121 research outputs found
Learning Curve, Training Program, and Monitorization of Surgical Performance of Peritoneal Surface Malignancies Centers
No full textCytoreductive surgery (CRS) and HIPEC is a complex procedure with high cost and significant morbidity and mortality. The associated learning curve (LC) is steep and could reliably be evaluated using specific statistics. The Risk adjusted sequential probability ratio test is an effective and robust method to monitor surgical performance both in the learning and audit phase of a PSM center development. Several factors are associated with surgical performance and the most critical is mentoring of the trainee by an expert. Rare PSM like PMP and peritoneal mesothelioma are specific clinical circumstances that require further effort in the training process. Their extremely low incidences make reasonable regional centralization to ease centers’ quality control and improve cost effectiveness. A well-structured tutor based training program has been implemented in Europe. This initiative is expected to improve the standardization of the combined procedure and improve the quality of the services across the continent336 K
Clinical surveillance after macroscopically complete surgery for Low-grade appendiceal mucinous neoplasms (LAMN) with or without limited peritoneal spread : long-term results in a prospective series
No full textBackground
Low-grade appendiceal mucinous neoplasm (LAMN) is the most common primary lesion of pseudomyxoma peritonei, a disease whose standard treatment is cytoreduction and hyperthermic intraperitoneal chemotherapy. The optimal management of LAMN is not well defined. This study prospectively assessed a clinical surveillance strategy for LAMN with or without limited peritoneal spread.
Methods
During 2003–2017, the study prospectively enrolled 41 patients treated by macroscopically complete surgery for LAMN with or without limited peritoneal spread (pelvis and right lower quadrant). Follow-up assessment included thoracic-abdomino-pelvic computed tomography scan and serum tumor markers scheduled after surgery, then every 6 months for 5 years, and yearly thereafter. All specimens were reviewed by a dedicated pathologist.
Results
Appendectomy and five right colectomies were performed for 36 patients. Nine patients also underwent macroscopically complete cytoreduction of mucinous peritoneal disease, and four patients had hysterectomy plus bilateral salphingo-oophorectomy. Appendiceal rupture was evaluable in 38 of the 41 patients, being present in 21 patients (51.2%). Mucin, cells, or both outside the appendix were observed in 24 patients (58.5%). The median follow-up period was 58 months (range 9.3–162 months). The 5-year recurrence-free survival rate was 95.1%. Only two patients experienced peritoneal recurrences (4.9%), respectively 18 and 22 months after appendectomy. Their primary lesions were LAMNs with and without appendix wall rupture or extra-appendiceal mucin, respectively. No death occurred.
Conclusion
These findings strongly suggest that radically resected LAMN, even with limited peritoneal spread, carries a low recurrence risk. Furthermore, appendix wall perforation and the presence of mucin, cells, or both outside the appendix were not associated with a higher risk of metachronous peritoneal dissemination. In this setting, clinical and radiologic surveillance is a viable choice
Peritoneal carcinomatosis: Feature of dissemination. A review
No full textPeritoneal carcinomatosis is a common event that develops in the natural history of many neoplastic diseases, representing a major problem encountered in cancer management. Peritoneal seedings are often associated with neoplastic ascites resulting in a source of significant discomfort to the patient. Considered in the past as a terminal condition, peritoneal carcinomatosis was approached during the last two decades as a curable disease. The introduction of cytoreductive surgery or peritonectomy in the treatment of peritoneal neoplastic diseases drastically changed the natural history of peritoneal carcinomatosis. Another technique that showed an important impact on disease control is intraperitoneal hyperthermic perfusion, one of the most fascinating treatments of peritoneal carcinomatosis that results in an impressive increase in overall survival and quality of life in treated patients with low morbidity. This review illustrates the modality of dissemination of peritoneal carcinomatosis in relation to the primary tumor site and grade of malignancy. Peritoneal carcinomatosis is a term used to define an advanced stage of many abdominal neoplastic diseases that differ in biologic aggressiveness and prognosis. The different presentation of peritoneal carcinomatosis in relation to a different primary tumor and different grade of malignancy strongly influences the potentially therapeutic radical approaches using new and advanced modalities like cytoreductive surgery and intraperitoneal hyperthermic perfusion
Cytoreductive Surgery and HIPEC in the First-Line and Interval Time Points of Advanced Epithelial Ovarian Cancer
No full textMesothelioma
No full textMalignant mesothelioma is a disease affecting serosal surfaces derived from the mesothelium comprising the pleura, peritoneum, pericardium, and tunica vaginalis testis [...
