Combined Interval Cytoreductive Surgery and Carboplatin-Based Hyperthermic Intraperitoneal Chemotherapy in Advanced Primary High-Grade Serous Ovarian Cancer.

Combining interval cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) improves survival in advanced epithelial ovarian carcinoma (EOC). Although limited, growing evidence regarding carboplatin-based HIPEC highlights its potential. This retrospective study included all patients with advanced primary high-grade serous ovarian cancer who underwent interval CRS combined with carboplatin-based HIPEC at our Canadian tertiary care center between 2014 and 2020. We identified 40 patients with a median age of 61 years. The median peritoneal cancer index was 13 and complete cytoreduction was achieved in 38 patients (95%). Median hospital stay was 13 days and there were four admissions to the intensive care unit (10%) and six readmissions (15%). Severe adverse events occurred in eight patients (20%) and there was no perioperative death. Recurrence was seen in 33 patients (82%) with a median DFS of 18.0 months and a median overall survival of 36.4 months. Multivariate analyses showed that age, peritoneal cancer index, completeness of cytoreduction, occurrence of severe complications, and bowel resection did not significantly impact DFS or OS in our cohort. Interval CRS combined with carboplatin-based HIPEC for advanced primary EOC is associated with acceptable morbidity and oncological outcomes. Larger studies are required to determine the long-term outcomes.

Cytoreductive surgery (CRS) and heated intraperitoneal chemotherapy (HIPEC) for peritoneal mesothelioma: Canadian practices and outcomes.

INTRODUCTION: Peritoneal mesothelioma (PM) is a rare malignancy originating from the peritoneal lining. Cytoreductive surgery (CRS) and heated intraperitoneal chemotherapy (HIPEC) is the standard-of-care for patients with isolated PM. Due to a paucity of prospective data there are several different HIPEC protocols. The aims of this study are to describe the CRS and HIPEC protocols for PM and patient outcomes across Canada. METHODS: A multicenter retrospective study was performed on patients diagnosed and treated for PM with CRS and HIPEC in four major peritoneal disease centers in Canada between 2000 and 2021. Data on patient characteristics, treatment patterns, postoperative morbidity, recurrence, and survival were collected. RESULTS: A total of 72 patients were identified. Mean age was 52 years (17-75) and 37.5% were male. Epithelioid (70.1%) and multicystic (13%) mesothelioma were the most common subtypes. Twenty-one patients (30%) were treated with neoadjuvant chemotherapy. CRS and HIPEC was performed in 64 patients (91.4%). Of these, the mean PCI was 22 (2-39) and cisplatin+doxorubicin was the most common HIPEC regimen (n = 33, 51.6%). A semi-closed coliseum technique was used in 68.8% of HIPECs and the mean duration of surgery was 486 min (90-1052). Clavien-Dindo III or IV complications occurred in 12 patients (16.9%). With a median follow-up of 24 months (0.2-104.4), we found a 5-year overall survival of 61% and a 5-year recurrence-free survival of 35%. CONCLUSION: CRS and HIPEC is a safe and effective treatment modality for well-selected patients with PM, with some achieving prolonged survival.

The Impact of Computed Tomography Measurements of Sarcopenia on Postoperative and Oncologic Outcomes in Patients Undergoing Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy.

Cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS-HIPEC) is a treatment option for peritoneal metastases (PM) but is associated with significant postoperative morbidity. The aim of this study was to determine the prognostic value of computed tomographic (CT)-measured sarcopenia on postoperative outcomes and survival in patients undergoing CRS-HIPEC for PM from various origins. A retrospective cohort study was conducted between 2012 and 2020. Three-hundred and twelve patients (mean age 57.6 ± 10.3, 34.3% male) were included, of which 88 (28.2%) were sarcopenic. PM from a colorectal origin was the most common in both groups. The proportion of major postoperative complications (Clavien-Dindo ≥ III) was not higher in the sarcopenic group (15.9% in sarcopenic patients vs. 23.2% in nonsarcopenic patients, p = 0.17). The mean Comprehensive Complication Index scores, HIPEC-related toxicities, length of hospital stay, and duration of parenteral nutrition were comparable regardless of sarcopenia status. In the multivariate logistic regression analysis of severe complications, only peritoneal carcinomatosis index reached statistical significance (OR, 1.05; 95% CI, 1.01 to 1.08, p = 0.007). Sarcopenia did not impact origin-specific overall survival on Cox regression analysis. Sarcopenia was not associated with worse rates of postoperative severe complications or worse survival rates. Future prospective studies are required before considering sarcopenia as part of preoperative risk assessment.

