Peritoneal metastasis of advanced epithelial ovarian carcinoma treated with cytoreductive surgery and hyperthermic intraperitoneal chemotherapy: A retrospective international multicentric data analysis.

INTRODUCTION: The purpose of our study was to evaluate outcome data after cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) in patients with peritoneal metastasis originating from advanced epithelial ovarian carcinoma (PMOC). PATIENTS AND METHODS: A retrospective international multi-institutional registry was established through collaborative efforts of participating units affiliated with the Peritoneal Surface Oncology Group. RESULTS: One thousand four hundred and ninety-one patients from 11 specialized units underwent CRS and HIPEC that of those 326 (21.9%) upfront surgeries, 504 (33.8%) interval surgery, and 661(44.3%) recurrent cases. Complete Cytoreduction(CC0/1) was achieved in 1213 patients (81.3%). Treatment -related mortality was 0.8%, major operative complications (Grades 3-5) was 25.1%. Factors associated with major operative complications include prior surgical score (PSS for recurrent cases; RC) PSS>2,p = 0.000), PCI(≤15, >15 cut-off level; p ≤ 0.000), completeness of cytoreduction (CC, p=0.000), high CA125 levels (>25 mg/dl), presence of ascites, high CRP (>5 mg/dl) levels and low albumin levels (below to 2.5 mg/dl) (p ≤ 0.05). The median survival was 58 months in upfront surgery(UFS), 60 months in interval surgery(IS), and 42 months in RC. The overall survival for five years was 45% for UFS, 37% for IS, 28% for RC cases. CCscore (p = 0.000), CA125, CRP and albumin levels (p ≤ 0.05) were predictors for progression free survival. PCI(p ≤ 0.000), major postoperative complications (p = 0.004), incomplete CRS(CC2/3)(p < 0.001), prior chemotherapy (hazard ratio [HR], 3-8; p < 0.001) and PSS>2 for RC were independent predictors of poor overall survival. CONCLUSION: The combined treatment strategy for PMOC may be performed safely with acceptable morbidity and mortality in the specialized units.

Spiliotis-Farfarelos Maneuver for the Management of Small Bowel Obstruction and Frozen Pelvis in Patients With Peritoneal Metastasis.

The management of the advanced peritoneal disease is demanding especially in cases of extensive bowel infiltration and the obstruction of the gastrointestinal tract in different sites. Patients with bowel obstruction due to peritoneal carcinomatosis have an overall survival that ranges from three to eight months to four to five weeks based on the operability or not of the disease, respectively. The decision to operate should carefully consider the balance between the probability of symptomatic relief and the risk of severe perioperative complications and survival after surgery. The extent of the disease and postoperative malnutrition could further complicate patients' postoperative course. We aim to present an operative maneuver of bowel preparation and fixation in cases of extensive infiltration of the small bowel by peritoneal carcinomatosis (PC) in order to eliminate the risk of postoperative fistula formation or anastomotic leakage.

Mitomycin-C versus oxaliplatin during cytoreductive surgery and HIPEC for peritoneal metastases secondary to colorectal carcinoma: a retrospective analysis.

PURPOSE: Combining cytoreductive surgery (CRS) with Hyperthermic Intraperitoneal Chemotherapy (HIPEC) can benefit patients with peritoneal metastasis from colorectal cancer, however the optimal choice of the HIPEC chemotherapy is still under debate. The present study compares the clinical outcome in patients with peritoneal metastases treated with CRS and HIPEC using Mitomycin - C versus Oxaliplatin. METHODS: We retrospectively analyzed patients that underwent CRS and HIPEC for recurrent colorectal cancer with peritoneal metastases. Patient characteristics, procedure details, and clinical outcomes were evaluated. RESULTS: 114 consecutive patients were included in the analysis (62 males - 52 females, mean age 58,3 years). The mean intraoperative PCI-score was 15.3 (range: 3 - 36). The mean follow-up period was 28.2 months. Patients receiving MMC - based HIPEC had significantly higher mean overall survival compared to oxaliplatin (54 versus 26 months), translated to a hazard ratio of 0.26 (95% CI 0.128 - 0.529, p<0.01). The HIPEC regimen as well as the completeness of cytoreduction were the only independent prognostic factors of survival in our sample. CONCLUSIONS: Our results imply that the use of MMC offers a survival advantage over oxaliplatin when used for HIPEC in CRC PC. A randomised trial comparing oxaliplatin and MMC would enhance decision-making in such patients.