Correlation between biological and mechanical properties of extracellular matrix from colorectal peritoneal metastases in human tissues
No full textAbstract Peritoneal metastases (PM) are common routes of dissemination for colorectal cancer (CRC) and remain a lethal disease with a poor prognosis. The properties of the extracellular matrix (ECM) are important in cancer development; studying their changes is crucial to understand CRC-PM development. We studied the elastic properties of ECMs derived from human samples of normal and neoplastic PM by atomic force microscopy (AFM); results were correlated with patient clinical data and expression of ECM components related to metastatic spread. We show that PM progression is accompanied by stiffening of the ECM, increased cancer associated fibroblasts (CAF) activity and increased deposition and crosslinking in neoplastic matrices; on the other hand, softer regions are also found in neoplastic ECMs on the same scales. Our results support the hypothesis that local changes in the normal ECM can create the ground for growth and spread from the tumour of invading metastatic cells. We have found correlations between the mechanical properties (relative stiffening between normal and neoplastic ECM) of the ECM and patients’ clinical data, like age, sex, presence of protein activating mutations in BRAF and KRAS genes and tumour grade. Our findings suggest that the mechanical phenotyping of PM-ECM has the potential to predict tumour development
Prognostic impact of cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) in gastric cancer patients: A meta-analysis of randomized controlled trials
No full textgastric cancer patients frequently develop peritoneal metastases (PM) with a poor long-term prognosis. A solid body of evidence underlines the beneficial role of cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) on survival, but to date, there is a lack of consensus regarding the optimal strategy in the treatment of locally advanced primary tumors with or without peritoneal metastasis. The present meta-analysis aims to assess the impact of CRS + HIPEC on survival analyzing the results of randomized studies only
Antitumor activity of miR-34a in peritoneal mesothelioma relies on c-MET and AXL inhibition: persistent activation of ERK and AKT signaling as a possible cytoprotective mechanism
No full textAbstract
Background
The value of microRNAs (miRNAs) as novel targets for cancer therapy is now widely recognized. However, no information is currently available on the expression/functional role of miRNAs in diffuse malignant peritoneal mesothelioma (DMPM), a rapidly lethal disease, poorly responsive to conventional treatments, for which the development of new therapeutic strategies is urgently needed. Here, we evaluated the expression and biological effects of miR-34a\u2014one of the most widely deregulated miRNAs in cancer and for which a lipid-formulated mimic is already clinically available\u2014in a large cohort of DMPM clinical samples and a unique collection of in house-developed preclinical models, with the aim to assess the potential of a miR-34a-based approach for disease treatment.
Methods
miR-34a expression was determined by qRT-PCR in 45 DMPM and 7 normal peritoneum specimens as well as in 5 DMPM cell lines. Following transfection with miR-34a mimic, the effects on DMPM cell phenotype, in terms of proliferative potential, apoptotic rate, invasion ability, and cell cycle distribution, were assessed. In addition, three subcutaneous and orthotopic DMPM xenograft models were used to examine the effect of miR-34a on tumorigenicity. The expression of miRNA targets and the activation status of relevant pathways were investigated by western blot.
Results
miR-34a was found to be down-regulated in DMPM clinical specimens and cell lines compared to normal peritoneal samples. miR-34a reconstitution in DMPM cells significantly inhibited proliferation and tumorigenicity, induced an apoptotic response, and declined invasion ability, mainly through the down-regulation of c-MET and AXL and the interference with the activation of downstream signaling. Interestingly, a persistent activation of ERK1/2 and AKT in miR-34a-reconstituted cells was found to counteract the antiproliferative and proapoptotic effects of miRNA, yet not affecting its anti-invasive activity.