Two-step cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for pseudomyxoma peritonei with high peritoneal carcinomatosis index.

BACKGROUND: Complete cytoreductive surgery (CRS) combined with hyperthermic intraperitoneal chemotherapy (HIPEC) is the only curative treatment for pseudomyxoma peritonei (PMP) arising from the appendix. High peritoneal carcinomatosis index (PCI) is associated with an increased risk of surgical complications. The objective of this study was to present the results of a planned two-step surgical strategy to decrease postoperative morbidity and improve resectability of patients with very high PCI. METHODS: All consecutive patients who underwent a planned two-step surgical approach for PMP between January 2012 and March 2020 were retrospectively included. This approach was offered for patients with low-grade PMP with PCI > 28 for which feasibility of a complete CRS in one operation was uncertain. The first surgery included a complete CRS of the inframesocolic compartment and omentectomy. HIPEC was delivered at the second surgery, after complete CRS of the supramesocolic compartment. Postoperative morbidity was assessed using the Clavien-Dindo classification and survival results were also collected. RESULTS: Eight patients underwent the two-step approach. The median PCI was 33 (29-39) and the median time between the two procedures was 111 days (90-212 days). One patient was deemed unresectable at the second surgery. The rate of major morbidity was 0% for the first step and 25% for the second step, with no mortality. Median follow-up was 53.8 months (3-73 months). CONCLUSION: A two-step surgical management for low-grade PMP patients with very high PCI is safe and feasible, with acceptable postoperative morbidity and no compromise on oncological outcomes.

A rare case of recurrent epidermoid anal cancer treated with cytoreductive surgery and hyperthermic intraperitoneal chemotherapy-case report.

BACKGROUND: Anal cancer is a rare cancer with chemoradiation being the mainstay of treatment for locoregional presentation. In North America, the most common subtype is anal squamous cell carcinoma (epidermoid). A surgical approach is considered for persistent or recurrent anal disease and systemic chemotherapy for metastatic disease. We are presenting a unique case of recurrent anal cancer with isolated peritoneal malignancy, an oligometastatic state which is rare in itself. It was treated with cytoreductive surgery and hyperthermic intraperitoneal chemotherapy. There are currently no clear guidelines for the aforementioned presentation. The discussion drew on the feasibility and safety of this approach. CASE PRESENTATION: A 68-year-old woman diagnosed with an epidermoid anal cancer (stage 3B) was initially treated with chemoradiation therapy (Standard Nigro Protocol) in 2014. At the 5-year mark post-treatment, she was diagnosed with a recurrent anal epidermoid cancer in the form of isolated peritoneal carcinomatosis proven by biopsy. After declining systemic chemotherapy, she underwent cytoreductive surgery and hyperthermic intraperitoneal chemotherapy with Mitomycin-C©. Peritoneal carcinomatosis index was evaluated at 10, and intraoperative frozen sections were positive for carcinoma of epidermoid origin compatible with anal cancer. A completeness of cytoreduction score of 0 was achieved during the cytoreductive surgery, and her hospital course was unremarkable. She remains disease-free 12 months later. CONCLUSIONS: To our knowledge, this is the first case reporting the disease presentation of anal cancer with oligometastatic dissemination to the peritoneum. Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy were performed. Thus far, this approach seems to be a safe and feasible option for short-term control of the disease.

Evaluation of repeat cytoreductive surgery and heated intraperitoneal chemotherapy for patients with recurrent peritoneal carcinomatosis from appendiceal and colorectal cancers: a multicentre Canadian study

