Progress in the management of primary and recurrent ovarian carcinomatosis with peritonectomy procedure and HIPEC in a high volume centre

Abstract

Introduction: The treatment of advanced primary or recurrent ephitelial ovarian cancer still remains an open and a critical question. The addition of HIPEC to cytoreductive surgery has shown improving overall survival rates. The aim of our study is to describe the progress in its management in our Unit and what we have learned after more than 350 HIPEC procedures.

Methods: From 1997 to 2016 we conducted a retrospective analysis from a prospective database. We described and analyzed 4 cut-points, 1997–2004, 2009, 2012 and 2016.

Results: From 1997 to September 2016, 358 patients have been operated in our Unit by CRS with peritonectomy procedures plus HIPEC for stage IIIc and IV ovarian cancer. The HIPEC procedures rate was 4,7 HIPEC per years in the first years up to 35 HIPEC/year in last era. Mean age was 56,7 years (28–78). Median PCI was 15,8. (range 3–36). R0-cytoreduction was 95%. Severe morbidity and mortality were observed in 15 % and 2%, respectively. The 3 y OS was 77% in primary and 79% in recurrent ovarian cancer. The stage IV was not a risk factor for survival. R1 cytoreduction and positive lymph nodes were risk factors in multivariate analysis.

Conclusion: The addition of HIPEC to CRS improves overall survival rates for primary and recurrent ovarian cancer. This therapeutic strategy was incorporated twenty years ago for a few teams in the world and today there is an emerging and strong evidence that could consider it as an standard treatment for the ovarian carcinomatosis.     

Does having a gastrectomy delay time to feeding and prolong hospital stay in patients undergoing cytoreductive surgery and hyperthermic intraperitoneal chemotherapy?

Aim: Cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) is routinely used to treat selected patients with peritoneal carcinomatosis, but can be associated with prolonged hospital stay, significant morbidity and mortality. Our objective was to assess whether patients undergoing gastrectomy as part of CRS/HIPEC were at increased risk of delayed feeding time and prolonged hospital stay.

Methods: Two hundred and fourteen consecutive patients with peritoneal carcinomatosis treated with CRS/HIPEC between 2001 and 2016 were stratified by whether CRS included gastrectomy (n?=?19, 9%) and compared. Primary outcomes were time to full feeds and rate of serious morbidity (Clavien–Dindo grades III–V). Secondary outcomes were durations of ICU and hospital stays.

Results: Of 214 patients undergoing CRS/HIPEC, those undergoing gastrectomy (19, 8.9%) had increased time to full feeds (8 vs. 5 days, p?p?p?=?0.013). There was no significant increase in serious complications, although increased risk of pneumonia was noted (21% vs. 4.1%, p?=?0.011). Undergoing gastrectomy was not independently prognostic in multivariable analysis including high peritoneal tumour load (PCI >12), multiple CRS procedures (number >2) and operation duration (>480?min) in which operative duration remained independently prognostic (p?Conclusions: After surgery, early oral refeeding may be beneficial in the majority of patients undergoing CRS/HIPEC. However, patients found to have high peritoneal tumour load with extended surgery and those who underwent gastrectomy should be considered for early post-operative TPN due to the significant risk of delayed time to full feeds.     

201 consecutive cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) procedures in a single Asian tertiary centre

Introduction: Peritoneal carcinomatosis (PC) is increasingly being treated with cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC). We provide a review of a high-volume Asian institute's experience and survival outcomes with this procedure.

Methods: Data were prospectively collected from 201 consecutive CRS and HIPEC procedures performed in a single institution between April 2001 and November 2015. Our primary endpoints were overall survival (OS) and disease-free survival (DFS), and secondary endpoints were morbidity and mortality.

Results: 77% of patients were Chinese, 9% were Malay, 6% were Indian and 8% were other ethnicities. Primary tumours were colorectal (30%), ovarian (32%), appendiceal (20%), primary peritoneal (6.5%), mesothelioma (4.5%) and others (5%). The median peritoneal cancer index (PCI) was 12, and 92% of patients achieved a completeness of cytoreduction score (CC) of 0. High-grade morbidity occurred in 25.8% of cases, and there were no 30-day mortalities. At 5-years, the OS was 55.1% and DFS was 20.3%. Factors associated with improved OS on multivariate analysis were PCI <15 (p?p?=?0.016).

