Search Results (326)

For patients diagnosed with a malignancy at high risk of developing peritoneal metastases, the concept of prophylactic hyperthermic intraperitoneal chemotherapy (HIPEC) has emerged. The aim of the present study is to assess the role of prophylactic HIPEC in gastric cancer patients at high risk of PC, based on the currently available data in the literature. In total, 14 RCTs and 16 non-RCTs were identified and included in the present review, with 1383 patients included in the RCTs (627 of whom underwent HIPEC) and 1647 patients included in the non-RCTs (with 609 undergoing HIPEC). Prophylactic HIPEC appears to be useful and effective in treating patients with high-risk gastric cancer, improving both overall and disease-free survival. The heterogeneity of data regarding treatment protocols and complication rates suggests that further research is necessary to develop optimal therapeutic approaches and personalized treatment options; in particular, large-scale randomized control trials are needed in order to elucidate the potential benefits associated with the use of prophylactic HIPEC. Full article

Background and Objectives: Incisional hernia is a common complication following cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC). This study aimed to identify patient and surgical factors associated with its occurrence. Materials and Methods: We conducted a retrospective analysis of 122 patients undergoing CRS and HIPEC. Logistic regression models were applied to identify predictors of incisional hernia development. Results: Incisional hernia occurred in 23.8% of patients. Hypertension was identified as an independent factor associated with increased risk. Peritoneal Cancer Index (PCI), operative time, and abdominal wall closure technique were not found to be significantly associated with hernia development. Conclusions: Preoperative identification of high-risk patients may support the adoption of targeted preventive strategies, including prophylactic mesh placement and enhanced postoperative surveillance. Full article

Background and Objectives: This study aimed to compare the effects of HIPEC procedures using oxaliplatin and mitomycin C on serum electrolyte, glucose, and lactate levels, with a specific focus on the carrier solutions employed. Materials and Methods: A retrospective analysis was performed on 82 patients who underwent cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (HIPEC) for colorectal peritoneal metastases. Patients were assigned to one of two groups based on the chemotherapeutic agent used: oxaliplatin (n = 63) or mitomycin C (MMC, n = 19). The oxaliplatin group was further subdivided based on the carrier solution used: 5% dextrose (D5W, n = 29) or peritoneal dialysate (n = 34). The assignment of regimens was based on institutional protocols and surgeon preference. Pre- and post-HIPEC serum levels of sodium, potassium, bicarbonate, glucose, and lactate were compared. Results: Significant biochemical changes were observed across groups, depending on both the chemotherapeutic agent and carrier solution. In the MMC group (peritoneal dialysate), only lactate increased significantly post-HIPEC (p = 0.001). In the oxaliplatin–peritoneal dialysate group, significant changes were observed in bicarbonate (p = 0.009), glucose (p = 0.001), and lactate (p < 0.001), whereas sodium and potassium remained stable. The oxaliplatin–D5W group showed significant changes in all parameters: sodium (p = 0.001), potassium (p = 0.001), bicarbonate (p = 0.001), glucose (p < 0.001), and lactate (2.4 → 7.6 mmol/L, p < 0.001). Between-group comparisons revealed significant differences in sodium, potassium, glucose, and lactate changes (p < 0.05), but not in bicarbonate (p = 0.099). Demographic and clinical characteristics—including age, sex, primary disease, ICU stay, and 90-day mortality were similar across groups. Conclusions: The use of dextrose-containing solutions with oxaliplatin was associated with marked metabolic disturbances, including clinically meaningful hyponatremia, hypokalemia, and hyperglycemia in the early postoperative period. These findings suggest that the choice of carrier solution is as important as the chemotherapeutic agent in terms of perioperative safety. Closer postoperative electrolyte monitoring is recommended when using dextrose-based regimens. The retrospective design and sample size imbalance between groups are acknowledged limitations. Nonetheless, this study offers clinically relevant insights and lays the groundwork for future prospective research. Full article