Background: Peritoneal recurrences after cytoreductive surgery (CRS) and heated intraperitoneal chemotherapy (HIPEC) for appendiceal and colorectal cancers are frequent. This study aimed to evaluate the safety, technical feasibility and perioperative and long-term outcomes of repeat CRS/HIPEC in patients with recurrent peritoneal carcinomatosis of colorectal and appendiceal origin. Methods: Data were collected from patients treated from 2000 to 2016 for recurrent peritoneal carcinomatosis from appendiceal or colorectal cancer with CRS/HIPEC at 2 specialist centres. Data on demographics, procedure details, morbidity and survival were recorded. Analyses compared the iterations of CRS/HIPEC to assess the safety and effectiveness of repeat surgery. Results: Of all patients who underwent CRS/HIPEC in the 2 centres, 37 patients underwent a repeat procedure. Operative time was similar for the first and second surgeries (412.1 v. 412.5 min, p = 0.74) but patients had a significantly lower peritoneal carcinoma index score with the second surgery (21.8 in the first iteration v. 9.53 in the second iteration, p < 0.001) and significantly less blood loss (1762 mL in the first iteration v. 790 mL in the second iteration, p = 0.001). There was a nonsignificant decrease in grade III­IV complications and there was no 30-day mortality associated with repeat procedures. For patients with colorectal cancer, median disease-free survival was 9.6 months and median overall survival was 40 months. For patients with appendiceal cancer, median disease-free survival was 15 months and overall survival was 64.4 months. Conclusion: Repeat CRS/HIPEC procedures for recurrent appendiceal and colorectal peritoneal carcinomatosis are safe in well-selected patients, without increased morbidity or mortality, and they are associated with significant long-term survival, particularly for patients with appendiceal cancers. These results support the use of repeat CRS/HIPEC in these patients.

Contexte: Les récurrences péritonéales après une chirurgie cytoréductrice (CCR) et une chimiothérapie hyperthermique intrapéritonéale (CHIP) pour les cancers de l'appendice et colorectaux sont fréquentes. Cette étude visait à évaluer l'innocuité, la faisabilité technique et les résultats périopératoires et à long terme d'une reprise de CCR/CHIP chez les patients qui présentent une récurrence de carcinomatose péritonéale ayant son origine au niveau colorectal ou de l'appendice. Méthodes: Des données ont été recueillies sur des patients traités entre 2000 et 2016 pour une récurrence de carcinomatose péritonéale ayant son origine au niveau colorectal ou de l'appendice par CCR/CHIP dans 2 centres spécialisés. On a tenu compte des données démographiques, des détails des interventions, ainsi que de la morbidité et de la survie. Des analyses ont permis de comparer les premières et deuxièmes CCR/CHIP pour évaluer l'innocuité et l'efficacité des chirurgies répétées. Résultats: De tous les patients soumis à des CCR/CHIP dans les 2 centres, 37 ont subi l'intervention de nouveau. Le temps opératoire a été similaire pour les premières et les deuxièmes chirurgies (412,1 c. 412,5 min, p = 0,74), mais les patients présentaient un score de carcinomatose péritonéale beaucoup plus bas lors de la deuxième chirurgie (21,8 pour la première intervention c. 9,53 pour la seconde, p < 0,001) et des pertes sanguines significativement moindres (1762 mL pour la première intervention c. 790 mL pour la seconde, p = 0,001). On a noté une diminution non significative des complications de grades III­IV et on n'a déploré aucune mortalité à 30 jours en lien avec la reprise de l'intervention. Pour les patients atteints d'un cancer colorectal, la survie médiane sans maladie a été de 9,6 mois et la survie médiane globale a été de 40 mois. Pour les patients atteints d'un cancer de l'appendice, la survie médiane sans maladie a été de 15 mois et la survie médiane globale a été de 64,4 mois. Conclusion: La reprise des CCR/CHIP pour les récurrences de carcinomatose péritonéale ayant leur origine au niveau colorectal ou de l'appendice est sécuritaire chez les patients soigneusement sélectionnés, sans accroissement de la morbidité ou de la mortalité, et elles sont associées à une survie à long terme significative, particulièrement chez les patients ayant un cancer de l'appendice. Ces résultats appuient la reprise des CCR/CHIP chez ces patients.

Impact of anesthesia management during cytoreductive surgery plus hyperthermic intraperitoneal chemotherapy for the treatment of colorectal peritoneal carcinomatosis on intra- and postoperative outcomes: A systematic review protocol.