Conclusions: The combined treatment of CRS and HIPEC is beneficial and is associated with reasonable morbidity and mortality in Asian patients with PC from colorectal, ovarian, appendiceal, primary peritoneal and mesothelioma primaries. Complete cytoreduction and extent of disease are the most important prognostic factors for survival.     

Cytoreductive surgery with hyperthermic intraperitoneal chemotherapy for peritoneal malignancy: preliminary results of a multi-disciplinary teamwork model in Asia

Background: Cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) is an emerging surgical procedure for peritoneal carcinomatosis (PC). CRS/HIPEC is a complicated treatment that requires multi-disciplinary teamwork (MDT), which may be lacking when establishing a CRS/HIPEC programme. Herein, we report our preliminary treatment outcomes with the early implementation of an MDT model for CRS/HIPEC.

Methods: From April 2015 to December 2016, 45 patients with a diagnosis of PC who received CRS/HIPEC were reviewed retrospectively in a single institution in Taiwan.

Results: Among the 45 patients, CRS was mainly performed by laparotomy (n?=?42), and only three patients with limited PC underwent laparoscopic CRS. The first 13 patients received treatment before the MDT had been established (group 1), and the other 32 patients were treated after the MDT had been established (group 2). The highest peri-HIPEC body temperature in group 2 was significantly lower than that in group 1 (36.8?°C vs. 37.5?°C, p?p?=?0.202). Pre-CRS/HIPEC abdominal pain significantly increased the risk of post-operative major complications (p?=?0.017).

Conclusions: Our experience suggests that the early implementation of an MDT model when establishing a CRS/HIPEC programme at a single institution may result in a higher complete cytoreduction rate and lower major complication rate, and also shorten the learning curve of this complicated procedure.     

Iterative procedures combining cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for isolated peritoneal recurrence

Purpose: The aim of this study was to analyse feasibility, morbidity and outcome of repeat complete cytoreductive surgery (CRS) plus hyperthermic intraperitoneal chemotherapy (HIPEC). CRS combined with HIPEC is becoming the gold standard treatment for resectable peritoneal carcinomatosis in highly selected patients. As yet treatment of isolated peritoneal recurrence with iterative CRS and HIPEC has not been thoroughly explored.

Materials and methods: We selected 16 patients presenting isolated peritoneal recurrence who had undergone iterative CRS and HIPEC from a dataset of 322 CRS associated with HIPEC performed between 1996 and 2012.

Results: Peritoneal carcinomatosis (PC) was due to colorectal and ovarian cancer, peritoneal mesothelioma and pseudomyxoma peritonei (PMP). Disease-free survival (DFS) was 13 months after the first procedure and 13.7 months after the second one. Overall morbidity rate was 43.7% (7/16) for all patients, with grade III–IV complications in three patients (18.7%).

Conclusions: Iterative procedures combining cytoreductive surgery and HIPEC are feasible with acceptable morbidity and mortality rates in strictly selected patients. DFS following repeated CRS and HIPEC is comparable to that registered after the first procedure.     

Cytoreductive surgery combined with hyperthermic intraperitoneal chemotherapy for the treatment of primary peritoneal serous carcinoma: Results of a Chinese retrospective study

Purpose Primary peritoneal serous carcinoma (PPSC) is a rare condition with a poor survival rate, even after treatment with debulking surgery followed by systemic chemotherapy. This study evaluated the efficacy and safety of cytoreductive surgery (CRS) combined with hyperthermic intraperitoneal chemotherapy (HIPEC) for the treatment of PPSC.

Patients and methods This retrospective study included 22 female patients with primary advanced PPSC (group A, n?=?12) or recurrent PPSC (group B, n?=?10) treated with 25 CRS?+?HIPEC procedures. The primary end point was overall survival (OS), and the secondary end points were safety profiles.

