Treatment of Peritoneal Surface Malignancies by Cytoreductive Surgery (CRS) and Hyperthermic Intraperitoneal Chemotherapy (HIPEC) in Spain: Results of the National Registry of the Spanish Group of Peritoneal Oncologic Surgery (REGECOP).

INTRODUCTION: Treatment of Peritoneal Surface Malignancies (PSM) with cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) has achieved results never seen before in these patients, which classically have a poor prognosis. The possibility of conducting clinical trials in these diseases is complicated, since some of them are rare, so the analysis of large databases provides very valuable scientific information. The aim of this study is to analyze the global results of the National Registry of the Spanish Group of Peritoneal Oncologic Surgery (REGECOP), whose objective is to register all patients scheduled for HIPEC nationwide. METHODS: This is a retrospective analysis of the data recorded in the REGECOP from 36 Spanish hospitals from 2001 to 2021. There were 4159 surgical interventions in 3980 patients. RESULTS: 66% are women and 34% are men with a median age of 59 years (range 17-86). 41.5% of the patients were treated for Peritoneal Metastases (PM) of colorectal cancer (CRC); 32.4% were women with ovarian cancer (OC) with PM; 12.8% were treated for pseudomyxoma peritonei (PMP); 6.2% had PM from gastric cancer (GC); 4.9% had PM of non-conventional origin; and, finally, 2.1% of cases were patients diagnosed with peritoneal mesothelioma. The median Peritoneal Cancer Index (PCI) was 9 (0-39), and complete cytoreduction was achieved in 81.7% of the procedures. Severe morbidity (Dindo-Clavien grade III-IV) was observed in 17.7% of surgeries, with 2.1% mortality. Median hospital stay was 11 days (0-259). Median overall survival (OS) was 41 months for CRC patients, 55 months for women with OC, was not reached in PMP patients, was 14 months for GC patients, and 66 months in mesothelioma patients. CONCLUSIONS: large databases provide extremely useful data. CRS with HIPEC in referral centers is a safe treatment with encouraging oncologic results in PSM.

Peritoneal Mesothelioma in a High Volume Peritoneal Surface Malignancies Unit.

Diffuse malignant peritoneal mesothelioma (PM) is a rare neoplasm, traditionally associated with a poor prognosis. There are other varieties of PM that are even less frequent and of uncertain malignancy. Cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) has achieved prolonged survival in selected patients. The aim of this study is to analyze the patients with PM assessed in our center. Clinicopathological characteristics, diagnostic procedures and survival results from patients with PM appraised at our unit, according to the applied treatment, were analyzed. Seventeen patients were assessed between 2007 and 2019. Three cases had multicystic PM that were treated with complete CRS + HIPEC; all patients are alive and free of disease after a long follow-up. Three other cases had biphasic PM; a curative treatment could be performed in none of them, and their survival was minimal (<6 moths). Lastly, 11 cases with epithelioid PM were treated. Two cases were considered unresectable at laparoscopy (PCI 39); one of them had a long survival (67 months) with three iterative laparoscopic palliatives HIPECs for refractory ascites. The other nine cases were treated with curative CRS + HIPEC, with a median PCI of 14 (range 4-25), and a median overall survival (OS) of 58 months, with a 5-year OS of 47.4%. In conclusion, CRS + HIPEC, when possible, appears to be the optimal treatment for patients with PM. Knowledge of this therapeutic option is crucial, both to offer it to patients and to avoid delays in their referral to appropriate centers for treatment.

Gastric Cancer with Peritoneal Metastases: Current Status and Prospects for Treatment.

Gastric cancer (GC) has a poor prognostic and only one in four patients will have survived by 5 years after diagnosis. These poor results are due to the fact that most patients are diagnosed in advanced stages; peritoneal metastases (PM) are especially frequent and are difficult to treat. Currently, PM are considered a terminal stage of GC with a poor survival rate and are treated with palliative systemic chemotherapy. Since the beginning of the century, the treatment of PM from different origins has evolved; cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) have become the treatment of choice for many malignant diseases that affect the peritoneum. CRS and HIPEC have also been used for patients with GC and PM, achieving survival results that have never been achieved when using systemic chemotherapy alone. The use of HIPEC can even prevent the development of peritoneal recurrences in patients with locally advanced GC as adjuvant therapy, can reduce the volume of peritoneal disease as neoadjuvant therapy, and can control symptoms in a palliative setting. The aim of this review is to collate the current scientific evidence regarding the treatment of PM of GC origin with surgery and intraperitoneal chemotherapy.

OVA-LEAK: Prognostic score for colo-rectal anastomotic leakage in patients undergoing ovarian cancer surgery.