BACKGROUND: The impact of the anesthesia management during cytoreductive surgery (CRS) plus hyperthermic intraperitoneal chemotherapy (HIPEC) for the treatment of colorectal peritoneal carcinomatosis (CRPC) on postoperative outcomes might be of major importance in the process of postoperative recovery. It might have a significant impact on intra- and postoperative outcomes, but the evaluation of this impact seems to be under-reported. To investigate the question whether the anesthesia management was reported in previous studies done in this population and if it had any impact on postoperative outcomes, we propose to conduct a systematic review of the published literature. METHODS: For this review, we will follow the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocols (PRISMA-P). Medline/PubMed, Embase, EBM Reviews and the Cochrane Database of Systematic Reviews (CDSR) will be systematically consulted for eligible studies without age, gender, ethnic, and language restriction. The goal of this review will be to assess whether anesthesia monitoring, dosing, and analgesia protocols were reported in this literature on this specific procedure and whether the impact of the anesthesia management on intraoperative safety and postoperative recovery was evaluated. RESULTS: The results of this systematic review will allow to answer the initial question: has the impact of anesthesia management on intraoperative safety and patients' postoperative recovery already been studied and reported in the past for this type of major surgery? And does anesthesia have any impact on postoperative outcomes? DISCUSSION: In the hypothesis that the impact of anesthesia management on patients' postoperative recovery has never been studied, or very little reported in previous studies in this type of major surgery, it would be justified to conduct a randomized controlled trial on this specific objective. REGISTRATION: This systematic review protocol was registered in PROSPERO, under the registration number CRD42019124162.

Peritoneal carcinomatosis index predicts survival in colorectal patients undergoing HIPEC using oxaliplatin: a retrospective single-arm cohort study.

BACKGROUND: Peritoneal carcinomatosis (PC) from colorectal cancer is associated with poor prognosis. Cytoreductive surgery (CRS) combined with hyperthermic intraperitoneal chemotherapy (HIPEC) has improved survival for patients with colorectal peritoneal carcinomatosis. However, standardization of HIPEC protocols, including which chemotherapeutic agent to use, is lacking in the literature. Therefore, we sought to report survival outcomes from colorectal cancer patients undergoing CRS/oxaliplatin-based HIPEC at our institution over the last 10 years. METHODS: Colorectal PC patients treated with CRS/oxaliplatin-based HIPEC 2004-2015 were included. Demographic, clinical, and oncologic data were abstracted from the medical record. Overall (OS) and disease-free survival (DFS) were calculated using Kaplan-Meier analysis. Univariate/multivariate Cox regression analysis was done. RESULTS: Laparotomy was performed in 113 patients for colorectal PC; 91 completed a curative intent CRS/HIPEC. At 3 and 5 years, OS for the CRS/HIPEC cohort was 75% and 55%, and DFS was 50% and 25%, respectively. On multivariate analysis, incremental increases in peritoneal carcinomatosis index (PCI) were associated with worse OS (p = 0.0001) and DFS (p = 0.0001). Grade III/IV complications were also associated with worse OS. CONCLUSIONS: A standardized regimen of CRS and oxaliplatin-based HIPEC for colorectal PC is effective with favorable OS and DFS and acceptable complication rates.

Long term survival analysis after hyperthermic intraperitoneal chemotherapy with oxaliplatin as a treatment for appendiceal peritoneal carcinomatosis.

BACKGROUND AND OBJECTIVES: Complete cytoreductive surgery (CRS) followed by hyperthermic intraperitoneal chemotherapy (HIPEC) have been proven to lengthen survival in appendiceal peritoneal carcinomatosis (PC-A). The aim of this study was to analyze survival results of this therapy in our institution over the last 10 years. METHODS: Data was retrospectively reviewed and analyzed. Treatment consisted of CRS plus HIPEC with oxaliplatin. Ronnett's histologic classification was used (peritoneal mucinous carcinomatosis (PMCA), PMCA with intermediate features (PMCA-I) and disseminated peritoneal adenomucinosis (DPAM)). Overall survival (OS) and disease-free survival (DFS) estimates were calculated using Kaplan-Meier survival curves. RESULTS: 109 patients with PC-A underwent laparotomy with curative intent. Of those, 92 underwent CRS plus HIPEC. Median follow-up was 42 months. The 5 and 10-year OS rates for the HIPEC group were 82.2% and 76.5%. The 5 and 10-year OS estimates for DPAM and PMCA-I subgroups were 100% and 100%, 78.1% and 72.9%, respectively. For the PMCA subgroup, the 3 and 5-year OS were 61.4% and 40.1%, respectively. The 5 and 10-year DFS estimates were 71.9% and 42.7%. CONCLUSION: CRS plus HIPEC with oxaliplatin represent an effective therapeutic approach for PC-A. Long term OS estimates for patients treated at our institution are encouraging.

