Hyperthermic intraperitoneal chemotherapy (HIPEC) for ovarian cancer: a "useless intraoperative fever" or the next hot voice in the surgical management of the "silent killer"?

The aim of our opinion letter is to highlight the recent findings in the field of hyperthermic intraperitoneal chemotherapy (HIPEC) use in ovarian cancer management. Two recent studies reveal that ovarian cancer patients treated with HIPEC can extend their survival independently of the timing offered-either at the initial cytoreductive effort or at the time of disease relapse. The research field is flourishing and further data are awaited from randomised control trials. Although, HIPEC is not considered yet as the standard of care in the management of ovarian cancer patients, the initial findings of its use are promising.

The current practice of cytoreductive surgery and HIPEC for colorectal peritoneal metastases: Results of a worldwide web-based survey of the Peritoneal Surface Oncology Group International (PSOGI).

BACKGROUND: At present, selected patients with resectable colorectal peritoneal metastases (CRC-PM) are increasingly treated with a combination therapy of cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC). The aim of this study was to investigate the current worldwide practice. METHODS: HIPEC experts from 19 countries were invited through the Peritoneal Surface Oncology Group International (PSOGI) to complete an online survey concerning their personal expertise and current hospital and countrywide practice. RESULTS: It is estimated that currently more than 3800 patients with CRC-PM (synchronous and metachronous) are annually treated with CRS and HIPEC in 430 centers. Integration of CRS and HIPEC in national guidelines varies, resulting in large treatment disparities between countries. Amongst the experts, there was general agreement on issues related to indication, surgical technique and follow up but less on systemic chemotherapy or proactive strategies. CONCLUSION: This international survey demonstrates that CRS and HIPEC is now performed on a large scale for CRC-PM patients. Variation in treatment may result in heterogeneity in surgical and oncological outcomes, emphasising the necessity to reach consensus on several issues of this comprehensive procedure. Future initiatives directed at achieving an international consensus statement are needed.

Re-admissions for delayed complications after cytoreductive surgery and HIPEC.

BACKGROUND: Peritoneal metastasis (PM) is currently treated with the complex procedure of cytoreductive surgery and hyperthermic intra-peritoneal chemotherapy (CRS + HIPEC). This procedure presents high morbidity and mortality rates, but they have only been examined in the immediate post-operative period. The aim of our study is to present, describe and analyze the post-operative events, secondary to a cytoreductive surgery and HIPEC procedure that occurs after the patients' discharge from the hospital. PATIENTS AND METHODS: We examine retrospectively 219 patients who were discharged from our hospital from the initial 230 patients with PM, who were operated on from August 2005 to August 2015 and underwent CRS and HIPEC. Complications are investigated from the patient's discharge date until the 90th post-operative day, and are categorized with the Clavien-Dindo classification. RESULTS: We identified 17 patients (7.8%) who developed late complications. No major differences in patient characteristics were identified between this group of 17 patients and the rest, apart from a slightly higher PCI (23.5 vs. 22.3). Mean length of stay at the re-admission was 11.7 days. 5 of the patients (29.4%) had to be re-operated on, whereas we found a mortality of 11.8% (2/17 patients). The most common complications involved abdominal abscesses (17.6%), ureteral strictures (17.6%) and enterocutaneous fistulae (17.6%). CONCLUSION: Our study highlights the late complications following CRS plus HIPEC procedures, that occur after the patient's discharge from the hospital, an issue that has not been investigated thoroughly yet and may have serious impact on the post-operative quality of life. The role of adjuvant chemotherapy following CRS and HIPEC procedures in the onset of such complications appears to be important and needs further investigation.

Treatment of peritoneal surface malignancies with hyperthermic intraperitoneal chemotherapy-current perspectives.