Results A total of 25 CRS?+?HIPEC procedures were performed in these 22 patients. The median OS was 31.0 months (95% confidence interval (CI) 22.3–39.7), and the 1-, 3-, and 5-year survival rates were 100%, 45.5%, and 27.3%, respectively. Subgroup analyses revealed that the median OS was 31.0 months (95% CI 19.8–42.2) for group A vs. 38.5 months (95% CI 9.6–67.4) for group B (P?=?0.832, log rank test); 51.5 months (95% CI 34.9–68.1) for peritoneal cancer index (PCI)?≤?15 vs. 20.3 months (95% CI 12.6–28.0) for PCI > 15 (P?=?0.000, log rank test); and 38.5 months (95% CI 22.5–54.5) for completeness of cytoreduction (CC) of 0–1 vs. 23.5 months (95% CI 15.3–31.7) for CC of 2–3 (P?=?0.178, log rank test). There were no perioperative deaths. Serious adverse events (SAEs) occurred in two patients (9.1%). A univariate analysis identified PCI ≤ 15 as the only prognostic predicator (hazard ratio (HR) 13.1, 95% CI 2.7–63.4, P?=?0.001).

Conclusions CRS?+?HIPEC could contribute to favourable outcomes for select PPSC patients with acceptable safety profiles.     

Current status and future prospects of clinical trials on CRS + HIPEC for gastric cancer peritoneal metastases

Abstract

Purpose: There is no standard treatment for peritoneal metastases (PM) from gastric cancer (GC). The aim of this review is to evaluate the clinical trials on cytoreductive surgery (CRS) plus hyperthermic intraperitoneal chemotherapy (HIPEC) for GC PM.

Materials and methods: The published clinical trials on CRS?+?HIPEC for GC PM are critically evaluated, and survival and safety are the primary endpoints. In addition, the registered ongoing clinical trials are summarised.

Results: The natural course of GC PM is <5 months. CRS?+?HIPEC could improve the overall survival (OS). In prospective studies, the median OS was 11.0 months in the CRS?+?HIPEC group vs. 5.4 months in the CRS alone group. In case-control studies, the median OS was 13.3 months in the CRS?+?HIPEC group vs. 7.9 months in the CRS alone group. In cohort studies, the median OS after CRS?+?HIPEC was 13.3. The median 1-, 2- and 5-year survival rates after CRS?+?HIPEC were 50.0%, 35.8% and 13.0%, respectively. There is no statistically significant increase in serious adverse events that are directly attributed to CRS?+?HIPEC.

Conclusions: The combination of CRS and HIPEC is a promising integrated treatment strategy for GC PM that has encouraging initial results, calling for urgent further evaluation of this strategy in randomised control trials (RCTs).     

A novel treatment protocol with 6 cycles of neoadjuvant chemotherapy followed by cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (HIPEC) in stage III primary ovarian cancer

BackgroundFew prospective studies investigated neoadjuvant chemotherapy (NAC), interval cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) in advanced ovarian cancer. We report the results of a phase II study where 6 rather than 3 cycles of NAC, followed by CRS and HIPEC, were adopted (HIPEC_ovaio, EudraCT number 2007-005674-31).Materials and methodsBetween 2007 and 2014, 56 patients with stage III primary ovarian cancer and peritoneal carcinomatosis were assigned to 6 cycles of platinum and taxane-based NAC. Of these, two had progression, 8 underwent palliative surgery, and 46 had CRS and HIPEC.ResultsA complete pathological response was observed in 9 patients. Of 46 patients who completed the treatment protocol, 29 had no macroscopic residual tumor. Postoperative grade III morbidity rate was 28.2%; no grade IV complications or mortality events were observed. Five-year overall survival (OS) of the entire series was 36 ± 7% (median: 36, 95% CI: 26–45 months). In 46 patients treated by CRS and HIPEC, 5-year OS was 42 ± 8% (median: 53, 95% CI: 29–76 months), and 5-year progression-free survival was 26 ± 7% (median: 23, 95% CI: 19–27 months). Completeness of cytoreduction, peritoneal cancer index and FIGO stage resulted as significant prognostic factors.ConclusionsA novel protocol consisting of 6 cycles of NAC, followed by CRS and HIPEC, is associated with notable improvement in peritoneal carcinomatosis, limited postoperative morbidity risk and high survival rates in responders, and could deserve further investigations in randomized clinical trials.     