OBJECTIVE: The objective of the present study was to define and validate an anastomotic leak prognostic score based on previously described and reported anastomotic leak risk factors (OVA-LEAK: https://n9.cl/ova-leakscore) and to establish if the use of OVA-LEAK score is better than clinical criteria (surgeon's choice) selecting anastomosis to be protected with a diverting ileostomy. MATERIAL & METHODS: This is a retrospective, multicentre cohort study that included patients who underwent cytoreductive surgery for primary advanced or relapsed ovarian cancer with colorectal resection and anastomosis between January 2011 and June 2021. Data from patients already included in the previous predictive model were not considered in the present analysis. To validate the performance of our logistic regression model, we used the OVA-LEAK formula (Annex I: https://n9.cl/ova-leakscore) for estimating leakage probabilities in a new independent cohort. Then, receiver operating characteristic (ROC) analysis was performed and area under the curve (AUC) was used to measure the performance of the model. Additionally, the Brier score was also estimated. 95% confidence intervals (CI) for each of the estimated performance measures were also calculated. RESULTS: 848 out of 1159 recruited patients were finally included in the multivariable logistic regression model validation. The AUC of the new cohort was 0.63 for predicting anastomotic leak. Considering a cut-off point of 22.1% to be 'positive' (to get a leak) this would provide a sensitivity of 0.45, specificity of 0.80, positive predictive value of 0.09 and negative predictive value of 0.97 for anastomotic leak. If we consider this cut-off point to select patients at risk of leak for bowel diversion, up to 22.5% of the sampled patients would undergo a diverting ileostomy and 47% (18/40) of the anastomotic leaks would be 'protected' with the stoma. Nevertheless, if we consider only the 'clinical criteria' for performing or not a diverting ileostomy, only 12.5% (5/40) of the leaks would be 'protected' with a stoma, with a rate of diverting ileostomy of up to 24.3%. CONCLUSIONS: Compared with subjective clinical criteria, the use of a predictive model for anastomotic leak improves the selection of patients who would benefit from a diverting ileostomy without increasing the rate of stoma use.

GECOP-MMC: phase IV randomized clinical trial to evaluate the efficacy of hyperthermic intraperitoneal chemotherapy (HIPEC) with mytomicin-C after complete surgical cytoreduction in patients with colon cancer peritoneal metastases.

BACKGROUND: The French PRODIGE 7 trial, published on January 2021, has raised doubts about the specific survival benefit provided by HIPEC with oxaliplatin 460 mg/m2 (30 minutes) for the treatment of peritoneal metastases from colorectal cancer. However, several methodological flaws have been identified in PRODIGE 7, specially the HIPEC protocol or the choice of overall survival as the main endpoint, so its results have not been assumed as definitive, emphasizing the need for further research on HIPEC. It seems that the HIPEC protocol with high-dose mytomicin-C (35 mg/m2) is the preferred regime to evaluate in future clinical studies. METHODS: GECOP-MMC is a prospective, open-label, randomized, multicenter phase IV clinical trial that aims to evaluate the effectiveness of HIPEC with high-dose mytomicin-C in preventing the development of peritoneal recurrence in patients with limited peritoneal metastasis from colon cancer (not rectal), after complete surgical cytoreduction. This study will be performed in 31 Spanish HIPEC centres, starting in March 2022. Additional international recruiting centres are under consideration. Two hundred sixteen patients with PCI ≤ 20, in which complete cytoreduction (CCS 0) has been obtained, will be randomized intraoperatively to arm 1 (with HIPEC) or arm 2 (without HIPEC). We will stratified randomization by surgical PCI (1-10; 11-15; 16-20). Patients in both arms will be treated with personalized systemic chemotherapy. Primary endpoint is peritoneal recurrence-free survival at 3 years. An ancillary study will evaluate the correlation between surgical and pathological PCI, comparing their respective prognostic values. DISCUSSION: HIPEC with high-dose mytomicin-C, in patients with limited (PCI ≤ 20) and completely resected (CCS 0) peritoneal metastases, is assumed to reduce the expected risk of peritoneal recurrence from 50 to 30% at 3 years. TRIAL REGISTRATION: EudraCT number: 2019-004679-37; Clinicaltrials.gov: NCT05250648 (registration date 02/22/2022, ).

Review of management and treatment of peritoneal metastases from gastric cancer origin.