Peritoneal carcinomatosis (ptc) represents advanced malignant disease and has generally been associated with a grim prognosis. Peritoneal surface malignancy is often the major source of morbidity and mortality; it is of major concern in cancer management. Although ptc is categorized as metastatic disease, it represents a special disease pattern considered to be a locoregional disease limited to the abdominal cavity. The combination of cytoreductive surgery (crs) and intraoperative hyperthermic intraperitoneal chemotherapy (hipec) has successfully been used as locoregional treatment for selected patients with ptc from gastric, colorectal, and ovarian cancer; with mesothelioma; and with pseudomyxoma peritonei. In the prophylactic setting, hipec can also be used to prevent ptc in high-risk patients, and the first results of the "second-look" approach are promising. Patient selection-in which the risks of perioperative morbidity and mortality, which are analogous to those for any other major gastrointestinal surgery, are assessed-is of utmost importance. Those risks have to be weighed against the anticipated survival benefit, which depends mainly on tumour biology, extent of disease, and probability of achieving complete crs. The present review discusses the principles of crs and hipec, the most significant recent clinical data, and current perspectives concerning the application of this treatment modality in various malignancies. Ongoing trials and future directions are noted. It appears that the combination of crs and hipec is an indispensable tool in the oncologist's armamentarium.

Screening for predictors of adverse outcome in onco-geriatric surgical patients: A multicenter prospective cohort study.

AIMS: The aim of this study was to investigate the predictive ability of screening tools regarding the occurrence of major postoperative complications in onco-geriatric surgical patients and to propose a scoring system. METHODS: 328 patients ≥ 70 years undergoing surgery for solid tumors were prospectively recruited. Preoperatively, twelve screening tools were administered. Primary endpoint was the incidence of major complications within 30 days. Odds ratios (OR) and 95% confidence intervals (95% CI) were estimated using logistic regression. A scoring system was derived from multivariate logistic regression analysis. The area under the receiver operating characteristic curve (AUC) was applied to evaluate model performance. RESULTS: At a median age of 76 years, 61 patients (18.6%) experienced major complications. In multivariate analysis, Timed Up and Go (TUG), ASA-classification and Nutritional Risk Screening (NRS) were predictors of major complications (TUG>20 OR 3.1, 95% CI 1.1-8.6; ASA ≥ 3 OR 2.8, 95% CI 1.2-6.3; NRS impaired OR 3.3, 95% CI 1.6-6.8). The scoring system, including TUG, ASA, NRS, gender and type of surgery, showed good accuracy (AUC: 0.81, 95% CI 0.75-0.86). The negative predictive value with a cut-off point >8 was 93.8% and the positive predictive value was 40.3%. CONCLUSIONS: A substantial number of patients experience major postoperative complications. TUG, ASA and NRS are screening tools predictive of the occurrence of major postoperative complications and, together with gender and type of surgery, compose a good scoring system.

Peritoneal carcinomatosis: intraoperative parameters in open (coliseum) versus closed abdomen HIPEC.

BACKGROUND: Peritoneal carcinomatosis (PC) is associated with a poor prognosis. Cytoreductive surgery (CRS) and HIPEC play an important role in well-selected patients with PC. The aim of the study is to present the differences in the intraoperative parameters in patients who received HIPEC in two different manners, open versus closed abdomen. PATIENTS AND METHODS: The population includes 105 patients with peritoneal carcinomatosis from colorectal, gastric, and ovarian cancer, sarcoma, mesothelioma, and pseudomyxoma peritonei. Group A (n = 60) received HIPEC using the open technique and Group B (n = 45) received HIPEC with the closed technique. The main end points were morbidity, mortality, and overall hospital stay. RESULTS: There were two postoperative deaths (3.3%) in the open group versus no deaths in the closed group. Twenty-two patients in the open group (55%) had grade III-IV complications versus 18 patients in the closed group (40%). There are more stable intraoperative conditions in the closed abdomen HIPEC in CVP, pulse rate, and systolic pressure parameters. CONCLUSIONS: Both methods are equal in the HIPEC procedures. Perhaps the closed method is the method of choice for frail patients due to more stable hemodynamic parameters.

Cytoreductive surgery and HIPEC in recurrent epithelial ovarian cancer: a prospective randomized phase III study.