Background and Objectives: The combined use of cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) is employed for the treatment of peritoneal carcinomatosis (PC). To achieve optimal cytoreduction, there may be a need for extensive resection and subsequent reconstruction of urologic structures. This study was designed to evaluate the outcomes of urinary tract resection or repair performed in CRS/HIPEC in terms of operative and oncological outcomes. Materials and Methods: After institutional review board approval, data from 550 consecutive patients who underwent the CRS/HIPEC procedure from January 2007 to July 2018 at six university hospitals was retrieved from prospectively maintained databases. Data from patients who had a concomitant curative resection and reconstruction of the bladder, ureter, or kidney during the CRS/HIPEC procedure were analyzed retrospectively. Results: A total of 50 out of 550 patients had undergone resection with a repair of the urinary tract due to tumor invasion or iatrogenic injury. Postoperative (within 30 days) urologic complications were observed in 9 of the 50 patients. It was found that having a peritoneal cancer index (PCI) equal to or greater than 20 (p < 0.009) was the sole significant risk factor associated with the occurrence of early urinary complications. Survival time post CRS/HIPEC treatment did not significantly differ between patients with and without urologic complications (median overall survival: 23 vs. 27 months, p = 0.683). Conclusions: Despite urinary tract issues during CRS/HIPEC for PC, including a PCI over 20 and potential complications from resection or repair, the procedure still offers significant survival benefits. Full article

High-grade serous ovarian cancer (HGSOC) is an aggressive gynecological malignancy characterized by intraperitoneal spread and chemotherapy resistance. Chemotherapies have demonstrated limited effectiveness in HGSOC, underscoring the urgent need to evaluate how the tumor microenvironment (TME) was reshaped by chemotherapy in different sites of tumor foci. In this study, we performed single-cell transcriptomic analysis to explore the TME in samples obtained from various sites of tumor foci, with or without the history of Neoadjuvant chemotherapy (NACT). We discovered that chemotherapy reshaped the tumor immune microenvironment, evident through the reduction in human leukocyte antigen (HLA) diversity and the increase in PDCD1/CD274 in CD8_ANXA1, LAMP3+ dendritic cell (DC_LAMP3), and EREG+ monocytes (mono_EREG). Moreover, cancer.cell.2, cancer-associated C3+ fibroblasts (CAF_C3), and Fibrocyte_CD34, which are prone to accumulate in the metastatic site and post-NACT group, harbored poor clinical outcome, reflected in the immune exclusion and tumor progression signaling. Cell–cell communication identified a stronger interaction between cancer.cell.2 and CAF_C3, as well as Fibrocyte_CD34, in post-NACT samples, indicating that chemotherapy reshapes pre-existing cell clusters in a site-dependent manner. Our findings suggest that chemotherapy and sites of foci were critical for the transcriptional reprogramming of pre-existed cell clusters. Our study offers a single-cell phenotype data substrate from which to develop a personalized combination of chemotherapy and immunotherapy. Full article

Background: Peritoneal metastases from gastric cancer (GCPM) represent a significant clinical challenge in terms of therapeutic options and prognosis. Cytoreductive surgery (CRS) combined with hyperthermic intraperitoneal chemotherapy (HIPEC) has demonstrated promising survival benefits within a multimodal approach, particularly in carefully selected patients. Methods: This retrospective single-center study evaluated outcomes in patients with synchronous GCPM treated with CRS + HIPEC following neoadjuvant chemotherapy. The primary endpoints included overall survival (OS), disease-free survival (DFS), and identification of prognostic factors associated with poor outcomes. Additionally, we sought to characterize patients achieving long-term survival (OS ≥ 24 months). Results: The median OS and DFS were 18 and 13 months, respectively. A peritoneal cancer index (PCI) ≥ 7 and major postoperative complications were independently associated with reduced survival. Recurrence was significantly linked to PCI ≥ 7 and signet ring cell histology. Stratification by survival outcome identified PCI ≥ 7 as the only statistically significant variable differentiating average- and long-survival groups. Moreover, elevated PCI was independently associated with a higher incidence of major postoperative complications. Conclusions: CRS + HIPEC may offer a survival advantage over the use of systemic therapy exclusively in appropriately selected patients, particularly those with limited peritoneal disease burden. These results underscore the importance of accurate patient selection to balance surgical risks and maximize oncological benefits in the treatment of GCPM. Full article