Cytoreductive surgery and HIPEC for peritoneal metastasis. Justified hope or desperate illusion? Fifteen years of experience from a Greek Peritoneal Surface Malignancy center.

PURPOSE: Peritoneal spread of neoplastic diseases is considered a fatal condition with a dismal prognosis. Few therapeutic options were offered to these patients and surgery had only palliative character. However, advances in surgical techniques and new drugs development, have changed the management of this terminal stage disease. Cytoreductive surgery (CRS) followed by hyperthermic intraperitoneal chemotherapy (HIPEC), has been proposed as a promising alternative to palliative surgery and systemic chemotherapy, since 1980s. Many changes through all these years have refined the technique and standardized indications and limits. METHODS: A retrospective study was performed in our medical records, of all patients treated with CRS and HIPEC since 2006. Survival, complications and prognostic factors were studied in a total of 632 patients. RESULTS: Female patients were 419 and males were 213. Mean age was 52.6 years. Peritoneal metastases secondary to colorectal cancer were the most frequent treated disease (87 patients), whereas hepatobilliary-pancreatic neoplastic diseases and sarcomas were the less frequent causes of peritoneal carcinomatosis. Patients with peritoneal metastases from ovarian cancer, treated with systemic chemotherapy and then received interval cytoreductive surgery with HIPEC, were the largest group that are still alive (43%), while only 35% of patients with hepatobilliary-pancreatic cancer and peritoneal disease are alive at present. Gender, age, peritoneal cancer index (PCI), completeness of cytoreduction score (CCs), and number of complications were important prognostic factors of overall survival. CONCLUSIONS: Peritoneal carcinomatosis is still considered a final stage disease with a poor prognosis. The confinement of the neoplastic disease in the peritoneal cavity has led to the development of local therapies with promising results. CRS and HIPEC have evolved significantly over the past several years and are at the present the most valuable treatment in highly selected patients with peritoneal carcinomatosis.

Small Bowel PCI Score as a Prognostic Factor of Ovarian Cancer Patients Undergoing Cytoreductive Surgery (CRS) with Hyperthermic Intraperitoneal Chemotherapy (HIPEC), a Retrospective Analysis of 130 Patients.

Ovarian cancer is the leading cause of death among gynecologic malignancies. Combining cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (HIPEC) can benefit patients with advanced ovarian cancer. We evaluate the role of small bowel peritoneal cancer index (sb-PCI) score as a prognostic factor. We retrospectively analyzed characteristics and clinical outcomes of patients that underwent intermediate cytoreductive surgery combined with HIPEC after neoadjuvant chemotherapy and patient's characteristics underwent debulking surgery plus HIPEC for recurrence disease. One hundred thirty patients were included. Eighty-five of them (65.4%) were treated for recurrent ovarian cancer, while 45 (34.6%) underwent intermediate cytoreductive surgery after neoadjuvant chemotherapy with a mean age of 52 years. Mean intraoperative peritoneal cancer index (PCI) was 11.84 with a mean sb-PCI score of 5.57. Univariate analysis revealed that PCI, sb-PCI, and completeness of cytoreduction (CC) were parameters that correlated significantly with overall survival, while after multivariate analysis sb-PCI and CC were identified as independent prognostic factors of survival. A statistically significant correlation between sb-PCI score and overall survival of patients with advanced ovarian cancer was revealed. Further larger future studies are required to confirm our conclusion in order to change the treatment of advanced ovarian cancer patients.

Narrative review of hyperthermic intraperitoneal chemotherapy (HIPEC) in patients with advanced ovarian cancer: a critical reappraisal of the current evidence.