BACKGROUND: The current treatment of ovarian cancer consists of cytoreductive surgery (CRS) and systemic chemotherapy. The aim of this study was to examine if hyperthermic intraperitoneal chemotherapy (HIPEC) is an alternative modality to treat this category of patients along with a second attempt of surgical resection and second- or third-line systemic chemotherapy afterward. METHODS: In an 8-year period (2006-2013), 120 women with advanced ovarian cancer (International Federation of Gynecology and Obstetrics [FIGO] IIIc and IV) who experienced disease recurrence after initial treatment with conservative or debulking surgery and systemic chemotherapy were randomized into two groups. Group A comprised 60 patients treated with CRS followed by HIPEC and then systemic chemotherapy. Group B comprised 60 patients treated with CRS only and systemic chemotherapy. RESULTS: The mean survival for group A was 26.7 versus 13.4 months in group B (p < 0.006). Three-year survival was 75 % for group A versus 18 % for group B (p < 0.01). In the HIPEC group, the mean survival was not different between patients with platinum-resistant disease versus platinum-sensitive disease (26.6 vs. 26.8 months). On the other hand, in the non-HIPEC group, there was a statistically significant difference between platinum-sensitive versus platinum-resistant disease (15.2 vs. 10.2 months, p < 0.002). Complete cytoreduction was associated with longer survival. Patients with a peritoneal cancer index score of <15 appeared also to have longer survival. CONCLUSIONS: The use of HIPEC along with the extent of the disease and the extent of cytoreduction play an important role in the survival of patients with recurrence in an initially advanced ovarian cancer.

Cytoreductive surgery and HIPEC for peritoneal carcinomatosis in the elderly.

BACKGROUND: The combined treatment of peritoneal carcinomatosis with cytoreductive surgery and hyperthermic intraperitoneal chemotherapy is a rigorous surgical treatment, most suitable for young and good performance status patients. We evaluated the outcomes of elderly patients undergoing CRS and HIPEC for peritoneal carcinomatosis with careful perioperative care. METHODS: All consecutive patients 70 years of age or older who were treated for peritoneal carcinomatosis over the past five years were included. Primary outcomes were perioperative morbidity and mortality. Secondary outcomes were disease-free survival and overall survival. RESULTS: From a pool of 100 patients, with a diagnosis of PC who underwent CRS and HIPEC in our center, we have included 30 patients at an age of 70 years or older and the results were compared to the patients younger than 70 years. The total morbidity rate was 50% versus 41.5% in the group younger than 70 years (NSS).The mortality rate was 3.3% in the elderly group versus 1.43%in the younger group (NSS). Median overall survival was 30 months in the older group versus 38 months in the younger group. CONCLUSION: Cytoreductive surgery and HIPEC for peritoneal carcinomatosis may be safely performed with acceptable morbidity in selected elderly patients.

Reoperation combining re-cytoreductive surgery and re-HIPEC for recurrent peritoneal carcinomatosis.

PURPOSE: Cytoreductive surgery (CS) and hyperthermic intraperitoneal chemotherapy (HIPEC) is the proper treatment for resectable peritoneal carcinomatosis (PC). The aim of this study was to evaluate the postoperative course and long-term outcome of repeat CS (reCS) plus repeat HIPEC (reHIPEC) in patients with recurrent disease, after primary CS plus primary HIPEC. METHODS: From 2004 to 2012 85 patients were subjected to primary CS + HIPEC. Fourteen of those patients developed recurrent PC and were subjected to reCS+reHIPEC during the same time period. Eligibility criteria included limited extent of the peritoneal disease, and interval of more than 12 months from the primary CS+HIPEC. The origins of the tumors were ovarian cancer (n=7) colorectal cancer (n=3), pseudomyxoma peritonei (n=3), and uterine sarcoma (n=1). RESULTS: At second laparotomy, mean peritoneal cancer index (PCI) was 5.3 + 2.8. Among the 14 procedures, HIPEC was used in all patients. The postoperative mortality was 0% and grade 3-4 postoperative complications occurred in 4 patients. The overall 1-, 2- and 3- year overall survival rate was 90, 40 and 30%, respectively. CONCLUSION: ReCS+reHIPEC is feasible and yields an accepted survival in highly selected patients.

Surgical management of endometrial cancer. A critical review.

Endometrial cancer (EC) is a common gynecological malignancy. Prognosis depends on 3 main factors: histological subtype, depth of invasion into the myometrium and lymph node involvement. Surgery remains the gold standard of treatment for this cancer. The aim of this article was to review the surgical approach and the new techniques along with the clarification of some controversial aspects concerning the management of advanced disease stages and the role of lymph node dissection. Surgery of EC remains the treatment of choice in the management of early stage disease. The role of lymph node dissection remains controversial.