Objective: Chemotherapy-induced peripheral neuropathy often has a lasting impact on the quality of life without existing causal treatment options. The aim of this study was to systematically investigate the temporal occurrence of paclitaxel-induced peripheral microcirculatory dysfunction. Methods: Thirty-one female SKH-1 mice received six cycles of paclitaxel intraperitoneally in the treatment group and six cycles of saline in the control group. Intravital fluorescence analyses were performed in the groups 180 min after saline administration and immediately, 60 min, 120 min, and 180 min after paclitaxel administration to evaluate the effects on microcirculation and inflammation. Results: In addition to signs of systemic inflammation, the intravital microscopy revealed a marked reduction in functional capillary density, increased venous leukocyte adhesion, and endothelial permeability that persisted for at least three hours in paclitaxel-treated mice. Conclusions: Our results show that paclitaxel-induced microcirculatory disturbances manifest immediately after application and last at least for 3 h. This suggests that options for prevention or at least amelioration could potentially be most effective if initiated parallel to the induction of chemotherapy and continued for a prolonged period of at least 3 h. Whether and to what extent the prolongation of the preventive strategies influences CIPN in the long term needs to be studied further. Full article

Goblet cell adenocarcinomas (GCAs) are an exceedingly rare subtype of tumors, almost exclusively occurring in the appendix, and characterized by features overlapping both adenocarcinomas and neuroendocrine tumors (NETs), which has historically led to confusion and varied nomenclature. This study presents a comprehensive review of the literature highlighting particularities of this type of malignancy, starting from a rare case of a 54-year-old female operated on in our clinic for an appendiceal tumor, initially suspected to be a mucinous neoplasm based on colonoscopic biopsy, which was ultimately confirmed to be goblet cell adenocarcinoma on both intraoperative frozen section and definitive pathological examination. Exhibiting signs and symptoms associated with an abdominal mass, she underwent a right hemicolectomy with partial omentectomy for locally advanced, high-grade, invasive goblet cell adenocarcinoma of the appendix with lymphatic macro metastases and epiploic invasion, categorized as AJCC stage IVb carcinomatosis. The patient received FOLFOX adjuvant. Six months later, she required reoperation due to the progression of carcinomatosis, which was again confirmed histopathologically. A second-line oncological protocol comprising irinotecan, capecitabine, and bevacizumab was initiated. Given the rarity of GCAs and the absence of a consensus on nomenclature, classification, and diagnostic criteria, we conducted a comprehensive literature review to highlight current trends related to this entity, including its classification within different systems (Tang, Yozu, WHO, AJCC), as well as the therapeutic surgical approaches—ranging from simple appendectomy to extensive multiorgan resection, cytoreductive surgery (CRS) combined with hyperthermic intraperitoneal chemotherapy (HIPEC), and the use of systemic therapy. Adhering to these recommendations will enhance communication among pathologists, surgeons, and oncologists regarding the natural history and prognosis of this rare malignancy. Full article

Cisplatin (Cis) is a widely used chemotherapy drug, but its nephrotoxicity limits its clinical application. Acute kidney injury (AKI) is a common complication, restricting long-term use. This study investigates the mechanisms of cisplatin-induced AKI and explores potential therapeutic targets. C57BL/6J mice were intraperitoneally injected with 20 mg/kg cisplatin to establish an AKI model. Serum creatinine, urea nitrogen, and tubular injury biomarkers (NGAL, KIM-1) progressively increased, indicating kidney dysfunction. Mitochondrial ATP levels significantly decreased, along with reduced mitochondrial fission and fusion, suggesting mitochondrial dysfunction. Increased oxidases and reduced antioxidants indicated redox imbalance, and metabolic reprogramming was observed, with lipid deposition, impaired fatty acid oxidation (FAO), and enhanced glycolysis in proximal tubular epithelial cells (PTECs). Nuclear factor erythroid 2-related factor 2 (NRF2) is a key transcriptional regulator of redox homeostasis and mitochondrial function. We found NRF2 levels increased early in AKI, followed by a decrease in vivo and in vitro, suggesting activation in the stress response. Nfe2l2 knockout mice showed aggravated kidney injury, characterized by worsened kidney function and histopathological damage. Mechanistically, Nfe2l2 knockout resulted in redox imbalance, reduced ATP synthesis, mitochondrial dysfunction and metabolic dysregulation. Furthermore, we activated NRF2 using dimethyl fumarate (DMF), observing a reduction in kidney damage and lipid deposition in mice. In conclusion, activating NRF2-dependent antioxidant pathways plays a crucial role in protecting against cisplatin-induced AKI. NRF2 may serve as a potential target for developing therapeutic strategies to prevent cisplatin nephrotoxicity. Full article