Postoperative complications affect long-term outcomes after cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for colorectal peritoneal carcinomatosis.

BACKGROUND AND OBJECTIVES: Morbidity after cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS + HIPEC) for colorectal peritoneal carcinomatosis (PC) may negatively affect survival. The objective was to determine the impact of postoperative complications (CX) on survival in patients undergoing CRS + HIPEC for colorectal PC. METHODS: All patients undergoing laparotomy for planned CRS + HIPEC for colorectal PC at a single institution from 1999 to 2014 were included. Patients were divided into three groups: CRS + HIPEC without CX (+HIPEC-CX); CRS + HIPEC with postoperative complication (+HIPEC + CX); and aborted CRS and HIPEC due to unresectable disease (-HIPEC). Postoperative morbidity were defined as Clavien II+ complications. Kaplan-Meier survival analyses and multivariable Cox proportional hazard modeling were used to describe the disease-free (DFS) and overall survival (OS). RESULTS: One hundred and twenty-two patients were included in the analysis (50 +HIPEC - CX, 40 +HIPEC + CX, 32-HIPEC). Overall complication rate was 42%. OS at 1-, 3-, and 5-years in patients undergoing successful CRS + HIPEC were 97%, 67%, and 45%. CX after successful CRS + HIPEC was independently associated with worsened OS (HR1.58, 95%CI, 1.19-1.97) but not DFS (HR1.11, 95%CI, 0.56-2.20). PCI also independently predicted worsened DFS (HR1.12, 95%CI, 1.06-1.18) and OS (HR1.08, 95%CI, 1.04-1.12). Patients with unresectable disease had significantly worse OS (HR6.50, 95%CI, 1.37-7.01). CONCLUSIONS: CX after CRS + HIPEC significantly affect OS. Patient selection and perioperative care are of paramount importance in the management of CRS + HIPEC for colorectal PC.

Impact of electrocautery and hyperthermic intraperitoneal chemotherapy on intestinal microvasculature in a murine model.

BACKGROUND: Electrocautery (EC) is used during cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC). Using a murine model, we studied the effect of HIPEC on small bowel EC lesions and surrounding normal tissues. METHODS: Thirty-two rats were divided into five groups: a control group with EC lesions; EC plus intraperitoneal heated 5% dextrose (D5W); EC plus oxaliplatin (OXA, 460 mg/m(2)); EC plus mitomycin C 10 mg/m(2) (MMC10); EC plus MMC 35 mg/m(2) (MMC35). EC lesions and surrounding tissue microvasculature were analysed after intravenous injection of fluorescein. RESULTS: In the ileum OXA significantly reduced EC lesions microvasculature compared with the control group; MMC10 caused greater reduction than the control, D5W and MMC35 groups. Surrounding tissue microvasculature was significantly reduced by MMC35 exposure when compared to the control, OXA or MMC10 groups. In the jejunum EC injuries exposed to OXA or MMC10 had significantly reduced microvasculature compared to the control, heated D5W and MMC35 groups. Surrounding tissue microvasculature was significantly reduced by MMC35 exposure when compared to the OXA group. There was no significant microvasculature difference between the EC lesions made before or after HIPEC. CONCLUSION: HIPEC with OXA and MMC10 potentiates small bowel wall EC injuries. MMC35 reduces surrounding unharmed tissue microvasculature. There was no effect of hyperthermia alone on microvasculature.

Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy with oxaliplatin for peritoneal mesothelioma: preliminary results and survival analysis.