Clinical efficacy of cytoreductive surgery and hyperthermic chemotherapy in peritoneal carcinomatosis from gastric cancer

Evaluation of: Yang XJ, Huang CQ, Suo T et al. Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy improves survival of patients with peritoneal carcinomatosis from gastric cancer: final results of a Phase III randomized clinical trial. Ann. Surg. Oncol. 18(6), 1575–15781 (2011).

Peritoneal carcinomatosis (PC) is the most common pattern of metastasis and recurrence in patients with gastric cancer and is associated with poor clinical outcome and survival. Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (HIPEC) was recently established as a new treatment option for PC of gastrointestinal cancer. However, the role of cytoreductive surgery in gastric cancer and the intrinsic role of HIPEC remains unclear. The evaluated article presented a single center Phase III study, randomizing 68 patients with PC from gastric cancer to surgical cytoreduction only (CRS; n = 34) versus cytoreduction plus HIPEC with cisplatin and mitomycin (CRS+HIPEC; n = 34). Median overall was 6.5 months in the CRS group and 11.0 months in the CRS+HIPEC group (p = 0.046). Serious adverse events were acceptable in both groups. Multivariate analysis found CRS+HIPEC, synchronous PC, complete cytoreduction, systemic chemotherapy >6 cycles and no incidence of severe adverse events independent predictive factors for survival. This was the first study to show the positive effects of HIPEC in addition to CRS in PC independently of the tumor entity. In patients with gastric cancer, multimodal treatment concepts combining surgical cytoreduction and HIPEC may provide a new option in carefully selected patients.     

Hyperthermic intraperitoneal chemotherapy with cisplatin and paclitaxel in advanced ovarian cancer: a multicenter prospective observational study

Objective

Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) have been recently reported with favorable oncological outcomes as treatment of advanced epithelial ovarian cancer (EOC). The aim of this study was to demonstrate the feasibility of CRS+HIPEC with cisplatin and paclitaxel for the treatment of advanced EOC.

Methods

This is a prospective observational study of 54 patients, from April 2007 to October 2013, with primary or recurrent peritoneal carcinomatosis due to EOC. The mean age was 54.51±9.34. Thirty patients (59%) had primary EOC, and 24 patients (41%) had recurrent disease.

Results

Mean peritoneal cancer index was 10.11 (range, 0 to 28), complete cytoreduction (CC0) was achieved for 47 patients (87%), CC1 for seven patients (13%). Patients with suboptimal cytoreduction (CC2 and CC3) were not included in the study. The mean stay in intensive care unit was 4.73±5.51 days and the mean hospitalization time was 24.0±10.03 days. We did not observe any intraoperative death. Seven patients (13%) required additional operations. Three patients (5.6%) died within 30 days from the procedure. Severe complications were seen in 19 patients (35.2%). During the follow-up period, disease recurred in 33 patients (61.1%); the median disease-free survival time was 12.46 months and the median overall survival time was 32.91 months.

Conclusion

CRS+HIPEC with cisplatin and paclitaxel for advanced EOC is feasible with acceptable morbidity and mortality. Additional follow-up and further studies are needed to determine the effects of HIPEC on long term survival.     

Repeated cytoreductive surgery and hyperthermic intraperitoneal chemotherapy in peritoneal carcinomatosis from appendiceal cancer: Analysis of survival outcomes

Background

Cytoreductive surgery (CRS)/hyperthermic intraperitoneal chemotherapy (HIPEC) is the procedure of choice in patients with peritoneal dissemination from appendiceal cancer. Although recurrence rates are 26%–44% after first CRS/HIPEC, the role of repeated CRS/HIPEC has not been well defined. We hypothesize that patients undergoing multiple CRS/HIPEC's have meaningful long term survival.

Methods

A retrospective study of a prospective database of 294 patients with peritoneal carcinomatosis (PC) was conducted, of these 162 had PC of appendiceal origin. Twenty-six of these patients underwent 56 CRS/HIPEC. Survival and outcomes was analyzed.