Background: Peritoneal surface malignancies (PSM) are aggressive cancers with limited treatment access in low- and middle-income countries (LMICs). While cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) have improved survival outcomes globally, their feasibility in LMICs remains underexplored. This first multicenter study in North Africa evaluates the implementation and outcomes of CRS with or without HIPEC in resource-limited settings. Methods: A retrospective cohort study of 391 patients with PSM (colorectal cancer, pseudomyxoma peritonei, ovarian cancer, gastric cancer, or mesothelioma) treated with CRS ± HIPEC between 2014 and 2020 at four tertiary centers in Morocco, Tunisia, and Algeria. Primary outcomes included overall survival (OS), disease-free survival (DFS), and severe postoperative morbidity (Clavien-Dindo ≥ IIIa). Cox regression was used to identify independent prognostic factors. Results: Among 391 patients, complete cytoreduction (CC-0/1) was achieved in 88%, and HIPEC was performed in 39%. Severe morbidity occurred in 22%, with HIPEC, spleno-pancreatectomy, and incomplete cytoreduction (CC-2) identified as significant risk factors. The median OS was 68 months, with 1- and 5-year survival rates of 97% and 56%, respectively. Patients undergoing CRS + HIPEC had significantly longer OS than CRS alone (70 vs. 64 months, p = 0.016), though DFS was not significantly different between groups. Independent predictors of improved OS included HIPEC, CC score, PCI, and primary tumor type. Conclusions: This first North African multicenter study establishes the feasibility and efficacy of CRS and HIPEC in LMICs, achieving survival outcomes comparable to high-income settings. The findings support expanding advanced PSM treatment programs in resource-limited settings, emphasizing structured training and multidisciplinary collaboration to improve access and outcomes. Full article

Background: Peritoneal relapse after cytoreduction and hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) is common. Repeat CRS/HIPEC offers the potential for long-term survival in the appropriately selected patient. Methods: We performed a retrospective review of a single institution database to assess perioperative outcomes after repeat CRS/HIPEC for appendiceal (pAC) and colorectal (pCRC) cancers. Kaplan–Meier and Cox estimates were used to assess survival. Results: Of 157 patients, 103 patients underwent initial CRS/HIPEC for pAC (n = 67) or pCRC (n = 36) histologies. Twenty-seven pAC patients (27/67, 40%) and 23/36 pCRC patients (63%) developed disease recurrence. Relapsed patients had a higher burden of disease (PCI), operative length and blood loss and received adjuvant chemotherapy (all p < 0.05). Nine of the 27 relapsed pAC patients and 5 of the 13 relapsed pCRC patients underwent repeat CRS/HIPEC. The median time to repeat CRS/HIPEC was 18 months (4–26 months), and a CCR-0 and CCR-1 were achieved in 79% and 21%, respectively. The 1-, 3- and 5-year OS for pAC patients who underwent repeat CRS/HIPEC was 88.9%, 88.9% and 77.8%, and the 1- and 3-year OS for pCRC patients was 100% and 25%, respectively. Repeat CRS/HIPEC for pAC was associated with significant improvement in OS (p = 0.03), while for pCRC, no significant difference was observed (p = 0.99). Conclusions: Repeat CRS/HIPEC for isolated peritoneal recurrence is safe and offers the potential for long-term survival. Patient selection is key to ensure optimal cytoreduction when considering repeat CRS/HIPEC. Full article