BACKGROUND: Peritoneal mesothelioma is a rare disease with poor prognosis. The present study reports single center experience with cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy with oxaliplatin (HIPEC-OX) over an eight-year period. METHODS: Prospectively collected data of all consecutive patients with epithelial or multicystic peritoneal mesothelioma from August 2004 to October 2012 was analyzed. Patients with sarcomatoid or biphasic peritoneal mesothelioma were not included due to general poor prognosis. Treatment consisted in CRS and HIPEC-OX (460 mg/m(2)) at 43 °C during 30 min. For statistical analysis, Kaplan-Meier survival curves were plotted and compared using log-rank tests. Cox proportional-hazards regression model was used to analyze the influence of different variables on survival. RESULTS: Nineteen patients with peritoneal mesothelioma underwent laparotomy with CRS and HIPEC-OX with curative intent (15 epithelial, and 4 multicystic). Mean follow-up was 36.7 months. The estimated one-year and three-year overall survival rates were respectively 100% and 91%. The estimated one-year and three-year disease-free survival rates were respectively 77% and 50%. Complications were graded according to the Clavien-Dindo classification [1] and major complications occurred in 57% of cases. There was no postoperative mortality. Histological grade was not a prognostic factor of disease-free survival (p = 0.37). CONCLUSION: When comparing survival results as well as morbidity-mortality rates, the present study shows that CRS and HIPEC-OX is a valid treatment for peritoneal mesothelioma.

Hyperthermic intraperitoneal chemotherapy with oxaliplatin as treatment for peritoneal carcinomatosis arising from the appendix and pseudomyxoma peritonei: a survival analysis.

BACKGROUND: Appendiceal peritoneal carcinomatosis (PC) is rare and its long-term prognosis is poor. The aim of this study was to evaluate the results of an aggressive treatment approach used in our institution for the last eight years. METHODS: Data from all patients with PC arising from the appendix were prospectively collected and analyzed. Treatment consisted of complete surgical cytoreduction (CRS), followed by hyperthermic intraperitoneal chemotherapy (HIPEC) with oxaliplatin (460 mg/m2) at 43°C over 30 minutes. Ronnett's histologic classification was used for tumor grading. RESULTS: Between February 2003 and April 2011, 78 patients underwent laparotomy with curative intent. The mean follow-up period was 33.7 months. A total of 58 patients received HIPEC, but 11 patients could not have CRS and received no HIPEC. Nine patients with a negative second-look surgery also received no HIPEC. The five-year overall survival for the entire cohort was 66.2%; 100% for the negative second-look patients, 77% for the HIPEC patients and 9% for the unresectable patients (P<0.0001). A total of 15 patients (25.9%) had isolated peritoneal recurrence, no patient had visceral recurrence only, and five patients (8.6%) had both. In regards to the five-year disease-free survival for the HIPEC patients, histologic grade (disseminated peritoneal adenomucinosis 100%, peritoneal mucinous carcinomatosis with intermediate features 40%, peritoneal mucinous carcinomatosis 20%; p=0.0016) and completeness of cytoreduction (CCR-0 56%, CCR-1 24%; P=0.0172) were prognostic factors. There was one postoperative mortality. The major complication rate for patients treated with HIPEC was 40%, including intra-abdominal abcess (17%), hemorrhage (12%) and anastomotic leak (10%). One patient in the HIPEC group experienced temporary grade II neuropathy and grade III thrombocytopenia. CONCLUSIONS: This therapeutic approach seems both feasible and safe in selected patients. Recurrence is, however, frequent and represents a challenge.

Cytoreductive surgery with hyperthermic intraperitoneal chemotherapy: an emerging treatment option for advanced goblet cell tumors of the appendix.

BACKGROUND: The debate remains whether appendiceal goblet cell cancers behave as classical carcinoid or adenocarcinoma. Treatment options are unclear and reports of outcomes are scarce. Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS+HIPEC) is considered optimal treatment for peritoneal involvement of other epithelial appendiceal tumors. METHODS: Prospective cohorts of patients treated for advanced appendiceal tumors from three peritoneal malignancy centres were collected (1994-2011). All patients underwent complete CRS+HIPEC, when possible, or tumor debulking. Demographic and outcome data for patients with goblet cell cancers were compared to patients with low- or high-grade epithelial appendiceal tumors treated during the same time period. RESULTS: Details on 45 goblet cell cancer patients were compared to 708 patients with epithelial appendix lesions. In the goblet cell group, 57.8 % were female, median age was 53 years, median peritoneal cancer index (PCI) was 24, and CRS+HIPEC was achieved in 71.1 %. These details were similar in patients with low- or high-grade epithelial tumors. Lymph nodes were involved in 52 % of goblet cell patients, similar to rates in high-grade cancers, but significantly higher than in low-grade lesions (6.4 %; p < 0.001). At 3 years, overall survival (OS) was 63.4 % for goblet cell patients, intermediate between that for high-grade (40.4-52.2 %) and low-grade (80.6 %) tumors. On multivariate analysis, tumor histology, PCI, and achievement of CRS+HIPEC were independently associated with OS. CONCLUSIONS: This data supports the concept that appendiceal goblet cell cancers behave more as high-grade adenocarcinomas than as low-grade lesions. These patients have reasonable long-term survival when treated using CRS+HIPEC, and this strategy should be considered.

