HIPEC in Ovarian Cancer Is the Future and Always Will Be? Results from a Spanish Multicentric Survey.

Ovarian cancer is the leading cause of death due to gynecological tumors in the female population. Despite optimal first-line treatment, including cytoreduction and platinum-based systemic chemotherapy, recurrences are frequent. The use of hyperthermic intraperitoneal chemotherapy (HIPEC) has been criticized, especially because of the lack of randomized controlled trials (RCTs) with convincing results to support the use of HIPEC in patients with ovarian cancer with peritoneal dissemination. In 2018, the clinical trial published by Van Driel et al. reported improved outcomes in favor of HIPEC treatment with cisplatin. In this study, we conducted a national survey within the Spanish group of peritoneal surgical oncology (Grupo Español de Cirugía Oncológica Peritoneal, GECOP) to explore the impact of the results of this RCT on clinical practice. A total of 33 groups completed the survey. Routine clinical practice was not changed in 28 of the 33 groups (85%) based on the results of the Van Driel trial. Despite the results of this RCT, most groups considered that more RCTs are needed and that, in the future, HIPEC may become the standard of care. In conclusion, the results from RCTs evaluating HIPEC treatment in patients with ovarian cancer has not been transferred to clinical practice.

Interval cytoredutive surgery and HIPEC in advanced ovarian cancer with small-bowel disease: results and reflections

Introduction: Small-bowel involvement in patients with ovarian cancer has been strongly correlated with the possibility of cytoreduction and thus with survival. The main objective of this study was to evaluate the prognostic significance of small-bowel involvement in patients undergoing optimal-complete interval cytoreductive surgery (CRS) and Hyperthermic Intraperitoneal Chemotherapy (HIPEC).Methods: We included a series of patients diagnosed with stage IIIC-IVA (pleural effusion) high-grade serous epithelial ovarian cancer and in whom CRS + HIPEC was indicated after neoadjuvant systemic chemotherapy (NACT). The study period extended from January 2008 to January 2020, with a minimum follow-up of 12 months from the inclusion of the last patient. A multivariate analysis using Cox regression allowed us to identify the variables that were independently related to disease-free survival.Results: A total of 144 patients were selected, 13 (9%) of whom were excluded from the analysis, because their disease was considered unresectable. The study included a series of 131 patients with a median age of 62 years (34-79 years) and a median Peritoneal Cancer Index (PCI) calculated during surgery of 9 (1-35). The median PCI of bowel areas 9-12 (SB-PCI) was 3 (1-10). Performance of a CC-1 cytoreduction (HR: 1.93, 95% CI: 1.02-3.64, p = 0.042) and SB-PCI greater than 3 (HR: 2.25, 95%CI: 1.13-4.48, p = 0.21) were independent factors associated with shorter disease-free survival.Conclusion: Small-bowel involvement, even in patients with a macroscopically complete resection, showed a correlation with worse prognostic outcomes and could be considered as a variable in the postoperative management of these patients. (AU)

Interval cytoredutive surgery and HIPEC in advanced ovarian cancer with small-bowel disease: results and reflections.

INTRODUCTION: Small-bowel involvement in patients with ovarian cancer has been strongly correlated with the possibility of cytoreduction and thus with survival. The main objective of this study was to evaluate the prognostic significance of small-bowel involvement in patients undergoing optimal-complete interval cytoreductive surgery (CRS) and Hyperthermic Intraperitoneal Chemotherapy (HIPEC). METHODS: We included a series of patients diagnosed with stage IIIC-IVA (pleural effusion) high-grade serous epithelial ovarian cancer and in whom CRS + HIPEC was indicated after neoadjuvant systemic chemotherapy (NACT). The study period extended from January 2008 to January 2020, with a minimum follow-up of 12 months from the inclusion of the last patient. A multivariate analysis using Cox regression allowed us to identify the variables that were independently related to disease-free survival. RESULTS: A total of 144 patients were selected, 13 (9%) of whom were excluded from the analysis, because their disease was considered unresectable. The study included a series of 131 patients with a median age of 62 years (34-79 years) and a median Peritoneal Cancer Index (PCI) calculated during surgery of 9 (1-35). The median PCI of bowel areas 9-12 (SB-PCI) was 3 (1-10). Performance of a CC-1 cytoreduction (HR: 1.93, 95% CI: 1.02-3.64, p = 0.042) and SB-PCI greater than 3 (HR: 2.25, 95%CI: 1.13-4.48, p = 0.21) were independent factors associated with shorter disease-free survival. CONCLUSION: Small-bowel involvement, even in patients with a macroscopically complete resection, showed a correlation with worse prognostic outcomes and could be considered as a variable in the postoperative management of these patients.

