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Indian Journal of Cancer Oct 2022Non-carcinoid appendix epithelial tumors are rare. These tumors include low-grade and high-grade mucinous neoplasm also adenocarcinomas. We aimed to investigate the...
BACKGROUND
Non-carcinoid appendix epithelial tumors are rare. These tumors include low-grade and high-grade mucinous neoplasm also adenocarcinomas. We aimed to investigate the clinicopathological features, treatment, and risk factors of recurrence.
METHODS
Patients diagnosed between 2008 and 2019 were retrospectively analyzed. Categorical variables were expressed as percentages and compared using the Chi-square test or Fisher's exact tests. Overall survival and Disease-free survival of the groups were calculated by the Kaplan-Meier method, and the log-rank test was used to compare the survival rates.
RESULTS
A total of 35 patients were included in the study. Of the patients, 19 (54%) were women and the median diagnosis age of patients was 50.4 years (19-76). As for pathological types, a total of 14 (40%) patients were mucinous adenocarcinoma and 14 (40%) patients were Low-Grade Mucinous Neoplasm (LGMN). Lymph node excision and lymph node involvement were 23 (65%) and 9 (25%) patients respectively. The majority of patients were stage 4 (27, 79%) and 25 (71%) of these patients had peritoneal metastasis. A total of 48.6% patients had been treated with cytoreductive surgery and hyper-thermic intraperitoneal chemotherapy. Median Peritoneal cancer index value was 12 (2-36). The median follow-up time was 20 (1-142) months. Recurrence developed in 12 (34%) of patients. When risk factors for recurrence are considered, there was a statistically significant difference in appendix tumors with high-grade, adenocarcinoma pathology, ones with peritoneal cancer index ≥12 and not having pseudomyxoma peritonei. Median disease-free survival was 18 (13-22, 95% CI) months. Median overall survival could not be reached while the 3-year survival rate was 79%.
CONCLUSION
The risk of recurrence is higher in high-grade appendix tumors, having peritoneal cancer index ≥ 12, not having pseudomyxoma peritonei and adenocarcinoma pathology. High-grade appendix adenocarcinoma patients should be followed closely for recurrence.
PubMed: 36861708
DOI: 10.4103/ijc.IJC_395_20 -
Medicina (Kaunas, Lithuania) Jan 2023The peritoneum is a common site for the dissemination of digestive malignancies, particularly gastric, colorectal, appendix, or pancreatic cancer. Other tumors such as... (Review)
Review
The peritoneum is a common site for the dissemination of digestive malignancies, particularly gastric, colorectal, appendix, or pancreatic cancer. Other tumors such as cholangiocarcinomas, digestive neuroendocrine tumors, or gastrointestinal stromal tumors (GIST) may also associate with peritoneal surface metastases (PSM). Peritoneal dissemination is proven to worsen the prognosis of these patients. Cytoreductive surgery (CRS), along with systemic chemotherapy, have been shown to constitute a survival benefit in selected patients with PSM. Furthermore, the association of CRS with hyperthermic intraperitoneal chemotherapy (HIPEC) seems to significantly improve the prognosis of patients with certain types of digestive malignancies associated with PSM. However, the benefit of CRS with HIPEC is still controversial, especially due to the significant morbidity associated with this procedure. According to the results of the PRODIGE 7 trial, CRS for PSM from colorectal cancer (CRC) achieved overall survival (OS) rates higher than 40 months, but the addition of oxaliplatin-based HIPEC failed to improve the long-term outcomes. Furthermore, the PROPHYLOCHIP and COLOPEC trials failed to demonstrate the effectiveness of oxaliplatin-based HIPEC for preventing peritoneal metastases development in high-risk patients operated for CRC. In this review, we discuss the limitations of these studies and the reasons why these results are not sufficient to refute this technique, until future well-designed trials evaluate the impact of different HIPEC regimens. In contrast, in pseudomyxoma peritonei, CRS plus HIPEC represents the gold standard therapy, which is able to achieve 10-year OS rates ranging between 70 and 80%. For patients with PSM from gastric carcinoma, CRS plus HIPEC achieved median OS rates higher than 40 months after complete cytoreduction in patients with a peritoneal cancer index (PCI) ≤6. However, the data have not yet been validated in randomized clinical trials. In this review, we discuss the controversies regarding the most efficient drugs that should be used for HIPEC and the duration of the procedure. We also discuss the current evidence and controversies related to the benefit of CRS (and HIPEC) in patients with PSM from other digestive malignancies. Although it is a palliative treatment, pressurized intraperitoneal aerosolized chemotherapy (PIPAC) significantly increases OS in patients with unresectable PSM from gastric cancer and represents a promising approach for patients with PSM from other digestive cancers.