Cytoreductive surgery plus hyperthermic intraperitoneal chemotherapy with oxaliplatin for peritoneal carcinomatosis arising from colorectal cancer.

BACKGROUND: Peritoneal carcinomatosis (PC) from colorectal cancer is associated with a poor prognosis. Cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) have improved survival compared to systemic chemotherapy. We evaluate the results of this treatment in our institution. METHODS: Treatment consisted of complete CRS followed by HIPEC with oxaliplatin (460 mg/m(2) ) in 2 L/m(2) of D5W at 42°C during 30 min. RESULTS: From 2004 to 2011, 40 patients with PC from colorectal cancer were included and 25 CRS + HIPEC were performed. Six patients had a negative second-look surgery and nine had unresectable disease. Median follow-up was 22.8 months. Overall 3- and 5-year survival rates for the cohort were 56% and 33%. The 3- and 5-year overall survival rates were 61% and 36% for HIPEC group, 82% and 67% for patients with negative second-look, and 22% and 0% for the unresectable group (P = 0.0087). 3-year disease-free survival for HIPEC group was 22%. Major complication and mortality rate for HIPEC group were 20% and 4%. Peritoneal carcinomatosis index (P = 0.0374) and lymph node status (P = 0.027) were prognostic indicators. CONCLUSIONS: CRS + HIPEC with oxaliplatin for PC from colorectal cancer is an effective treatment with encouraging survival results.

Ocular melanoma in a patient successfully treated for diffuse malignant peritoneal mesothelioma: a case report.

BACKGROUND: Diffuse malignant peritoneal mesothelioma and ocular melanoma are both rare tumors. To the best of our knowledge there is only one previous report of three cases in a family with known susceptibility to malignancies associating diffuse malignant peritoneal mesothelioma and ocular melanoma, with no sporadic cases previously reported. CASE PRESENTATION: We describe the case of a 59-year-old man with a history of diffuse malignant peritoneal mesothelioma, who presented with ocular melanoma 41 months after cytoreductive surgery and hyperthermic intraperitoneal chemotherapy. We also briefly review the literature. CONCLUSIONS: Diffuse malignant peritoneal mesothelioma is an uncommon but aggressive disease. As diffuse malignant peritoneal mesothelioma characteristically remains confined to the abdominal cavity, any new extra-abdominal symptom should eventually raise suspicion of another primary tumor. Few cases of diffuse malignant peritoneal mesothelioma associated with other primary tumors have been reported. As ocular melanoma is also infrequent, we suspect a genetic predisposition to these tumors. There is emerging evidence supporting the role of BAP1 mutations in the pathogenesis of these two neoplasias.

Surgical cytoreduction and intraperitoneal chemotherapy for peritoneal carcinomatosis arising from the appendix.

BACKGROUND: Peritoneal carcinomatosis (PC) originating in the appendix is a rare disease for which the long-term prognosis is poor. The aim of our study was to evaluate the results of an aggressive treatment approach used in our institution in the last decade. METHODS: We prospectively collected and analyzed data from all patients with PC. Treatment consisted of complete surgical cytoreduction of the tumour followed by intraperitoneal chemotherapy. Chemotherapy was either early postoperative intraperitoneal chemotherapy (EPIC) or hyperthermic intraperitoneal chemotherapy (HIPEC). We used Ronnett's classification for tumour grading (disseminated peritoneal adenomucinosis = grade 0, peritoneal mucinous carcinomatosis with intermediate features = grade 1 and peritoneal mucinous carcinomatosis = grade 2). RESULTS: From September 1997 to June 2005, 37 patients underwent laparotomy with curative intent; 13 received EPIC and 11 HIPEC. Thirteen patients could not have complete cytoreductive surgery and received no intraperitoneal chemotherapy. The estimated 5-year overall survival was 56% (95% confidence interval [CI] 34%-77%) for all patients, 58% (95% CI 30%-86%) for patients who underwent EPIC and 60% (95% CI 10%-100%) for patients who underwent HIPEC (p = 0.97). Histologic grade was an important prognostic indicator as all patients with grade 0 tumours survived whereas no patients with grade 2 tumours survived (p < 0.001). Patients with grade 1 tumours had an estimated 87% (95% CI 64%-100%) 5-year overall survival. There was no mortality attributed to surgery. The overall complication rate was 36%, including fistulas (16%), intra-abdominal abscesses (12%) and hemorrhage (9%). CONCLUSION: This therapeutic approach seems both feasible and safe in select patients. Patients with high-grade tumours are poor candidates for this treatment.