Cytoreductive Surgery With or Without HIPEC After Neoadjuvant Chemotherapy in Ovarian Cancer: A Phase 3 Clinical Trial.

BACKGROUND: Cytoreductive surgery (CRS) and administration of hyperthermic intraperitoneal chemotherapy (HIPEC) have shown their efficacy in multiple malignancies and also could offer a prognostic benefit for patients with advanced ovarian cancer. METHODS: A prospective, single-center, parallel-group, randomized phase 3 clinical trial analyzed patients with a diagnosis of carcinomatosis from ovarian cancer treated with neoadjuvant systemic chemotherapy (NACT). In this trial, 71 patients were randomized to receive CRS alone (36 patients) or CRS with HIPEC (35 patients) using cisplatin (75 mg/m2 for 60 min at 42 °C). The primary end point was disease-free survival (DFS). Overall survival (OS), morbidity, and quality of life (QoL) were the secondary end points. RESULTS: During a median follow-up period of 32 months, the median DFS was 12 months in the control group (CRS) and 18 months in the experimental group (CRS and HIPEC). The findings showed HIPEC to be an independent protective factor against the development of recurrence (hazard ratio [HR], 0.12, 95 % confidence interval [CI], 0.02-0.89; p = 0.038). The median OS was 45 months in the control group and 52 months in the experimental group. The respective morbidity rates for any grade (1 to 5) were respectively 58.3 % and 45.7 % (p > 0.05), with a mortality rates of 2.8 % and 2.9 % (p > 0.05). In the dimensions evaluated, CRS with or without HIPEC had no impact on QoL. CONCLUSIONS: For patients who had advanced ovarian cancer treated with NACT, CRS and HIPEC was associated with better DFS and OS, but without a difference in postoperative morbidity, mortality, or in the QoL evaluation.

Impact of Immune Response in Short-term and Long-term Outcomes After Minimally Invasive Surgery for Colorectal Liver Metastases: Results From a Randomized Study.

BACKGROUND: The potential benefit related to laparoscopic liver surgery (LLS) for colorectal liver metastases outcomes is not well known. MATERIALS AND METHODS: Serum cytokines associated with Th1 (tumor necrosis factor-α) and Th2 [interleukin (IL)-10 and IL-6] phenotypes were measured in 36 patients operated on for colorectal liver metastases by open liver surgery (OLS) and LLS. Measurements were performed at 3 time points: 1 day before surgery, day 3 postoperative, and 1 month postoperative. We compared the postoperative inflammatory response influence between LLS and OLS on long-term outcomes. RESULTS: In both groups, only IL-6 levels on day 3 postoperative were higher than those measured preoperatively and at 1 month. Comparing the tumor necrosis factor-α levels between the LLS and OLS groups, preoperative (7.28 vs. 2.36), day 3 (7.99 vs. 4.08) and 1 month (7.39 vs. 1.99) postoperative levels were higher in the OLS group (P<0.01, <0.01, and <0.01, respectively). In contrast, IL-10 levels were higher in the LLS group preoperatively (7.51 vs. 4.57) and on day 3 postoperative (13.40 vs. 4.57) (P=0.03 and 0.01, respectively). A cut-off IL-6 level of ≥4.41 in the first month was associated with a higher risk of recurrence (logrank=4.8, P=0.02). CONCLUSIONS: Both LLS and OLS induce an initial increase in IL-6 that normalizes one month after surgery, showing a similar pattern. In addition, a cut-off IL-6 value of 4.41 pg/mL was established, with a higher concentration at 1 month postoperative possibly related to a higher risk or recurrence.

Acute renal disease in patients with ovarian peritoneal carcinomatosis treated with cytoreduction and HIPEC: the influence of surgery and the cytostatic agent used.

BACKGROUND: The main objective of this study was to evaluate the differences between cisplatin and paclitaxel in the development of postoperative renal toxicity, using as a reference the RIFLE (Risk, Injury, Insufficiency, Loss, and End-stage renal function) and AKIN (Acute Kidney Injury Network) criteria in patients with primary or recurrent ovarian cancer with peritoneal dissemination treated with cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (HIPEC). METHODS: One hundred fifty-two patients who were treated between December 2007 and June 2017 were analyzed. RESULTS: Patients who received previous platinum-based chemotherapy had higher baseline creatinine levels than those who had not (p = 0.05). A total of 11 (7.2%) and 4 (2.6%) patients developed an acute renal dysfunction (ARD) during the postoperative period of cytoreduction and HIPEC according to the RIFLE and AKI criteria respectively. RIFLE detects a higher rate of ARD due to different parameters such as GFR (7.2% versus 2.6%, p = 0.016). Performing ostomy (p = 0.007; OR: 39.320; 95% CI = 2.74-56.13) and using of cisplatin during HIPEC treatment (p = 0.017; OR = 13.619; 95% IC = 1.600-25.95) were factors independently related to a higher rate of ARD. CONCLUSION: ARD has a multifactorial origin. Cisplatin was associated with the development of a higher rate of ARD than paclitaxel. Diagnosis of ARD did not correlate with worse survival figures.