Topics: Humans; Oxaliplatin; Peritoneal Neoplasms; Antineoplastic Combined Chemotherapy Protocols; Peritoneum; Stomach Neoplasms; Hyperthermia, Induced; Combined Modality Therapy; Survival Rate; Retrospective Studies; Colorectal Neoplasms
PubMed: 36837456
DOI: 10.3390/medicina59020255 -
Cancers Feb 2023Pseudomyxoma peritonei (PMP) is a rare peritoneal condition where mucus-secreting tumorous cells progressively produce a thick, gelatin-like substance. The prognosis of...
BACKGROUND
Pseudomyxoma peritonei (PMP) is a rare peritoneal condition where mucus-secreting tumorous cells progressively produce a thick, gelatin-like substance. The prognosis of patients with PMP is determined by the degree of cellularity within the mucin (low-grade (LAMN) vs. high-grade (HAMN) histologic features) and by the extent of the disease.
METHODS
Prognostic relevance of tumor markers CA19-9 and CEA, gender, Peritoneal Cancer Index (PCI), and completeness of cytoreduction (CC) after cytoreductive surgery were evaluated on 193 consecutive PMP patients, based on a retrospective analysis of prospectively gathered data from a German tertial referral center.
RESULTS
We demonstrated that low PCI, CC0 status, low-grade histology, and female gender were independent positive prognostic factors for both overall survival (OS) and progression-free survival (PFS). Furthermore, LAMN patients with achieved CC0 status show significantly better OS and PFS compared to those with CC1 status ( = 0.0353 and = 0.0026 respectively). In contrast, the duration and drug of hyperthermic intraperitoneal chemotherapy (HIPEC) were not prognostic in any comparison. Increased CA19-9 and CEA levels were significantly associated with HAMN cases, but also predicted recurrence in patients with low-grade histologies.
CONCLUSION
Our study confirmed the prognostic role of tumor markers and emphasized the importance of CC status and PCI in a large cohort of PMP- and LAMN patients.
PubMed: 36831667
DOI: 10.3390/cancers15041326 -
Cancers Feb 2023Pressurized intraperitoneal aerosol chemotherapy (PIPAC) is a novel intraperitoneal drug delivery method of low-dose chemotherapy as a pressurized aerosol in patients... (Review)
Review
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 (I 28.41%, = 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.
PubMed: 36831468
DOI: 10.3390/cancers15041125 -
Frontiers in Oncology 2023Pseudomyxoma peritonei (PMP) is a rare malignant disease characterized by a massive multifocal accumulation of mucin within the peritoneal cavity. The current treatment...
INTRODUCTION
Pseudomyxoma peritonei (PMP) is a rare malignant disease characterized by a massive multifocal accumulation of mucin within the peritoneal cavity. The current treatment option is based on complete cytoreductive surgery combined with hyperthermic intraperitoneal chemotherapy. However, the recurrence is frequent with subsequent progression and death. To date, most of the studies published in PMP are related to histological and genomic analyses. Thus, the need for further studies unveiling the underlying PMP molecular mechanisms is urgent. In this regard, hypoxia and oxidative stress have been extensively related to tumoral pathologies, although their contribution to PMP has not been elucidated.
METHODS
In this manuscript, we have evaluated, for the first time, the intratumoral real-time oxygen microtension (pO2mt) in the tumor (soft and hard mucin) and surrounding healthy tissue from five PMP patients during surgery. In addition, we measured hypoxia (Hypoxia Inducible Factor-1a; HIF-1α) and oxidative stress (catalase; CAT) markers in soft and hard mucin from the same five PMP patient samples and in five control samples.
RESULTS
The results showed low intratumoral oxygen levels, which were associated with increased HIF-1α protein levels, suggesting the presence of a hypoxic environment in these tumors. We also found a significant reduction in CAT activity levels in soft and hard mucin compared with healthy tissue samples.
DISCUSSION
In conclusion, our study provides the first evidence of low intratumoral oxygen levels in PMP patients associated with hypoxia and oxidative stress markers. However, further investigation is required to understand the potential role of oxidative stress in PMP in order to find new therapeutic strategies.
PubMed: 36776312
DOI: 10.3389/fonc.2023.1076500 -
Cancers Jan 2023Pseudomyxoma peritonei (PMP) is an uncommon pathology, and its rarity causes a lack of scientific evidence, precluding the design of a prospective trial. A diagnostic...
Diagnostic and Therapeutic Algorithm for Appendiceal Tumors and Pseudomyxoma Peritonei: A Consensus of the Peritoneal Malignancies Oncoteam of the Italian Society of Surgical Oncology (SICO).
Pseudomyxoma peritonei (PMP) is an uncommon pathology, and its rarity causes a lack of scientific evidence, precluding the design of a prospective trial. A diagnostic and therapeutic algorithm (DTA) is necessary in order to standardize the disease treatment while balancing optimal patient management and the correct use of resources. The Consensus of the Italian Society of Surgical Oncology (SICO) Oncoteam aims at defining a diagnostic and therapeutic pathway for PMP and appendiceal primary tumors applicable in Italian healthcare. The consensus panel included 10 delegated representatives of oncological referral centers for Peritoneal Surface Malignancies (PSM) affiliated to the SICO PSM Oncoteam. A list of statements regarding the DTA of patients with PMP was prepared according to recommendations based on the review of the literature and expert opinion. A consensus was obtained on 33 of the 34 statements linked to the DTA; two flowcharts regarding the management of primary appendiceal cancer and peritoneal disease were approved. Currently, consensus has been reached on pathological classification, preoperative evaluation, cytoreductive surgery technical detail, and systemic treatment; some controversies still exist regarding the exclusion criteria for HIPEC treatment. A shared Italian model of DTA is an essential tool to ensure the appropriateness and equity of treatment for these patients.