Results

The percentage of patients with pre-surgical PCI scores ≥20 for the first, second, and third CRS/HIPEC was 65, 65, and 25%, respectively. Complete cytoreduction (CC 0-1) at first, second, and, third surgeries was 96, 65 and 75%, respectively.The mean operating time was 10.1 h. There was no 30-day peri-operative mortality. Following the first, second, and third CRS/HIPEC 27, 42, and 50% experienced grade III complications, respectively.Mean follow up was 51, 28, and 16 months from the first, second, and third CRS/HIPEC, respectively. Overall survival rate for the first CRS/HIPEC was 100, 83, 54, and 46% at years 1, 3, 5 and 10, respectively; from the second CRS/HIPEC 91, 53, and 34% at 1, 3, and 5 years, respectively; and from the third CRS/HIPEC was 75% at one year.

Conclusion

Repeat CRS/HIPEC can lead to meaningful long term survival rates in patients with appendiceal peritoneal carcinomatosis with morbidity and mortality similar to those of the initial CRS/HIPEC.     

Pattern of recurrence after interval cytoreductive surgery and HIPEC following neoadjuvant chemotherapy in primary advanced stage IIIC/IVA epithelial ovarian cancer

ObjectiveThe aim of this study was to evaluate the patterns of recurrence and factors affecting the same after interval cytoreductive surgery and hyperthermic intraperitoneal chemotherapy in primary stage IIIC and IV A epithelial ovarian cancer.MethodsIn this retrospective multicentric study, all patients with FIGO stages III-C and IV-A epithelial ovarian carcinoma were treated with CRS and HIPEC after receiving neoadjuvant chemotherapy. Relevant clinical and demographic data were captured. Multivariable logistic regression was performed to evaluate the factors affecting recurrence after CRS and HIPEC.ResultsFrom January 2017 to Jan 2020, 97, consecutive patients of Stage IIIC/IVA epithelial ovarian cancer underwent interval cytoreductive surgery and HIPEC after receiving neoadjuvant chemotherapy. The median duration of follow up duration was 20 months [1–36months]. 21/97 (21.6%) patients presented with disease recurrence. Visceral recurrences involving the lungs, liver and brain were seen in 8/21 (38%) of cases and comprised the commonest sites. On multivariable analysis, nodal involvement (p = 0.05), selective peritonectomy (p = 0.001) and leaving behind residual disease <0.25 mm (CC1) (p = 0.01) was associated with increased risk of disease recurrence. Extent of peritonectomy (OS,p = 0.56, PFS p = 0.047, Log Rank test) and nodal positivity (OS, p = 0.13,PFS,p = 0.057, Log Rank test) were found to impact progression free survival but had no impact on overall survival.ConclusionThere is a higher incidence of systemic recurrences in patients with Stage IIIC/IVA epithelial ovarian carcinoma after CRS and HIPEC. Extent of peritonectomy and nodal clearance impacts patterns of recurrence and progression free survival.     

Patterns and Timing of Recurrence following CRS and HIPEC in Colorectal Cancer Peritoneal Metastasis

IntroductionCytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy (CRS/HIPEC) is an established treatment of Colorectal Peritoneal Metastases (CRPM). This study aims to determine the timing and patterns of recurrent disease on imaging following complete CRS/HIPEC.MethodsRetrospective analysis of a national peritoneal tumour service database identified CRPM patients with complete CRS/HIPEC(CC0) from 2005 to-2018. Patients with<2 years follow-up or and those where post-operative histology from the CRS/HIPEC procedure did not confirm CRPM from their original colorectal cancer were excluded. Time to recurrence was measured from surgery to first radiologically illustrated recurrence. CT was the primary modality used, supplemented by PET-CT or MRI if required. Outcomes of interest were survival data (including overall survival (OS), disease-free survival (DFS) and peritoneal-recurrence free survival (PRFS)), timing and patterns of recurrent disease.Results146 of the 176 patients identified were eligible for inclusion. Median OS for all study patients was 45.2 months (95% CI 38–53 months), median DFS was 11.7 months (95% CI 9–14 months), and median PRFS was 25.2 months (95% CI 14.7–30 months). Recurrent disease was seen in 112 cases (77%), radiologically classified as intraperitoneal in 50 patients (44%), single site systemic in 21 patients (19%) and multi-site in 41 patients (37%). CT detection rate for disease recurrence was 88%. Subgroup analyses showed that PCI ≥12, positive nodal primary disease and synchronous peritoneal disease were associated with worse outcomes.ConclusionPatients selected for CRS/HIPEC for CRPM have an OS > 45 months, with the majority recurring systemically within a year. Peritoneal recurrence is a later event after several years. Surveillance programs in this group should be most intensive in the first 2 years after surgery, using CT with oral and intravenous contrast.     