The implementation of hyperthermic intraperitoneal chemotherapy (HIPEC) in the management of advanced stage epithelial ovarian cancer (EOC) as a standard practice remains debatable despite the emerging data supporting its beneficial effect when used to supplement cytoreductive procedures. The aim of the present review was an attempt to accumulate the currently available evidence on the use of HIPEC for patients with primary and recurrent EOC and to address directives of future research. Based on the currently available literature, the progress in cytoreductive surgical procedures and chemotherapy has brought significant improvement in the management and survival outcomes of selected patients with advanced EOC. The addition of HIPEC seems encouraging based on the outcomes of high-quality clinical trials. There are significant parameters on the use of CRS and HIPEC such as patient selection, the sequencing of procedures, the type of chemotherapy agent and time and the temperature of hyperthermic procedures which require additional investigation. Multidisciplinary team management by surgeons, gynaecologists, oncologists, pathologists and radiologists is of critical importance. Also, additional large prospective well-designed randomised studies are needed in order to update our current knowledge and provide guidelines to improve the management of patients with EOC.

The impact of PRODIGE 7 on the current worldwide practice of CRS-HIPEC for colorectal peritoneal metastases: A web-based survey and 2021 statement by Peritoneal Surface Oncology Group International (PSOGI).

INTRODUCTION: The PRODIGE 7-trial investigated the additional value of Hyperthermic Intraperitoneal Chemotherapy (HIPEC) to cytoreductive surgery (CRS) for patients with colorectal peritoneal metastases (CPM). The results of PRODIGE 7 were presented at the 2018 ASCO meeting showing that 30 min oxaliplatin-based HIPEC did not improve overall survival. The current study investigated the impact of PRODIGE 7 on the worldwide practice of CRS and HIPEC. MATERIALS AND METHODS: CRS-HIPEC experts from 19 countries were invited through the Peritoneal Surface Oncology Group International (PSOGI) to complete an online survey concerning the current CRS-HIPEC practice in their hospital and country, and were asked to appraise the effect of PRODIGE 7. RESULTS: The survey was completed by 18/19 experts. Although their personal opinions of CRS-HIPEC were barely influenced by PRODIGE 7, they reported a substantial impact on daily practice. This included a switch towards Mitomycin-C based HIPEC-regimens and prolongation of HIPEC perfusion time, a reduction in the number of referrals from non-HIPEC centers, a reduction in national consensus, the removal of HIPEC from national guidelines, and a reduced reimbursement rate. CONCLUSION: The PRODIGE 7 has had a major impact on the practice of CRS-HIPEC for CPM worldwide. HIPEC remains an attractive option with potential for control and eradication of disease and further studies into the optimal HIPEC-regimen are urgently needed. Meanwhile, given the complexity of the treatment of patients with CPM, and the proven benefits of optimal CRS, referral of patients with potentially resectable CPM to expert centers is recommended whilst the precise role of HIPEC is further evaluated.

Delayed genital necrosis after cytoreductive surgery and hyperthermic intraperitoneal chemotherapy with Mitomycin-C.

INTRODUCTION: Genital necrosis (GN) is a rare complication of cytoreductive surgery with hyperthermic intraoperative chemotherapy (CRS/HIPEC) which can be confused with necrotizing fasciitis. We present an analysis of GN after CRS/HIPEC to define its natural history. METHODS: We identified patients with GN after CRS/HIPEC at two peritoneal surface malignancy institutions. Patient demographic, surgical, and postoperative data were extracted from prospective databases. RESULTS: Of 1597 CRS/HIPECs performed, 13 patients (0.8%) had GN. The median age was 57 years (IQR: 49-64) and 77% (n = 10) were male. Mitomycin-C was the perfusion agent in all cases of GN (100%). The median time to GN onset after CRS/HIPEC was 64 days (IQR: 60-108) and 2 (15%) patients were receiving systemic chemotherapy at the time of GN onset. Symptoms included severe pain (100%), edema (100%), labial or scrotal skin ulceration (92%), signs of infection (39%), and fever (15%). Seven (54%) patients had thrombocytosis >400 ∗109/L, whereas coagulation tests were within normal reference range in 100% cases. All patients initially underwent conservative treatment, with antibiotic therapy administered in 62% (n = 8). Surgical debridement was performed in 9 (70%) cases with median time after GN onset of 57 (IQR: 8-180). CONCLUSION: GN is a debilitating complication after CRS/HIPEC with delayed onset and a protracted clinical course. Optimal treatment results could be achieved with initial conservative management until complete lesion demarcation followed by surgical debridement. The pathophysiology of GN is unclear, and we call for other researchers attention to better understand the complication and prevention.