Conclusions
Our preclinical data showing impressive inhibitory effects induced by miR-34a on DMPM cell proliferation, invasion, and growth in immunodeficient mice strongly suggest the potential clinical utility of a miR-34a-replacement therapy for the treatment of such a still incurable disease. On the other hand, we provide the first evidence of a potential cytoprotective/resistance mechanism that may arise towards miRNA-based therapies through the persistent activation of ..
The Significance of the Morphological Appearance of Peritoneal Lesions on Imaging in Patients With Peritoneal Malignancies-A Report From Phase 1 of the PRECINCT Study
No full textBackground and Aim: This is a report from Phase 1 of the prospective, observational, PRECINCT (Pattern of peritoneal dissemination and REsponse to systemic Chemotherapy IN Common and uncommon peritoneal Tumours) study, in which we studied the incidence of disease at pathological evaluation in different morphological appearances of peritoneal malignancies (PM) on imaging. Methods: Radiological findings were captured in a specific format that included a description of the morphological appearance of PM and a correlation performed with pathological findings. Results: In 630 patients enroled at seven centres (September 2022–December 2023), 24 morphological terms were used. Among prespecified terms (N = 8 used in 6350 [92.2%] regions), scalloping was pathologically positive in 93.5%, confluent disease in 78.8%, tumour nodules in 69.6%, thickening in 66.1%, infiltration in 56.3%. Among unspecified appearances (N = 16) for 540 (7.8%) regions, ‘enhancement’ was positive in 41.5%, micronodules in 65.3% and nodularity in 60.2%. Hierarchal clustering placed gastric cancer and rare tumours together and colorectal cancer, ovarian cancer and peritoneal mesothelioma in one cluster. Conclusions: The incidence of disease at pathological evaluation for most morphological appearances was high (> 50%). Morphological description should be provided in routine radiology reports. A set of standardized terms with their description should be developed by a consensus among experienced radiologists
Multi-institutional study of peritoneal sarcomatosis from uterine sarcoma treated with cytoreductive surgery and hyperthermic intraperitoneal chemotherapy
No full textObjective Uterine sarcoma (US) is a rare tumor representing 1% of female genital tract malignancies. Peritoneal sarcomatosis (PS) after US, diminishes median overall survival (OS) and progression-free survival (PFS) with cytoreductive surgery (CRS) alone, with or without systemic chemotherapy is <1 year and 6 months, respectively. A multi-institutional review of PS from US was conducted to evaluate CRS and hyperthermic intraperitoneal chemotherapy (HIPEC) and effects on survival outcomes. Methods A retrospective review of 36 patients from 7 specialized international centers was performed. Selection criteria included PS of uterine origin with CRS/HIPEC treatment. Clinical data were analyzed. OS and PFS were estimated with Kaplan-Meier method. Results Thirty-six patients underwent a total 38 HIPEC procedures performed from 2005 to 2014; 35 previous treatment and 1 primary treatment. Twenty-nine (81%) LMS patients, 3 (8%) endometrial stromal sarcoma (ESS), 3 (8%) adeneosarcoma (AS), and 1 (3%) categorized as other. Median PCI was 16 (range: 2–39), 10 patients had PCI ≥20. Thirty-four patients (94%) had complete cytoreduction (CC 0–1), 19 patients recurred. CRS/HIPEC OS at 1, 3, and 5-years was 75%, 53%, and 32% respectively, with median OS of 37 months (CI 95%: 20–54). PFS in 32 patients with CC at 1, 3, and 5-years was 67%, 32% and 32%, respectively with median PFS of 18.9 months (CI 95%: 6.7–31). Conclusions CRS/HIPEC is a promising treatment modality for patients with PS. Histological subtype may influence survival. A global prospective registry of patients to further assess the efficacy of CRS/HIPEC is needed
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