Backgroud: Ovarian cancer is the deadliest gynecologic malignancy, with most patients presenting with peritoneal dissemination at diagnosis. Complete cytoreduction and sensitivity to platinum-based systemic chemotherapy remain the most significant prognostic factors. However, even after optimal first-line management, over half of patients relapse due to residual microscopic disease. Intraperitoneal chemotherapy aims to target this component, with normothermic intraperitoneal chemotherapy long-term (NIPEC-LT) and hyperthermic intraperitoneal chemotherapy (HIPEC) being the most studied approaches. While NIPEC-LT has demonstrated improved survival in select trials, concerns regarding toxicity and catheter-related complications have limited its adoption as standard care. Conversely, HIPEC has shown survival benefits, particularly in patients undergoing interval cytoreductive surgery (iCRS) after neoadjuvant chemotherapy, leading to its inclusion in clinical guidelines. However, HIPEC is administered as a single intraoperative treatment, limiting its prolonged effect. Objectives and Method: This study investigates the combination of HIPEC and postoperative NIPEC-LT in the BICOV-1 trial, a prospective, non-randomized phase I study evaluating the feasibility, safety, and oncologic outcomes. The primary objective is to assess the treatment completion rates and morbidity. The secondary endpoints include disease-free survival (DFS), overall survival (OS), and quality-of-life measures. Combining HIPEC and NIPEC-LT is a rational approach, as both have shown independent benefits and do not overlap in toxicity. HIPEC-induced biological changes may enhance the effectiveness of subsequent intraperitoneal chemotherapy. This trial will provide essential data for future phase II/III studies assessing the role of intensified intraperitoneal treatment in ovarian cancer management. Full article

Background: PIPAC is an innovative treatment that delivers low-dose aerosolized chemotherapy into the abdominal cavity of patients with peritoneal surface malignancies (PSMs). However, its role in the multimodal management of PSMs is unclear. Methods: We retrospectively analyzed data from 64 patients who underwent PIPAC for PSMs of a primary or secondary origin between June 2020 and December 2024 (median age of 64 years). Primary tumor sites included gastric (42.2%), colorectal (23.4%), ovarian cancer (21.9%), and others (12.5%). The median PCI was 15 (IQR 9–25), with ascites present in 60.9% of cases and a positive cytology in 48.4%. Results: A total of 82 PIPAC sessions were performed in 64 patients. The mean operation time was 96 min. Severe adverse events, defined as the Common Terminology Criteria for Adverse Events (CTCAE) of a grade ≥ 2, occurred in four patients (6.2%). The median hospital stay was 3 days, and systemic chemotherapy was resumed within 14 days after the procedure in 27 patients. Among the entire cohort, 37.5% received bidirectional therapy and 62.5% received palliative treatment, with a lower peritoneal cancer index (PCI) in the bidirectional group (9.5 vs. 23). The median overall survival (OS) was 32 months from diagnosis. Sixteen patients (25%) underwent two or more PIPAC sessions and showed an advantage in survival compared to patients who underwent only one procedure (3-year OS: 63.2% vs. 38.4%, p 0.030). Conversion surgery was achieved in 34.4%. Patients treated with a bidirectional intent demonstrated a longer OS (3-year: 66.0% vs. 33.9%, p 0.011). Colorectal and ovarian tumors exhibited better long-term outcomes compared to gastric cancer. Conclusions: PIPAC is a promising treatment for PSMs, with a low morbidity rate. Its favorable safety and short interval to systemic therapy resumption support its use as part of a bidirectional strategy. Full article

Introduction: Peritoneal metastasis (PM) is the most common site of recurrence following curative resection for advanced gastric cancer (GC). Along with disease progression, it can lead to complications such as intestinal obstruction, hydronephrosis, obstructive jaundice, and ascites, significantly impairing the patient’s quality of life. Therefore, peritoneal metastasis is considered a critical target for treatment. In general, these patients are treated with systemic chemotherapy; however, the therapeutic effect is often limited due to the anticancer agents’ poor penetration into the peritoneal cavity. We aim to identify factors associated with the best overall survival (OS) in GC patients with peritoneal metastasis. Methods: Patients with advanced GC who were diagnosed as having macroscopic PM or positive peritoneal cytology by staging laparoscopy were enrolled. We introduced intraperitoneal Paclitaxel (IP-PTX) combined with S-1 plus oxaliplatin (SOX). Gastrectomy with lymph node dissection was performed as conversion surgery when the PM showed an excellent response. Results: Ninety-six patients received IP-PTX + SOX, with a median of 16 courses. The 1- and 5-year OS rates were 70.2% and 24.5%, respectively, with a mean survival time (MST) of 20.0 months. No chemotherapy-related mortality was observed. Conversion surgery was performed in 44 patients (45.8%), with a 1-year OS rate of 100%. Conclusions: Combination chemotherapy using the IP-PTX + SOX regimen is highly effective and is recommended as induction chemotherapy for patients with PM from GC. Conversion gastrectomy should be considered following an excellent response, particularly in patients with peritoneal cancer index (PCI) scores below 20. Full article