Hyperthermic intraperitoneal chemotherapy with oxaliplatin for peritoneal carcinomatosis arising from appendix: preliminary results of a survival analysis.

BACKGROUND: Peritoneal carcinomatosis (PC) arising from the appendix is a rare disease for which the long-term prognosis is poor. The aim of this study was to evaluate the results of an aggressive approach used in our institution over the last 5 years. METHODS: Data from all patients with PC arising from the appendix were prospectively collected and analyzed. Treatment consisted in complete surgical cytoreduction followed by hyperthermic intraperitoneal chemotherapy (HIPEC) with oxaliplatin (460 mg/m(2)) in 2 L/m(2) of D5W at 43 degrees C during 30 min. Ronnett's histologic classification was used for tumor grading. RESULTS: From February 2003 to March 2007, 38 patients with PC arising from the appendix underwent laparotomy with curative intent. Mean follow-up was 23 months. Twenty-three patients received HIPEC but ten patients could not have complete cytoreductive surgery and received no HIPEC. Five patients with a negative second-look surgery also received no HIPEC. Three-year overall survival (OS) was 100% for the negative second-look patients, 86% for the HIPEC patients, and 29% for the unresectable patients (P = 0.0098). Three-year disease-free survival (DFS) was 49% for the HIPEC patients. Histologic grade was a prognostic factor with regard to DFS for the HIPEC patients (P = 0.011). There was one postoperative mortality. The overall major (grade III-V/V) complication rate for treated patients was 39%, including intra-abdominal abscess (22%), hemorrhage (18%), and anastomotic leak (9%). CONCLUSION: Although these results are preliminary, this therapeutic approach seems both feasible and safe in selected patients.

Treatment of peritoneal carcinomatosis from colorectal cancer: impact of complete cytoreductive surgery and difficulties in conducting randomized trials.

BACKGROUND: Colorectal peritoneal carcinomatosis (PC) is a frequent and very lethal event. However, cure may be possible with maximal cytoreductive surgery associated with early postoperative intraperitoneal chemotherapy (EPIC). METHODS: Between 1996 and 2000, we conducted a two-center prospective randomized trial comparing EPIC plus systemic chemotherapy with systemic chemotherapy alone, both after complete cytoreductive surgery of colorectal PC. Only 35 patients could be included among the 90 who were theoretically required, mainly because of patient dissatisfaction with the inclusion criteria. For this reason, the trial was stopped prematurely. RESULTS: Analysis of these 35 patients showed that complete resection of PC resulted in a 2-year survival rate of 60%-far above the classic 10% survival rate among patients with colorectal PC treated with systemic chemotherapy and symptomatic surgery. In this small series, EPIC did not demonstrate any advantage for survival. CONCLUSIONS: This supports the use of complete cytoreductive surgery in selected patients and calls for a prospective randomized trial comparing adjuvant systemic chemotherapy with intraperitoneal chemohyperthermia after complete resection.

Pharmacokinetics of heated intraoperative intraperitoneal oxaliplatin after complete resection of peritoneal carcinomatosis.

The results of three prospective clinical trials are reported: the first one was aimed at determining the appropriate dose of heated (42 degrees C) intraperitoneal oxaliplatin following complete resection of peritoneal carcinomatosis by studying its pharmacokinetics. The recommended dosage was set at 460 mg/m2 in 2 L/m2 of peritoneal instillation. Using these data another phase 2 study on 24 patients with colorectal peritoneal carcinomatosis treated with the preceding regimen was initiated; the 2-year survival rate was 74% after a minimal follow-up of 18 months. A pharmacokinetic study using intraperitoneal oxaliplatin at the same dose but in various hypotonic solutions did not show any specific pharmacologic advantage and was associated with excessive postoperative bleeding.