Closed hyperthermic intraperitoneal chemotherapy with CO2 recirculation system compared with the open Coliseum technique in peritoneal malignity treatment

BackgroundCytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) for peritoneal carcinomatosis can be performed in two ways: first, the standard open abdominal technique (Open HIPEC); or second, the closed technique. In recent years, a new technique has been introduced to perform closed HIPEC; the Peritoneal Recirculation System (PRS-1.0 Combat) with CO₂ recirculation technology (PRS Closed HIPEC). The objective of this study is to present our experience with the PRS Closed HIPEC by comparing the intraoperative, postoperative and oncological results with the standard Open HIPEC technique (the Coliseum technique).MethodsData on patients undergoing CRS and HIPEC at the Sanchinarro University Hospital, Madrid from October 2012 to June 2021 were collected in a prospective database. The inclusion criteria were patients with primary or recurrent peritoneal metastases in gastrointestinal malignancies or ovarian cancer. The presence of an unresectable peritoneal carcinomatosis, the coexistence of another oncological disease, unresectable and distant metastases were the exclusion criteria.ResultsFrom October 2014 to June 2021, 84 patients underwent CRS and HIPEC at the Sanchinarro University Hospital, Madrid with curative intent. Since the introduction of the PRS Closed HIPEC technique in 2016, 65 patients have been treated. Before the introduction of PRS Closed HIPEC, 19 cases were performed using the Coliseum technique (the Open HIPEC group). The intraoperative results were similar in the two groups. Complete cytoreduction was achieved in all cases in the Open HIPEC group and in 98% in the PRS Closed HIPEC group. The rate of major complications was similar between the groups. Median Overall Survival (OS) resulted better in the Closed HIPEC group (67 months) with respecto to the Open group (43 months) (p < 0,001). Median Disease-Free Survival (DFS) was 15 months in the Open HIPEC group and 40 months in the PRS Closed HIPEC group (p < 0.001).ConclusionThe Peritoneal Recirculation System with CO₂ recirculation technology (PRS Closed HIPEC) is a reproducible and safe technique and may represent a valid alternative for the administration of HIPEC.     

Hyperthermic intraperitoneal chemotherapy with oxaliplatin and without adjuvant chemotherapy in stage IIIC ovarian cancer

ObjectiveTo assess the feasibility and efficacy of cytoreductive surgery (CRS) followed by hyperthermic intraperitoneal chemotherapy (HIPEC) without adjuvant chemotherapy for relapsed or persistent advanced ovarian cancer.MethodsThis observational study included stage IIIC ovarian cancer patients due to undergo CRS (interval debulking or recurrent surgery) followed by HIPEC with oxaliplatin (460 mg/m²) for 30 min.ResultsTwenty-two patients (12 interval debulking procedures and 10 recurrence procedures) were enrolled between September 2003 and September 2007. HIPEC was not performed in four patients because of operative findings. No patient received adjuvant chemotherapy after HIPEC. Patients were followed up routinely until recurrence or death. Median peritoneal cancer index at surgery was 6 (range: 1-18). Before HIPEC, all patients had completeness of cytoreduction scores of 0 or 1. Median length of hospital stay was 21 days (range 13-65). Ten patients (55.6%) had CTCAE grade 3-4 toxicity, including three patients (16.7%) requiring reoperation. No postoperative mortality was observed. With a median follow-up of 38 months (CI 95% 23.8-39.2), median overall survival was not reached. The 3-year overall survival rate was 83% (CI 95% 54-95). Median disease-free survival was, respectively, 16.9 months (CI 95% 10.2-23.2) and 10 months (CI 95% 4.5-11.3) for patients undergoing interval debulking or recurrence surgery.ConclusionHIPEC without adjuvant chemotherapy is both feasible and safe, but with a high rate of grade 3-5 toxicity. Survival results are encouraging but should be confirmed in a randomized trial.     