Gastric cancer (GC) is the third cause of cancer-related deaths in the world, with less than 25% survivors at 5 years. These results are largely related to the high incidence of peritoneal metastases (PM) in these patients. Nowadays, the standard treatment for GC with PM is palliative systemic chemotherapy (SCT) with a survival of 6 months. From the 2000s, the combination of cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) has been gaining popularity for different neoplastic diseases that involve the peritoneal surface. The use of CRS and HIPEC has been studied for GC with PM, with promising results in selected patients, obtaining survival rates never seen before. Moreover, HIPEC and other intraperitoneal chemotherapy techniques have been used to prevent peritoneal recurrences in patients diagnosed on locally advanced GC without macroscopic PM (adjuvant or prophylactic HIPEC). Even, intraperitoneal chemotherapy [laparoscopic HIPEC and neoadjuvant intraperitoneal and systemic chemotherapy (NIPS)] has been used as neoadjuvant treatment to reduce peritoneal disease burden in order to improve the rate of patients in whom complete cytoreduction can be achieved. Finally, patients with high volume peritoneal disease can be treated by palliative intraperitoneal chemotherapy to control the symptoms resulting from malignant ascites, using laparoscopic HIPEC or pressurized intraperitoneal aerosol chemotherapy (PIPAC). This review aims to update the management of PM from GC origin in these different clinical scenarios, based on the literature and the experience of the authors.

Intraperitoneal hyperthermic chemotherapy after cytoreduction in patients with peritoneal metastases from endometrial cancer. The next frontier?

BACKGROUND: Endometrial cancer is the most common malignancy of the female genital tract. For cancers detected at an advanced stage or intraperitoneal relapse, the prognosis is poor. Optimal cytoreductive surgery (CRS) is the most accepted treatment; however, patients with advanced intraperitoneal disease might benefit from hyperthermic intraoperative peritoneal chemotherapy (HIPEC). The aim of this study was to analyze recurrence-free survival (RFS) after CRS and HIPEC in a large series of patients with peritoneal metastases from endometrial cancer. METHODS: Patients with a diagnosis of endometrial cancer with primary or recurrent peritoneal dissemination were included. All patients underwent CRS plus HIPEC. Data were prospectively collected in the Spanish Group of Peritoneal Oncological Surgery (GECOP) database. RESULTS: Forty-three patients with endometrial cancer and peritoneal metastasis were included. Fifteen patients (35%) were diagnosed with G3 endometrioid carcinomas and 28 (65%) with other non-endometroid histologies. A completeness of cytoreduction score of CC-0 was achieved in 41 patients (95%). RFS at 5 years was 23%, being factors related to worse RFS: treatment with preoperative chemotherapy (p = 0.027), resection of more than three peritoneal areas (p = 0.010), cytoreduction of the upper abdominal space (p = 0.023), HIPEC treatment with paclitaxel (p = 0.013), and the presence of metastatic lymph nodes (p = 0.029). CONCLUSIONS: Better RFS rates after CRS and HIPEC were observed for patients with the following characteristics: cytoreductive surgery without preoperative chemotherapy, complete surgery performed with limited surgical maneuvers, treated with cisplatin, and no lymph node metastases. SYNOPSIS: Endometrial cancer has a poor prognosis when diagnosed at advance stage. Patients with intraperitoneal metastases from endometrial cancer may benefit from CRS plus HIPEC with improvement in the recurrence-free survival results.

Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy (HIPEC) for Gastric Cancer with Peritoneal Carcinomatosis: Multicenter Study of Spanish Group of Peritoneal Oncologic Surgery (GECOP).

BACKGROUND: Gastric cancer (GC) with peritoneal carcinomatosis (PC) is traditionally considered a terminal stage of the disease. The use of a multimodal treatment, including cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC), can benefit these patients. Our goal was to evaluate the morbidity and survival outcomes of these patients. METHODS: This is a retrospective, multicenter study from a prospective national database of patients diagnosed with PC secondary to GC treated with CRS and HIPEC from June 2006 to October 2017. RESULTS: Eighty-eight patients from seven specialized Spanish institutions were treated with CRS and HIPEC, with median age of 53 years; 51% were women. Median Peritoneal Cancer Index (PCI) was 6, and complete cytoreduction was achieved in 80 patients (90.9%). HIPEC was administered in 85 cases with 4 different regimens (Cisplatin + Doxorubicin, Mitomycin-C + Cisplatin, Mitomycin-C and Oxaliplatin). Twenty-seven cases (31%) had severe morbidity (grade III-IV) and 3 patients died in the postoperative period (3.4%). Median follow-up was 32 months. Median overall survival (OS) was 21.2 months, with 1-year OS of 79.9% and 3-year OS of 30.9%. Median disease-free survival (DFS) was 11.6 months, with 1-year DFS of 46.1% and 3-year DFS of 21.7%. After multivariate analysis, the extent of peritoneal disease (PCI ≥ 7) was identified as the only independent factor that influenced OS (hazard ratio [HR] 2.37, 95% confidence interval [CI] 1.26-4.46, p = 0.007). CONCLUSIONS: The multimodal treatment, including CRS and HIPEC, for GC with PC can improve the survival results in selected patients (PCI < 7) and in referral centers.