Peritoneal Surface Disease Severity Score (PSDSS), AGO-score and TIAN model in patients with platinum-sensitive recurrent ovarian cancer treated by cytoreductive surgery plus HIPEC.

In patients with platinum sensitive recurrent ovarian cancer selected for a secondary cytoreduction, the use of prognostic scores allows predicting the possibilities of a new complete cytoreduction. The aim of this work is to evaluate the usefulness of PSDSSov, the AGO-score and the TIAN-model as prognostic tools in these patients. Sixty four patients with recurrent platinum sensitive ovarian cancer treated by cytoreduction and HIPEC were analyzed between January 2008 and December 2016. Since 2012, the data needed to calculate the PSDSS, AGO-score and TIAN model were collected prospectively. Fifty patients (78%) received systemic chemotherapy before cytoreduction and HIPEC. In 57 patients (89%) a CC-0 was achieved. Patients with PSDSSov I-II and TIAN model of "low risk" had a DFS at 1 and 5 years of 71% and 57%, respectively, without reaching the median of DFS. PSDSSov is a useful prognostic tool and can be used in decision making in patients with peritoneal carcinomatosis due to recurrent platinum-sensitive ovarian cancer. Its combination with the Tian model makes it possible to identify patients with an especially favorable prognosis.

Surgical resection of liver metastasis in pancreatic and periampullary carcinoma.

INTRODUCTION: Once liver metastases in pancreatic and periampullary carcinoma are diagnosed, guidelines do not recommend resection of the primary tumor. In this stage of the disease, therapeutic regimes with chemotherapy are the standard treatment. However, it is unclear whether combinations of extensive surgery and novel chemotherapy treatments confer a survival benefit in selected patients. EVIDENCE ACQUISITION: We provide a systematic review about liver metastases in pancreatic and periampullary carcinoma treated by surgery utilizing EMBASE, Medline/PubMed, Cochrane and Scopus databases according to PRISMA guidelines. EVIDENCE SYNTHESIS: In pancreatic and periampullary carcinoma, the number of lesions that can be resected includes a mean or median of 1-3; the size of the lesions should not exceed 3 cm and the most frequent surgical technique used were wedge or atypical resections. Overall morbidity and mortality after liver resection from pancreatic tumors were 0-68% and 0-9.1%, respectively, and from periampullary carcinomas were 0-82% and 0-21%, respectively. Considering both types of carcinomas, the rate of recurrence was up to 91%. Median overall survival ranged from 5.5 to 16.6 months for liver metastases from pancreas carcinoma, and from 5 to 23 months for periampullary carcinoma, with better prognosis for duodenal carcinomas. CONCLUSIONS: Perioperative chemotherapy is the cornerstone of treatment in patients with liver metastasis from pancreatic and periampullary carcinoma. Liver resection from early liver metastases could be acceptable in selected patients with oligometastatic disease and small single lesions taking into account the individual risk of complications.

Clinical and pathological features of "small" GIST (≤2 cm). What is their prognostic value?

INTRODUCTION: Small GIST (<2 cm) are tumors whose biological behavior is benign and frequently involutes. Despite their increasing incidence, few studies have addressed the characteristics of these GIST. The aim of this work is to clarify the management of this entity. PATIENTS AND METHOD: The characteristics of ≤2 cm GIST were initially described, and then compared with those >2 cm. This series comprises 104 patients and they were divided according to tumor size in 4 groups: tumors which are ≤2 cm (group 1, G1), >2 and ≤ 5 cm (G2), >5 and ≤ 10 cm (G3) and >10 cm (G4). RESULTS AND DISCUSSION: Most of small GIST were asymptomatic and incidental, and were located in the stomach. There is an association between patients with associated tumors and asymptomatic GIST. A high overall mortality rate of up to 40% is observed being disease-specific mortality 4.5%. The disease-specific mortality increases proportionally with size. The overall survival (OS) at 5 years are lower for both <2 cm (61%) and >10 cm (53%) than the rest (85-91%). When analyzing the impact of tumor association on <2 cm GIST, we observed that the OS of patients with non-associated tumors was much higher than in the associated ones (90% vs 32% at 5 years, respectively), while no differences were observed in the disease specific survival. CONCLUSIONS: Small GIST are tumors that are very often incidentally discovered in the course of complementary examinations. Its prognosis is very good, but it depends on the associated tumor.