Peritoneal carcinomatosis 2011; it's about time for chemosurgery.

The aim of this article was to offer a review on the management of peritoneal carcinomatosis (PC) from cancers of different primary origins. Peritoneal surface malignancies have been traditionally regarded as end-stage conditions amenable to merely palliative options, treated with systemic chemotherapy alone with very poor response and a median survival of less than 6 months. The combination of aggressive cytoreductive surgery (CRS), involving peritonectomy procedures and multivisceral resections with hyperthermic intraoperative intraperitoneal chemotherapy (HIPEC) to treat microscopic residual disease is a new concept. This method was established with several phase III studies in well selected patients with PC in whom sufficient cytoreduction could be achieved. Despite the need for more high quality phase III studies, there is now a consensus among many surgical teams around the world about the use of this new combination strategy as a standard of care in pseudomyxoma peritonei, peritoneal mesothelioma and colorectal cancer patients. This review summarizes the current status and possible progress in the future.

The role of cytoreductive surgery and hyperthermic intraperitoneal chemotherapy in the management of recurrent advanced ovarian cancer: a prospective study.

PURPOSE: Ovarian cancer is the leading cause of death from gynecological cancer. The current treatment of this type of cancer consists of cytoreductive surgery (CRS) and systemic chemotherapy. The aim of this study was to examine if the hyperthermic intraoperative chemotherapy (HIPEC) is an alternative modality to treat this category of patients along with a second attempt of surgical resection and second or third line systemic chemotherapy. METHODS: Forty-eight patients suffering from advanced ovarian cancer (FIGO stages III and IV) who recurred after initial treatment with conservative or debulking surgery and systemic chemotherapy were included in this study. Twenty-four patients (group A) were treated with CRS followed by HIPEC and then systemic chemotherapy. Due to various reasons the remaining 24 patients (group B) were treated with CRS and systemic chemotherapy alone. RESULTS: The median survival for group A was 19.4 months vs. 11.2 months in group B (p <0.05). One-year survival was 85% in group A vs. 35% in group B (p <0.05). The 3-year survival rate was 50% in group A vs. 18%. in group B (p <0.01). The resection status was found to be a significant predictor of overall survival (p <0.05). Patients with peritoneal cancer index (PCI) score < 15 appeared also to have longer survival. CONCLUSION: The use of HIPEC along with the extent of the disease and the extent of cytoreduction play an important role in the survival of patients with a recurrence in an initially advanced ovarian cancer.

Doppler-guided haemorrhoidal artery ligation, rectoanal repair, sutured haemorrhoidopexy and minimal mucocutaneous excision for grades III-IV haemorrhoids: a multicenter prospective study of safety and efficacy.

OBJECTIVE: The isolated use of Doppler-guided haemorrhoidal artery ligation (DGHAL) may fail for advanced haemorrhoids (HR; grades III and IV). Suture haemorrhoidopexy (SHP) and mucopexy by rectoanal repair (RAR) result in haemorrhoidal lifting and fixation. A prospective evaluation was performed to evaluate the results of DGHAL combined with adjunctive procedures. METHOD: The study included 147 patients with HR (male patients: 102; grade III: 95, grade IV: 52) presenting with bleeding (73%) and prolapse (62%). RESULTS: More ligations were required for grade IV than grade III HR (10.7 + 2.8 vs 8.6 + 2.2, P < 0.001). SHP (28 patients) and RAR (18 patients) at 1-4 positions were deemed necessary in 46 (31%) patients. Minimal (muco-)cutaneous excision (MMCE) was added in 23 patients. SHP/RAR was applied more frequently in grade IV HR (60%vs 16%, P < 0.001). In patients not having MMCE, SHP/RAR was added in 57% of grade IV cases (P < 0.001). Complications included residual prolapse (10; two second surgery), bleeding (15; two second DGHAL), thrombosis (four), fissure (three) and fistula (one). Analgesia was required not at all, up to 1-3 days, 4-7 days and >7 days by 30%, 31%, 16% and 14% of the patients, respectively. SHP/RAR was associated with greater discomfort (17%vs 6%, P < 0.001). No differences were found between SHP and RAR. At an average follow-up of 15 months, 96% of patients were asymptomatic and 95% were satisfied. CONCLUSIONS: DGHAL with the selective application of SHP/RAR is a safe and effective technique for advanced grade HR.