PubMed: 36765686
DOI: 10.3390/cancers15030728 -
Cancers Jan 2023The reiteration of surgical cytoreduction (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) in patients affected by recurrent peritoneal metastases is still...
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 ( < 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%, = 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.
PubMed: 36765565
DOI: 10.3390/cancers15030607 -
Cureus Jan 2023Primary appendiceal carcinomas are rare and often found incidentally when the appendix is surgically removed. Adenocarcinoma predominates the histological types of...
Primary appendiceal carcinomas are rare and often found incidentally when the appendix is surgically removed. Adenocarcinoma predominates the histological types of malignancies, with mucinous adenocarcinoma being the most prevalent of the various subtypes. Pseudomyxoma peritonei (PMP), a complication seen in mucinous adenocarcinoma of the appendix (MAA), is the collection of mucinous ascites in the intra-abdominal cavity and the thickening of the surrounding viscera by mucin-producing tumor cells. PMP initially presents with increased abdominal discomfort and girth and, in later stages, presents with obstructive abdomen symptoms. These symptoms are nonspecific and can be a challenge to pinpoint. Such was the case for our patient, in this case report, who initially presented with dyspepsia and later demonstrated compressive symptoms and weight loss, raising concern for malignancy. An appendiceal pathology was of concern when his right lower quadrant pain acutely worsened during an abdominal ultrasound, and imaging and biopsy confirmed MAA with PMP. The aim of this report is to shed light on the management of recurrent MAA. Our patient's recurrent MAA was managed with debulking procedures and three rounds of hyperthermic intraperitoneal chemotherapy (HIPEC) and was managed postoperatively with folinic acid, fluorouracil, and irinotecan (FOLFIRI) and bevacizumab, which in its totality helped achieve a progression-free survival of more than two years. We believe that cytoreduction and intraoperative chemotherapy prolong survival in patients with recurrent disease, as was the case with our patients. Our patient also demonstrated benefit as his disease stabilized after starting bevacizumab; however, more studies need to be performed at a larger scale to show a consistent relationship.
PubMed: 36741631
DOI: 10.7759/cureus.33294 -
Frontiers in Surgery 2022Anesthetic management for patients of pseudomyxoma peritonei (PMP) is challenging. This case report describes a patient of PMP with high intra-abdominal pressure....
Anesthetic management for patients of pseudomyxoma peritonei (PMP) is challenging. This case report describes a patient of PMP with high intra-abdominal pressure. Intubation was performed in lateral position; the intraabdominal pressure was relieved slowly to prevent significant hemodynamic changes. Additionally, positive pressure ventilation was performed to reduce the risk of re-expansion pulmonary edema. During the operation, transfusion and infusion therapy was performed with target-mediated fluid therapy according to stroke volume variation (SVV) and cardiac index (CI) and blood gas analysis.
PubMed: 36726956
DOI: 10.3389/fsurg.2022.1017500 -
Frontiers in Surgery 2022Pseudomyxoma peritonei (PMP) is a rare disease, with the overall survival (OS) influenced by many factors. To date, no ascites characteristics have been reported to...
BACKGROUND
Pseudomyxoma peritonei (PMP) is a rare disease, with the overall survival (OS) influenced by many factors. To date, no ascites characteristics have been reported to predict OS of patients with PMP. The present study therefore aims to describe the ascites characteristics for PMP and identify prognostic factors for survival.
METHODS
Between June 2010 and June 2020, 473 PMP patients who underwent cytoreductive surgery and hyperthermic intraperitoneal chemotherapy were included in a retrospective study. Survival analysis was performed with the Kaplan-Meier method by the log-rank test and a Cox proportional hazards model. Associations between categorical variables were analyzed using the chi-squared test.
RESULTS
Among all included patients, 61% were women. The median OS was 47 months (range, 4-124 months) at the last follow-up in December 2020. Ascites characteristics can be divided into light blood ascites, "Jelly" mucus ascites, and faint yellow and clear ascites. Multivariate Cox analysis showed that the degree of radical surgery, ascites characteristics, and pathological grade were independently associated with OS in PMP patients. The chi-squared test documented that faint yellow "Jelly" ascites were related to low-grade PMP and light blood ascites were associated with high-grade PMP ( < 0.01).
CONCLUSIONS
Light blood ascites, incomplete cytoreduction surgery, and high-grade histopathology may predict poor OS in appendix-derived PMP.
PubMed: 36726946
DOI: 10.3389/fsurg.2022.967296