Upfront or intermediate treatment of advanced ovarian cancer patients with cytoreduction plus HIPEC: Results of a retrospective study.

BACKGROUND: Newly diagnosed advanced-stage ovarian cancer patients are treated with neoadjuvant chemotherapy, primary or intermediate cytoreductive surgery, and hyperthermic intraperitoneal chemotherapy (HIPEC). The aim of this study is to evaluate the optimal timing of cytoreduction plus HIPEC for advanced ovarian cancer patients. METHODS: Advanced ovarian cancer patients treated with cytoreductive surgery plus HIPEC at three different hospitals between 2005 and 2019 were subgrouped regarding their time of management with cytoreduction plus HIPEC, upfront or intermediate. We retrospectively assessed the overall survival (OS), the progression-free survival (PFS), and the disease-free survival (DFS) of these groups. RESULTS: A total of 112 ovarian cancer patients were contained. Of whom, 47 patients were in the upfront group with 24 (51.1%) to be alive, while 65 patients were included in the intermediate group with 34 (52.3%) to be alive. OS (48 vs. 30 months) and DFS (42 vs. 20 months) indicated no significant difference. Although the same median PFS was observed in both groups (10 months), a higher mean PFS was observed in the upfront group (11.9 vs. 9 months, p = 0.023). CONCLUSION: The treatment of advanced ovarian cancer patients with upfront cytoreductive surgery plus HIPEC is feasible with the same survival results. Further, larger prospective studies need to verify our results.

Is there a role of repeat cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) in patients with relapse from peritoneal metastatic disease? A survival analysis.

PURPOSE: We aimed to evaluate the role of repeat cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) in the management of patients with recurrent peritoneal metastatic disease (PM) with special consideration to perioperative outcomes and long-term survival outcomes. METHODS: Patients with recurrent PM who underwent CRS and HIPEC for the management of the disease for an interval of 15 years were retrospectively analyzed. Primary tumor location, peritoneal cancer index, completeness of cytoreduction (CC), morbidity, mortality, overall survival (OS), and progression-free survival (PFS) after the 1st and 2nd HIPEC were assessed. RESULTS: A total of 48 patients who underwent repeat CRS and HIPEC for the management of disease relapse were included in this study. The median OS from initial diagnosis was 37 months (range: 12-128) while the PFS after the second CRS and HIPEC was 12 months (range: 0-36). A total of 30 complications were recorded among which 18.8% were classified as major. CC-0 resection was a significant indicator of survival either on univariate or on multivariate analysis. CONCLUSIONS: The outcomes of the present study indicate the feasibility of repeat CRS and HIPEC procedures in patients with recurrent peritoneal metastasis with significant morbidity, acceptable mortality and long-term survival outcomes which were highly associated with CC status.

Survey on the current gynaecological approach of ovarian cancer patients: The utility of HIPEC.

BACKGROUND: The aim of this survey was to acquire an overview of the current management of ovarian cancer with an emphasis on the utility of hyperthermic intraperitoneal chemotherapy (HIPEC).Methods: An email was sent to Oncologists prior to PSOGI International Symposium on Advanced Ovarian Cancer, Athens 11-13 April 2019. Doctors submitted responses on the relevant website. The self-report survey contained 17 questions. RESULTS: In total, 467 Medical Oncologists, Surgical Oncologists or Gynaecologic Oncologists were participated and answered to this survey. The resectability of disease was evaluated by laparoscopy from 48.5% of the participants, while 51.5% answered that they stage their patients pre-surgically with the use of CT or MRI. The preferred first intervention in advanced ovarian cancer patients is the neoadjuvant chemotherapy followed by interval cytoreductive surgery (72%). Regarding the use of HIPEC, almost half of the participants answered that there is role of HIPEC use in ovarian cancer patients undergoing interval debulking surgery, while almost 70% answered positively about the utility of HIPEC use in ovarian cancer recurrence. As for the role of lymphadenectomy in advanced ovarian cancer patients, half of the responders answered negatively. Finally, only 25% of the participants responded that they always check the BRCA status of their ovarian cancer patients, despite the possible differentiation of treatment based on the molecular profiling (80%). CONCLUSIONS: The results of this survey indicate the utility of HIPEC in treatment of ovarian cancer patients and the differences in the overall management of ovarian cancer patients in the current clinical practice.