Cytoreductive surgery combined with hyperthermic intraperitoneal chemotherapy (HIPEC) in patients with gastric cancer and peritoneal carcinomatosis.

BACKGROUND: Gastric Cancer (GC) with Peritoneal Carcinomatosis (PC) has long been regarded as a terminal disease. Over the past two decades, cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) has changed the traditional concept of peritoneal metastases from being a systemic disease, to being considered a locoregional dissemination. PATIENTS AND METHODS: A prospective study was performed at a high-volume Carcinomatosis Center to evaluate survival, morbi-mortality and prognostic factors for survival in a cohort of patients with GC and PC treated with CRS + HIPEC between June 2006 and December 2016. RESULTS: Thirty-five patients were included in the study. Median follow-up was 54 months. Postoperative major complications (>grade IIIa) occurred in 25.7% of patients, including 2 deaths (mortality 5.7%). The median overall survival (OS) was 16 months and the 1-, 3- and 5-year OS rates were 70.8%, 21.3% and 21.3% %, respectively. The median OS for patients with PCI ≤6 was 19 months, in contrast to 12 months for the 19 patients with PCI >6. Three patients were included with only a positive cytology and their median OS was not reached. Perineural invasion was the only factor that had a negative influence in prognosis (HR 18.8) in multivariate analysis. CONCLUSION: Although GC with PC still has a poor prognosis, survival has improved in selected patients with CRS + HIPEC and perioperative systemic chemotherapy. Patients with isolated positive cytology or peritoneal carcinomatosis with PCI less than 6 had encouraging survival rates.

Hyperthermic intraoperative intraperitoneal chemotherapy (HIPEC) with primary or secondary cytoreductive surgery in the treatment of advanced epithelial ovarian cancer.

BACKGROUND: Peritoneal dissemination is the most common route of spread of epithelial ovarian cancer (EOC). Cytoreductive surgery (CRS) followed by platinum-based systemic chemotherapy is the current standard treatment in advanced stages, with suboptimal results. The aim of this study is to analyze the outcome of advanced EOC treated with CRS plus hyperthermic intraoperative intraperitoneal chemotherapy (HIPEC) combined with systemic chemotherapy. METHODS: We analyze a cohort of women treated with CRS plus HIPEC for peritoneal carcinomatosis secondary to EOC from May 2007 to December 2014. We included both patients with peritoneal disease at first diagnosis of EOC and peritoneal recurrences after initial treatment. RESULTS: We performed 61 CRS with HIPEC procedures, 31 cases as primary treatment (4 as upfront therapy and 27 after neoadjuvant chemotherapy) and 30 as secondary treatment (recurrences). Median Peritoneal Carcinomatosis Index (PCI) was 9; the cytoreduction was optimal in 92% of the procedures. Severe morbidity (Grade III-IV of Clavien-Dindo classification) was 29.5%, without mortality. Median follow-up was 23 months and median disease-free survival (DFS) was 14 months (14 in primary surgery group and 17 in recurrence group, P=0.51). Median overall survival (OS) was 57 months; in primary surgery group, OS was 96.8% at 1 year, and 55% at 5 years, and median OS was not reached; OS in recurrence group was 89.3% at 1 year and 47.1% at 5 years, and median OS was 57 months. CONCLUSIONS: CRS with HIPEC is a treatment option for EOC with good results in terms of morbidity and survival, in experienced centers.

Enfermedad de paget perianal / Extra mammary paget disease: report of one case

Extra mammary Paget disease is rare and mostly affects perianal and vulvar zones, in patients of both sexes and from the sixth decade of life. We report a 66 years old woman with a vulvar Paget disease, subjected to a vulvectomy. Two years later, a pruriginous and erythematous plaque appeared in the perianal region. The pathological study informed an extra mammary Paget disease. The patient was subjected to a perianal excision and the correction of the surgical defect in a second intervention. After one year of follow up, there is no evidence of disease relapse.

La enfermedad de Paget de localización extramamaria (EPEM) es una patología infrecuente que afecta preferentemente a zonas perianal y vulvar en pacientes de ambos sexos y desde la sexta década de vida. Presentamos un caso clínico tratado en conjunto por los Servicios de Cirugía General, Cirugía Plástica, Ginecología y Anatomía Patológica del Hospital Universitario de Getafe.