggest low recurrence rates or need for further interventions over follow-up. LEVEL OF EVIDENCE: III.

Pressurized Intraperitoneal Aerosol Chemotherapy (PIPAC) in the Treatment of Gastric Cancer: Feasibility, Efficacy and Safety-A Systematic Review and Meta-Analysis.

Background: Pressurized Intraperitoneal Aerosol Chemotherapy (PIPAC) is an emerging technique for delivering chemotherapy directly to the peritoneum via a pressurized aerosol. Its growing attention stems from its effectiveness in treating peritoneal carcinomatosis (PC) originating from various primary tumors, with gastric cancer (GC) being among the most prevalent. This study aimed to systematically investigate PIPAC's therapeutic role in gastric cancer peritoneal metastasis (GCPM). Methods: The systematic review and meta-analysis followed the PRISMA 2020 guidelines, searching Pubmed, Web of Science, and SCOPUS databases. The meta-analysis of relative risks and mean differences compared patients undergoing one or two PIPAC sessions with those completing three or more, assessing various outcomes. Results: Eighteen studies underwent qualitative analysis, and four underwent quantitative analysis. Patients with three or more PIPAC procedures had shorter hospital stays (MD = -1.2; 95%CI (-1.9; -0.5); p < 0.001), higher rates of histopathological response (RR = 1.77, 95%CI 1.08; 2.90; p = 0.023), and significantly improved overall survival (MD = 6.0; 95%CI 4.2; 7.8; p < 0.001). Other outcomes showed no significant differences. Conclusions: PIPAC demonstrated efficacy in carefully selected patients, enhancing histopathologic response rates and overall survival without prolonging hospital stays. This study underscores the necessity for randomized controlled trials and precise selection criteria to refine PIPAC's implementation in clinical practice.

Exploring the Survival Determinants in Recurrent Ovarian Cancer: The Role of Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy.

BACKGROUND: Recurrent ovarian cancer (ROC) significantly challenges gynecological oncology due to its poor outcomes. This study assesses the impact of cytoreductive surgery (CRS) combined with hyperthermic intraperitoneal chemotherapy (HIPEC) on ROC survival rates. MATERIALS AND METHODS: Conducted at the Medical University of Lublin from April 2011 to November 2022, this retrospective observational study involved 71 patients with histologically confirmed ROC who underwent CRS and subsequent HIPEC. RESULTS: The median overall survival (OS) was 41.1 months, with 3-year and 5-year survival rates post-treatment of 0.50 and 0.33, respectively. Patients undergoing radical surgery for primary ovarian cancer had a median OS of 61.9 months. The key survival-related factors included the Peritoneal Carcinomatosis Index (PCI) score, AGO score, platinum sensitivity, and ECOG status. CONCLUSIONS: The key factors enhancing ROC patients' survival include radical surgery, optimal performance status, platinum sensitivity, a positive AGO score, and a lower PCI. This study highlights the predictive value of the platinum resistance and AGO score in patient outcomes, underlining their role in treatment planning. Further prospective research is needed to confirm these results and improve patient selection for this treatment approach.