Misdiagnosis of appendiceal neoplasms as ovarian tumors: Impact of prior gynecologic surgery on definitive cytoreduction and HIPEC

BackgroundFemale patients with pelvic/adnexal masses often undergo gynecologic operations due to presumed ovarian origin. The diagnosis of an appendiceal tumor is often only made postoperatively after suboptimal cytoreduction has been performed. We hypothesized that an index gynecological procedure increases the morbidity of definitive cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) in patients with appendiceal mucinous tumors.MethodsA single-center retrospective review was performed to identify female patients undergoing CRS/HIPEC for appendiceal tumors from 2012 to 2020.ResultsDuring the 8-year period, CRS/HIPEC was performed in 36 female patients with appendiceal mucinous tumors. Eighteen patients (50.0%) had received a prior pelvic operation by gynecologists (PPO Group) for presumed ovarian origin before referral for definitive CRS/HIPEC. The median peritoneal cancer index (PCI) was higher in the PPO group (21 vs. 9, p = 0.04). The median number of days from gynecologic procedure to definitive CRS/HIPEC was 169 days. Compared to patients who did not undergo a prior gynecologic operation, those in the PPO group had higher intraoperative blood loss (650 vs 100 mL, p < 0.01) during CRS/HIPEC as well as longer length of stay (12 vs 8 days, p = 0.02) and higher overall morbidity (72.3% vs 33.3%, p = 0.02). After controlling for PCI, prior gynecologic operation increased risk of 30-day morbidity after definitive CRS/HIPEC (OR 11.6, p < 0.01).ConclusionA multi-disciplinary approach is needed for the primary evaluation of patients with pelvic masses of undetermined origin. A gynecological resection is associated with increased morbidity during definitive cytoreduction and HIPEC for appendiceal mucinous tumors.     

细胞减灭术加腹腔热灌注化疗治疗卵巢癌腹膜转移癌的临床研究

目的 研究细胞减灭术（CRS）加腹腔热灌注化疗（HIPEC）治疗卵巢癌腹膜转移癌的疗效及安全性。方法 46例晚期（A组,FIGO Ⅲc/Ⅳ期,n=16和复发性,B组,n=30）卵巢癌腹膜癌患者接受了CRS+HIPEC治疗,分析其临床资料,主要终点指标为总生存期,次要指标为安全性。结果 A、B两组患者的中位总生存期（OS）分别为74.0月和57.5月（P=0.68）。腹膜癌指数（PCI）≤20（n=24）和＞20（n=22）的中位OS分别为76.6和38.5月（P=0.01）。CC 0~1分和CC 2~3分的中位OS分别为79.5和24.3月（P=0.00）。对复发性卵巢癌腹膜癌患者来说,铂类敏感型和耐药型患者的中位OS分别为6 5 . 3 和2 0 . 0 月（P=0.05）。无围手术期死亡病例,5例患者出现术后并发症。多因素分析显示,CC 0~1分、术后化疗≥6周期为改善生存的独立预后因素。结论 CRS+HIPEC可延长卵巢癌腹膜癌患者的总生存期,安全可行。     

Prognostic value of pre-operative systemic immune-inflammation index and platelet to lymphocyte ratio in peritoneal carcinomatosis of ovarian origin

Background and objectivesThe aim of this study was to investigate the impact of systemic immune-inflammation index (SII), platelet to lymphocyte ratio (PLR) and neutrophil to lymphocyte ratio (NLR) on the survival outcomes of patients who underwent to cytoreductive surgery (CRS) and HIPEC for ovarian peritoneal carcinomatosis.MethodsA retrospective analysis of 68 cases following surgery at our department between 2015 and 2020 was performed. Receiver Operating Characteristic (ROC) curve was used with Youden index to calculate the optimal cutoff values for SII, PLR and NLR.ResultsUnivariate analysis revealed that high preoperative values of SII, PLR and NLR were correlated with worse overall survival (OS) and disease-free survival (DFS) in these patients. In the multivariable analysis, high SII was recognized as an independent prognostic factor for OS (CI 95%: 0.002- 3.835, p = 0.097) and high PLR was recognized as an independent prognostic factor for DFS (CI 95%: 0.253–2.248, p = 0.007).ConclusionSII and PLR could be useful prognostic tools to predict outcomes of patients who underwent to CRS and HIPEC for ovarian peritoneal carcinomatosis.     