Morbidity and mortality of cytoreductive surgery and hyperthermic intraperitoneal chemotherapy in the management of peritoneal carcinomatosis.

PURPOSE: Peritoneal carcinomatosis (PC), which has been regarded as a lethal condition, may now be treated, achieving a long-term disease-free survival with cytoreductive surgery by treating macroscopic tumor seeding and hyperthermic intraperitoneal chemotherapy (HIPEC) by treating residual microscopic disease. The purpose of this study was to analyse the morbidity and mortality of this procedure. METHODS: A total of 39 consecutive patients were included in this retrospective study. After complete resection of the PC, HIPEC was performed via the coliseum technique. The chemotherapeutic agents used depended on the tumors' histology. RESULTS: Postoperative mortality and morbidity rates were 5.1%% (2/39) and 43.5% (17/39), respectively. The most frequent complications were pulmonary complications (31%), gastrointestinal fistulas (20%), hematologic toxicity (16%) and postoperative bleeding (11%). Statistical correlations were evidenced between morbidity and PC index (p<0.004), duration of surgery (p<0.001) and blood loss (p<0.001). CONCLUSION: This approach has resulted in a relatively high but acceptable percent of adverse events considering the expected advantage for survival.

Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy in the management of peritoneal carcinomatosis. Preliminary results and cost from two centers in Greece.

PURPOSE: To report our preliminary experience in the combined treatment of peritoneal carcinomatosis (PC) using cytoreductive surgery plus hyperthermic intraperitoneal chemotherapy (HIPEC). PATIENTS AND METHODS: This prospective study included patients with PC from gynaecological, gastric and colon cancer, treated in two centers. Cytoreductive surgery included the peritonectomy procedures described by Jacquet and Sugarbaker as well as multivisceral resections in order to achieve a complete macroscopical cancer eradication. The HIPEC that followed was performed via the open abdomen technique. RESULTS: Twenty-four patients (3 men and 21 women, mean age 60 years) were treated. Twelve patients had PC from ovarian cancer, 7 from colon, 3 from gastric and 2 from uterine cancer. The mean duration of the procedure was 7.83 h (range 5 -12.30). Macroscopically, complete cytoreduction (CC) was achieved in 18 (75%) patients. Two (8.3%) patients died in the first 30 days. The overall morbidity was 42% and 2 patients were reoperated. The mean follow up was 22 months (range 3-36). The overall 1-year survival was 59.1%; concerning the gynaecological cancers it was 53.8% (mean survival 11.7 months) and for gastrointestinal cancers it was 44.4% (mean survival 9.5 months). CONCLUSION: Our preliminary data suggest that the combined treatment of cytoreduction plus HIPEC for PC is associated with acceptable mortality and morbidity and offers an improved survival in these patients. An optimal patient selection and establishment of experienced centres are of paramount importance.

Management of advanced abdominopelvic tumors with combined radiofrequency ablation and surgical debulking.

AIM: Advanced abdominopelvic tumors due to rectal cancer, gynecological cancer or sarcomas are often unresectable using surgery alone. This study presents the combination of radiofrequency ablation (RFA) and surgical debulking for such tumors. METHODS: Between November 2005 and June 2007 we treated 4 patients with tumor fixation to the pelvic side wall and to the sacroiliac joint. Two of these patients had recurrent gynecological cancer while the other 2 had rectal cancer. All 4 of them had received prior treatment. The radiofrequency probe was placed in the center of the tumor. A 5- to 8-cm tissue core was ablated and aspirated or curetted out. This was repeated centrifugally out to the tumor capsule. RESULTS: Control of the tumor for more than 12 months was achieved in 3 patients. One patient died 14 months after the procedure due to tumor progression. Two patients are still alive 12 and 14 months after the operation without symptoms. The other patient is alive 6 months after the operation in a disease-free condition. CONCLUSIONS: Combined RFA and surgical debulking is beneficial as an alternative palliative method in patients with inoperable abdominopelvic tumors.