Unresectable peritoneal metastasis treated by pressurized intraperitoneal aerosol chemotherapy (PIPAC) leading to cytoreductive surgery and hyperthermic intraperitoneal chemotherapy

BackgroundPIPAC is a recent method of intraperitoneal chemotherapy. The aim of this study was to describe the clinical characteristics of the patients who became amenable to CRS & HIPEC after PIPAC treatment.MethodsAll patients diagnosed with unresectable PM who became resectable throughout PIPAC treatment were included. Outcome criteria were adverse events following PIPAC procedure and rate of secondary CRS and HIPEC.ResultsFour hundred thirty-seven PIPAC were done in 146 consecutive patients. Among them, 26 patients (17.8%) who underwent 76 PIPAC were scheduled for CRS and HIPEC after reduction of the peritoneal burden. PM were from gastric, peritoneal mesothelioma, ovarian, colorectal and small bowel in 13, 7, 4, 1 and 1 patients, respectively. At the time of the first PIPAC, median age was 58.6 years (32–76.3). Median PCI was 16 (1–39). All patients had systemic chemotherapy in between PIPAC session. Median consecutive PIPAC procedure was 3 (1–8). Complications occurred in 3 PIPAC session (4%) and there was no major complication (CTCAE III or higher). Complete CRS and HIPEC was achieved in 21 patients of the 26 scheduled (14.4%). The remaining 5 patients were considered unresectable at the exploratory laparotomy. Among patients who underwent CRS and HIPEC, with median follow-up of 7 (1–26) months, 14 patients (66.7%) were alive without recurrence, 2 patients (9.5%) were alive with recurrence and 5 patients (23.8%) died.ConclusionsComplete CRS and HIPEC can be achieved in strictly selected patient with unresectable PM at diagnosis after repeated PIPAC session with palliative intent.     

Effects of CytoReductive surgery plus hyperthermic IntraPEritoneal chemotherapy (HIPEC) versus CytoReductive surgery for ovarian cancer patients: A systematic review and meta-analysis

BackgroundThe effects of Hyperthermic IntraPEritoneal Chemotherapy (HIPEC) and CytoReductive Surgery (CRS) for ovarian cancer patients remain controversial.MethodsA systematic review and meta-analysis was conducted using PubMed, Embase and Web of Science databases to investigate Overall Survival (OS), Disease Free Survival (DFS) and adverse effects between HIPEC and CRS group. Results: In our overall analysis (13 studies), patients in the HIPEC group exhibited a significantly improved OS (HR = 0.56, 95% CI = 0.41–0.76, P < 0.01) and DFS (HR = 0.61, 95% CI = 0.48–0.77, P < 0.01). Subgroup analysis revealed improved OS (HR = 0.57, 95% CI = 0.40–0.83, P = 0.04) and DFS (HR = 0.61, 95% CI = 0.47–0.80, P < 0.01) for primary ovarian cancer in favour of HIPEC group. However, recurrent ovarian cancer patients who received HIPEC exhibited only significantly improved OS (HR = 0.48, 95% CI = 0.24–0.96, P < 0.01) but not DFS (HR = 0.59, 95% CI = 0.33–1.08, P = 0.09). In addition, both significantly improved OS and DFS were also observed in patients who received HIPEC in the subgroups based on the following factors: studies published before 2015, studies with ≥100 total patients, a single drug used for HIPEC, 90-min HIPEC duration and a regimen of CRS plus HIPEC followed by chemotherapy. Moreover systematically reviewed toxicity, morbidity, mortality and long-term outcomes were tolerable after HIPEC.ConclusionsThe addition of HIPEC to CRS could significantly improve OS of ovarian cancer patients, albeit optimal drug regimen is not clear.